Monthly Archives: September 2022

Treatment of Methamphetamine Withdrawal with Methylphenidate and Modafinil

DOI: 10.31038/PSYJ.2022443

Abstract

Background: Methamphetamine is globally abused. Like other addictions, methamphetamine abuse is a chronic relapsing disorder requiring for effective treatment and medications to promote the prevention of relapse. Methamphetamine use is accompanied with a state of well-being and also with increased wakefulness, physical activity, concentration and energy. Prolong use results to weight loss, aggression, memory deficits, poor impulse control, low concentration, severe dependency, unstable mood, hallucinations and delusions.

Conclusions: Some studies support the efficacy and safety of methylphenidate and modafinil in the treatment of methamphetamine withdrawal symptoms.

Keywords

Methylphenidate; Modafinil; Methamphetamine withdrawal

Introduction

In the industrialized and modern world, mainly developed countries, the rate of physical and mental diseases is going up therefore, policy makers, health decision makers and research workers have been paying out more consideration, care, concern, and currency to the treatment and direction [1-10] epidemiology, etiology, rate and prevention of mental disorders [11-31].

The most common cause of substance use disorders is psychiatric disease. A significant number of people self-medicate to decrease or improve their mental disorders such as irritability, anxiety, agitation, depression, mania, aggression, exhaustion, insomnia, impotency, and pain. Considering increasing level of mental problems globally, substance use disorders and substance related diseases, especially and mainly stimulants induced disorders have been considered as progressing dilemma [32-71]. At present, outpatient and inpatient referrals of psychiatric problems resulted from substance use and abuse are going up [72-110].

Use of methamphetamine produces a state of well-being accompanied with enhanced energy, wakefulness, and physical activity [1,111]. Repeatedly and extended use results to driven drug abuse, reduced weight, increased aggression, violence, memory deficits, poor impulse control, low concentration, prolonged health consequences, severe dependency, unstable mood and affect, delusions and hallucinations [112,113]. Methamphetamine is universally abused. In the United States, 18 million people over age 12 have experienced methamphetamine in their lives [112]. Similar to other addictions, methamphetamine abuse is a chronic relapsing disorder requiring for effective medications to promote the prevention of relapse.In Iran, in the past years, methamphetamine was illegally smuggled in from other countries mainly the West, but at the present time it is illegally synthesized and provided here in ‘underground’ laboratories. We should mention that the methamphetamine illegally synthesized in Iran is much more powerful and harmful and also is frequently associated with psychosis [114,115].

Following use of methamphetamine, cocaine  andalcohol, dopamine discharged into the nucleus accumbens and prefrontal cortex strengthen alcohol, cocaine, and methamphetamine seeking behaviors [116-120].

Presently there is not any approved medication for the treatment of methamphetamine withdrawal symptoms. Although administration of methylphenidate and modafinil is for the treatment of ADHD and narcolepsy [1] however, we are prescribing them for the management and treatment of severe methamphetamine withdrawal craving; because we theorize that (our rationale) biochemistry involved in the use of modafinil, methamphetamine and methylphenidate is more or less the same (all of them raise the level of dopamine [114-123]. We suggest more research studies and clinical trials that demonstrates data collected from comparing of modafinil and methylphenidate in the treatment or reduction of methamphetamine withdrawal symptoms.

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Three Losses: A Mind Genomics Exploration of Messages Which Drive Anxiety

DOI: 10.31038/ASMHS.2022661

Abstract

Three studies explored how systematically designed combinations of messages drive the subjective estimation of anxiety. The topics were loss of assets, loss of income, and loss of health, respectively. Respondents evaluated unique sets of 60 vignettes comprising 2-4 messages from a pre-selected set of 36 messages. Deconstruction of the ratings using ordinary least-squares regression revealed the basic anxiety-provoking potential of the loss (additive constant from the model), as well as the part-worth additional contribution of the particular element (the 36 coefficients). The data matrix was enriched by breaking out the respondents in each study into geo-demographic groups, into groups defined by when they experienced the anxiety. The creation of equations for the key subgroups revealed both differences in basic anxiety from size of the additive constant, as well as differences in the power of specific messages to drive anxiety. The approach using Mind Genomics coupled with a detailed self-profiling questionnaire, provides a new way to create an experimentation-oriented method to understand the mind and anxiety, a method which is fast, inexpensive, iterative, and generates scalable databases.

Introduction

We live in an uncertain world, one filled with dangers, resulting in bad things happening to good people [1] causing anxiety, and eventuating into a source of poetry, prose [2], not to mention words spoken to family, friends, and professional helpers in the field of mental health.

One need only go to Google® or some other source, to get a sense of the pervasiveness of anxiety. Table 1 shows the number of ‘hits’ in Google Scholar®, for the years 1980, 1985, 1990, etc., up to 2020. The topics are anxiety, anxiety about losing one’s assets, anxiety about losing one’s income, and anxiety about losing one’s health, the three major topics dealt with in this paper. Table 1 reveals clear the increase in ‘hits’, show the pervasive interest in anxiety. A reading of this literature will reveal the various aspects, viz., externalities driving anxiety, personal proclivities, and the like. There are numerous references to the physiological correlates of anxiety and situational correlates, along with expected discussions and analyses of personal predilections towards anxiety [3].

Table 1: Number of ‘hits’ in the academic literature pertaining to loss and other personal issues of the topic. Data from Google Scholar®

table 1

Understanding Anxiety from the Vantage Point of Mind Genomics

People are fascinated by the life stories of other people A great deal is known about the everyday, perhaps not always from science, but certainly from inter-personal interactions, as well as from published material. If personal experience is not sufficient, we have at our disposal the whole gamut of literature, the diverse ways of describing daily life, presented in an artistic manner to delight as well as to report. With this introduction, then, to the world of anxiety, what can experimentation contribute that has not been contributed in a far more elegant way by the literature, not to mention the analysis of countless sessions, whether with professionals, or far more frequently, with friends?

Conventional research methods give a sense of the nature of the experience (viz., in-depth interviews and focus groups), the distribution of different variations of th experience (viz., polls and quick surveys), as well as the nature of the world surrounding the experience (viz., behavioral studies, anthropological and sociological studies). Absent, however, is a delineation of the experience in a way which combines qualitative approaches to dive deeply into the topic, and quantitative approaches which provides data that can be used to create a database, and from there extract new insights into the topic.

Mind Genomics is an emerging branch of experimental psychology, with roots in psychophysics, in statistics, and in consumer research. The objective of Mind Genomics is to understand the way we respond to the topics of our daily lives, through systematic experiments about responses to descriptions of the ‘ordinary’ [4]. Mind Genomics quantifies how we respond to the general topics, issues, and specific actions of the everyday. For example, the topic of this paper is anxiety, specifically the anxiety emerging from the possible loss of assets, or income, or health, respectively, all three topics important to people. How can we explore the way people think about the anxiety emerging from the disruption of daily life, specifically disruption one of the three areas, assets, income, or health, respectively. How do we respond? Can we quantify our feelings? Are there different patterns of response?

Mind Genomics grew out of the interest in the way people think. Over the 40 years that Mind Genomics developed, the author was active in the world of psychophysics and perception, the study of how we perceive the outside world. It became increasingly obvious that scientists studying various aspects of ordinary behavior were attempting to bring disciplined evaluation from science into the world of the everyday. Missing, however, was an integrated approach, one that could be applied across many different areas, easy to do, and with the potential to easily, and affordably create a large, searchable database which could tell us about the way people think. The focus of Mind Genomics was not to put individuals into unusual situations and observe reactions to the unusual, but rather study reactions to the far more frequent ‘usual,’ the warp and woof of life usually ignored because it is always in view.

Explicating the Approach by Investigating Three Sources of Anxiety Emerging from ‘Loss’

This paper grew out a set of studies called Deal With It!, designed and executed 20 years ago, in 2002. The studies focused on actual issues driving everyday anxiety. The objective was to understand the relation between descriptions of anxiety-provoking situations, and the stated feeling of anxiety experienced by the respondent, who read the descriptions.

The actual process follows these steps:

Step 1: Select the Topics

The actual Deal with It! study comprised an investigation of 15 different topic areas. The respondent was invited to participate by an email invitation. Pressing the embedded link led to the ‘wall’ of studies shown in Figure 1. The respondent selected the study, and participated in the study. This choice of studies allowed the respondent to select a topic of interest. All 15 studies shown in Figure 1 were run. This paper presents and discusses only the results from three of the 15 studies (loss of assets; loss of income; loss of health, respectively).

fig 1

Figure 1: The Wall showing the 15 ‘Deal With It!’ studies. The respondent chose the study in which to participate.

Step 2: Create the Elements according to a Specific Plan

Mind Genomics works by the approach in experimental psychology known as S-R, stimulus-response. The stimuli are messages (elements), messages that will be later combined in a specified manner described below. It is important to select a representative set of these messages, covering various aspects of the topic. One of the benefits of Mind Genomics is the ability to do small initial experiments to identify promising messages. These preparatory efforts are not discussed here.

The basic structure of elements in a Mind Genomics study comprises a set of questions (categories of ideas), and for each set of questions a limited set of answers. Thus, for the Deal With It! studies presented here the underlying structure comprised the topic (viz., nature of loss), then four questions, and then nine answers for each question. Table 2 shows the underlying structure.

Table 2: Structure underlying the creation of the elements

table 2

It is important to keep in mind that the set of answers should be chosen so that a combination of answers (our elements) generates the rough outline of a ‘story’ when the elements are combined into vignettes, viz., combinations comprising 2-4 elements. Each vignette can comprise at most one answer from each question, or may be absent answers from one or two questions, as dictated by the design.

There are three requirements for the elements listed in Table 2:

  1. The questions should be answered by declarative phrases. These phrases should be as short as possible.
  2. The declarative phrases should paint ‘word’ pictures, even though they are phrases, and not complete sentences. Word pictures are important because they convey idea quickly.
  3. The four sets of answers comprise the same number of answers in each set. This property makes it possible and straightforward to create experimental designs, templates for the vignettes.
  4. The actual elements appear in Table 3. Table 3 shows the full text of the different elements and, to the right side, the abbreviated text for the element which appears in the data tables The top part of Table 3 shows the 13 elements common to all three studies. These elements describe one’s feelings, and general actions from the outside. The bottom part of Table 3 shows the unique elements from each of the three studies. In the interest of brevity and readability the data tables present the abbreviated text.

Table 3: Elements in the three studies

table 3

table 3(2)

table 3(3)

Step 3: Combine the Elements into Unique Sets of 60 Combinations (Vignettes)

Mind Genomics moves away from the traditional and hallowed approach of isolating a variable, and studying that variable thoroughly. The rationale for moving away from the traditional ‘isolate and study’ comes from two realizations.

  1. The reality of our everyday experience is that the experience comprises mixtures of stimuli, not single stimulus in solitude. We could be instructed to pay attention to one stimulus in the mix, and disregard other stimulus, but our mind and our behavior appears to be wired to deal with compound stimuli, with mixtures. The focus on one single aspect is artificial. That focus may work with conventional science, but humans live in a world where they respond most naturally to ever-changing mixtures of stimuli, and NOT to pure stimuli. Pure stimuli are artificial, and the results may fail to mirror what happens in everyday life when stimuli must ‘fight each other’ to gain attention.
  2. When people judge aspects of their everyday life, they typically use a common scale for the different combinations of the same type of stimuli that they encounter. For example, when a person deals with traveling on a road, most roads of the same type are subject to the same judgment criteria. This makes the person’s job easy, and routine, allowing the person to focus on other issues of the moment. However, were each aspect of the travel on the road to be separately evaluated, such as weather, pavement, trees, time of year, etc., it may well turn out that the respondent uses different criteria to judge each aspect, making it impossible to truly compare travel on one street to travel on the other. The plethora of details, abstracted and evaluated one at a time, makes it likely that the respondent will change the criterion for evaluation for each aspect, to make the criterion fit the topic. The researcher might well think that the respondent is using the same criterion for all judgments whereas in actuality the respondent is dynamically changing the criterion to be appropriate for each isolated aspect. There is no way the researcher could know that unless the respondent were to volunteer, but the respondent might not yet know just what criterion had been used for each of the judgments.

Given the foregoing issue, Mind Genomics studies work in a manner more similar to nature, albeit in manner which is carefully choreographed. The test stimuli no longer are single ideas such as those in Table 2. Rather, the test stimuli become combinations of messages which tell a story, or at least have the surface appearance of something which might actually exist. Her is an example for ‘loss of health.’

Diagnosis of uncontrollable disease…

You never expected it to happen to you or someone close to you…

At a turning point in your life…

You trust your God will help you get through this

The respondent does not rate each of the four phrases (elements), but rather reads the combinations, and assigns a single rating to the combination. Although the messages are compounded into one vignette, the respondent usually has no problem assigning a single rating to the combination. The respondent may not consciously know the criteria used to assign the rating, and may feel that she or he guessed, but subsequent analyses show that the respondent’s ratings generate an interpretable pattern, and the pattern points to consistent criteria for judgment.

The actual combinations follow a prescribed grouping, called an experimental design. The experimental designs for Mind Genomics were created with the property that each of 60 vignettes comprised 2-4 elements, that a vignette could be absent elements from one or two questions but not from three questions, and that the 36 elements were statistically independent of each other. A vignette could have at most one element (answer) from any question, ensuring that a vignette would never present to the respondent pairs of elements which contradicted each other.

The final and most important feature was that the experimental design could be permuted [5]. Permutation means that the basic design could be changed, by having the elements vary; for one permutation an element could be assigned to code A1, whereas for another permutation the same element could be assigned to code A3. The permutation allowed the creation of hundreds of alternative designs, all similar mathematically, but with the elements having different codes. The elements remained within their groups, viz., an element in Question A always remained in that group, but its code changed. The permutation generated several hundred equivalent designs. The permutation made it unlikely that two respondents would ever evaluate the same combination of elements. Finally, the permutation allowed the researcher to explore a wide range of combinations, rather than having to ‘know’ the most promising area to assess. It is this ability to assess a wide range of combinations which makes the Mind Genomics processes a tool to explore in the absence of any knowledge whatsoever.

The design was structured so that the set of 60 ratings assigned to the 60 vignettes in that design (one respondent) could be analyzed by OLS (ordinary least-squares) regression.

For each vignette, the respondent was instructed to read the vignette as a complete entity, and rate the combination, using an anchored scale, as shown in Figure 2.

fig 2

Figure 2: The instruction page

Step 4: Create a Detailed Self-profiling Questionnaire

A hallmark of the It! studies was the extensive questionnaire, requiring information from the respondent about WHO the respondent is, WHAT the respondent believes/does, and WHEN the actual participation in the study occurred. Keep in mind that the It! studies were run in the early days of Mind Genomics, around 2000-2004, when the respondents were far more willing to participate in longer studies executed on the Internet. Thus, at that time, there was no issue with adding a few more minutes to the Internet-based interview in order to accommodate the extensive self-profiling questionnaire (Table 4).

Table 4: The self-profiling questionnaire

table 4

Step 5: Run the Studies

The studies were placed on a protected server in the United States, owned by Moskowitz Jacobs, Inc. Respondents in the panel owned by Open Venue, Ltd. Of Toronto, Canada, were invited to participate. These panelists had previously signed up to participate in on-line studies. All respondents lived in the United States, even though the panel provider, Open Venue, was Canadian. Throughout the past two decades, as internet-based research has proliferated, it has become increasingly easy to work with a panel provider in one country, who could source respondents in another country, while the researcher lived in a third country.

Analysis-Transforming Ratings, Creating Individual-level Models, Creating Summary Tables

The data from these studies generate a ‘wall of numbers.’ The easiest way to discover patterns is through a straightforward, four step analysis, which reduces the number of data points to those which are strong. It is a great deal easier to discern patterns with 1-5 strong performing elements (all others not shown) than it is to discern patterns with a number-dense array of 36 data points.

The analysis follows these steps:

  1. At the level of the individual respondent transform the original assigned 9-point rating into a new binary value. Ratings of 1-6 (can deal with it) are transformed to 0. Ratings of 7-9 (cannot deal with it) are transformed to 100. A vanishingly small random number is added to each transformed value, whether the transformation creates a 0 or a 100, respectively. The rationale for transforming the ratings into two numbers comes from the world of consumer research and polling, wherein it is not sufficient to report mean ratings from an anchored Likert Scale, like our 9-point scale, but also necessary to make practical, important decisions using the data. Managers often express discomfort when they work with Likert sales, mainly because they cannot straightforwardly interpret the scales and the statistics. A binary scale moves the result to a yes/no, an all-or-none, something that the managers finds more palatable to help drive action.
  2. At the level of the individual respondent, use the 60 ‘cases’, viz., data from the 60 vignettes (experimental design and transformed rating) to create an equation or a model representing the linear relation between the presence/absence of the 36 elements and the binary value of the transformed rating. The equation is expressed as: Binary Rating = k0 +k1(A1) + k2(A2)…k36(D9)
  3. The foregoing equation expresses the relation between the independent elements, which either appear in a vignette (coded as 1 in the regression analysis), or is absent from the vignette (coded as 0 for the regression analysis).
  4. The additive constant is the estimated proportion or probability of getting a value ‘100’ (viz., original rating of 7-9), in the absence of elements. Of course, by design all vignettes comprise a minimum of two and a maximum of four elements so there cannot be any vignettes without any elements. Nonetheless, the OLS (ordinary least squares) regression estimates the value of k0 for each respondent. We interpret the additive constant as a baseline for anxiety.
  5. The OLS regression now returns with data for each individual respondent. Whereas before we began with raw data comprising 60 rows for each respondent, the OLS regression returns with data comprising one row for each respondent, both a 60-fold reduction, and the source of insights as shown below. We now move to the second stage of analysis, working only with the output of the OLS regression, done at the level of each respondent.
  6. The new data, viz., second data matrix, comprises one row for each respondent. The row contains the study identification, the unique identification number for the respondent, the information about the respondent from the self-profiling questions (see Table 3). Following this information about the study and the respondent are 37 columns, the additive constant and the 36 columns, one column reserved for the coefficient of each element.
  7. We are now ready to create the third data matrix, which will be much simpler. Steps ‘E’ and ‘F’ reduced the data to a manageable format. One last step remains to make the data even easier to understand. We know from statistical analyses that for a coefficient to be ‘statistically significant’ (viz., the coefficient be different from 0), the magnitude of the coefficient for these designs must be approximately 7-9 or higher. Thus can recode each of the 36 coefficients for each respondent. When the original coefficient for a respondent is +10 or higher for an element the element we replace the coefficient by the number ‘100’. When the coefficient is less than 10 for the element (including negative numbers), we replace the coefficient by the number ‘0.’ In this way each respondent generates a series of 36 0’s or 100’s, showing which elements drive anxiety (viz., cannot deal with it.).
  8. Recall that the respondent completed the self-profiling questionnaire. It is straightforward now to sort the set of transformed profiles into groups, based upon the specific question in the-self profiling questionnaire. In turn, the data being sorted comprises the now-transformed profile of 36 coefficients, which are either 100 (original coefficient for the element being 10 or higher), or 0 (original coefficient for the element being lower than 10). Step G above explicated the transformation.
  9. The analysis can now move more quickly, using matrices comprising 0’s and 100’s, instead of a matrix of coefficients as estimated for each respondent (F, above). The final step creates averages for each of the 36 elements, for all respondents from a specified subgroup of individuals. The interpretation of the averages is straightforward. The average transformed coefficient for an element from a specified group of respondents is defined as the proportion of respondents in that group who felt that they just ‘cannot handle’ the anxiety (or other internal feeling), when they read the particular element embedded in a vignette.
  10. Recall that the additive constant can be interpreted as a ‘baseline’ level of anxiety, albeit a derived baseline, emerging from the OLS regression Thus, the average additive constant within a subgroup of respondents can be defined as the likely baseline of anxiety (viz. ‘I cannot deal with it’) for the topic itself for this particular group of respondents.
  11. Finally, the tables for the strong performing elements are deliberately shortened. For the total panel, only those elements are shown which generate an average of 51 or higher (viz., 51% or more of the respondents in the defined group ‘cannot handle it.’) For the key subgroups defined by the self-profiling classification we make the criterion more stringent, with a value of 55 or higher required to appear in the table. This stringent criterion eliminates most of the elements, allowing patterns to emerge more easily.

Total Panel

It is clear from Table 5 that only a few elements perform strongly for the total panel. The strongest performing element, viz. the most anxiety provoking, is ‘You lose your home’ (loss of assets), with a mean of 70% expressing strong anxiety. The only other strong element occurs, ‘You believe your company will help you get through this’ (loss of health), with a mean of 60% expressing strong anxiety. We will see the ongoing recurrence of these two elements as strong drivers of anxiety.

Table 5: Strong performing (viz., anxiety-provoking) elements from the total panel. The coefficients are the percent of respondents in the total panel whose coefficient is 51 or higher.

table 5

When looking at the strong performing elements, it is important to keep in mind that there is no way that the respondents could have ‘gamed the system.’ The respondent evaluated 60 vignettes, each vignette comprising 2-4 elements. Exit interviews with respondents doing these types of studies have, year after year, revealed that most people think they are guessing. Clearly they are not. They are simply responding at a so-called ‘gut level.’ And, the results are no surprise, although it is disconcerting to see the lack of trust of people in business. Yet,the headlines at the time of this writing (summer, 2022) talking about the ‘great resignation’ and the ‘silent resignation.’ People do not trust their employers to help them.

Time of Day When Respondent Participated in the Study

  1. The first question in the self-profiling questionnaire required the respondent to record the time of day. Table 6 shows that there are time-anxiety relationships, mostly in terms of the additive constant (Add Con). When considered as a baseline level of anxiety, the additive constant is lowest in the afternoon (12 PM-6 PM), and much higher in the evening (6 PM-10 PM). Worries about income are highest in the morning, worries about assets and health are lowest in the morning.
  2. In terms of the specific elements, the pattern is difficult to discern, except for one’s worry of the loss of one’s home, which is very frequent at all times of the day, but most frequent when the respondent participates in the late evening and during the morning.

Table 6: Strong performing (viz., anxiety-provoking) elements from respondents participating in the study at four defined time periods of the day. The coefficients are the percent of respondents in the total panel whose coefficient is 55 or higher.

table 6

Immediacy of the Loss

  1. In the self-profiling questionnaire the respondent was instructed to select whether or not the respondent felt that the anxiety-provoking situation was happening or is possibly happening, versus not happening. The response ‘happening yes/maybe’ show different patterns than ‘happening/no.’ The additive constant showing the base level of anxiety for the topic is higher for those reporting ‘happening’ than for those reporting ‘not happening,’ but only for losing assets and for losing income. That is, the basic level of anxiety for monetary loss is higher when it is actually happening. In contrast, the thought of losing one’s health, whether happening or not, shows the same level of anxiety (Table 7).
  2. As one would expect, the specific elements driving strong anxiety responses (viz., ‘can’t deal with it’) differ by type of loss. The strong anxiety is the thought of losing one’s home. That is, 70% of the respondents report strong anxiety, viz., 70% of the respondents show coefficients for this element of +10 or higher.
  3. Finally, the thought of external sources of aid is also anxiety producing, not for losing assets but for losing income (relying on insurance aid causes anxiety), and losing health (relying on charities or on one’s company causes anxiety).

Table 7: Strong performing (viz., anxiety-provoking) elements from respondents who are experiencing the issue vs. respondents who are not experiencing the issue. The coefficients are the percent of respondents in the total panel whose coefficient is 55 or higher.

table 7

Frequency of Occurrence of the Specific Anxiety

  1. Our analysis focuses only on those who report experiencing the anxiety daily.
  2. Lose assets-shows a moderate additive constant. The element which drives anxiety is losing one’s home.
  3. Lose income-a higher additive constant of 47, but no strong performing elements.
  4. Lose health-a moderate additive constant of 41, but three strong performing elements based on ‘outside help’ (company, charities, local hospital), and one strong performing element based on the sickness (lose control of bodily functions) (Table 8).

Table 8: Strong performing (viz., anxiety-provoking) elements from respondents who experience the issue daily or frequently, respectively. The coefficients are the percent of respondents in the total panel whose coefficient is 55 or higher.

table 8

Geo-demographics of the Respondents

  1. Females show a higher additive constant than do males (viz., greater proclivity for anxiety) for loss of assets and loss of income, respectively. In contrast, males show a higher additive constant for loss of health.
  2. Younger respondents show a higher additive constant for loss of assets and loss of income, respectively. In contrast, older respondents show a slightly higher additive constant for loss of health.
  3. Higher-income respondents show a higher additive constant for loss of assets and loss of income, respectively. Lower income respondents show higher additive constant for loss of health.
  4. Respondents frequently find help distressing when that help is presented as coming from third parties (charities, insurance, one’s company, etc.) Respondents age 60+ find the help of one’s company quite distressing, both in the case of losing one’s assets (82% find the mention of company to drive anxiety), and in the case of losing one’s health (70% find the mention of company to drive anxiety) (Table 9).

Table 9: Strong performing (viz., anxiety-provoking) elements from respondents self-defined in terms of gender, age, and income, respectively. The coefficients are the percent of respondents in the total panel whose coefficient is 55 or higher.

table 9

Location of the Anxiety Occurrence

As part of the self-profiling classification, the respondent was instructed to select the one or two locations where the experience of anxiety occurs. The actual question was phrased as: Q8:Where do you generally think about this Situation? (Check 2)

  1. Table 10 suggests that the basic level of anxiety differs by type of loss and by location. There is no clear pattern, other than loss of assets and loss of income are both high in various places, whereas loss of health is far lower, other than at work (viz., additive constant of 39 for work versus 29 or lower elsewhere).
  2. Table 10 shows notable differences in the ability to elements to drive anxiety, as well as differences in basic anxiety experienced, with different additive constants for the same location across three sources of anxiety. Recall that the additive constant is a measure of the basic proclivity of the respondent to experience anxiety when the loss or situation is stated in the vignette. For example, when the respondent is at work, the most severe anxiety is occasioned by the thought of losing one’s assets (additive constant = 55). When the respondent is at work, the thought of losing income is less anxiety provoking (additive constant = 44). Finally, when the respondent is at work the thoughts about losing health is the least anxiety-provoking (additive constant = 39).
  3. It is anxiety about the loss of one’s health which emerges in many different places, and triggered by the greatest number of elements. For losing assets and losing income anxiety is triggered by two or three elements, respectively. For losing health anxiety is triggered by six elements.
  4. The complexity emerging from Table 10 may require the reader to scan the table, so that the reader’s focus can allow the relevant patterns to emerge.

Table 10: Strong performing (viz., anxiety-provoking) elements from respondents self-defined in terms Where the anxiety is experienced. The coefficients are the percent of respondents in the total panel whose coefficient is 55 or higher.

table 10

Emotions Experienced after Participating in the Study

Question 6 in the self-profiling questionnaire instructed the respondent to introspect about her or his global feeling after having evaluated the 60 different vignettes. The respondent was allowed to check all that apply. Table 11 shows the number selecting each emotion, the additive constant for their proclivity to experience anxiety, and the elements most able to drive anxiety for the particular subgroup of respondents. As was the case for many of the other tables (except self-profiling geo-demographics shown in Table 9), each section of the table is sorted in descending order by additive constant.

Table 11: Strong performing (viz., anxiety-provoking) elements from respondents self-defined in terms of how the respondent feels after evaluating the 60 vignettes. The coefficients are the percent of respondents in the total panel whose coefficient is 55 or higher.

table 11

The first observation is that the rank order of additive constants makes sense, at least at the most general level. Those who check off ‘angry’ or ‘depressed’ show the highest additive constant. Those who check off optimistic and relaxed show the lowest additive constant. There are no surprises here, other than that the data appear to show consistency across different measures, in a way that would be hard to ‘game.’

The second pattern is the nature of the elements which drive anxiety.

  1. For losing assets the elements driving anxiety are help from charities, from company, and from insurance, respectively. These elements ‘jump’ out from individuals/emotions showing low additive constants. That is these elements disturb people who are otherwise not prone to feeling anxiety, reflected in the low additive constants.
  2. For losing income the emergent pattern differs. The strong drivers of anxiety are expectation of help from insurance, and expectation of help from the government. These elements drive anxiety, no matter what the respondent feels.
  3. For losing health anxiety is strongest when the messages are help from charities, from the company, and from supplemental insurance, no matter what the emotion felt, and no matter how high the additive constant (basic proclivity to anxiety).

The Person’s Self-chose ‘Relevant Responses’ to the Situation

Questions 16-30 in the self-profiling questionnaire instructed the respondent to check the activities that the respondent thought to be relevant for the particular anxiety-provoking situation which was the topic of the study. The question was phrased as: In the next few screens we will talk about various activities. For each activity please indicate how relevant it is to your situation. The phrasing did not direct the respondent to say what the respondent was actually doing, but rather what was thought to be relevant.

Table 12 shows that respondent differentiate among the relevant or appropriate responses to loss, at least based upon the additive constant. If we assume that the higher the additive constant represents the proclivity to anxiety for the specific loss, then the three losses engender different behaviors patterns of anxiety associated with the behaviors that the respondents feel to be ‘relevant’ in the wake of the loss.

  1. For loss of assets, the effort to deal with anger generates the highest additive constant (41), i.e., the highest proclivity to anxiety. Exercise generates the lowest additive constant (24).
  2. For loss of income, ‘talking’ generates the highest additive constant (52) whereas exercise generates the lowest additive constant (34).
  3. For loss of health, ‘talking’ again generates the highest additive constant (39) whereas exercise generates the lowest additive constant (14)
  4. There are different elements which drive anxiety. For losing assets it is clearly losing one’s home. For losing income it is clearly the mention of help from insurance, as well as losing one’s job because of one’s own mistakes. For losing health, it is loss of bodily functions as well as the dependence upon charity.

Table 12: Strong performing (viz., anxiety-provoking) elements from respondents self-defined in terms of what the respondent feels to be the relevant action to be taken given that loss occurs. The coefficients are the percent of respondents in the total panel whose coefficient is 55 or higher.

table 12

Discussion and Conclusions

An inspection of today’s scientific methods suggest that a great deal of the focus is placed on either filling ‘holes’ in the literature, or creating limited-scope hypotheses about a topic [6]. The ascendance of the hypothetico-deductive system, coupled with the increasing focus on inferential statistics to support hypotheses, mean that the studies become increasingly more focused, far more narrow. As a consequence, the scientific community has learned to deconstruct a topic such as responses to everyday anxiety provokers into small pieces, viz., testable hypotheses. An example might be that the most severe anxiety producer is the expected loss of one’s home, a statement that can be assessed by having the respondent rate the different losses in terms of severity. This is an attractive finding, one that can be tested, and which gives a ‘sense’ of how people think about anxiety. The finding is certainly better than simply saying that there are a number of anxiety producers, such as loss of home, loss of health, loss of income, and so forth.

When the researcher moves beyond the simple aspects, the one-at-a-time thinking, the traditional way of doing so have been to use qualitative methods, discussion, and observation (e.g., [7]). The researcher can get a sense of the nature of the way people cope with anxiety producing situations, e.g., by using one-on-one depth interviews with one or two people to discuss their feelings about the anxiety issue. Or, as if often the case, the researcher can use group discussions, where a group of individuals guided by a trained professional discusses a topic.

The contribution of Mind Genomics to the knowledge of anxiety is to move the approach to experimentation and collection of ancillary information about the respondent. Mind Genomics can determine whether defined subgroups of individuals show identifiable, interpretable patterns of responses to test stimuli. These groups are those emerging from using the self-profiling classification (Table 3) as a system for creating these subgroups. The results can be new insights into the mind of the person, responses generates to systematically controlled and varied verbal stimuli (viz., the elements in the vignettes).

The Role of the Additive Constant

As noted in the methods section, the additive constant is the ‘adjustment factor’ incorporated into the regression to correct for the fact that the regression model may not actually go through the origin. In terms of the underlying mathematics, the additive constant is the estimated value of the dependent variable when all of the independent variables are 0. In Mind Genomics terms, the additive constant is the estimated value of the binary rating (viz., 7-9, ‘cannot deal with it’, i.e., makes me anxious) when there are no elements present. We choose to call it the predisposition to express anxiety.

The additive constant emerges from the pattern of responses to the 60 different vignettes. Thus, it is virtually impossible to ‘game’ the Mind Genomics experiment, in order to provide a desired, pre-defined additive constant. Furthermore when we look at the change in the additive constant across different situations different emotions, and so forth, we find that for the most part the rank order of the additive constants makes intuitive sense. For example, those who have just participated in the experiment and are feeling happy or optimistic show a lower additive constant than those who have just participated in the same experiment, albeit with different combinations of elements. Thus the additive constant can be analyzed in and of itself as a basic metric of predisposition to anxiety.

The Role of the ‘Transformed Coefficients’

As noted in the analytic section, the data from each respondent were used to create an individual-level equation relating the presence/absence of the elements to the likelihood of having an anxiety-driven response (viz., 7-9, cannot deal with it). The individual coefficients were transformed so that all coefficients of 10 or higher (viz. element ‘drives’ anxiety response) were transformed to one number, the value ‘100.’ All remaining coefficients under the value 10 (whether positive, zero, or negative) were transformed to 0 (viz., element does not ‘drive’ a strong anxiety response for that individual). This transformation of the coefficient enables the researcher to average the transformed values. The average represents the proportion of respondents in the group who feel that the element is felt to ‘drive’ anxiety. For our analysis, the story emerges when we look only at those elements driving a majority of the respondents to respond that ‘I can’t deal with it’ (viz. coefficient of 10 or higher).

When we look across the elements and groups, we begin to get a sense of what elements are thought by respondents to drive anxiety. Most surprising is the exceptionally negative response to elements talk about the ‘help’ proffered by groups, including charities, government, and one owns company, respectively This disbelief in organized help and corporate help is worth further investigation because the disbelief seems cynical in the face of the oft-proclaimed desire of groups be of help ‘when the situation arises.’ One hears organization proclaiming their aid, actual and emotional, in times of need. The disbelief by respondents could be considered to be an artifact, casting doubt on the entire effort because the disbelief goes head to head with the organization messages. Yet, the disbelief is credible. The experimental design makes it again impossible to ‘game the system,’ and so the disbelief, the cynicism must be respected and investigated.

Contributions of Mind Genomics to Our Knowledge of People

The published academic literature deals with many types of losses that people sustain, and the response to them. The majority of these studies focus on specific issues, such as loss of jobs and failure to pay mortgage, but most frequently on the loss of health and what it entails [8-12]. These studies focus narrowly on the topic, looking at the issue in depth. By their very nature, the studies are narrow and limited, rather than being holistic. In contrast, Mind Genomics presents a ‘deep dive’ into the problem, albeit one mediated by the S-R (stimulus-response) method from experimental science. Mind Genomics provides an easy-to-develop scalable database, useful to measure the subjective degree of anxiety, as well as identify the possible triggers, executed in a way where the ‘experiment’ is less threatening because of its superficial similarity to the now common Internet-based survey.

Acknowledgment

The author would like to acknowledge the efforts of the late Hollis Ashman of the Understanding and Insight Group, Inc., for her efforts in putting together the 15 It! studies, under the auspices of It! Ventures, LLC. It was through Hollis’ efforts that the studies were designed, executed, and initially reported during the years 2003 to 2006.

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The Mind of the West European Coffee Drinker Revealed through Mind Genomics

DOI: 10.31038/NRFSJ.2022522

Abstract

Respondents from three countries (France, Germany, and UK) each evaluated unique sets of 60 vignettes about coffee, created by combining elements (messages) according to an underlying experimental design. Respondents rated each vignette on an anchored 9-point scale of craving (1=do not crave. 9=crave extremely). The ratings were deconstructed into individual level models, showing the contribution of each message to craveability. By incorporating an extensive self-profiling classification questionnaire, the research paradigm, Mind Genomics, revealed the nature of how respondents think about coffee, showing the contribution of the message itself, as well as the country, and the nature of what the respondent does in terms of coffee behavior. The paradigm presents the potential for a deep understanding of the mind of the ordinary person, doing ordinary tasks, e.g., those involved with coffee, and allows the affordable and easy creation of large-scale databases of human behavior and decision making.

Introduction

As this paper is being written the world of coffee is actively evolving. From a drink in a modern day ‘coffee house’ enjoyed in leisure, coffee has become what might well be the most popular beverage in the world, emblematic of different social norms around the world, and today a source of involvement in societal-moral issues. Coffee has evolved into a drink that people enjoy together in coffee houses, chatting, reading paper, starting their morning with a quick cup, or passing the day leisurely [1,2]. Moving further, coffee ready to drink comes in a variety of ‘forms’, whether traditional ‘black’, doctored up with all sorts of other ingredients [3,4]. Coffee has emblemized social change. During the past decades consumers have fallen in love with Italian espresso coffee, so much so that that one can feel an Italiphila (love of things Italian) pervading the word through the world-wide reception of espresso [5-7].

This most popular drink has, in turn, evolved into a topic of social concern. In, study after study the academic literature has started to focus on social issues, such as the environment as well as ‘fair trade’ for the farmers who grow the coffee beans [8-11]. The sheer popularity of coffee in daily life and the social significance of fair trade to pay the farmer the real value of the coffee make the topic irresistible to academics. Google® has 62,400 hits for the topic ‘coffee and fair trade’, Google Scholar® has about 8x as many, 481,000 hits for coffee and fair trade!

Despite the importance of coffee, there are relatively a handful of academic papers on the topic of coffee itself. Some of these are studies the sensory properties of coffee, and the different pattern of preferences for these sensory properties. For example, Geel et al. (2005) reported that four patterns of the acceptance emerging from the response to 11 coffees: “Based on consumer preferences, four consumer groups were identified, “pure coffee lovers” (23%), “coffee blend drinkers” (30%), “general coffee drinkers” (37%) and “not serious coffee drinkers” (10%). The “pure coffee lovers” prefer the more astringent, bitter, roasted, nutty and full-bodied flavour of the pure coffee samples. The less intense coffee flavour character, but higher sweetness and root flavour, typical of chicory blended instant coffee, were attributes that were preferred by the “coffee blend lovers”. The “general coffee drinkers” seem to consume coffee out of habit and are less concerned about the specific sensory properties of the coffee [12].”

The academic literature is equally sparse when it comes to what to communicate about coffee in order to entice prospective buyers. From the author’s own experience, the companies selling coffee do extensive research, from basic attitudes and usage studies (A&U) dealing with coffee as part of life, and then concept tests to find out the acceptance of new ideas, and finally advertising evaluation to find out ‘what works’.

One might think that the knowledge is extensive in corporations about the aspects of coffee, specifically the most persuasive messaging. The author’s experience, however, over the past 46 years since 1976 would suggest just the opposite. There seems to be no systematic study about coffee messaging that the author has ever encountered in the public literature, nor has the author encountered evidence of this systematic approach in private consulting. There are tests of individual messages, but no large scale, systematic tests of the mind of the coffee consumer regarding the language of coffee. When directly confronted with the request ‘show me the book of messages which work with consumers’ no one, either in academia or in business has been ever able to provide the request ‘book’ or at least ‘database.’

Getting into the Mind of the Coffee Consumer through Mind Genomics

Given the importance of coffee, there is an extraordinarily amount known about the consumer attitudes towards coffee and the consumption patterns of the actual product, most of the information residing in the file cabinets and stored and archived ‘banker’s boxes’ of study results owned by corporations usually residing in dead storage. Indeed, the author’s own experience with Maxwell House Division of General Foods Corporation in the mid 1980’s suggested that for General Foods Corporation alone, the consumer research budget was in the millions of dollars, with hundreds of reports issued by the market research department as well as by the sensory evaluation department. What new, if anything, can consumer-focused scientific research add with to what has been developed with the large corporate budgets? Can we learn new things about the way people think about coffee?

Despite the richness of information, from the public domain (popular press, from companies, and from presumably more objective science there still is a lot to be discovered, which is where the emerging science of Mind Genomics enters. Mind Genomics was developed from a different world view, that of looking at how people make decisions when confronted with compound stimuli, mixtures of messages, the more typical situation in nature. Mind Genomics traces its heritage to conjoint measurement [13] and to experimental design [14].

Mind Genomics paints word pictures of products (and intangibles, such as service), these word pictures created from defined combinations of simple phrases that a person would encounter during everyday experience. The combinations are called ‘vignettes.’ Using statistical methods such as OLS (ordinary least-squares) regression to deconstruct the response to the mixture into the driving power of the components, viz., elements. Mind Genomics studies ends up being far deeper, and often far more ‘actionable’ for science and business purposes than information and ‘insights’ emerging from conventional qualitative, quantitative, and behavioral studies [15,16].

The foregoing approach of mix/evaluate/deconstruct is quite different from that used in conventional research, where the respondent is presented with one idea or question after another, forced to focus on an array of topics which keep changing. In such a system, viz. the typical questionnaire, the respondent must keep changing her or his frame of reference, first thinking for example about the occasion, and then about the product, and then about feelings, etc.

It! Studies – the Lure of Mind Genomics Databases across Products and Across Countries

After successful research with Mind Genomics in the world of foods, the McCormick & Company approached the author and colleague Jacqueline Beckley of the Understanding and Insight Group, Inc. to extend the scope of Mind Genomics studies that they had already run. Rather than applying Mind Genomics to one topic of food, the research sponsor at McCormick, Director Dr. Hamed Faridi, wanted to look at a whole set of foods, the elements appropriate for that food, but with common elements dealing with emotion benefits. This effort become the 2001 Crave It! study, a study of 30 foods then repeated with teens, rather than with adults [17]. The study was massive by any consideration, with each study comprising more than 100 respondents, and exactly 36 elements, combined into unique sets of 60 vignettes for each respondent. The results were analyzed ‘globally’ to identify recurring themes among people. The data suggested that across all the 30 studies, three patterns continued to emerge: Elaborates, Imaginers, and Classics. These groups, so-called ‘mindsets’ clearly differed in terms of the particular elements which appealed to them. The Elaborates focuses on the food, the Imaginers on the situation, and the Traditionals on the typical factors involved with the food, such as enjoyment, price, etc.

About a year later, the same idea was supported by the Firmenich Corporation, this time looking at foods in three western European countries, France, Germany and the UK, respectively. The structure was the same, and at that time the focus was on the re-emergence of the three now ‘canonical’ groups of respondents, again based upon the pattern of their coefficients when the data from each country and each food were more deeply analyzed [18]. Nothing of the sort had been done before. The notion was conceived of and developed by Pieter Aarts of Belgium, Klaus Paulus of Germany, and the It! Ventures LLC in the US (Jacqueline Beckley and Howard Moskowitz). The studies, sponsored by Firmenich in Switzerland, were designed to understand how people respond to different ideas and descriptions of food, not so much using the traditional attitude and usage sales, but rather using the new method of experimentation offered by Mind Genomics.

The Eurocrave Studies on Coffee

The three studies reported here come from the early days of Mind Genomics, when getting respondents showed that respondents could participate with little difficult, as long as they were somewhat motivated. During the early years of this century the novelty of the Internet was such that people were intrigued. The respondents were sent invitations, and offered a chance to participate in a sweepstakes for money. This sufficed to bring in thousands of respondents, these thousands choosing to participate in a study that interested them.

The actual Mind Genomics study, positioned as a ‘survey’, was actually an experiment. The word ‘experiment’ is negatively tinged, but the word survey and the word opinion is not. The Mind Genomics approach begins with a topic, requires a set of four questions, and nine answers to each question. The questions tell a story, or provide distinct types of information. These early studies, of which Crave It! and Eurocrave! are examples, show the early focus on acquiring as much information as possible about a topic?

The ingoing notion of Mind Genomics was and remains the idea that we can learn a lot by presenting a person with combinations of messages, and instruct the respondent to rate the combination. Rather than polishing the combination so the combination becomes a dense paragraph, albeit a well-written one, the Mind Genomics experiments virtually ‘throws’ the ideas at the respondent, instructing the respond to react to the combination. The approach is a bit off-putting at first, because respondents are far more accustomed to well written, dense paragraphs. An analogy is the difference between a compote comprising many fruits versus a thrown-together fruit salad.

The structure required four questions, each with nine answers. The objective of the experimental design was to ensure that the elements would be put together in such a way that each vignette would have at most one answer from two, three, or four questions. The actual design, four questions by nine answers per question, is a template, required for ‘bookkeeping’, so that a vignette would never have two answers from a single question, answers that might contradict each other.

Table 1 shows the raw materials, the elements, from the three studies, one in the UK, one in France, and one in Germany. The elements are in the native language. As much as possible the elements were the same across countries, but that equivalence of elements was not possible in the case of brands or stores present in one country but not in the other. Table 1 shows that the same idea might be expressed in slightly different ways by country. Thus, one should look at the elements as specific instantiations of more general ideas, instantiations which may differ across countries. This caveat means that the data should not be rigorously compared across countries, simply because the execution of the same idea in one country might be quite different from the execution of the same idea in another country.

Table 1: Elements for the three-country Eurocrave study on coffee

TABLE 1

One of the hallmarks of Mind Genomics is the use of language that is best characterized as ‘colloquial.’ That is, the elements themselves are phrased in the way a person of the country might talk. In the actual Mind Genomics experiment this effort to be simple and colloquial will end up playing an important role. The language itself will allow the respondent to ‘graze’ through the text, rather than force the respondent to think about the answer. That is, the simple declarative format will simplify the respondents task, with the respondent simply looking at easy-to-understand sets of phrases.

Running the Mind Genomics Experiment

In conventional studies, specifically surveys, the study is set up so that the respondent must focus on a single question, answer it, and then move on to the next. The effort is made to minimize respondent bias although it is in the nature of respondents to want to please the researcher, and to give the correct answer Whether the respondent can actually come up with the ‘correct answer’ is not important. What is important is the pervasive subconscious nature to be right or at least to be consistent. Such biases abound in survey research. Researchers attempt to counteract these biases by such strategies as rotating the order questions in order to reduce effects due to test order, and disguise the nature of the topic so that that the respondent cannot really guess about the goal of the question.

The Mind Genomics approach to the interview is described as a survey to people, but as stated above, the reality is that Mind Genomics constitutes really a well -controlled experiment. The experimenter presents test stimuli (viz., combinations of messages, the aforementioned elements shown in Table 1), obtains a response (a rating of the vignette by the respondent), repeats the task, collects the data, and then relates the presence/absence of the elements to the ratings. The respondent simply rates the combination, almost it would appear from exit interview, assigning the ratings in what is report as a guessing, or in a state of indifference because the task seems daunting.

The respondent in the Mind Genomics experiments does not evaluate one phrase at a time, viz., rate 36 phrases. Rather, the respondent in a study is exposed to 60 different combinations of these elements, each combination comprising 2-4 elements, no more than one element or answer from a question. The respondent is simply instructed to the read the vignette (combination of elements) as one idea, and rate the combination on a nine-point scale. The scale is simple, anchored at both ends:

Using this 9-point scale, please show how you feel about the COFFEE as described:

1 = Do not crave it at all … 9= Definitely crave it

Most people participating in the study, or even just inspecting the set of 60 vignettes, the combinations of elements, feel that the elements have been thrown together randomly. Nothing could be further from the truth. The underlying structure for the 60 combinations is dictated precisely by an experimental design, a blueprint, which defines the specific elements present in each combination.

The experimental design provides these convenient features and benefits:

  1. Each vignette comprises a specific set of elements. The minimum number of elements is two, the maximum number is four. By design, many of the vignettes are incomplete. Each element appears equally often, five times in 60 vignettes, and absent 55 times from the 60 vignettes. Doing the arithmetic shows that each of the four questions contributes 45 elements to the 60 vignettes and is absent from the remaining 15 of the 60 vignettes.
  2. No vignette comprises more than one element (answer) from a specific question. The underlying rationale is that no vignette can carry mutually contradictory information of the same type (e.g., no vignette can comprise two brands).
  3. Each respondent tests a unique set of 60 vignettes, different from the 60 vignettes tested by any other respondent. This approach, permuted designs, was patented by author Moskowitz and colleague Alex Gofman [19].
  4. The happy outcome of the structure is that one can create an equation relating the presence/absence of the 36 elements to the rating (or a transform of the rating), at the level of a single respondent, or at the level of a group of respondents. This ‘within subjects’ feature allows clustering algorithms to identify groups of respondents with similar patterns of coefficients, viz., ‘mind-sets’ in the language of Mind Genomics [20].

The studies for Eurocrave were set up in the United States. Local field services in the three countries invited respondents to participate by internet survey. The respondent was invited to participate by the local field service in the country, a field service with a specialty in recruiting panelists for web-based, viz. online, studies.

It is important to keep in mind that even as far back as 2002, two decades ago, it was virtually impossible to source a sufficient number of respondents from one’s friends and colleagues. The notion that people want to participate in research interviews, whether with live interviewers or on the web, is simple unreasonable, then, and increasingly so. One cannot expect people to offer their time for free. It is important to compensate them, and even more important to work with companies specializing in providing people to participate in consumer research studies. The criticism that these may become ‘professional respondents’ is far less cogent than the almost certain fact that depending upon the goodwill of random people, even students in a class, will probably end up with fewer respondents than needed.

Each of the three countries had a pre-created ‘wall’ listing the different foods being covered in the Eurocrave project. Figure 1 shows the wall for the German study. The wall was designed with three properties in mind.

fig 1

Figure 1: The wall for the Eurocrave study (Germany)

  • The studies (really names of the foods) appeared in random order, to minimize the selection of studies in one position, e.g., the top right.
  • When a study had 120 respondents who successfully completed the study, the study temporarily ‘disappeared’ from the wall, so it could not be chosen. The respondent had to choose from among the less popular studies.
  • The happy consequence of this strategy was that respondents only participated in a study, which interested them.

The respondent was led to the correct study, read the introduction informing the respondent of the topic and the length of time (15 minute), and then presented the respondent with the vignettes, one after another. As soon as the respondent pressed the rating key the vignette disappeared, and the next vignette appeared in its place. There was no opportunity to change the rating once it was assigned. Afterwards, the respondent completed a self-profiling questionnaire dealing with different aspects of who the respondent IS, what the respondent THINKS regarding coffee, as well as the time of day that the respondent was completing the study.

Strategy for Analysis and for Presentation of Results

Most users of data do not feel comfortable with Likert scales, like the scale for craveability. They do not know what the scale means, even though respondents seem to have no trouble using the scale, AND the scale allows for valid statistical analysis.

Many researchers feel that they learn more when they can divide the scale into two parts, viz. NO and YES, respectively. It is easier for managers to understand NO vs YES. To make the research easier to understand, the data were divided into two points, ratings 1-6 transformed to 0, ratings 7-9 transformed to 100. This division was arbitrary but made intuitive sense. After the foregoing transformation, a vanishingly small random number was added to each transformed value, so that the ratings were slightly different from 0 or 100, and slightly different from each other when they had been transformed. This addition of the small random number enabled the dependent variable for each respondent to show some variation across vignettes, even when the respondent confined her or his ratings to the lower part of the scale (1-6, always transformed to 0) or to the upper part of the scale (7-9 always transformed to 100). The variation ensured the data be further processed at the level of the individual respondent.

The individual data were analyzed by OLS (ordinary least-squares) regression, which estimated the additive constant (k0) and the 36 coefficients (k1-k36), one coefficient for elements A1-D9, respectively. The regression equation is expressed as: Transformed Rating = k0 + k1(A1) + k2(A2) …. K36(D9).

The regression equation summarizes the data for a respondent or group of respondents. The additive constant, k0, can be interpreted ais the estimated proportion of respondents who would rate a vignette 7, 8 or 9, respectively, in the absence of elements. Of course, the underlying experimental design ensures that no vignette will comprise fewer than two elements, so the additive constant is a purely estimated parameter. The additive constant plays a role, becoming a baseline value of the likelihood of respondent assigning a positive rating of 7, 8 or 9. High additive constants (e.g., 50 or more) mean that the respondent has a predilection for up-rating vignettes. In this ‘happy’ situation, a vignette simply has to feature elements which are slightly positive, and avoid elements which are negative. Low additive constants (e.g., lower than 30, for example) mean that for a vignette to get a high rating of 7, 8 or 9, respectively, the elements ought to be strong performers because the predilection of the respondent is to use the lower part of the scale.

The analysis of the ratings by OLS regression produces a large data set, namely 37 numbers for each respondent. The 37 numbers per respondent is far smaller than the matrix required to code the raw data for the respondent. The original data for each respondent constituted requires 60 rows of numbers, beginning with information about who the respondent is, what the respondent does, et., continuing then into 36 columns (one column for each element), then the rating, and then the transformed rating. This matrix contains one row per vignette per respondent. Across all 60 rows for a single respondent the information about the respondent remains the same, but the data fields corresponding to the structure of the vignette (which element appear, which do not appear), and the rating, change from vignette to vignette.

The Mind Genomics exercise produces a great deal of data, specifically 37 numbers per subgroup of respondents. It is impractical and counterproductive to report the data from each element across all of the relevant subgroups (viz. total panel and key self-defined subgroups, as well as emergent mind-sets). The amount of data for one subgroup overwhelms. Multiply that amount of information by the number of subgroups relevant to an analysis, and one can easily end up with 100+ cells of data. Looking for a pattern across 100 cells is data is simply too difficult.

One of the ways to cut down on the amount of data, and allow important data through, is to eliminate any coefficient less than a certain value for any of the 36 elements. The standard error of the coefficient is 4-5 for these studies, so a coefficient of 8 or 9 is likely to be significant, and more important, likely to signify something relevant about the topic. Thus, a coefficient of 10 or higher can be considered important. Other coefficients, viz., those below 10, need not be shown, and thus allowing the patterns to emerge. For this paper we will only look at coefficients of +10 or higher. As we begin the analysis of the data, it will quickly become apparent that most of the elements do not have strong performing coefficients, simplifying our search for patterns. Furthermore, each data table will show highlighted elements, viz., elements which score well (coefficient of 10 or higher) for at least three subgroups. These are ‘strong performers,’ viz., ‘strong performing elements.

Results

Who the Person Is – Total and Gender

We begin the analysis with the total panel and with males and females (Table 2). The first analysis looks at the additive constant. Recall that the additive constant is a baseline, or at least can be interpreted as a baseline. Looking at Table 2, we see that the additive constants differ by country. Those for the UK and France are 41, moderate, but the elements show low coefficients. The additive constant for Germany is low, 30, but more elements are strong performers.

Table 2: Strong performing elements for total panel and for gender

table 2

From study after study one of four patterns emerge, to describe the value of the additive constant and the value of the coefficients:

  • Low additive constant, low values for the coefficients – an unpopular idea. A good example is credit cards. The values of the additive constant are usually 0 or even negative up to about 20.
  • Moderate additive constant, low values for the coefficients. The value for the additive constant is 20-50. Here the basic idea is neutral, buoyed up by some good ideas if any.
  • Moderate additive constant, high values for many coefficients. The value for the additive constant is again 20-50-. Here the basic idea is neutral Here the respondent is discriminating among the elements, with some elements really being winners.
  • High additive constant, low values for many coefficients. The value for the additive constant is 50 or higher. Here the basic idea is very good, and the respondent does not really find elements to strongly augment the already-high basic response to the vignette.

The second analysis looks at the strong performing elements. Surprisingly, the three countries exhibit few strong performing elements, at least for total sample and gender. Respondents in each country show only one strong performing element each across all three groups (total, two genders). The elements are different, but all from Question or Group A, dealing with the description of the product itself. This finding surprises because of the absence of strong-performing elements, but is in line with other studies from Mind Genomics which point to the importance of an appetizing description of the product as a driver of strong performance.

UK: AE2 Fresh coffee, made from 100% Colombian coffee beans

France: AF8 Expresso: saveur intense en une gorgée

Germany: AG1 Kaffee: frisch gemahlen und aufgebrueht

Who the People Are – Age

The self-profiling classification allowed the respondent to report their age. Table 3 shows age does not play an important role. The additive constants show a mixed pattern, increasing with age in the UK, decreasing with age in France (except for a very low additive constant for those 18-25), and not clear in Germany, which presented only two ages.

Table 3: Strong performing ‘coffee elements’ for three countries, by age

table 3

The strong elements in country are different, but again it is important to note that the strongest elements come from the first group of elements, the first question, about the product.

UK: AE2 Fresh coffee, made from 100% Colombian coffee beans

France: AF8 Expresso: saveur intense en une gorgée

When the Respondent Participated – Time of Day

One of the foci of the It! studies, such as our coffee study, was the question regarding differences in the additive constant and in the coefficients. Table 4 shows the relevant data.
These patterns emerge:

  1. The additive constants are almost all quite low. It is the elements which must do the work.
  2. The additive constants increase from morning to night, suggesting a more positive ‘basic response’ to the message at night. The pattern is not perfect, however, but is worth noting because there may be an increasing sensibility about the quality of the coffee as the day progresses, with the quality of the coffee less important than the ability to ‘wake one up’, expected to be the case in the morning hours.
  3. The only time which does not feature many very strong performing elements is 6pm to 9pm.
  4. UK respondents do not show strong performing elements emerging in the three hour period of 9PM to 12 Midnight, whereas in contrast, French and German respondents do.
  5. The strong performing elements are:

Table 4: Strong performing ‘coffee elements’ for three countries, by daypart (three hour segments)

table 4

UK: AE2 Fresh coffee, made from 100% Colombian coffee beans

France: AF8 Expresso: saveur intense en une gorgée

DF3 De la marque Carte Noir

Germany: AG6 Cappucino: herzhaft, schaumig und weich

AG1 Kaffee: frisch gemahlen und aufgebrueht

AG5 Kaffee und Milch zum perfekten Milchkaffee gemischt

How the Respondent Felt – Self-Reported Thirst

As part of the self-profiling questionnaire the respondent selected the level of thirst experienced. Once again across the three countries on a few elements perform well for different levels of perceived thirst (Table 5)

Table 5: Strong performing ‘coffee elements’ for three countries, by self-reported degree of thirst

table 5

There are two patterns here worth noting:

  1. The additive constant is much higher when the respondent reports a high degree of thirst
  2. All strong performing elements showing up in three or more states of thirst come from Question A, dealing with product.

UK: AE2 Fresh coffee, made from 100% Colombian coffee beans

France: AF8 Expresso: saveur intense en une gorgée

Germany: AG6 Cappucino: herzhaft, schaumig und weich

AG1 Kaffee: frisch gemahlen und aufgebrueht

Coffee Behavior – Frequency of Coffee Consumption

Table 6 shows that the vast majority of respondents participating in this study were frequent coffee drinkers. One of the more interesting things emerging from Table 6 is that those who drink coffee less frequently, viz., once a day, find more evocative elements of interest.

Table 6: Strong performing ‘coffee elements’ for three countries, by self-reported frequency of drinking coffee

table 6

UK: AE2 Fresh coffee, made from 100% Colombian coffee beans

France: AF8 Expresso: saveur intense en une gorgée

Germany: AG6 Cappucino: herzhaft, schaumig und weich

Coffee Behavior – Day-part of Coffee Consumption

Depending upon one’s culture, coffee can be consumed any time during the day or night. It is only a matter of cultural norms and one’s predilections. Table 7 shows that the most frequent day-part differs by country. Looking at the frequency of 30 respondents or more we find the following:

Table 7: Strong performing ‘coffee elements’ for three countries, by self-reported time of day when coffee is consumed

table 7

UK – breakfast most, and then evening and finally mid-morning parts. Highest additive constant in the mid-afternoon, lowest in the evening.

AE2 – Fresh coffee, made from 100% Colombian coffee beans

France – breakfast most, then mid-afternoon, and finally mid-morning. French respondents do not say that they drink coffee in the afternoon. The same size additive constant for breakfast, mid-morning, and mid-afternoon, respectively.

Germany – breakfast most, then mid-afternoon, then mid-morning. The same additive constant across all times (from breakfast to just before dinner)

AG1 – Kaffee: frisch gemahlen und aufgebrueht

AG6 – Cappucino: herzhaft, schaumig und weich

The ‘bottom line’ is that there are dramatic differences across countries, and even differences in the performance of elements in a single country across dayparts. The patterns are difficult to summarize.

Coffee Behavior – Where Coffee is Purchased or Consumed

In the self-profiling questionnaire the respondents checked off the places where they purchase or consumed coffee. Table 8 shows the distribution of the responses across five venues. The venues are not equally represented across the three countries, however, primarily due to low base sizes of respondents.

Table 8: Strong performing ‘coffee elements’ for three countries, by self-reported venue of purchase or consumption

table 8

UK – Not in a department store nor in a local restaurant known in one’s area. The UK respondents purchase their coffee in a supermarket or food store. It may well be that the respondents don’t think of drinking coffee after a meal in a local restaurant as a real ‘coffee occasion’.

France – The French respondents purchase their coffee in a supermarket, and do think about coffee consumed in a local restaurant, but again without the strong focus of that as being a real ‘coffee occasion.’ (The base size is only 19 respondents). The French respondents consider coffee at a department store as a real coffee occasion.

Germany – The German respondents think of all venues (food store, department store, supermarket, coffee shop) as coffee occasions, but do not think of local restaurants and coffee as coffee occasions. German respondents show the greatest number of strong-performing elements associated with venue.

Coffee Attitudes – Features Selected as Important

The self-profiling classification questionnaire contained a question about what features of coffee the respondent felt to be important. The respondent could select up to three features. These features comprise, respectively, sensory aspects (appearance, aroma, taste), emotional aspects (memories, associations, brand), package features (packaging), and consumption features (portion size, social situation, mood).

Table 9 shows the patterns. As one would expect, aroma and taste, the sensory impressions, are chosen most frequently. The remaining features are distributed in different ways by country and show different patterns. In the interest of simplicity, we focus only on groups comprising 30 respondents or more.

Table 9: Strong performing ‘coffee elements’ for three countries, by self-reported selection of ‘what is important’

table 9

UK – Brand and mood are chosen most frequently.

Those choosing brand show a higher additive constant (50), but few strong performing elements. No brand elements are chosen!

Those choosing mood show a lower additive constant (31) and only two strong performing elements

France – Only brand chosen frequently, with an additive constant of 47.

One brand element chosen, Carte Noire, but with a low coefficient, 8.

Germany – brand and mood chosen most frequently after aroma and taste.

Brand has an additive constant of 33, with the only brand performing well being Tschibo (coefficient of 9)

Mood has an additive constant of 47 but no mood or emotional elements score well!

Once again the data suggest a disconnect between what respondents say may be important and the strength of their reactions. When actually presented with that information in an element which paints a word picture, an element which instantiates the general idea, the element may not perform well.

Emergent Mind-Sets – Similar Patterns of Coefficients

A hallmark of Mind Genomics is the effort to uncover basic groups of individuals, with these groups showing similar patterns of behavior or responses to test stimuli. These test stimuli are granular in nature, such as our study of responses to coffee. The focus on granularity, on the rich specifics contained within the granularity means that these emergent basic groups, so-called mind-sets, represent the way people think about the particular topic, at the particular time. Mind Genomics does not try to create general groups of people, although these groups may emerge, such as the division of people into Elaborates, Imaginers, and Traditionals, names given to the three mind-sets emerging many times in the early work on foods [18].

The creation of these ‘mind-sets’ is done in a purely statistical fashion. The steps to create the mind-sets are listed below, and follow the well-accepted approach in statistics known as ‘clustering’ [20]:

  1. For a given dataset, create the individual-level models, expressed as: Transformed Rating = k0 + k1(A1) + k2(A2) …. K36(D9).
  2. Work only with the 36 coefficients, discard the additive constant k0.
  3. Compute the ‘distance’ between pairs of respondents using the expression: (1-Pearson Correlation, although expressed as 1-R).
  4. The Pearson Correlation measures the strength of a linear relation between two sets of measures (viz., the linear relation between the 36 pairs of coefficients for two respondents).
  5. The clustering program (k-means) puts the objects (viz., the respondents) into groups, based strictly on mathematical criteria, namely that the distance be large between the centroids (averages) of the groups (clusters) should be large, and the distances be small between the pairs of respondents.
  6. The analysis created both two clusters and three clusters.
  7. It is the researcher’s job to determine the underlying pattern, if any, for each country, for each mind-set. The criteria are to choose the smallest number of clusters (parsimony), as well ensure that the mind-sets tell a story (interpretability).
  8. There is no need to have the mind-sets for the three countries be the same
  9. Three clusters (mind-sets) emerged for the UK and for France, two clusters emerged for Germany.

Table 10 presents the strong performing elements by country and mind-set within country:

Table 10: Strong performing ‘coffee elements’ for three countries, by mind-sets for each country

table 10

UK: One large mind-set (UK-MS2) and two smaller mind-sets (UK-MS1 and UK-MS3).

The three mind-sets show approximately the same magnitude of the additive constant (43-50)

Only one of these mind-sets shows strong performing elements, UK-MS1.

Mind-Set UK-MS3 shows only one strong performing element, AE2 Fresh coffee, made from 100% Colombian coffee beans.

France: Two large mind-sets (FR-MS1, FR-MS3) and one small mind-set (FR-MS2).

The additive constants and the strong performing elements are different.

FR-MS1 shows the highest additive constant (72), and react most strongly to descriptions of emotional experience.

FR-MS2, the smallest mind-set, shows strong responses to the elements. The base size of 11 respondents in FR-MS2 may be too low to assume FR-S2 is a ‘real’ mind-set. It may simply be the result of forcing the clustering to come up with three mind-sets.

FR-MS3 responds strongly to statements about product and features (Question A)

Germany: Only two mind-sets emerged for Germany, with the third mind-set having very respondents, and thus not shown.

All elements for Germany come from product and features (Question A).

In most Mind Genomics studies the search for mind-sets generates strongly defined, exceptionally different groups. Surprisingly, this does not seem to be the case for coffee, despite the hundreds of millions of dollars spend on advertising. It may well turn out that there is simply not enough differences among coffees to create sharply different mind-sets, based simply on description. That is, ‘coffee may just be coffee.’ There are not enough intrinsic features in coffee to drive radically different mind-sets, despite the popularity of coffee, or perhaps the underlying reason for that popularity!

Discussion

Improving Research by Reducing Bias

The approach presented here with coffee emerges with some clear patterns, the clearest of which is that the strongest performing elements in these Mind Genomics studies come from the question about product description. Although the respondents are presented by systematically varied vignettes, combinations of messages, and cannot possible ‘game’ the system, they act in a consistent manner. It is impossible to know the ‘correct’ answer when presented with a rapidly changing set of 60 vignettes. The demands on the respondent are very strong, and militate against overthinking. Yet again and again what emerges are the same types of messages. No matter how we attempt to provide additional types of information the pattern re-emerges. Only a few messages are strong.

It is important to reiterate the fact that the design in this study prevents bias. With the continuing presentation of vignettes, most respondents simply ‘turn off,’ responding automatically. The data do not suggest that the respondent down-rates the vignettes out of irritation. Yet, in many ‘exit interview’ respondents have said, by way of complaint that they felt they were guessing, that they were unable to discern a pattern which would lead to the ‘correct answer. Respondents do try to guess in these situations. The fact that they cannot discern the pattern simply means that they must react at an intuitive level, or react randomly. Yet, if respondent were to react randomly, then we would see many more elements from Questions B, C and D emerging as strong performers. They do not. The respondents do respond in a truthful manner, even if the respondents do not think so. The result may be the accuracy emerging by of averaging well-meaning ‘guesses’, with the result being the ‘correct answer’ as Surowiecki discusses in his work on the Wisdom of the Masses [21].

To summarize the differences then, the conventional questionnaire instructs the respondents to think about different aspects of the product and situation, in our case here ‘coffee.’ The respondent may be asked dozens of questions. The pattern of responses gives us an idea of how the respondent feels about coffee. The respondent may subconsciously change the responses to questions to be perceived as consistent. Indeed, the emphasis is often on answering consistently, digging into one’s own thinking to answer the question as best as possible. The interview can be perceived as a test, and there is always the worry about ‘interviewer bias,’ a concern with a history of at least three quarters of a century [22-24]. In contrast, the Mind Genomics approach creates an experiment, comprising known combinations of messages, presents these combinations, acquires the response, and estimates the driving power of each element.

A New Type of Insight

Traditional research in the world of psychology and consumer behavior has focused on attitudes towards product or services, looking at the way different ‘types’ of people respondent, or looking at how some antecedent experimental manipulation affects the response. From these data, whether through discussion, observation, or experimentation, the researcher is able to fill one more ‘hole in the literature,’ one more gap in the web of knowledge. It is through the accretion of these pieces of information, individual moments of insights, and the integrative ability of analysts with a wide scope and imagination, that the ‘story’ builds, and understanding increases.

The approach presented here, while incomplete by necessity, provides a grander, more holistic view of the topic. The study here on coffee is not only on one particular problem, one recurrent issue, but is rather an attempt to create a new type of database, multi-dimensional in nature. On the one hand we have the topic, coffee, which has been well explored on different, scientifically relevant dimensions. On the other hand, we have a product consumed around the world, which, when examined closely, lacks a deep reservoir of integrated information about the nature of people and coffee. We don’t know what messages attract people. We know that people differ, but we don’t know how they differ. Nor do we have any real idea of the co-variation of factors, such as the responsivity of individuals to coffee messages, these individuals classified by who they are, when they participate, what they hold to be important, and so forth.

The Mind Genomics paradigm creates this type of information, doing so easily and quickly. Rather than plugging ‘holes’ in the literature, closing gaps, and growing science one finding at a time, Mind Genomics becomes a holistic knowledge-development tool, creating information that is both novel and in fact occasionally fascinating.

Creating Large Databases

As emphasized throughout this paper, Mind Genomics is actually a well-constructed experiment with defied independent variables and responses. The outcome of the experiment is a database. This set of three studies shows how one can construct the database for three countries, for one product, working with respondents from each country. The studies are rapid, taking days, and cost-efficient, with estimates today as of this writing being $4-$6 per respondent for a smaller version of Mind Genomics (16 elements), with easier to find respondent. Thus, in terms of economics, the per country cost of a Mind Genomics study with 16 elements, rather than 36, is less than $1,000, low by today’s standards. Indeed, the potential exist for the enterprising consumer researcher or marketer to spend less than $100,000 to create a world-wide database of a particular product, at a particular point in time. We can only speculate about the vast increase in knowledge this database will bring, across cultures, across time, and across different mind-sets within a culture. The dream of the It! Studies, developed around the year 2000, is now immediately doable by virtually anyone (see www.BimiLeap.com and www.PVI360.com)

Acknowledgments

The author gratefully acknowledges the foundational work for Eurocrave, sponsored by Firmenich in Switzerland, with the guidance and help of Pieter Aarts of ScentTaste (Belgium), and Klaus Paulus (Germany). The late Hollis Ashman of the Understanding and Insight Group in the USA did much of the design work prior to the study, and analytics after the study.

References

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BMI and Physical Activity in College Students Assessed Using the International Physical Activity Questionnaire (IPAQ)

DOI: 10.31038/NRFSJ.2022521

Abstract

A volunteer sample of 100 first-year college students were recruited to examine their body fat percentage levels and to investigate the association between their body fat and their levels of physical activity. Body fat percentage scores were regressed stepwise on college students’ vigorous physical activity, moderate physical activity, walking, and gender. The results of the regression indicated that the model explained 35.0% of the variance, and two factors such as vigorous PA and gender were significant predictors of first-year college students’ body fat percentage, F(1.78)=56.00, p<0.001. The rest of the variables entered were the moderate PA and walking, and these were not significant factors.

Keywords

BMI, Physical Activity, IPAQ

Introduction

More than 70% of U.S. adults and 30% of college students were classified as either overweight or obese, and it is reported that 18.4% of adolescents were classified as obese [1-6]. Although the etiology of obesity is multifactorial, insurmountable evidence supports the premise that obesity is highly correlated with physical inactivity [7,8]. Of the various factors leading to obesity in college students, physical activity levels have been consistently reported to be a significant factor in maintaining normal body weight and lowering the risks of developing chronic conditions, including type II diabetes, heart diseases, hyperlipidemia, and hypertension [9,10]. To prevent young adults from developing chronic diseases, the American Health Association (AHA) recommends individuals get at least 150 minutes per week of moderate-intensity aerobic physical activity [11,12]. Despite this recommendation, only half of the adults aged 18 and over met the 2008 federal physical activity guidelines from 2016 to 2018 [13]. In a meta-analysis conducted by Keating and his colleagues (2005) on the college students’ physical activity levels, they found that half of the college student population did not meet the AHA’s recommended physical activity [14]. It is noteworthy that according to an observational study by Clemente et al. (2015), male students walked more steps and spent more time in a moderate and vigorous activity than female students [15-17].

Examining the levels of physical activity requires a thorough process of measuring all types of physical activities and calculating the energy expenditure associated with each type and level of physical activity. International Physical Activity Questionnaire (IPAQ) is designed to measure individuals’ level of physical activity and its metabolic equivalents (METs), allowing researchers to examine the relationship between these factors [18]. Liu and his colleagues’ study conducted in 2015 demonstrated that physical activity levels were a mediating factor in the subjects’ body mass index measured by the IPAQ forms. They also found that lower BMI scores were positively correlated with moderate and vigorous physical activity, while higher BMI scores were positively correlated with insufficient physical activity [19]. A cross-sectional study of a volunteer sample of 738 college students conducted by Huang and his colleagues that examined the collective effects of dietary intake and physical activity on college students’ BMI found a correlation between physical activity and BMI in late adolescents and early adults, supporting the hypothesis that physical activity was a significant predictor of BMI [20].

The BMI has been widely used in research and clinical practice in the last 30 years when reporting adults’ obesity in predicting their health risks for chronic diseases. However, Coral and his colleagues pointed out the limitations of the BMI measure in a cross-sectional study of 13, 601 subjects from the National Health and Nutrition Examination Survey (NHANES): the diagnostic accuracy of BMI in measuring adiposity is limited because the BMI does not account for variations in body composition (i.e., the relative proportion of total fat versus skeletal muscle mass) [21-23]. Therefore, it is a concern when research is aimed at predicting college students’ future health risks based on the BMI measure because some college students who are either athletes or are extremely muscular were misclassified as obese. To address this concern, the National Heart, Lung, and Blood Institute recommends using not only BMI but other anthropometric measures that are a good indication of individuals’ health risks, including body fat percentage, waist circumference, and waist-hip ratio. In the past decades, numerous studies have steadily reported the danger of college students’ weight gain based on their BMI. However, only a small portion of the research measures college students’ obesity using BMI and anthropometric measures to predict their future health risks [24-27]. Despite a multitude of studies reporting first-year college students’ weight gain, the majority of the findings of such studies did not measure the first-year college students’ baseline anthopometric information [28]. Thus, this study aimed to measure in-coming first-year college students’ baseline obesity before their exposure to the college lifestyle and investigate the association between young adults’ body fat percentage levels and their physical activity levels.

Methodology

Subjects

A volunteer sample of 100 college freshmen was recruited from a total of 900 incoming freshmen in Fall 2015. Recruitment strategy was conducted through trained undergraduate student volunteers. These volunteers were visiting the foyers of college resident dormitories to distribute flyers to freshman students on the opportunity to participate in this study.

Procedures

Before participating in this research researchers handed out informed consent forms to explain the purpose of the research and any potential harms and benefits and discomforts that were associated with participating this research in order to prevent any potential harms or coercion of student participants. After that, participants were asked to complete a survey that asks questions about their eating behaviors and physical activity. The questions are general and do not imply that they are in any inappropriate behavior. The survey takes about 25 minutes to complete. After survey completion, participants’ height, weight, waist circumference, tricep skinfold and calf skinfold were measured.

Measures

International Physical Activity (IPAQ) short form was used to measure college students’ physical activity levels, and anthropometric (physical measures) were be taken for height, weight, waist circumference, tricep skinfold and calf skinfold using standardized protocols from National Institute of Health (NIH).

Results

Demographic Information

Of the 100 first-year college students in the study, 57% (n=57) were males and 43% (n=43) were females. The mean age was 18.53 (SD=1.20) for males and 18.26 (SD=0.51) for females, where the youngest students were 18 year old and the eldest were 25 years old. Table 1 depicts the participants’ anthropometric data, including weight in kilogram, and height, waist, and hip in centimeters.

Table 1: Participants’ Anthropometric Information

Weight (kg)

Mean (SD)

Height (cm)

Mean (SD)

Waist

Mean (SD)

Hip

Mean (SD)

Body Fat

Mean (SD)

Male

72.80 (13.24)

174.02(9.96)

80.32(9.72)

98.77(7.75)

14.04(6.45)

Female

64.06(16.77)

161.62(7.42)

79.06(13.55)

99.78(10.78)

25.21(9.11)

Body Fat Percent Distributions by Gender

As illustrated in Table 2, the study subjects (n=100) were classified as essential fat (n=7), athletes (n=35), fitness (n=18), acceptable (n=26), and obese (n=14) based on the American Council on Exercise (ACE)’s fat norms for men and women. The majority of male students (n=39, 90.7%) and female student (n=47, 82.5%) were found to be within the normal body fat percentages. Concerning the first-year students’ obesity, obesity rates of females were almost twice higher than that of males: 9.3% of male and 17.5% of female students, respectively.

Table 2: ACE’s Body Fat Percentage Distributions by Gender

American Council on Exercise (ACE)’s Fat Norms for Men and Women

Essential Fat

Athletes

Fitness

Acceptable

Obese

Men

(2-5%)

(6-13%)

(14-17%)

(18-24%)

(>25%)

Women

(10-13%)

(14-20%)

(21-24%)

(25-31%)

(>32%)

This Study
Men

7.0% (n=3)

58.1% (n=25)

11.6% (n=5)

14.0% (n=6)

9.3% (n=4)

Women

7.0% (n=4)

17.5% (n=10)

22.8% (n=13)

35.1% (n=20)

17.5% (n=10)

The statistical analysis verified a significant difference in the mean body fat percentage of male students compared to that of female students (Welch’s two-sample t-test: t=-7.309 with df=98, p<0.05). The mean body fat percentages of the male students were 14.04% (SD=6.45), and those of the female students were reported to be 25.21% (SD=9.11).

Levels of Physical Activity by Gender

As seen in Table 3, descriptive data analyses on college students’ levels of physical activity showed that male students engaged in more days of physical activities per week compared to female students.

Table 3: Mean Days of Physical Activities (PA) per Week

   

Male

   

Female

   
Days of PA  
Per Week

n

Mean

SD

n

Mean

SD

P-value

Vigorous PA

43

3.19

2.42

57

1.33

1.84

0.00*

43

4.16

2.51

57

3.00

2.19

0.09

43

5.33

2.33

57

4.91

2.22

0.77

(Note: Physical Activity (PA), * Statistically significant at 0.05)

Of the three levels of physical activity, the most common type of physical activity was walking in both male and female students: 5.33 days for males and 4.91 days per week for females. It is noteworthy that there was a statistically significant difference in first-year students’ mean days of vigorous physical activity per week. Specifically, the mean days of vigorous physical activity per week for male students was almost three times higher than those of the first-year female students: t=7.619 (df=98), p<0.05.

Predictors of Obesity by Levels of Physical Activity and Gender

The main purpose of this study was to assess the association of body fat percentage scores with college students’ vigorous physical activity, moderate physical activity, walking, and gender in the context of stepwise regression. Before each of the possible predictor entered into the regression equation one at a time, the main assumptions of the multiple regression models were examined. The normal Q-Q plots were used to check the normality of the data, which appears to be normally distributed. The multicollinearity test showed all the factor’s VIF scores were less than four, which implies that the predictors were not highly correlated with each other. The results of the regression in Table 4 indicated that the full model explained 35% of the variance in body fat percentages, and vigorous PA and gender were two significant predictors of first-year college students’ body fat percentage: F(1.78)=56.00, p<0.001. The rest of the variables entered were the moderate PA and walking, and these were insignificant factors.

Table 4: Regression results of body fat percentages dependent on vigorous PA, moderate PA, waking, and gender

Step

Variables

R2

AdR2

R2 Change

p-value

1

Vigorous PA

0.06

0.51

0.60

0.01*

2

Moderate PA

0.07

0.05

0.01

0.19

3

Walking

0.10

0.07

0.02

0.08

4

Walking

0.35

0.33

0.25

0.00

*Statistically significant at 0.05

Discussion/Limitations

The incoming first-year college students’ body fat levels were measured by the average thickness of subcutaneous fat in their two body regions, including calf and triceps. Surprisingly, the average body fat percentages of the participants were found to be lower than the national obesity rate of young adults. However, it is noteworthy that the first-year female students’ body fat percentage was reported to be almost twice higher than that of male students.

The mean days of different types of physical activity per week were compared between the male and female students to see if there were any gender differences of body fat levels, and the vigorous physical activity was shown to be an important factor among the three types of physical activities: vigorous physical activity, moderate physical activity, and walking. When three types of the physical activity levels were entered into the stepwise regression along with the gender factor, vigorous level of physical activity and gender were the significant factors in explaining the levels of the first-year college students’ body fat percentages. In addition, when the vigorous physical activity level was entered in the model, it accounted for six percent of the variance, and this indicates that first-year students who were engaging in the vigorous level of physical activity were less likely to be obese.

There were some limitations of this study that might influence the result. One of the weaknesses of this study might be the fact that the first-year college students’ levels of physical activity were measured by an instrument that heavily relies on participants’ recall and self-report in nature. Although the IPAQ-SF’s validity and reliability were well-documented in several studies, one of the common drawbacks of the IPAQ-SF was that it tends to overestimate physical activity levels.

While first-year college students’ body fat percentage levels were found to be lower than the national average young adults’, the timing of the body fat measurement could be an important factor leading to a lower body fat percentage of the subjects. The first-year students’ body fat was measured during the freshman orientation period rather than few months into their academic semester where they could be exposed to different college lifestyle related factors, including types of food choices, levels of stress, academic demands. Lastly, anthropometric data such as body weight, height, and waist and hip circumference were collected from the first-year college students; therefore, there is a potential sample bias that participants who were reluctant to disclose their anthropometric data could have been excluded from this study.

Conclusion

Obesity rates of first-year female students were to be almost twice higher than those of male students. Such gender gap could be explained by the type of physical activity performed, where male students were more often doing the vigorous level of physical activity than the female students.

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Review on the Skeletal Effects of Rapid Palatal Expansion in Late Mixed Dentition

DOI: 10.31038/JDMR.2022524

Abstract

Introduction: Rapid palatal expansion is utilized in Orthodontics to treat maxillary transverse deficiencies. Such deficiencies can cause functional defects, misalignments, and mandibular shifts that can impact one’s function, comfort, and quality of life. This review aimed to synthesize the clinical findings of rapid palatal expanders.

Methods: A literature search of skeletal effects of maxillary rapid palatal expansion was performed using PubMed and Google Scholar. Inclusion criteria consisted of studies that measured changes in maxillary width over at least one year of expansion and retention or radiographic confirmation of skeletal expansion with a sample size of over 15 subjects. Exclusion criteria were subjects with developmental defects, such as cleft palate, or any type of surgical assisted rapid palatal expansion. A total of 12 articles were found from January 1990 to April 2022 and included in this review.

Results: All 12 articles reported that rapid palatal expansion notably increases the maxillary skeletal transversal dimension. Across all studies, the amount of intercanine expansion from rapid palatal expansion ranged from 2.5 to 4.0 mm, and the amount of intermolar expansion ranged from 3.9 to 6.5 mm. The studies also showed a significant expansion of nasal cavity (airway), various facial sutures being affected, occurrence of buccal tipping of all maxillary teeth, mandibular spacing being gained, and that relapse, although present, had an insignificant effect on the long-term retention of expansion.

Conclusion: Rapid palatal expanders are effective in producing both immediate and long-term transverse expansion in subjects in late mixed dentition.

Keywords

Rapid palatal expansion, Mixed dentition, Orthodontics, Tooth-borne, Maxillary expansion, Midpalatal suture, Computed tomography analysis, Retention, Skeletal changes

Introduction

Rapid palatal expansion (RPE) is utilized in Orthodontic treatment to correct maxillary transverse deficiencies. Patients with maxillary transverse deficiencies may present with functional problems such cross bites, misaligned teeth due to lack of arch coordination, and even mandibular shifts that can develop into future skeletal asymmetry [1]. RPE treatment has long been advocated to solve maxillary constriction. There is a wide variety of maxillary palatal expansion appliances in use today, all with similar effectiveness [2].

The American Association of Orthodontics states that the most critical factor for RPE success is timing and thus routine orthodontic screenings in children are highly recommended to diagnose and treat problems such as cross bites [3]. RPE is most effective in children and young adolescents because their palatal and maxillary sutures are still malleable, as they have not yet completely fused. Transverse expansion of the maxilla is accomplished by banding an expander appliance on the patient’s upper dentition; the appliance has an inbuilt jackscrew that is turned to provide leveraged force that pushes the appliance apart, which then provides force that widens the skeletal base of the palate. Most of the force is applied to split the midpalatal suture; however, the pterygopalatine, inter maxillary, intranasal, maxillonasal, front maxillary, and frontonasal sutures are also affected [4]. Early indicators of maxillary expansion success is evident by the formation of a diastema between the front teeth and an increased intermural width. When these sutures are completely fused, usually by early adulthood, they require more invasive methods of separation such as surgical or manipulate induced separation of the sutures.

It is critical to note that maxillary expansion is one of the most difficult procedures to achieve and maintain, due to the body’s tendency for relapse from disruption of the neuromuscular equilibrium including factors such as (but not limited to): teeth tipping back, incomplete alveolar bone remodelling (necrosis or fenestrations), and periodontal fiber inelasticity. Multiple studies have found that rapid palatal expanders have relapse rates of up to 60% [5,6]. Additionally, because the force is distributed between the maxilla and the teeth, this expansion is a combination of both dental tipping and skeletal expansion, even though purely skeletal expansion is what is desired as the expansion from the dental tipping relapses quickly (within one year) as the teeth upright over time due to equilibrating intraoral pressures [1].

While there are many individual studies that present the results of RPE, the aim of this study is to present a more focused review. Many earlier studies presented the immediate effects of RPE but did not account for the fact that maxillary expansion often partially relapses after treatment, thus overestimating expansion. Studies included in this review had either: 1) skeletal effects of expansion verified through radiographic analysis (such as confirming sutural bone deposition or transverse maxillary bone deposition) or 2) sufficient elapsed time (1 year) for the bone to remodel and teeth to be stable in their new expansive positions. This study also distinguishes between anterior and posterior maxillary expansion and presents intercanine and intermural distance in order to present quantifiable data. The data provided in this study can be useful for clinicians to predict the changes in intercanine and intermural distances to help clinician’s treatment plan more effectively.

Methods

This study consisted of a literature review in which the sources were all obtained from a search through published papers in PubMed and Google Scholar. Search terms included RPE; rapid palatal expansion; retention; radiographic analysis; tooth-borne; maxillary expansion; midpalatal suture; mixed dentition; computed tomography analysis; retention; skeletal changes.

Inclusion and Exclusion Criteria

Inclusion criteria consisted of only English language articles from January 1990 to April 2022 that included sufficient elapsed time (>1 year follow up) or radiographic confirmation of skeletal expansion. Only studies with a sample size greater than 15 subjects were considered.

Exclusion criteria consisted of studies involving patients with developmental defects such as cleft lip or palate or developmental disorders and those with miniscrew-assisted rapid palatal expansion and surgically assisted rapid palatal expansion.

Study Selection

A total of 501 articles were found from Pubmed (n=220) and Google Scholar (n=281). After removing duplicates and screening by inclusion/exclusion criteria, a total of 12 articles met the selection criteria (Figure 1).

fig 1

Figure 1: Literature search flow chart

Results

Across all twelve studies, the range of intercanine expansion was 2.5-4.0 mm; the range of intermural expansion was 3.9-6.5 mm (Table 1). The control for intercanine expansion ranged from 0.05 to 3.0 mm, and for intermural expansion, the control ranged from 0.02 to 0.8 mm. When broken down by using radiographic versus cast analysis: Half of the 12 studies analysed RPE radiographically and found intercanine expansion ranged from 2.5 mm to 3.5 mm whereas the controls ranged from 0.25 mm to 0.30 mm expansion. Intermural expansion ranged from 4.5 to 6.0 mm whereas control ranged from 0.02 mm-0.80 mm. The other 6 studies analysing the casts of RPE patients found that RPE intercanine expansion ranged from 2.9 to 4.0 mm whereas the control ranged from 0.05 mm to 0.30 mm. Intermural expansion ranged from 4.4 to 6.1 mm, and control ranged 0.55 mm to 0.61 mm. One meta-analysis analysing 18 studies revealed an overall average gain in intercanine dimension of 2.91 mm and intermural expansion of 4.38 mm. Together, these studies support existing literature that rapid palatal expanders are effective in promoting transverse expansion.

Table 1: Summary of Findings – Changes in Intercanine & Intermolar Widths, Experimental vs. Control

(Article Number) Author Last Name

Average Age, (Sample Size) Experimental-Intercanine Expansion Experimental-Intermolar Expansion Control-Intercanine Width Control-Intermolar Width
(1) Mehtaa [7]

13.9 ± 1.14 (21)

N/A 6.1 N/A .02
(2) Kavand [8]

14.4 ± 1.3 (18)

N/A

4.5 N/A N/A
(3) da Silva [9]

8.0 (32)

3.05 ± 1 5.05 ± 1.0 0.04 0.55
(4) Reed [10] 13.3 (55) N/A 5.4 ± 2.1 N/A N/A
(5) Bazargani [11] 9.3 (26) 2.5 4.75 ± 1 0.25 0.80
(6) Celenk-Koka [12] 13.8 ± 1.4 (20) N/A 4.2 ± 1.7 N/A N/A
(7) McNamara [13] 12.2 ± 1.3 (112) 3.9 ± 2.7 4.4 ± 1.8 0.30 0.60
(8) Fenderson [14] 11.7 ± 1.7 (41) 3.9 ± 5.8 6.1 ± 2.3 N/A N/A
(9) Geran [15] 8.8 (51) 4.0 4.3 0.21 0.70
(10) O’Grady [16] 9.0 (27) 4.0 3.9 0.30 0.55
(11) Moussa [17] 13.7 (165) 2.5 5.5 0.05 0.60
(12) Adkins [18] 14.0 (21) 2.9 ± 1.4 6.5 ± 1.2 N/A N/A

Anatomically, the studies found that patients undergoing RPE underwent a significant increase in maxillary width, nasal cavity, and nasopharynx volume as well due to midpalatal suture expansion [1,2,4,8,9,10]. Most of the patient groups demonstrated a triangular-shaped sutural opening that was wider anteriorly, and that the arch development in the maxilla resulted in a complimentary 2.5 mm average space gain in the mandibular arch perimeter as well [1,3,4]. In terms of the dent alveolar changes, the studies found that RPE resulted in slight palatal movement of maxillary incisors, mild buccal crown tipping of all the maxillary dentition, with up righting of the mandibular dentition as a result of the curve of Wilson being levelled over time [2,6,7,9,10].

Discussion

Rapid palatal expanders have been used to increase the maxillary transverse dimension. While there are many individual studies examining the effect of rapid palatal expanders, this literature review presents quantifiable clinical results of expansion verified through stable retention. The existing reviews in the literature focused on RPE’s effects on other anatomical structures or analysed surgically assisted rapid palatal expansion. This review adds to the literature by synthesizing non-surgical RPE clinical finding.

The average age of patients across the studies ranged from 8.0 to 14.4 years old and had either mixed dentition or permanent dentition. Rapid palatal expanders have long been recommended for children and young adolescents before the palatal and maxillary sutures have fused. Because skeletal changes are less significant when matured due to increased rigidity [19], timing of treatment is important. Notably, our results showed that patients in early permanent dentition had more intermural width expansion. Sari et al compared rapid maxillary expansion in mixed dentition (average age 9.2 years) and early permanent dentition (average age 12.7 years) and found that intercanine and intermural widths increased and remained stable in both the mixed dentition and permanent dentition groups [20]. However, subjects in mixed dentition showed a greater tipping of the anchorage teeth and less increases in the ANB angle [20], suggesting that it might be better to delay RPE treatment until early permanent dentition. Another study evaluated the effects of RPE according to cervical vertebrae maturity, with the group treated before the pubertal peak (average age 11 years) showing significantly greater maxillary skeletal and intermural width compared to those treated after (average age 13.6 years) [21]. Based on our review, it appears that treatment with rapid palatal expanders is effective in both mixed and early permanent dentition with an emphasis to treat patients before palatal sutures fuse.

Furthermore, our study evaluated articles that had radiographic evidence of expansion or sufficient elapsed time for remodelling to be stable (>1 year). The results showed a retained increase in intercanine and intermural width. Many studies suggest a significant relapse in maxillary expansion following RPE with one study finding no significant difference in relapse rate between mixed or permanent dentition [22]. Contrarily, other studies have found good stability for intercanine and intermural widths following treatment [17,23], consistent with our findings. However, long-term stability of rapid palatal expansion still seems to be questionable with mixed results across studies. The short-term results are consistent [24], showing significant palatal and/or dental expansion. Nevertheless, orthodontists may experience some long-term relapse in intercanine and intermural expansion everyday practice due to natural neuromuscular equilibrium forces. Orthodontists can utilize the findings of this study to better accurately predict the amount of intercanine and intermural expansion that can be utilized to align the teeth. For this reason, long-term follow-up of children treated with RPE is important.

Limitations

One limitation of this review is that not all articles included control values for intercanine and intermural widths. Except for two studies, each study had uniquely different presentations of their findings. For example, some studies looked into sutural expansion, arch length (in addition to width), tipping of teeth, nasal/oropharyngeal cavity changes, and bone density/deposition to name a few. Additionally, variation in operator technique, RPE design, patient compliance, slight age variations, and physiologic differences are just a few of the factors that add to the complexity of synthesizing various studies.

Conclusion

Rapid palatal expanders are effective in promoting transverse expansion in subjects in late mixed dentition. When timed appropriately, RPE can be utilized to successfully promote maxillary expansion. A future review could focus on a more thorough, dual approach: combining long-term follow-up along with cone beam computed tomography measurements of skeletal expansion. Future review could also compare expansion in pure primary dentition vs early adolescent (mixed) dentition.

References

  1. Proffit WR, Fields HW, Sarver DM (2007) Contemporary Orthodontics St Louis: Mosby 689-693.
  2. Agarwal A and Mathur R (2010) Maxillary expansion. Int J Clin Pediatr Dent 3(3):139-146. [crossref]
  3. Baccetti T, Franchi L, Cameron CG, et al. (2001) Treatment timing for rapid maxillary expansion. Angle Orthod, 71(5), 343-350. [crossref]
  4. Ghoneima A, Ezzat AF, James H, et al. (2011) Effects of rapid maxillary expansion on the cranial and circummaxillary sutures. Am J Orthod Dentofacial Orthop 140(4): 510-519. [crossref]
  5. Bishara Samir E and Staley RN (1987) Maxillary expansion: clinical implications. Am J Orthod Dentofacial Orthop, 91(1): 3-14. [crossref]
  6. Velazquez P, Benito E, and Bravo LA (1996) Rapid maxillary expansion: A study of the long-term effects. Am J Orthod Dentofacial Orthop 109(4): 361-367. [crossref]
  7. Shivam M, Wanga D, Chia-Ling K, et al. (2021) Long-term effects of mini-screw-assisted rapid palatal expansion on airway: A three-dimensional cone-beam computed tomography study. Angle Orthod 91(2): 195-205. [crossref]
  8. Golnaz K, Lagravère M, Kula K, et al. (2019) Retrospective CBCT analysis of airway volume changes after bone-borne vs. tooth-borne rapid maxillary expansion. Angle Orthod 89(4): 566-574. [crossref]
  9. Silva Filho OG, Prado Montes LA, and Torelly LF (1995) Rapid maxillary expansion in the deciduous and mixed dentition evaluated through posteroanterior cephalometric analysis. Am J Orthod Dentofacial Orthop 107(3): 268-275. [crossref]
  10. Reed N, Ghosh J and Nanda RS (1999) Comparison of treatment outcomes with banded and bonded RPE appliances. Am J Orthod Dentofacial Orthop 116(1): 31-40. [crossref]
  11. Bazargani F, Feldmann I, Bondemark L (2013) Three-dimensional analysis of effects of rapid maxillary expansion on facial sutures and bones: a systematic review. Angle Orthod 83(6): 1074-1082. [crossref]
  12. Celenk-Koca T, Erdinc AE, Hazar S, et al. (2018) Evaluation of miniscrew-supported rapid maxillary expansion in adolescents: a prospective randomized clinical trial. Angle Orthod 88 (6): 702-709. [crossref]
  13. McNamara JA, Baccetti T, Franchi L, et al. (2003) Rapid maxillary expansion followed by fixed appliances: a long-term evaluation of changes in arch dimensions. Angle Orthod 73(4): 344-353. [crossref]
  14. Fenderson FA, McNamara JA, Baccetti T, et al. (2004) A long-term study on the expansion effects of the cervical-pull facebow with and without rapid maxillary expansion. Angle Orthod 74(4): 439-449. [crossref]
  15. Geran RG, McNamara JA, Baccetti T, et al. (2006) A prospective long-term study on the effects of rapid maxillary expansion in the early mixed dentition. Am J Orthod Dentofacial Orthop 129(5): 631-640. [crossref]
  16. O’Grady PW, McNamara JA, Baccetti T, et al. (2006) A long-term evaluation of the mandibular Schwarz appliance and the acrylic splint expander in early mixed dentition patients. Am J Orthod Dentofacial Orthop 130(2): 202-213. [crossref]
  17. Moussa R, O’Reilly MT and Close JM (1995) Long-term stability of rapid palatal expander treatment and edgewise mechanotherapy. Am J Orthod Dentofacial Orthop 108(5): 478-488. [crossref]
  18. Adkins MD, Nanda RS, Currier GF (1990) Arch perimeter changes on rapid palatal expansion. Am J Orthod Dentofacial Orthop 97(3): 194-199. [crossref]
  19. Wertz RA (1970) Skeletal and dental changes accompanying rapid midpalatal suture opening. Am J Orthod 58(1): 41-66. [crossref]
  20. Sari Z, Uysal T, Usumez S, et al. (2003) Rapid maxillary expansion. Is it better in the mixed or in the permanent dentition? Angle Orthod 73(6): 654-661 [crossref]
  21. Baccetti T, Franchi L, Cameron CG, et al. (2001) Treatment timing for rapid maxillary expansion. Angle Orthod 71(5): 343-350. [crossref]
  22. Mohan CN, Araujo EA, Oliver DR, et al. (2016) Long-term stability of rapid palatal expansion in the mixed dentition vs. the permanent dentition. Am J Orthod Dentofacial Orthop 149(6): 856-862. [crossref]
  23. Mew J (1983) Relapse following maxillary expansion: a study of twenty-five consecutive cases. Am J Orthod 83(1): 56-61. [crossref]
  24. Ciambotti C, Ngan P, Durkee M, et al. (2001) A comparison of dental and dentoalveolar changes between rapid palatal expansion and nickel-titanium palatal expansion appliances. Am J Orthod Dentofacial Orthop 119(1): 11-20. [crossref]

Neurosarcoidosis: What are the Evocative Signs on Magnetic Resonance Imaging (MRI)

DOI: 10.31038/JNNC.2022513

Clinical Image

Neurosarcoidosis is known as the involvement of the central nervous system in sarcoidosis, usually affects patients between 30 and 40 years of age, more predominantly in women. It can affect different organs such as the lung, lymph nodes, eyes, joints and more rarely (5% of cases) the central nervous system, which manifested with a clinical and radiological polymorphism that makes the diagnosis more difficult. Clinical symptomatology is very variable, rarely isolated without systemic sarcoidosis involvement, and in some cases the diagnosis is made only based on imaging data; if signs are present, they would be related to the type of intracranial involvement (leptomeningeal, pachymeningeal, parenchymal, pituitary stalk, etc.): headaches (hydrocephalus), endocrine signs of hypothalamic or pituitary involvement: diabetes insipidus, optic nerve involvement, facial nerve palsy, general signs: Tiredness, joint pain [1].

The diagnosis is difficult and relies on the Association of clinical and paraclinical arguments. The main ones are magnetic resonance imaging, cerebrospinal fluid study, intradermal tuberculin reaction, phosphocalcic and angiotensin-converting enzyme evaluation. MRI identified lesions present an iso or hyperintense signal in T1 signal, variable signal in T2, hypo signal diffusion with high ADC, are intensely and homogeneously enhanced after injection, and may involve a single or several compartments [2].

Pachymeninge

Thickening of the pachymeninges, which is most often in hyposignal, T2 enhances homogeneously.

fig 1

Figure 1: Brain MRI in a 56-year-old woman, partial left convulsive seizure for 3 months, shows an extra axial mass of the right frontal convexity in heterogeneous signal T2 (red arrow) with subcortical oedema (blue star) in Axial T2 and Flair (a, b). Without restriction on diffusion. In SWI (c) shows a leptomeningeal hemosiderosis, homogeneously enhanced in T1 contrast enhanced (d). This mass infiltrates the cortical sulci, with enhancement of the pachymeninges and leptomeninges (e, f).

Leptomeninges

The key sequence is contrast-weighted T1, shows focal or general leptomeningeal enhancement, node or smooth, about the basal aspects of the brain and the polygon of Willis ; sometimes it goes along the spaces of the Wirshow Robbin, as it may mimic parenchymal lesions.

Parenchyma

Parenchymal involvement is the most common and diverse, appearing as intraparenchymal masses or nodules, periventricular white matter involvement, or extension of leptomeningeal lesions through perivascular spaces.

Hypothalamic and Pituitary

Frequently associated with more extensive leptomeningeal involvement, as it can be isolated, it is observed in some cases only in the infundibulum.

Cranial Nerve

All cranial nerves can be affected, either in isolation or as part of a diffuse leptomeningeal injury. The two nerves that are most sought after are the facial nerve, which is often symptomatic, and the optic nerve [3].

The most important differential diagnoses of neurosarcoidosis are meningioma, dural metastasis, idiopathic hypertrophic cranial pachymeningitis, tuberculous, metastasis, lymphoma, multiple sclerosis, ADEM, primary brain tumors. Treatment based on corticosteroids is recommended as first-line therapy in patients with neurosarcoidosis, although immunosuppressive drugs are usually added due to the chronic course of this condition and to limit the side effects of steroids. With high rate of relapses.

References

  1. Shah R, Roberson GH, Curé JK (2009) Correlation of MR imaging findings and clinical manifestations in neurosarcoidosis. AJNR Am J Neuroradiol 30: 953-961. [crossref]
  2. Smith JK, Matheus MG, Castillo M (2004) Imaging manifestations of neurosarcoidosis. AJR Am J Roentgenol 182: 289-295. [crossref]
  3. Mahi M, Semlali S, En-Nouali H, Karouache A, Satte A, et al. (2007) Imagerie de la neurosarcoïdose. Feuillets de Radiologie 47: 357-362.

Facial Paralysis Revealing an Atypical Metastasis of Breast Cancer

DOI: 10.31038/JNNC.2022512

Abstract

Facial paralysis has many etiologies, the most frequent is the idiopathic cause, which is a diagnosis of elimination, then infectious, traumatic, and tumoral causes, dominated by the parotid tumor. Breast cancer rarely gives a perineural metastasis, estimated at 0.6%, of all secondary localizations, with a suggestive clinical presentation, especially the slow and progressive mode of appearance, the involvement of multiple cranial nerves, recurrent paresis, and a history of cancer. Perineural metastases of breast cancer are rare, but can occur, and this case demonstrates that any symptomatology in the patient with breast cancer must be considered in the overall context.

Keywords

Breast cancer, Facial nerve, Perineural metastasis

Introduction

Breast cancer is the leading cause of cancer death in women. The main metastatic sites are bone, lung, liver, brain and lymph nodes. Perineural metastases are extremely rare [1-3].

Observation

A 62-year-old woman, who was treated 10 years ago for invasive bifocal ductal carcinoma of the right breast, by mastectomy with lymph node dissection and chemotherapy. She reported a progressive and painless left facial deviation, with paresthesia of the lower extremities for 3 months. A brain scan with PDC injection showing nodular enhanced in the left cerebellopontine angle. A complementary cerebro-medullary magnetic resonance imaging showed bilateral micronodular thickening of the facial nerve and nodular thickening of the left trigeminal nerve, without any spinal cord abnormality, suggesting secondary localizations of breast carcinoma (Figures 1-3).

fig 1

Figure 1: Brain scan with injection of PDC, axial section showing a centimetric nodular lesion in the prepontine cistern on the trajectory of the left trigeminal nerve.

fig 2

Figure 2: Axial section of the brain MRI, diffusion sequence, showing a nodular perineural hypersignal of the left cranial nerves (V and VI).

fig 3

Figure 3: Brain MRI T1 enhanced, axial section, showing nodular contrast of the left trigeminal nerve.

Discussion

There are many etiologies of facial paralysis, the most common is idiopathic etiology, that is diagnosis of exclusion, followed by infectious, traumatic, and neoplastic etiologies, mainly parotid gland tumors. Breast cancer rarely causes neuronal metastases, estimated at 0.6%, and has an impressive clinical presentation, particularly slow and progressive onset, polycranial onset, recurrent paralysis, and a history of cancer.

Conclusion

Perineural metastases of breast cancer are rare but can occur, and the present case demonstrates that any chronic symptomatology in the breast cancer patient must be analyzed in the overall medical context.

References

  1. Gasperini J, Black E, Van Stavern G (2007) Perineural metastasis of breast cancer treated with optic nerve sheath fenestration. Ophtalmique Plast Reconstr Surg 23: 331-3. [crossref]
  2. Raghavan P, Mukherjee S, Phillips CD (2009) Imaging of the facial Neuroimaging Clin N Am 19: 407-425. [crossref]
  3. Delattre JY, Krol G, Thaler HT, Posner JB (1988) Distribution of brain metastases. Arch Neurol 45: 741-4. [crossref]

Effects of Abexol (D-002): A Mixture of Beeswax Alcohols, on Joint Discomforting Symptoms in Healthy Volunteers

DOI: 10.31038/JCRM.2022543

Abstract

Background and purpose: Joint symptoms or join discomfort are defined as the presence of pain, edema, morning stiffness and mobility limitation on most days for a minimum period of six weeks. These symptoms can affect individuals at different ages, leading to functional limitations in daily and professional activities. Treatment of joint symptoms remains symptomatic and is meant to control pain, improve function and quality of life. Abexol is the trade name of a mixture of beeswax alcohols (BWA) with antioxidant, gastro-protective and anti-inflammatory effects (research code: D-002). This double-blind study investigated the effects of Abexol (50-100 mg/day) on patients with joint symptoms for six weeks.

Methods: The primary efficacy outcome was the reduction of the total Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) score. The secondary efficacy outcome was the reduction on pain, joint stiffness, physical activity scores, and the reduction of the Visual Analogue Scale (VAS) score. Statistical analysis of all data was according to the Intention to treat method.

Results: At study completion Abexol significantly reduced the total WOMAC score (p<0.00001 versus baseline and p<0.0001 versus placebo) (78.5% versus baseline, 66.5% versus placebo), and the VAS score versus baseline (p<0.00001, 63.2%) and placebo (p<0.0001, 47.1%). Treatment was safe and well tolerated. Only one patient (placebo group) reported moderate adverse event.

Conclusions: Abexol given for six weeks improved joint symptoms and was safe and well tolerated.

Keywords

D-002, Abexol, Beeswax alcohols, Joint discomfort, WOMAC score, VAS score

Introduction

Joint symptoms are defined as the presence of pain, edema, morning stiffness and mobility limitation on most days for a minimum period of six weeks [1]. These symptoms can affect individuals at different ages, leading to functional limitations in daily and professional activities [2].

The health impact of joint symptoms prevalence estimates is difficult to establish because these symptoms are self-reported rather than medically diagnosed. However, there is evidence that both self-reported symptoms and medical diagnosis have good validity [3]. In addition, for population screening, evaluating joint symptoms is more feasible and may be an alternative for prevention, early diagnosis and insertion of interventions. The factors associated with the higher prevalence of joint symptoms are sex, age, overweight and heavy work [4].

Treatment of joint symptoms remains symptomatic and is meant to control pain, improve function and quality of life. The management of joint symptoms included a combination of non-pharmacological interventions and pharmacologic agents [5,6].

The use of analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) to provide symptom relief despite they do not solve the underlying causal pathological process [7,8]. Nevertheless, in view of the gastrointestinal and cardiovascular adverse effects of non-selective NSAIDs and specific ciclooxygenase 2 (COX-2), respectively, the search for better tolerated alternatives is justified [9,10].

Abexol (research code D-002) is a mixture of six high-molecular-weight alcohols (C24, C26, C28, C30, C32, and C34) obtained from beeswax (beeswax alcohols-BWA-), with a product specification of total high fatty alcohols not less than 85% [11]. D-002 has anti-inflammatory effects demonstrated in experimental models of acute and chronic inflammation [12,13]. On the other hand, gastroprotective [14-20] and antioxidant [16,21-26] effects of Abexol have been demonstrated in experimental and clinical studies.

The present study was conducted to investigated the effects of Abexol (50-100 mg/day) administered for six weeks in subjects with joint symptoms.

Materials and Methods

Study Design

The study was prospective, randomized, double-blinded, placebo controlled and conducted in accordance with the Declaration of Helsinki (World Medical Association, revised Brazil 2013) [27], as well as the recommendations of the World Health Organization and the Cuban regulations on Good Clinical Practices. The study protocol was approved by the Ministry of Public Health and by the Ethics Committee in Clinical Research of the Surgical Medical Research Centre, as well as register in the Cuban Public Registry of Clinical Trials.

Subjects were provided oral and written explanations about the nature of the trial and the study treatment in a language easily understood by the subjects in order to request their informed written consent, which was obtained from each of the participants at enrolment.

Eligible subjects were randomised to Abexol (50 mg) or placebo tablets, which should be taken once a day with the breakfast for six weeks, but such dose could be increase to 100 mg (two tablets, one with the breakfast and one with the dinner) whenever the low dose did not provide the expected benefit after week three on treatment. Subjects underwent to visits every 1 week. Physical examinations and assessment of WOMAC and VAS score were done at each visit. Treatment compliance, rescue medication (analgesics) consumption and adverse events were controlled from each visit, laboratory examinations were done at baseline and every three weeks.

Study Participants

Healthy volunteers with joint discomfort symptoms, of both sexes, aged between 20 and 75 years, were enrolled in the trial.

Healthy volunteers with joint discomfort symptoms include subjects with osteoarthritis symptoms that has been classified up to Class II, being:

Class I: Healthy subjects who has no limitation in daily activities.

Class II: Healthy subjects with mild joint discomfort in vocational activities.

Exclusion criteria were to diagnostic arthritis, any arthroscopy within the past year, intra-articular injection of steroids within the past three months, uncontrolled hypertension (diastolic pressure ³ 120 mm Hg) or diabetes (fasting glucose >7 mmol/L), active liver or renal disease, malignancies, or any other serious illnesses. Also, we excluded pregnant or lactating women, or those not taking adequate contraceptive measures and subjects with the following laboratory abnormalities: alanine -ALT- and/or aspartate amino tranferase-AST >45 U/L, creatinine >130 µmol/L, and/or those with any hospitalization during the six months prior to the study.

Unwillingness to follow-up, to experience adverse event that justified such decision and protocol violations (failure of treatment intake ≥5 days) were predefined causes of premature discontinuations of the study.

Treatment

Study treatments, produced under Licensees and Good Manufacturing Practices conditions, came from the manufacturers (Plants of Natural Products, MEDSOL Laboratory, Havana, Cuba). D-002 content was assessed by using a gas chromatography method. Placebo had similar composition to Abexol tablets, except the active ingredient that was replaced by lactose.

At visit 2, identical coded and packaged tablets of study treatments (Abexol or placebo) were given to study subjects. The randomisation code was computer-generated with a fixed, not stratified randomisation method, using balanced blocks and allocation ratio of 1:1. The dose of Abexol (50-100 mg/day) selected had been shown to produce effective antioxidant effects in clinical studies [16,21-26].

The entire code was kept confidential at the generating place. Sealed individual envelopes with codes of each subject were kept at the generating place and at the site of the Principal Investigator, which should be opened prematurely in case of occurring a serious adverse event, a situation that did not occur in the trial.

Treatment compliance was controlled by counting the remainder tablets and making interviews to subjects. At trial completion, non-used tablets were recovered. Compliance was considered good if the subjects consumed at least 85% of the tablets scheduled from the previous visit.

Subjects were not allowed to consume NSAIDs, steroids, cartilage or calcium supplements, or any other agent that may affect the study outcomes.

Efficacy Assessment

The primary end-point was to obtain a significant reduction of the total Western Ontario and McMaster Individual Osteoarthritis Composite (WOMAC) index [28,29] of not less than 30% as compared to placebo. At each visit, subjects completed the WOMAC questionnaire, which consists of three sections, one that assess pain intensity (5 questions), other joint stiffness (2 questions), and the third the physical function (17 questions). Individual responses were scored on the following scale: 0 (none), 1 (slight), 2 (moderate), 3 (severe) and 4 (extreme). The total score ranges from 0 (the best) to 96 (the worst).

Reductions in pain, stiffness and physical function scores and reduction of Visual Analogue Scale (VAS) scores [30] were secondary efficacy variables. For efficacy, the score reductions should be significant as compared to placebo.

Safety and Tolerability Assessment

The safety indicators included vital signs (body weight, pulse rate, blood diastolic and systolic pressure), and blood indicators (erythrocyte sedimentation, cholesterol, triglycerides, ALT, AST, serum fasting glucose and creatinine). Blood biochemical safety indicators were assessed with enzymatic methods by using reagent kits (Roche, Switzerland) and performed in the Hitachi 709 auto-analyser (Tokyo, Japan), erythrocyte sedimentation rate was assessed by conventional method, all done at the clinical laboratory of the Surgical and Medical Research Centre (Havana, Cuba). Controls of the precision and accuracy of the methods were performed.

We considered as adverse event (AE) all undesirable events that occurred to a subject during the study, disregarding the cause, whenever they newly appeared during the trial. Subjects were queried by investigators for any AE between study visits. AE were recorded in the case record forms, including their characteristics, dates of onset and disappearance, treatments adopted and responses achieved. Severity of AE was classified as mild, moderate or serious (SAE), mild being those easily tolerated that not required suspension of study medications and/or specific treatment, moderate those that caused discomfort enough and required stopping therapy and/or specific treatment, and SAE those disabling events that leaded to hospitalisation and/or deaths, if happened. AE that occurred within 30 days of consuming the last study doses, monitored by direct contact with the subjects, were included in this analysis. The causal relationships between AE and the treatments were classified by using the Naranjo algorithm [31].

Statistical Analysis

Data were analysed as per the intention to treat (ITT) approach. So, data of all randomized subjects were included in all analyses. The sample size estimation assumed a difference of ³30% between the reduction of WOMAC total scores from baseline with D-002 and placebo at study completion. Then, 25 subjects per treatment arm would be sufficient to detect such difference with 80% power and α = 0.05. Assuming a permissible dropout rate of 10%, 55 subjects were enrolled.

Continuous data were analyzed by using the following tests: unpaired and paired t tests, Bonferroni adjustment for multiple comparisons [32], or ANOVA, as appropriate. Categorical variables were compared with the Fisher Exact Probability test. All statistical tests for differences were 2-tailed. The following software was used for the comparisons: Statistics software for Windows (USA) and MS Excel. Statistical significance was taken at the 95% level (p<0.05).

Results

Baseline Characteristics

Fifty-five subjects were enrolled in the study. Of them, 50 were eligible for randomization. Five enrolled subjects did not pass to the active treatment step because of the following reasons: fasting glucose >7 mmol/L (3 subjects), creatinine > 130 µmol/L (2 subjects). Of the 50 subjects (29 women, 21 men) (mean age 65 years) included, 50 completed the trial.

All baseline characteristics of both groups were similar, so that subject randomization was effective (Table 1). Gender was predominantly female 29/50 (58%) vs. males 21/50 (42%). Study population included a high frequency (>30%) of some co-morbid conditions like hypertension (64%) and hypercholesterolemia (36%), and some negative lifestyle factors, overweight (48%), like sedentary life (38%) and smoking (22%). A total of 43/50 (86%) randomized subjects consumed some concomitant therapy during the study.

Table 1: Baseline characteristics of study population

 

Abexol (n = 25)

Placebo (n = 25)

Total (n = 50)

Age (years) (X ± SD)

65 ± 8

64 ± 9

65 ± 8

Body mass index (kg/m2)(X±SD)

26.7 ± 3.2

26.9 ± 3.3

26.8 ± 3.3

n

% n % n %

Class I

1 4.0 1 4.0 2

4.0

Class II

24

96.0 24 96.0 48 96.0

Sex: Women

15 60.0 14 56.0 29

58.0

Men

10

40.0 11 44.0 21

42.0

Personal history
Arterial hypertension

18

72.0 14 56.0 32  64.0

Overweight (kg/m2 ≥ 25, <30)

11 44.0 13 52.0 24

48.0

Sedentary life

11

44.0  8 32.0 19  38.0

Hypercholesterolemia

 9 36.0  9 36.0 18

 36.0

Smoking

 7

28.0  4 16.0 11  22.0

Obesity (kg/m2 ≥ 30)

 4 16.0  6 24.0 10

 20.0

Diabetes mellitus

 2

 8.0  3 12.0  5  10.0

Trastornos deTiiroides

 2  8.0  3 12.0  5

 10.0

Coronary disease

 1

 4.0  1  4.0  2

 4.0

Concomitant medications (CM)
Patients consuming CM

22

88.0 21 84.0 43 86.0

IACE

11 44.0  9 36.0 20

40.0

Diuretics

 8

32.0  9 36.0 17 34.0

Lipid lowering drugs

 6 24.0  6 24.0 12

24.0

β-blockers

 6

24.0  6  24.0  12 24.0

Antiplatelet drugs

 2  8.0  4 16.0  6

12.0

Hormones

 2

 8.0  3  12.0  5 10.0

Oral hypoglycemic drugs

 2  8.0  1  4.0  3

 6.0

Anxiolytics

 2

 8.0  1  4.0  3  6.0

Antiulcers drugs

 1  4.0  2  8.0  3

 6.0

Circulatory

 1

 4.0  1  4.0  2

 4.0

SD: Standard Deviation, n: Number of Cases. *The table includes only those consumed by ≥ 2 subjects.
No significant between group differences were found, (t test for independent samples for continuous variables, Fisher’s Exact Probability test for categorical variables)

Efficacy Analysis

Treatment compliance was very good and similar in both groups. At baseline the total WOMAC scores (mean ± SD) in the Abexol and placebo groups were 37.2 ± 7.6 and 37.6 ± 7.2, respectively, without significant differences between the groups (Table 2). At study completion Abexol significantly reduced the total WOMAC score (p<0.00001 versus baseline and p<0.0001 versus placebo) (78.5% versus baseline, 66.5% versus placebo).

Table 2: Changes in WOMAC Index scores

WOMAC Index scores

Abexol

Placebo

Baseline

37.2 ± 7.6

37.6 ± 7.2

Week 1

 32.1 ± 6.4**

36.7 ± 8.6
% change -13.7+

-2.4

Week 2  24.2 ± 9.6****+++ 36.1 ± 9.5
% change  -34.9+++ -4.0
Week 3  21.6 ± 9.4****++++ 36.2 ± 8.1
% change  -41.9++++ -3.7
Week 4  16.8 ± 8.5****++++ 35.6 ± 9.6
% change  -54.8++++ -5.3
Week 5  15.2 ± 8.1****++++ 34.7 ± 9.6**
% change  -59.1++++ -7.7
Week 6  8.0 ± 5.9****++++ 33.1 ± 8.7**
% change  -78.5++++ -12.0

Values are means ± SD.
**p<0.001; ***p<0.0001 ****p<0.00001 versus baseline (t test for dependent samples) (Bonferroni adjustment).
+p<0.05; +++p<0.001 ++++p<0.0001 versus placebo (t test for independent samples).

The mean ± SD baseline WOMAC pain scores were 8.5 ± 2.2 (Abexol group) and 8.7 ± 2.4 (placebo) (Table 3). After week 1 of treatment, pain score was significant lower in the Abexol (24.7% reduction versus baseline, p<0.001) and placebo (1.1% reduction versus baseline) groups, so that the net difference versus placebo was 23.6%. The treatment effect was enhanced over the trial, so that at the study completion pain score decreased significantly (p<0.0001) with Abexol (70.6% versus baseline, 56.8% versus placebo).

Table 3: Changes in pain, stiffness and physical function scores by treatment group

 

Pain score

Stiffness score Physical function
Abexol Placebo Abexol Placebo Abexol

Placebo

Baseline

8.5 ± 2.2

8.8 ± 2.4 2.8 ± 1.0 2.9 ± 1.0 26.5 ± 6.0 26.3 ± 6.1

Week 1

6.4 ± 2.9**+ 8.6 ± 2.7 2.2 ± 1.0**++ 2.8 ± 0.9 24.2 ± 5.6**

25.6 ± 6.4

% change

-24.7+

-1.1 -21.4+ -3.4 -8.7 -2.7

Week 2

5.4 ± 2.8****+++ 8.5 ± 2.9 1.6 ± 1.0****+++ 2.7 ± 1.0 19.2 ± 5.8****+++

25.1 ± 6.8

% change

-36.5+++

-2.3 -42.9+++ -6.9 -27.5+++ -4.6

Week 3

5.0 ± 2.7****++++ 8.3 ± 2.5 1.3 ± 1.0****++++ 2.6 ± 1.0 14.7 ± 6.5****++++

25.0 ± 6.0

% change

-41.2++++

-4.6 -53.6++++ -10.3 -44.5++++ -4.9

Week 4

4.2 ± 2.3****++++ 8.0 ± 2.6 0.8 ± 0.9****++++ 2.6 ± 1.0 12.5 ± 7.2****++++

24.5 ± 6.5

% change

-50.6++++

-8.0 -71.4++++ -10.3 -52.8++++ -6.8

Week 5

4.0 ± 2.1****++++

7.8 ± 2.8

0.6 ± 0.9****++++

2.5 ± 0.9

10.1 ± 6.4****++++

23.4 ± 6.9*

% change

-52.9++++

-10.3 -78.6++++ -13.8 -61.9++++

-11.0

Week 6

2.5 ± 1.8****++++

7.5 ± 2.4 0.3 ± 0.8****++++ 2.5 ± 0.9 6.2 ± 4.2****++++

23.0 ± 6.0*

% change

-70.6++++

-13.8 -89.3++++ -13.8 -76.6++++

-12.5

Values are means ± SD.
*p<0.0083; **p<0.001; ***p<0.0001; ****p<0.00001 versus baseline (t test for dependent samples) (Bonferroni adjustment).
+p<0.05; ++p<0.01; +++p<0.001 ++++p<0.0001 versus placebo (t test for independent samples).

At baseline the mean stiffness score was 2.8 ± 1.0 in the Abexol group, and 2.9 ± 1.0 in placebo. After week 1, the score was significantly reduced with Abexol (21.4% versus baseline, p<0.001; 18% versus placebo, p<0.01). At study completion the reduction in stiffness with Abexol (p<0.00001 versus baseline, p<0.0001 versus placebo) was of 89.3% as compared to baseline, and of 75.5% versus placebo.

The sequential changes in WOMAC physical function scores were similar to those occurred with the other subset and total WOMAC scores. Meanwhile the mean baseline values of Abexol (26.5 ± 6.0) and placebo (26.3 ± 6.1) groups were similar. The score reductions with Abexol were successively accentuated over the 6 week period, so that the decrease of the physical function score with Abexol at trial completion was of 76.6% and 64.1% as compared to baseline and placebo, respectively.

At baseline the VAS scores (mean ± SD) in the Abexol and placebo groups were 63.1 ± 15.0 and 63.5 ± 16.1, respectively, without significant differences between the groups (Table 4). After week 1 of treatment, the score was significantly reduced in Abexol (p<0.001 versus baseline) and p<0.05 versus placebo. At study completion Abexol had reduced significantly the VAS score (p<0.00001 versus baseline and p<0.0001 versus placebo) (63.2% versus baseline, 47.1% versus placebo)

Table 4: Changes in Visual Analogic Scale (VAS)

VAS Index scores

D-002

Placebo

Baseline

63.1 ± 15.0

63.5 ± 16.1

Week 1

 53.2 ± 17.5**

 59.7 ± 18.2*

% change

-16.0+

-7.1

Week 2

 49.2 ± 16.5****+

 57.9 ± 16.3*

% change

-23.1+

-8.7

Week 3

 44.2 ± 17.1****++

 57.0 ± 15.8*

% change

-30.8+

-7.6

Week 4

 40.0 ± 16.2****++

 55.1 ± 15.9**

% change

-34.1+

-15.4

Week 5

 35.1 ± 12.8****+++

 53.8 ± 17.5**

% change

-40.8+++

-15.4

Week 6

 23.2 ± 10.9****++++

 53.3 ± 15.1**

% change

-60.2+++

-13.4

Values are means ± standard deviations.
*p<0.0083; **p<0.0001; ****p<0.00001 versus baseline (t test for dependent samples) (Bonferroni adjustment).
+p<0.05; ++p<0.01; +++p<0.001 ++++p<0.0001 versus placebo (t test for independent samples).

Safety and Tolerability

Abexol given for six weeks was safe and well tolerated by the patients. The treatment did not affect physical safety indicators, and did not modify significantly the remaining blood indicators laboratory indicators investigated during the study (values not shown for simplicity) in any of the comparisons made. In addition, individual values remained within normal range.

One subject of the placebo group reported moderate adverse event (tendinitis) during the study.

Discussion

Using a randomized, double-blind placebo-controlled design the present study demonstrated, that Abexol improved pain in subjects with joint discomfort as compared to baseline and placebo, results consistent with previous clinical study.

Abexol effects were persistent over the trial, so that it produced sustained benefits, distinguishable from placebo.

Abexol and placebo groups were homogeneous at baseline, which indicates that randomization was effective, and that our results are not attributable to initial differences between the groups, but to Abexol treatment. The mean age of study subjects (65 years) falls within that expected for this disease. Most subjects (58%) were women, consistent with a higher prevalence of joint discomfort in women, mainly post-menopausal, a condition present in 29 of the 32 randomized women (90.6%). The high frequency of hypertension (64%), overweight (48%), sedentary life (38%), hypercholesterolemia (36%) and smoking (22%) among study subjects, not only reflects an undesirable occurrence of coronary risk factors, common in Cuban subjects of this age, but agrees with reports of co-morbidity of joint discomfort in middle-aged and older subjects [33].

Both groups displayed an improvement of total WOMAC values over the six weeks of treatment, including placebo, but these reductions, however, were greater in Abexol than in placebo group. A similar picture was seen for subset WOMAC scores. Abexol group significant reductions of the total (primary efficacy variable) and subset (secondary efficacy variables) WOMAC scores were evident from the week 1, with appreciable improvements with continued administration. At study completion pain, stiffness, physical function and total WOMAC scores decreased by 78.5%, 70.6%, 89.3% and 76.6% as compared to baseline, respectively (reductions versus placebo of 66.5%, 56.8%, 75.5%, and 64.1%, respectively). The use of WOMAC questionnaire is used for clinical trials targeting healthy subjects, for evaluating joint protection effects. The treatment with Abexol improves the symptoms and positively impacts on quality of life of affected subjects, consistently with results on VAS score.

At study completion the Abexol group significant reductions of the VAS scores (secondary efficacy variables) by 63.2% versus baseline and 47.1% versus placebo.

In contrast, although reductions with placebo were also seen, they remained almost stationary over the treatment. This improvement with placebo, however, was not totally unexpected, as it can occur in any efficacy measurement based on subjective assessment. Possible explanations for this finding could include that study subjects may have had high expectations of the benefits of study treatments, despite they were due informed about the use of placebo, so that the reductions observed in the placebo group could be influenced by this fact, as in other placebo-controlled studies in subjects with joint discomfort Price et al. 2008) [34].

Only one patient treated with Abexol was titrated to 100 mg/day during the last 3 weeks, a dose adjustment that alone did not seem to explain the differences found between the two groups. The evident significance of the score reductions with Abexol as compared to placebo and the fact that, opposite to the increasingly efficacy of Abexol, the magnitude of the placebo effect was steady over the trial support this appreciation.

There is experimental evidence of the anti-inflammatory effects of D-002, through the inhibition of the activity of the cycle and lipoxygenase enzymes, causes an inhibition of the synthesis of eicosanoids: prostaglandins and thromboxane by the cyclooxygenase route, and leukotrienes and lipoxins by lipoxygenase pathway. D-002 has an effect on COX, specific on COX-2 and on 5-LOX, the latter is involved in the production of leukotrienes B4, which constitutes a potent chemotactic factor for neutrophils, promoting the development of acute inflammation. The inhibition of both enzymes, frame it as a dual anti-inflammatory, blocks the synthesis of eicosanoids, and prevents inflammation associated [35].

The existing concern about the increased risk for cardiovascular disease and stroke with COX-2 inhibitors, and the gastrointestinal and renal complications produced by non-selective NSAIDs [9,10], remains open perspectives for new therapies, including complementary medicines. Some nutraceuticals with anti-inflammatory effects and good gastrointestinal safety profile have shown benefits in patients with joint discomfort Santini et al. 2017) [36,37].

Abexol resulted safe and well tolerated, consistent with previous clinical studies [18-20,22,23,25,26]. In particular, the absence of gastrointestinal adverse events matches well with the gastroprotective effects of Abexol [18-20].

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Cytoplasm, Cytosol and Cytoskeleton

DOI: 10.31038/JCRM.2022552

Abstract

The Endomembrane system is the system that deals with all tiny organelles present in the cell. The cytoskeleton and cytosol are structural elements that help provide the cell with its structure. The cytoplasm is everything in the cell except for the cytoskeleton and membrane-bound organelles. The cytoskeleton is composed of protein filaments and is found throughout the inside of a eukaryotic cell. The cytosol is the main component of the cytoplasm, it is the fluid that fills the inside of the cell. Both the structures like the cytoskeleton, and cytosol, are “filler” structures that do not contain essential biological molecules but perform structural functions within a cell. The part of the cell referred to as cytoplasm is slightly different in eukaryotes and prokaryotes. In eukaryotic cells, which have a nucleus, the cytoplasm is everything between the plasma membrane and the nuclear envelope. In prokaryotes, which lack a nucleus, cytoplasm simply means everything found inside the plasma membrane.

Cytoplasm

The cytoplasm of a eukaryotic cell consists not only of cytosol—a gel-like substance made up of water, ions, and macromolecules-but also of organelles and the structural proteins that make up the cytoskeleton, or “skeleton of the cell.” One major component of the cytoplasm in both prokaryotes and eukaryotes is the gel-like cytosol, a water-based solution that contains ions, small molecules, and macromolecules. In eukaryotes, the cytoplasm also includes membrane-bound organelles, which are suspended in the cytosol. The cytoskeleton, a network of fibers that supports the cell and gives it shape, is also part of the cytoplasm and helps to organize cellular components. The cytoplasm consists of all of the contents outside of the nucleus and is enclosed within the cell membrane of a cell. It is clear in color and has a gel-like appearance. The cytoplasm is composed mainly of water but also contains enzymes, salts, organelles, and various organic molecules.

Content and Structure

The cytoplasm can be divided into two primary parts: The endoplasm (endo-, –plasm) and ectoplasm (ecto-plasm). The endoplasm is the central area of the cytoplasm that contains the organelles. The ectoplasm is the more gel-like peripheral portion of the cytoplasm of a cell. Prokaryotic cells, such as bacteria and archaeans, do not have a membrane-bound nucleus. In these cells, the cytoplasm consists of all of the contents of the cell inside the plasma membrane. In eukaryotic cells, such as plant and animal cells, the cytoplasm consists of three main components. They are the cytosol, organelles, and various particles and granules called cytoplasmic inclusions.

  • Cytosol: The cytosol is the semi-fluid component or liquid medium of a cell’s cytoplasm. It is located outside of the nucleus and within the cell membrane.
  • Organelles: these are tiny cellular structures that perform specific functions within a cell. Examples of organelles include mitochondria, ribosomes, nucleus, lysosomes, chloroplasts, endoplasmic reticulum, and Golgi apparatus. Also located within the cytoplasm is the cytoskeleton, a network of fibers that help the cell maintain its shape and provide support for organelles.

Cytoplasm Functions

The cytoplasm functions to support and suspend organelles and cellular molecules. Many cellular processes also occur in the cytoplasm, such as protein synthesis, the first stage of cellular respiration (known as glycolysis), mitosis, and meiosis. The cytoplasm helps to move materials, such as hormones, around the cell and also dissolves cellular waste.

Cytoplasmic Inclusions

Cytoplasmic inclusions are particles that are temporarily suspended in the cytoplasm. They consist of macromolecules and granules. Three types of inclusions found in the cytoplasm are (1) Secretory inclusions, (2) Nutritive inclusions, and (3) Pigment granules. Examples of secretory inclusions are proteins, enzymes, and acids. Glycogen (glucose storage molecule) and lipids are examples of nutritive inclusions. Melanin found in skin cells is an example of a pigment granule inclusion.

fig 1

Figure 1: Cytoplasmic Streaming in plant cell

Cytoplasmic Streaming or Cyclosis

It is a process by which substances are circulated within a cell. Cytoplasmic streaming occurs in a number of cell types including plant cells, amoeba, protozoa, and fungi. Cytoplasmic movement may be influenced by several factors including the presence of certain chemicals, hormones, or changes in light or temperature.

Plants employ cyclosis to shuttle chloroplasts to areas receiving the most available sunlight. Chloroplasts are the plant organelles responsible for photosynthesis and require light for the process. In protists, such as amoebae and slime molds, cytoplasmic streaming is used for locomotion. Temporary extensions of the cytoplasm known as pseudopodia are generated that are valuable for movement and capturing food. Cytoplasmic streaming is also required for cell division as the cytoplasm must be distributed among daughter cells formed in mitosis and meiosis.

Cytosol

One major component of the cytoplasm in both prokaryotes and eukaryotes is the gel-like cytosol, a water-based solution that contains ions, small molecules, and macromolecules. In eukaryotes, the cytoplasm also includes membrane-bound organelles, which are suspended in the cytosol. The cytoskeleton, a network of fibers that supports the cell and gives it shape, is also part of the cytoplasm and helps to organize cellular components. The interior of a cell is composed of organelles, the cytoskeleton, and the cytosol. The cytosol often comprises more than 50% of a cell’s volume. Beyond providing structural support, the cytosol is the site wherein protein synthesis takes place, and provides a home for the centrosomes and centrioles. These organelles will be discussed more with the cytoskeleton.

Content and Structure

Even though the cytosol is mostly water, it has a semi-solid, Jello-like consistency because of the many proteins suspended in it. The cytosol contains a rich broth of macromolecules and smaller organic molecules, including glucose and other simple sugars, polysaccharides, amino acids, nucleic acids, and fatty acids. Ions of sodium, potassium, calcium, and other elements are also found in the cytosol. Many metabolic reactions, including protein synthesis, take place in this part of the cell.

Function

The jelly-like fluid that fills a cell is called cytoplasm. It is made up of mostly water and salt. The cytoplasm is present within the cell membrane of all cell types and contains all organelles and cell parts. The cytoplasm has various functions in the cell. Most of the important activities of the cell occur in the cytoplasm. The cytoplasm contains molecules such as enzymes which are responsible for breaking down waste and also aid in metabolic activity. The cytoplasm is responsible for giving a cell its shape. It helps to fill out the cell and keeps organelles in their place. Without cytoplasm, the cell would be deflated and materials would not be able to pass easily from one organelle to another. The cytosol is the part of the cytoplasm that does not contain organelles. Instead, the cytosol is confined by the boundaries of a matrix that fills the part of the cell that does not contain organelles.

Cytoskeleton

We often think about cells as soft, unstructured blobs, interestingly enough, the same is true for a cell. But in reality, they are highly structured in much the same way as our own bodies. They have a network of filaments known as the cytoskeleton (literally, “cell skeleton”), which not only supports the plasma membrane and gives the cell an overall shape, but also aids in the correct positioning of organelles, provides tracks for the transport of vesicles, and (in many cell types) allows the cell to move. Have we ever thought, what would happen if someone snuck in during the night and stole your skeleton? Just to be clear, that’s not very likely to happen, biologically speaking. But if it did somehow happen, the loss of your skeleton would cause your body to lose much of its structure. Your external shape would change, some of your internal organs might start moving out of place, and you would probably find it very difficult to walk, talk, or move. The cytoskeleton is a network of filaments and tubules that extends throughout a cell, through the cytoplasm, which is all of the material within a cell except for the nucleus. It is found in all cells, though the proteins that it is made of vary between organisms. The cytoskeleton supports the cell, gives it shape, organizes and tethers the organelles, and has roles in molecule transport, and cell signaling. All cells have a cytoskeleton, but usually, the cytoskeleton of eukaryotic cells is what is meant when discussing the cytoskeleton. Eukaryotic cells are complex cells that have a nucleus and organelles. Plants, animals, fungi, and protists have eukaryotic cells. Prokaryotic cells are less complex, with no true nucleus or organelles except ribosomes, and they are found in the single-celled organism’s bacteria and archaea. The cytoskeleton of prokaryotic cells was originally thought not to exist; it was not discovered until the early 1990s. The cytoskeleton is similar to the lipid bilayer in that it helps provide the interior structure of the cell the way the lipid bilayer provides the structure of the cell membrane. The cytoskeleton also allows the cell to adapt. Often, a cell will reorganize its intracellular components, leading to a change in its shape. The cytoskeleton is responsible for mediating these changes. By providing “tracks” with its protein filaments, the cytoskeleton allows organelles to move around within the cell. In addition to facilitating intracellular organelle movement, by moving itself the cytoskeleton can move the entire cells in multi-cellular organisms. In this way, the cytoskeleton is involved in intercellular communication.

Content and Structure

The eukaryotic cytoskeleton consists of three types of filaments, which are elongated chains of proteins: microfilaments, intermediate filaments, and microtubules. The microfilaments of this cell are shown in red, while microtubules are shown in green. The blue dots are nuclei. These three types of protein are distinct in their structure and specific function, but all work together to help provide intra-cellular structure. Because they are so diverse, it is very difficult to study the specific functions of the cytoskeletal components.

Microfilaments

Microfilaments are also called actin filaments because they are mostly composed of the protein actin; their structure is two strands of actin wound in a spiral. They are about 5 to 9 nanometers thick, making them the thinnest filaments and narrowest in all 3 types of protein fibers in the cytoskeleton. They are made up of many linked monomers of a protein called actin, combined in a structure that resembles a double helix. Because they are made of actin monomers, microfilaments are also known as actin filaments. Actin filaments have directionality, meaning that they have two structurally different ends.

Functions

Microfilaments have many functions. They aid in cytokinesis, which is the division of the cytoplasm of a cell when it is dividing into two daughter cells. They aid in cell motility and allow single-celled organisms like amoebas to move. They are also involved in cytoplasmic streaming, which is the flowing of cytosol (the liquid part of the cytoplasm) throughout the cell. Cytoplasmic streaming transports nutrients and cell organelles. Microfilaments are also part of muscle cells and allow these cells to contract, along with myosin. Actin and myosin are the two main components of muscle contractile elements. Actin filaments have a number of important roles in the cell. For one, they serve as tracks for the movement of a motor protein called myosin, which can also form filaments. Because of its relationship to myosin, actin is involved in many cellular events requiring motion. For instance, in animal cell division, a ring made of actin and myosin pinches the cell apart to generate two new daughter cells. Actin and myosin are also plentiful in muscle cells, where they form organized structures of overlapping filaments called sarcomeres. When the actin and myosin filaments of a sarcomere slide past each other in concert, your muscles contract. Actin filaments may also serve as highways inside the cell for the transport of cargoes, including protein-containing vesicles and even organelles. These cargoes are carried by individual myosin motors, which “walk” along actin filament bundles, like start superscript, 1, end superscript. Actin filaments can assemble and disassemble quickly, and this property allows them to play an important role in cell motility (movement), such as the crawling of a white blood cell in your immune system. Finally, actin filaments play key structural roles in the cell. In most animal cells, a network of actin filaments is found in the region of cytoplasm at the very edge of the cell. This network, which is linked to the plasma membrane by special connector proteins, gives the cell shape and structure. Actin is the most abundant protein in most eukaryotic cells. Most actin molecules work together to give support and structure to the plasma membrane and are therefore found near the cell membrane.

Intermediate Filaments

Intermediate filaments are a type of cytoskeletal element made of multiple strands of fibrous proteins wound together. These are the first class of proteins that compose the cytoskeleton. These structures are fibrous and rope-like in appearance. As their name suggests, intermediate filaments have an average diameter of 8 to 12 nm, in between that of microfilaments and microtubules.

Functions

Intermediate filaments come in a number of different varieties, each one made up of a different type of protein. One protein that forms intermediate filaments is keratin, a fibrous protein found in hair, nails, and skin. For instance, you may have seen shampoo ads that claim to smooth the keratin in your hair! Intermediate filaments, in the form of keratins are also present in animals with scales, horns, or hooves), vimentin, desmin, and lamin. All intermediate filaments are found in the cytoplasm except for lamins, which are found in the nucleus and help support the nuclear envelope that surrounds the nucleus. The intermediate filaments in the cytoplasm maintain the cell’s shape, bear tension, and provide structural support to the cell. They are not found in all animal cells, but in those in which they are present they form a network surrounding the nucleus often called the nuclear lamina. Other types of intermediate filaments extend through the cytosol. The filaments help to resist stress and increase cellular stability. Unlike actin filaments, which can grow and disassemble quickly, intermediate filaments are more permanent and play an essentially structural role in the cell. They are specialized to bear tension, and their jobs include maintaining the shape of the cell and anchoring the nucleus and other organelles in place.

Microtubules

Microtubules are the largest of the cytoskeleton’s fibers at about 23 nm. A microtubule is made up of tubulin proteins arranged to form a hollow, straw-like tube, and each tubulin protein consists of two subunits, α-tubulin and β-tubulin. Microtubules form structures like flagella, which are “tails” that propel a cell forward. They are also found in structures like cilia, which are appendages that increase a cell’s surface area and in some cases allow the cell to move. Despite the “micro” in their name, microtubules are the largest of the three types of cytoskeletal fibers, with a diameter of about 25 nm. Microtubules, like actin filaments, are dynamic structures: they can grow and shrink quickly by the addition or removal of tubulin proteins. Also similar to actin filaments, microtubules have directionality, meaning that they have two ends that are structurally different from one another. In a cell, microtubules play an important structural role, helping the cell resist compression forces. Microtubules are relatively unstable and go through a process of continuous growth and decay.

Functions

Most of the microtubules in an animal cell come from a cell organelle called the centrosome, which is a Microtubule Organizing Center (MTOC). The centrosome is found near the middle of the cell, and microtubules radiate outward from it. Microtubules are important in forming the spindle apparatus (or mitotic spindle), which separates sister chromatids so that one copy can go to each daughter cell during cell division. They are also involved in transporting molecules within the cell and in the formation of the cell wall in plant cells. In addition to providing structural support, microtubules play a variety of more specialized roles in a cell. For instance, they provide tracks for motor proteins called kinesins and dyneins, which transport vesicles and other cargoes around the interior of the cell. During cell division, microtubules assemble into a structure called the spindle, which pulls the chromosomes apart. Certain proteins will use microtubules as tracks for laying out organelles in a cell. Basically these long, cylindrical structures composed of the protein tubulin and organized around a centrosome, an organelle usually found in the center of the cell near the cell nucleus. Unlike actin molecules, microtubules work separately to provide tracks on which organelles can travel from the center of the cell outward. Microtubules are much more rigid than actin molecules, one end of each microtubule is embedded in the centrosome; the microtubule grows outward from there.

Flagella, Cilia, and Centrosomes

Microtubules are also key components of three more specialized eukaryotic cell structures: flagella, Cilia and Centrosomes. Prokaryotes also have structures like flagella, which they use to move. The eukaryotic flagella we’re about to discuss have pretty much the same role, but a very different structure.

We know that our friends the prokaryotes also have structures like flagella, which they use to move. Don’t get confused-the eukaryotic flagella we’re about to discuss have pretty much the same role, but a very different structure.

Flagella

Flagella (singular, flagellum) are long, hair-like structures that extend from the cell surface and are used to move an entire cell, such as a sperm. If a cell has any flagella, it usually has one or just a few. Motile cilia (singular, cilium) are similar, but are shorter and usually appear in large numbers on the cell surface. When cells with motile cilia form tissues, the beating helps move materials across the surface of the tissue. For example, the cilia of cells in your upper respiratory system help move dust and particles out towards your nostrils.

Cilia

Despite their difference in length and number, flagella and motile cilia share a common structural pattern. In most flagella and motile cilia, there are 9 pairs of microtubules arranged in a circle, along with an additional two microtubules in the center of the ring. This arrangement is called a 9 + 2 array. In flagella and motile cilia, motor proteins called dyneins move along the microtubules, generating a force that causes the flagellum or cilium to beat. The structural connections between the microtubule pairs and the coordination of dynein movement allow the activity of the motors to produce a pattern of regular beating.

Basal Body

The cilium or flagellum has a basal body located at its base. The basal body is made of microtubules and plays a key role in assembly of the cilium or flagellum. Once the structure has been assembled, it also regulates which proteins can enter or exit.

fig 2

Figure 2: 9 + 2 array in the electron microscopy

Centrosome

The basal body is actually just a modified centriole. A centriole is a cylinder of nine triplets of microtubules, held together by supporting proteins. Centrioles are best known for their role in centrosomes, structures that act as microtubule organizing centers in animal cells, they are small arrays of microtubules that are found in the center of a centrosome. A centrosome consists of two centrioles oriented at right angles to each other, surrounded by a mass of “pericentriolar material,” which provides anchoring sites for microtubules. The centrosome is duplicated before a cell divides, and the paired centrosomes seem to play a role in organizing the microtubules that separate chromosomes during cell division. However, the exact function of the centrioles in this process still isn’t clear. Cells with their centrosome removed can still divide, and plant cells, which lack centrosomes, divide just fine.

Other Structure

A number of motor proteins are found in the cytoskeleton. As their name suggests, these proteins actively move cytoskeleton fibers. As a result, molecules and organelles are transported around the cell. Motor proteins are powered by ATP, which is generated through cellular respiration. There are three types of motor proteins involved in cell movement.

Motor Proteins

Kinesins move along microtubules carrying cellular components along the way. They are typically used to pull organelles toward the cell membrane.

Dyneins are similar to kinesins and are used to pull cellular components inward toward the nucleus. Dyneins also work to slide microtubules relative to one another as observed in the movement of cilia and flagella.

Myosins interact with actin in order to perform muscle contractions. They are also involved in cytokinesis, endocytosis, and exocytosis.

Cytoskeleton Functions

As described above, the cytoskeleton extends throughout the cell’s cytoplasm and directs a several number of important functions. First, it gives the support and shape to the cell. This is especially important in cells without cell walls, such as animal cells, that do not get their shape from a thick outer layer. It can also give the cell movement. The microfilaments and microtubules can disassemble, reassemble, and contract, allowing cells to crawl and migrate, and microtubules help form structures like cilia and flagella that allow for cell movement. The cytoskeleton organizes the cell and keeps the cell’s organelles in place, but it also aids in the movement of organelles throughout the cell. It assists in the formation of vacuoles. For example, during endocytosis when a cell engulfs a molecule, microfilaments pull the vesicle containing the engulfed particles into the cell. Similarly, the cytoskeleton helps move chromosomes during cell division. One analogy for the cytoskeleton is the frame of a building. Like a building’s frame, the cytoskeleton is the “frame” of the cell, keeping structures in place, providing support, and giving the cell a definite shape. The cytoskeleton is not a static structure but is able to disassemble and reassemble its parts in order to enable internal and overall cell mobility. Types of intracellular movement supported by the cytoskeleton include transportation of vesicles into and out of a cell, chromosome manipulation during mitosis and meiosis, and organelle migration. The cytoskeleton makes cell migration possible as cell motility is needed for tissue construction and repair, cytokinesis (the division of the cytoplasm) in the formation of daughter cells, and in immune cell responses to germs. The cytoskeleton assists in the transportation of communication signals between cells. It forms cellular appendage-like protrusions, such as cilia and flagella, in some cells [1-69].

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A Case of White Matter Hyperintensities in the Brain

DOI: 10.31038/JCRM.2022542

Objective

This article is to differentiate the MRI findings between Parkinson’s disease and Multiple sclerosis. Therefore, this article focuses mainly the brain imaging only.

Case Report

An elderly gentleman- Mr C, diagnosed with vascular dementia was subjected to MRI due to decline in neuromotor function. He had recent symptoms of headache and reduced cognition. A diagnosis of Parkinsons or Parkinson Plus syndrome was made.

The MRI Brain sequence are as follow:

Axial: proton-density and/or T2 FLAIR/T2-weighted.

Sagittal: T2 FLAIR.

Gad contrast enhanced T1-weighted imaging.

Salient features in the T2/FLAIR MRI were reported as deep white matter hyperintensity that were asymmetrical, located primarily at periventricular and juxtacortical regions. Precontrast images show the lesions are hypointense on T1WIs with the “Dawson’s fingers” appearance. And post contrast images show enhancing white matter lesions (Figure 1).

fig 1

Figure 1: An example of similar lesions- as no patient consent taken for release of original images

Other key points were:

Some lesions being greater than 5 mm.

Some lesions were perpendicular.

Incomplete rim enhancement in larger lesions- gadolinium contrasted.

Further MR cervical spine was suggested to examine for additional lesions. A repeat MRI in 6-12 months was recommended, as new lesions on repeat imaging are common and not all lesions enhance simultaneously at onset. Also suggested for Visual Evoked Potential (VEP) to identify subclinical demyelination.

Discussion

Parkinson Disease (PD), is a neurodegenerative disease and movement disorder characterised by a resting tremor, rigidity and hypokinesia due to progressive degeneration of dopaminergic neurons in the substantia nigra [1-4]. It is characterised by nigrostriatal dopaminergic degeneration leading to neuronal loss in the substantia nigra, most conspicuous in the ventrolateral tier of neurons, and a number of other regions including parts of the basal ganglia, brainstem, autonomic nervous system and cerebral cortex. Upon MRI, loss of the normal swallow tail appearance of susceptibility- signal pattern in the substantia nigra- on axial imaging in a 3T is perhaps the most promising diagnostic sign. Apart from these changes, the signal intensity in substantia nigra depends on loss of neuromelanin and iron accumulation. In addition to aiding diagnosis, MRI is also used to identify features which may indicate secondary parkinsonism rather than primary disease, such as extensive small vessel ischaemic change.

Parkinson-plus syndrome refers to a loose group of neurodegenerative disorders that are characterised by features of Parkinson disease but with other neurological symptoms/signs. They have a poor response to levodopa, and mostly have fairly characteristic neuroimaging features.

Conditions included in Parkinson-plus syndrome include:

  • progressive supranuclear palsy (PSP)
  • multisystem atrophy (MSA)
  • dementia with Lewy bodies (DLB)

On the contrary, Multiple sclerosis (MS) is an inflammatory demyelinating condition.

In MS, the loss of myelin, is accompanied by a disruption in the ability of the nerves to conduct electrical impulses to and from the brain. This produces the various symptoms of MS. The sites where myelin is lost appear as plaque or lesions. In multiple sclerosis, these scars appear at different times and in different areas of the brain and spinal cord. The term multiple sclerosis itself means ‘many scars’. For some, MS is characterised by periods of relapse and remission while, for others, it has a progressive pattern.

Conclusion

The final conclusion of the case based on the MRI appearance was multiple sclerosis. However, a differential diagnosis of Parkinson/Parkinson Plus syndrome was not null and void as the MRI was performed on a 1.5 T machine. However, it is a clinical judgement nevertheless.

References

  1. Martina Absinta, Sati P, Masuzzo F, Nair G, Sethi V, et al. (2019) Association of Chronic Active Multiple Sclerosis Lesions with Disability In Vivo. JAMA Neurology 76: 1474-1483. [crossref]
  2. Okuda D, Mowry E, Beheshtian A, Waubant E, Baranzini SE, et al. (2009) Incidental MRI Anomalies Suggestive of Multiple Sclerosis: The Radiologically Isolated Syndrome. Neurology 72: 800-805. [crossref]
  3. Lövblad K, Anzalone N, Dörfler A, Essig M, Hurwitz B, et al. (2010) MR Imaging in Multiple Sclerosis: Review and Recommendations for Current Practice. AJNR Am J Neuroradiol 31: 983-989. [crossref]
  4. https://www.ninds.nih.gov/health-information/disorders/multiple-sclerosis