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Cross-regional Nexus Perspective in Anthropocene

DOI: 10.31038/GEMS.2023566

Abstract

In the context of global mobility, the traditional research framework based on a fixed location perspective is facing the need for adaptive innovation and change. In order to deepen the understanding of the evolution of the Anthropocene stratigraphic record and surface landscapes, this paper argues that the nexus approach and the systematic integration of spatial dimensions should be combined in the context of the Anthropocene to form a cross-regional nexus approach, to better cope with the complex issues and global challenges of the Anthropocene.

Keywords

Nexus approach, Cross-regional nexus perspective, Telecoupling, Metacoupling, Spatially dimensional systems integration, Anthropocene

Human beings are ever extending their activity space largely thanks to the technology progress in energy utilization, transport and information communication. The trajectory of human development since the 1760s indicated that the increasing enhancement of regional linkages and connectivity, and the growing higher human and resource mobility have become the prevailing trend and dominated pattern over the world. In these transformative changes, cities play a leading role as engine of the world technology advancement and the regional center for global production and consumption. The increasing connectivity and mobility have also gradually transformed the rural society based on local ecosystem services into the urban society based on non-ecosystem services and long-distance resource redistribution, and have profoundly changed the way humans interacting with nature. One of the most important changes in human-nature interrelationships, especially since the middle of the twentieth century, is the increasing interaction of coupled human and natural systems (CHANS) over long distances [1], and another is the fact that humans are influencing and modifying ecosystems to a greater extent than at any other time in history [2]. Over the past 70 years, human activities have greatly accelerated erosion and weathering on land; greenhouse gas emissions from agricultural, industrial and consumer activities are changing at an unprecedented rate, and the resulting fluctuations in the carbon cycle and climate change are threatening biodiversity and human survival. The changes taking place in the oceans are equally worrisome, and in addition to the widespread concerns about sea-level rise, ocean acidification and marine litter pollution, the recent release of nuclear-contaminated water from Fukushima, which was not sampled by scientists from neighboring countries, has created new uncertainties for marine ecosystems and human survival.

Given that these challenges cross the boundaries of culture, social governance and ecosystems, there is a need to re-examine human-environment interactions from a new perspective. The “Anthropocene” is a geological concept based on the fact that human activities have had a global impact on climate and ecosystems. Since the introduction of the concept of the Anthropocene [3], the field has attracted a wide range of research interest, with recent attempts to establish an Anthropocene gold spike profile being particularly noteworthy [4]. It is worth noting that the anthropogenic factors driving the evolution of stratigraphic records and surface landscapes in Anthropocene have transcended the boundaries of specific regions in the context of evolving globalization and continuing urbanization, making the traditional research framework in the field of Earth sciences based on a fixed locational perspective is facing the need for adaptive innovation and change. In the last decade or so, a series of illuminating research work has been carried out in the nexus approach and spatially dimensional systems integration in order to better understand the interactions between coupled human and natural systems over distances and their resulting socio-economic and environmental impacts across regions. Hoff first introduced the concept of the water-energy-food (WEF) nexus at the Bonn Conference in 2011 [5] to better deals with the challenges posed by global changes from a multi-sectoral perspective. Subsequently, the nexus approach aroused widespread academic interest. In the same year, Liu Jianguo and others proposed the comprehensive concept of Telecoupling at the symposium on “Telecoupling of Human and Natural Systems” at the meeting of the American Association for the Advancement of Science [6]. This theoretical framework for describing socio-economic and environmental interactions at a distance between coupled human and natural systems was elaborated in the later paper “Framing sustainability in a telecoupled world” [7].

The theoretical idea reflected in telecoupling has attracted widespread academic attention, and a series of related theoretical models have emerged in the global academic community in the same period of time that the theory was put forward and thereafter, typically representing “interregional sustainability” [8,9], urban land teleconnections [10,11], local- and tele-coupling [12], metacoupling [13], as well as the Coupled Human and Natural Cube [14]. Among them, metacoupling is a natural extension to the study of telecoupling, and the theoretical framework is actually an integration of intracoupling, pericoupling and telecoupling [13]. It takes into account human-nature interactions within a given system and across spatial distances by incorporating all target coupled systems from near to far, essentially integrating the study of “flow space” and place space [15], and thus not only overcoming the inherent limitations of single-system studies in the classical propositions of human-nature relations, but also compensating for some of the shortcomings of the telecoupling framework [16]. Although many advances have been made in research on the Anthropocene, the nexus approach, and spatial dimensional systems integration, respectively, the combination of the three remains little discussed in the literature. In the context of the Anthropocene, the nexus approach extended to multiple regions – i.e., cross-regional nexus analysis can deepen the understanding of the evolution of the Anthropocene stratigraphic record and surface landscapes. For example, in the framework of the “water-land-food-energy” nexus, water is needed for irrigation and is consumed by energy production that provides electricity for irrigation, while the trend towards the energization of food creates tensions between bioenergy and food production over land resources [17].

These problems of factor clamping and conflict arising from the competitive use of resources affect the food security of distal regions, such as urban areas, through the food system. Conversely, in the process of urbanization, there is also competitive use of soil and water resources in urban areas between different uses. For example, more soil and water resources for urban development or ecological construction means less soil and water resources that can be used for agricultural production. The result is naturally a reduction in the self-sufficiency rate of food in urban areas and a shift in the resource and environmental pressure on food supply to other regions, thus creating a process of cross-regional nexus between natural and human elements [18] (Figure 1). In conclusion, the cross-regional nexus perspective in Anthropocene provides a concrete entry point for revealing the implicit connection and indirect feedback between human beings and the environment in the “flow space”, which is of great significance to the study of human-earth relationship network system under the perspective of metacoupling, and its policy application is of great practical value in solving the many challenges of the Anthropocene and promoting sustainable development. Thus, theoretical and empirical research on cross-regional nexus in Anthropocene deserves the attention of scholars.

FIG 1

Figure 1: A typical case of cross regional nexus – urban food system

Authorship Contribution Statement

Enpu Ma: Conceptualization, Writing original draft, Funding acquisition. Liuwen Liao: Conceptualization, Funding acquisition. Yiwen Ji and Sen Yu: Discussing, Drawing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this original manuscript.

Acknowledgement

This research was funded by the National Natural Science Foundation of China (Grant No. 42101267 and 42101198).

References

  1. Liu J, Dietz T, Carpenter SR, et al. (2007) Coupled human and natural systems. AMBIO 36: 593-596.
  2. Millennium Ecosystem Assessment Panel. Ecosystem and human well-being: Synthesis. (2005) Washington DC, USA: Island Press.
  3. Crutzen P (2002) Geology of mankind. Nature 415.
  4. Colin NW, Jan Z, Colin S, Ian JF, Neil LR, et al. (2018) Global Boundary Stratotype Section and Point (GSSP) for the Anthropocene Series: Where and how to look for potential candidates. Earth-Science Reviews 178: 379-429.
  5. Hoff H (2011) Understanding the Nexus. Background Paper for the Bonn2011 Conference: The Water, Energy and Food Security Nexus. Stockholm Environment Institute, Stockholm.
  6. Liu J, McConnell W, Baerwald T, et al. (2011) Symposium on “Telecoupling of Human and Natural Systems” at the meeting of the American Association for the Advancement of Science.
  7. Liu J, Hull V, Batistella M, Mateus B, Ruth D, Thomas D, et al. (2013) Framing sustainability in a telecoupled world. Ecology and Society 18.
  8. Kissinger M, Rees WE (2010) An interregional ecological approach for modelling sustainability in a globalizing world: Reviewing existing approaches and emerging directions. Ecological Modelling 221: 2615-2623.
  9. Kissinger M, Rees WE, Timmer V (2011) Interregional sustainability: Governance and policy in an ecologically interdependent world. Environmental Science & Policy 14: 965-976.
  10. Seto KC, Reenberg A, Boone CG, Michail F, Dagmar H, Tobias L, et al. (2012) Urban land teleconnections and sustainability. Proceedings of the National Academy of Sciences of the United States of America. 109: 7687-7692.
  11. Guneralp B, Seto KC, Ramachandran M (2013) Evidence of urban land teleconnections and impacts on hinterlands. Current Opinion in Environmental Sustainability 5: 445-451.
  12. Fang CL, Zhou CH, Gu CL, Chen L, et al. (2016) Theoretical analysis of interactive coupled effects between urbanization and eco-environment in mega-urban agglomerations. Acta Geographica Sinica, 71: 531-550.
  13. Liu J (2017) Integration across a metacoupled world. Ecology and Society 22.
  14. Liu HM, Fang CL, Li YH (2019) The Coupled Human and Natural Cube: A conceptual framework for analyzing urbanization and eco-environment interactions. Acta Geographica Sinica 74: 1-19.
  15. Ma EP, Ye WY, Liao LW, Cai JM, et al. (2022) Human-land coupling enlightenment and driving forces of urban food system evolution: A case study of Beijing food system. Journal of Natural Resources 37: 2617-2635.
  16. Ma EP, Cai JM, Han Y, Liao LW, Lin J, et al. (2020) Research progress and prospect of telecoupling of Human-Earth system. Progress in Geography 39: 310-326.
  17. Food and Agriculture Organization of the United Nations. Bioenergy and food security (2008). China Agricultural Information 6: 4-6.
  18. Ma EP, Cai JM, Guo H, Lin J, Liao LW, et al. (2021) Theoretical framework and research priorities on food system couplings in an urbanization context. Acta Geographica Sinica 76: 2343-2359.

SARS-CoV-2: Prolonged Viral Shedding and Persistent PCR Positivity: A Case Study from Pakistan

DOI: 10.31038/MIP.2023412

Abstract

Introduction: Prolonged viral persistency and shedding are the major concerns associated with emerging variants of SARS-CoV-2. Complete viruses and viral fragments may persist for unusual and longer periods in both symptomatic and non-symptomatic patients.

Case presentation: In this study, we have reported unusual persistency of SARS-CoV-2 in 26 years old young patient from Islamabad, Pakistan.

Conclusion: In conclusion, to avoid viral persistency for a long duration, precise treatment and immune-boosting therapies must be recommended. Further, nontherapeutic interventions and preventive measures are necessary to avoid viral transmission and possible reinfection.

Keywords

COVID-19, Immunocompromised, Persistency, Viral shedding

Introduction

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19) is a major concern of twenty first century [1]. This detrimental zoonotic and highly transmissible virus is responsible for the ongoing pandemic and poses threats to public health globally [2]. Continuous efforts revealed the epidemiology, pathogenicity, presiding results, genomic sequences, and precise diagnostic approaches of SARS-CoV-2 infections. Despite these facts, the burden of pandemic is still increasing due to the emerging variants[3,4], microbial coinfections [5], recrudescence [6], reinfections [7], prolonged viral shedding [8] and persistent RNA positivity [9] (Table 1).

Table 1: Definitions

Terms

Descriptions

Persistency Unusual and prolonged presence of viral RNA in the body fluids.
Re-positivity Detecting the presence of viral RNA following negative RT-PCR tests up to 90 days.
Recrudescence Reactivation/ relapse of infection after clinical improvement within 90 days of first infection due to persisting viral fragments.
Reinfection Infection caused by same or phylogenetically distinct respiratory and non-respiratory viruses after natural immunity and or vaccination.

Recently, patients with COVID-19 revealed persistently positive SARS-CoV-2 nucleic acid test results despite resolved clinical symptoms have attracted a lot of attention [10]. Researchers assumed long-term persistency of virus in the human body even after apparent recovery or negative results of nasopharyngeal specimens via PCR. Viral load appeared to be higher in the upper respiratory tract within the first week after symptom onset, and later in the lower respiratory tract. Viral shedding and viral load are important determinants of disease progression and transmission [11].

In this study, we reported a ruled-out case of SARS-CoV-2 in young male patient of 26 years from Islamabad Pakistan, with extremely prolonged and persistent viral shedding for six weeks.

Case Presentation

A young student of 26 years with past medical history of respiratory tract problems including pulmonary tuberculosis, recovered in 2019 with COVID-19 symptoms including cough, fatigue, body pain and mild dyspnea introduced for the diagnosis of SARS-CoV-2 infection. The RT-PCR of nasopharyngeal samples were tested positive initially on April 20, 2021. Self-isolation was suggested with symptoms resolving treatment (paracetamol). The test was performed after RNA extraction (Qiagen Viral RNA Mini Kit) on ABI 7500 Real-Time PCR detection system with internal and external positive controls via the SARS-CoV-2 detection protocols.

After initial diagnosis, the patient was again COVID-19 positive after five days i.e. on April 25, 2021. At this stage, no clinical or physical examinations were performed while antibiotic treatment was recommended for five days. The symptoms were resolved during first week of antibiotic treatment. On May 18, 2021, persistency for SARS-CoV-2 with altered and mild symptoms were observed again. The major symptoms were anosmia and dyspnea (Figure 1 – Case timeline). Empirical antibiotic treatment was recommended to overcome the possible health problems i.e. Azithromycin 500 mg/day with two-fold increase compared to initial dose of 250 mg/day.

FIG 1

Figure 1: Case timeline of patient 1 (male, age 26 years)

To investigate the patients’ health status and immune response, recommended biochemical tests were performed on 33rd day of infection i.e. on May 22, 2021. Anti-SARS-CoV-2 antibody test was performed on Cobas e411 analyzer (Diagnostic Roche), a fully automated instrument employing Electro Chemiluminescence (ECL) technology for immunoassay analysis using FDA approved kits in human serum and plasma, revealed development of SARS-CoV-2 antibodies (titer 15.13 cut of index COI > 1).

The health status was normal with mild morbidity as the biochemical markers associated with COVID-19 including Ferritin, C-reactive proteins (CRP) and D-dimers were normal (Table 2). Complete blood count revealed drop in neutrophil counts while lymphocytes level was high (Table 3). Fortunately, the patient was declared recovered according to general discharge criteria (Figure 2) [12] on 43rd day of primary infection.

Table 2: Biochemical tests

Tests

Value

Reference value

Interpretation

Ferritin

160.9 ng/ml

14-250

Normal

CRP

0.13 mg/l

0.00-10.00

Normal

FDPs (D-Dimer)

0.1 mg/l

0.00-0.50

Normal

Antibodies

15.13 COI

Cut off 1.00

Reactive

Abbreviations: CRP: C-reactive proteins; FDPs: Fibrin Degradation Products, COI: Cut Off Index.

Table 3: Complete blood count

Parameters (units)

Reference value

Value

White blood cells (TLC) (10⁹/L)

4.00-11.00

5.8

Neutrophils (%)

50.00-70.00

40

Lymphocytes (%)

20.00-40.00

48

Monocytes (%)

3.00-12.00

10

Eosinophils (%)

0.50-5.00

02

Basophils (%)

0.00-1.00

0.0

Red blood cells, count (Mil/Cm)

4.00-6.00

5.02

Hemoglobin (Hb) (Gm/dl)

11.00-16.00

14.0

Hematocrit (PCV) (%)

37.00-54.00

46.5

MCV (f/L)

80.00-100.00

93.0

MCH (Pgm)

27.00-34.00

27.8

MCHC (g/L)

30.00-36.00

30.0

Platelets (10⁹/L)

150.00-450.00

333

MPV (f/L)

7.00-11.00

7.5

PDW (f/L)

8.30-25.00

16.2

Procalcitonin (mL/L)

1.08-2.82

1.82

Abbreviations: TLC: Total Leucocytes Counts, PCV: Packed Cells Volume, MCV: Mean Corpuscular Volume, MCH: Mean Corpuscular Hemoglobin, MCHC: Mean Corpuscular Hemoglobin Concentration, MPV: Mean Platelet Volume, PDW: Platelet Distribution Width.

FIG 2

Figure 2: Criteria of discharge/declaring recovered

Discussion

Viral load remains high in upper respiratory tract during first week of infection or onset of symptoms and tends to decrease with time. Virus median duration of shedding is 8 days post onset of symptoms and drops below 5% after 15.2 days post onset of symptoms [13]. However, recent studies demonstrated viral shedding for long duration in immune-compromised individuals [14] in both symptomatic and asymptomatic patients of older age [15]. The current study reported unexpected and persistent infection of SARS-CoV-2 in young patient of 26 years for more than six weeks. To our understanding, this is the first report addressing prolonged and persistent viral positivity from Pakistan.

RT-RNA based repeated RNA positivity was considered primary indication of persistent infection as documented in previous studies [16]. Persistent shedding was significantly associated with persistent dyspnea and anosmia. Detection of viral RNA and confirmed retest positivity for SARS-CoV-2 in recovered patients is clinical indication of prolonged viral persistency or relapse of infection [17]. Analgesics and Azithromycin were recommended to eradicate disease morbidity. In persistent COVID-19 treatment, azithromycin plus hydroxychloroquine were more efficient previously [18].

In contrast to our findings, a study reported SARS-CoV-2 persistency for 59 days in young female patient with the age of 25 years [16]. The patient recovered without any antibiotic and antiviral therapy as no consequences were observed with health issues and underlying morbidities. Another case report from Thailand revealed prolonged SARS-CoV-2 shedding in asymptomatic patient (age 30 years) for 110 days [15]. Symptoms resolution with shedding duration or asymptomatic patient could promote disease transmission and hence asymptomatic virus carriers can be still infectious [19]. Therefore, there is need of monitoring the surroundings of patients to prevent the risk of viral transmission.

Immunodeficiency plays a major role in prolonged viral shedding that can be observed even in asymptomatic individuals with weak immune system [14,20]. We demonstrated that delayed treatment, low dose medication, previous medical history, higher susceptibility due to weak immune system were responsible for persistent viral infection. Similarly, viral clearance in COVID-19 patients varies and delayed in patients with older age, multiple re-exposure, underlying comorbidities such as diabetes [21] respective therapies [22] and myeloma [23] etc. (Figure 3).

FIG 3

Figure 3: Major reasons of that can contribute to prolonged viral shedding (SARS-CoV-2)

The worldwide discharge criteria (Figure 2) are improved clinical symptoms and two PCR negative test, needs modification for accurate and precise diagnosis [12]. Various studies emphasize precise and accurate decision of prolonged viral shedding and true infection. Confirmation and differentiating these hurdles might provide an insight of infection and beneficial support to the physician while treating the victim [24].

In addition, the patients experiencing only mild symptoms with extreme infection develops a weaker immune response which might explain predisposition to the reinfection [25]. Prolonged viral shedding and its particles poses diagnostic challenges. It might complicate infection control, treatment and might significantly contribute its role in morbidity and mortality associated with COVID-19 [26].

We declared patient recovered based on general discharge criteria (Figure 2). Laboratory biochemical tests, development of antibodies and clearance of symptoms are major factors which helped declaring recovery of patient from this regime. In summary, the possibility of prolonged viral shedding is significantly associated with health status of patient, timely diagnosis, and treatment strategies without any discrimination of age and gender. Further, patients recovered in long duration should be vaccinated after few weeks of recovery to prevent reinfection with emerging variants of SARS-CoV-2.

Conclusion

Comorbidities, immunodeficiency, unspecific drugs, drug discontinuation and wanning immunity are the major contributors of prolonged and persistent viral infection. These regimes might further increase the susceptibility of patient for reinfection with various emerging variants. In this ruled out situation, the unusual persistency of SARS-CoV-2 and delayed viral clearance could be due to weak immune system, previous history of lung infection (tuberculosis) and drug discontinuation. In conclusion, to avoid viral persistency for long duration, precise treatment and immune boasting therapies must be recommended.

Funding

No funding or grant was received

Conflict of Interest

The authors declare no competing interest

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Social Intelligence and Significant Others Representations

DOI: 10.31038/PSYJ.2023563

Abstract

Despite the large number of publications devoted to this issue, modern psychology lacks valid methods for measuring social intelligence. We have developed a methodology for measuring social intelligence based on the assumption that social intelligence is reflected in the process of selecting an optimal strategy for overcoming conflict situations. A positive role of social intelligence in the structure of predictors of the professional activity of plant employees and learning activity of university students as well as negative correlations of social intelligence with the level of disharmony of interpersonal relationships was discovered. The level of social intelligence did not form significant correlations with the scales of the NEO-FFI questionnaire and also with the level of intelligence according to Raven’s test. The main purpose of our investigation was to explore the correlations between social intelligence and significant others representations. For this purpose, we have used a questionnaire that was developed by Markey, Funder and Ozer and was designed for the investigation of dyadic interpersonal relations. The list of significant others included father, mother, classmate, professor and course leader. Significant positive correlation was obtained between the accuracy of assessments of significant others in terms of friendliness and the level of social intelligence of students. In addition to observation by octants, the degree of compliance of the scores on the interpersonal behavior questionnaire was calculated separately for each element from the list of significant others. The regression equation was calculated, the predictor of which is the level of social intelligence, and the regressor is the degree of observation accuracy of the professor estimates.

Introduction

As a result of the review of various approaches to the study of social intelligence, it is possible to state a kind of theoretical pluralism in understanding the specifics of social intelligence. In particular, we note the absence of clear dividing lines between social and practical intelligence [1], attempts to integrate social and emotional intelligence [2], the identification of social and academic intelligence [3,4]. In the processes of social thinking and intelligence perceptions of oneself and others are of paramount importance. Namely: the “internal working model” according to Bowlby [5], representations of “generalized other” according to Cronbach and of “significant others” according to Chen, etc. [6,7]. Unlike scientific concepts, social representations can be fuzzy and based on episodic memories and specific examples. For example, Ford assigns an important role to “significant episodes of behavior”. These are representations of episodes related to the implementation of certain goals in a certain context. Coordination and optimization of goals (win-win fashion) is the most important condition for achieving success both in interpersonal relationships and in professional activities [8]. In fact, the choice of an effective strategy for overcoming a conflict situation is based on taking into account the already established features of the relationships between the parties of the conflict, involves assessing the nature of future relationships depending on the status, role and other characteristics of the opponents.

We assumed that the best response choice of the subjects in the selected episodes reflects the level of conflict competence and social intelligence of plant employees and university students and is an effective predictor of their professional and learning competence. We have made a suggestion that social intelligence as an important factor of social and communicative competence plays a significant role in the process of making decisions in conflict situations. In order to verify this assumption, we have worked out a method of strategies evaluation in conflict situations. Each experimental situation provided seven variants of answer. Every type of answers corresponded to certain conflict strategies and should be evaluated from one point up to seven points. In addition to the well-known strategies, such as “giving up”, “confrontation”, “compromise”, “cooperation”, “making concessions” and “consulting” we added “caustic remark” possibility. Every type of answers should be evaluated from one point up to seven points.

Social Intelligence Indexes

We used a correspondence degree of every subject answer with the so called “medians group profile”. A median of every test answer was computed. Euclid metrics as a measure of the correspondence of every respondent with the median group profile was used. The results of measuring social intelligence were compared with personality traits, the level of psychometric intelligence, indicators of the harmony of relationships, and a structural assessment of the professional competence of Ufa distillery plant employees and educational performance of the students of Ufa University of Science and Technology. Several assumptions put forward in our previous research work were confirmed based on the performed correlation studies, namely: 1. negative relationship between social intelligence and the level of disharmony in interpersonal relationships; 2. the important positive role of social intelligence in the structure of predictors of the efficiency of students and engineers; 3. the proposed assumption on the independent conceptual status of social intelligence has also found its partial empirical support. A total of 35 engineers and 100 students participated in the correlation study.

Social Intelligence: Cognitive Ability or Personal Feature?

However, the level of social intelligence did not form significant correlations either with the scales of the NEO-FFI questionnaire or with the level of psychometric intelligence (Table 1). As a result, the assumption put forward by us about the independent conceptual status of social intelligence also found its empirical confirmation [9,10].

Table 1: Coefficients of Spearman rank correlation between indicators of social and psychometric intelligence and personality traits of engineers.

Psychometric intelligence

N

E

O

A

C

Social intelligence

0.01

-0.05

-0.01

-0.02

-0.13

-0.16

Materials and Methods

Theoretical Assumptions and Methods of Investigation

Emphasizing the importance of ‘mental organization’ in the structure of personality and pointing out the significance of reckoning the life context of the particular individual, Allport endows the individual with such abilities that are inherent in social intelligence: the ability to quickly and adequately assess a person, to predict possible behavior, etc. [11]. As for Vernon [12] one of the characteristics of a socially intelligent person was that he or she was an outstanding judge of personality, whereas the implicit theories of personality also lie at the basis of such perception. Cronbach has argued that one’s implicit theory of personality consisted on his or her knowledge of “generalized other”: a mental list of important personality dimensions [13]. Kosmitski and John have marked out the main components of social intelligence. These are cognitive elements (forecasting, men comprehension, knowledge of social rules, openness in human relations) and behavioral abilities (social adjustment, warm-heartedness and etc.) [14].

Social Intelligence, the PAP Paradigm and Significant Other Representations

The principal-agent paradigm (PAP) assesses the ability of an agent to evaluate the preferences of a principal, based on known values that the principal holds for different features of the decision event. The PAP originated in the economics literature to assess how well an agent can learn how much value the principal attaches to different attributes of a set of objects. The agent observes several examples of the principal’s choices between exemplars of the set of objects in complex situations, and then must decide what the principal’s preferences would be in a new complex situation. Today such paradigm is widely used in emotional intelligence investigations [15]. We think that PAP is also important for the research in the social intelligence domain because this paradigm is connected with the concept of “significant other”. Significant other is a person that is important for an individual. According to Sullivan, personality is inextricably tied to social situations; to understand personality, it is important to examine reoccurring patterns of social relations in real social contexts.

Methods of Investigation

The main purpose of our investigation was to explore the correlations between social intelligence and significant others representations. We made an assumption that there is a significant correlation between social intelligence and the power of observation of the significant others. For this purpose, we have used a questionnaire that was developed by Markey, Funder and Ozer [16] for the investigation of dyadic interpersonal relations. As we know, Leary introduced a circular ordering of interpersonal variables known as the interpersonal circumplex. This circumplex structure implies that variables that measure interpersonal relations are arranged on the circumference of a circle orientated by the primary dominant-submissive and hostile-friendly dimensions [17]. We translated this test into Russian and used it for the measuring of student’s power of observation of the list of the significant others: father, mother, classmate, professor and course leader. We used a correspondence degree of every answer with the medians group profile as a measure of student’s observational ability of the assessment of the whole list of the significant others.

Results

The interpersonal behaviors questionnaire consists of 24 items and has 8 scales: (PA) Assured-Dominant, (BC) Arrogant-Calculating, (DE) Cold-Hearted, (FG) Aloof-Introverted, (HI) Unassured-Submissive, (JK) Unassuming-Ingenuous, (LM) Warm-Agreeable, (NO) Gregarious-Extraverted. 123 undergraduate students (74 girls and 49 boys, average age – 21.3 years) of the psychology department of the Ufa University of Science and Technology took part in our investigation. The subjects evaluated the above characters on all scales of this questionnaire. In Table 2 the results of averaging the scores for all five significant others by octants are presented. As a result, it can be concluded that the FG (M=5.24), BC (M=5.77) and HI (M=5.78) scales received the lowest scores, and the LM (M=9.96) and NO (M=9.54) scales received the highest score. In addition, the results of diagnostics on the PA scale (SD=1.55) turned out to be the most stable, and the LM scale (SD=2.14) is characterized by the greatest variability. Table 3 shows the Spearman correlation coefficients between the level of social intelligence and the indicators of students’ general accuracy of assessment, calculated by octants. As we can easily see the significant correlation between social intelligence and LM (Warm-Agreeable) has been discovered.

Table 2: Means and standard deviations of averaging the scores for all five significant others by octants

 

M

SD

PA

8.34

1.55

BC

5.77

1.91

DE

6.15

1.89

FG

5.24

2.09

HI

5.78

2.00

JK

8.39

2.04

LM

9.96

2.14

NO

9.54

1.85

Table 3: Spearmen rank coefficients between the level of social intelligence and the accuracy of the assessments by octants.

PA

BC

DE

FG

HI

JK

LM

NO

Social intelligence

0.14

0.09

0.16

0.11

-0.01

0.10

0.31*

0.02

*Correlation is significant at .01 level (2-tailed)

In addition to observation by octants, the degree of compliance of the scores of the interpersonal behavior questionnaire was calculated separately for each element from the list of significant others. Table 4 shows the coefficients of Spearman’s rank correlation between the level of social intelligence and the accuracy of assessments of the significant others. Despite the absence of significant correlations at least at the five percent level, we can state three correlation coefficients, highlighted in italics, the significance of which is close to critical. However, the normality of the distribution of observation indices allowed us to use linear regression analysis in addition to nonparametric correlations. Figure 1 shows a diagram of the regression equation that is significant at the level of p=0.05, the predictor of which is the level of social intelligence, and the regressor is the degree of accuracy of professor estimates. Thus, social intelligence turns out to be a predictor of the second indicator of observation accuracy.

Table 4: Spearmen rank coefficients between the level of social intelligence and the accuracy of the assessments of significant others.

Observation accuracy of mother

Observation accuracy of father

Observation accuracy of classmate

Observation accuracy of course leader

Observation accuracy of professor

Social intelligence

0.07

0.03

0.21

0.21

0.21

p-value

0.56

0.79

0.07

0.07

0.07

FIG 1

Figure 1: Graph of the regression equation between the level of social intelligence and the accuracy of professor assessments.

Conclusions, Suppositions and Future Research

Thus, we have proved the importance of the adequate cognitive significant others representations in the structure of social intelligence. Social intelligence as an important factor of social and communicative competence turned out to be a predictor of the power of observation of the significant others. We believe that these results can be considered as a confirmation of the ideas of Kihlstrom and Cantor, who offer a “knowledge view of social intelligence” and indicate the need to take into account the contexts in which certain life tasks are solved [18]. Thus, the solution of conflict situations in educational settings involves an assessment of the interpersonal characteristics of university students and lecturers. We need further investigations in order to understand why the only one LM index of the eight octants of the interpersonal circumplex is correlated with social intelligence. In this regard, it should be noted the work of Scandinavian researchers, who put forward and confirmed an interesting assumption about the positive relationship between social intelligence and the so-called “indirect” aggression. It turns out that socially intelligent individuals choose the safest behaviors. Along with a peace-loving strategy, indirect aggression is the best way to respond to conflicts [19]. Besides, we may consider these results as the confirmation of Riggio [20] suppositions about the tight connection between social intelligence and the “cognitive empathy” level. The important role of cognitive empathy in the structure of social intelligence is also noted by Rahim [21].

In this regard, the study of the psychological mechanisms of complementarity as a factor in the effectiveness of interpersonal communication is very promising [22,23]. In particular, we have developed a methodology for predicting relationships in conflict situations in the human-computer dialogue in the Dolphin Smalltalk programming system for Windows. The choice of one or another variant of relations in the dyad, made with the help of a computer mouse, was accompanied by appropriate graphic and sound illustrations demonstrating various gradations of dominance-submission and cooperation-alienation. Statistically significant positive correlations between the level of social intelligence of students and complementarity in affiliation in the «student – assistant lecturer” and “student – assistant professor” dyads were obtained [24].

Our study of imaginary interactions and situational patterns of complementarity with the help of human-computer dialogue found that classical complementary patterns of interaction turned out to be correlates of social intelligence only for interpersonal situations with assistant lecturers and assistant professors. The selective nature of the correlations between social intelligence and situational patterns of complementary relationships allows us to assume that classical complementarity models do not always sufficiently describe the picture of interpersonal interaction. For example, Schaefer noted that investigations of both parent-child and marital dyads consistently revealed two fundamental dimensions that were labeled autonomy and relatedness [25]. Moreover, the SASB model proposed by Benjamin describes both interpersonal (an individual relating to another) and intrapsychic (an individual relating to him or herself) behaviors [26]. Nevertheless, we believe that the development of methods for researching interpersonal communication through human-computer dialogue opens up the prospect of a broader and more systematic approach to the study of social and emotional intelligence.

Acknowledgements

This work was supported in part by a grant of Russian Humanitarian Scientific Fund «Social intelligence and professional competence of engineering and technical workers» No. 10-06-00525A and by a grant of Russian Fund of Fundamental Research “Social Intelligence and Complementarity of Interpersonal Relations”, project No. 13-06-00354A.

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Snow Patches and Glaciers in Japan – Commentary on the Definition and Classification of Glaciers

DOI: 10.31038/GEMS.2023563

Abstract

Glaciological studies have been conducted on several snow patches in Japan since 1910th,, including a recent report with the conclusion that some perennial snow patches in the Hida Mountains in north-central Japan are identified as glaciers. The identification was supported by all Japanese glaciologists at an open symposium organized by the Data Center for Glacier Research of the Japanese Society of Snow and Ice, recognizing that the snow patches have considerable amount of ice mass in the lower part of the snow patch, which shows the evidence of flow downwards along the valley. The international cryosphere-related organizations, however define the glacier as “stagnant or flowing ice mass”, and the international classification of glaciers published by the International Commission of Snow and Ice (ICSI) shows the necessity of flow only for some classes of glaciers such as the valley glacier, outlet glacier etc., and thus, the flowing is found not principally necessary to identify some groups of glaciers. Examining comparatively the pilot study in the Himalayan region given by the ICSI, several snow patches with ice masses in Japan are considered to belong the valley glacier, mountain glacier, or glacieret. However, the ICSI classification above includes vagueness on flow, size and thickness of the ice mass, distinction among valley glacier, mountain glacier, glacieret and snow patch. Those points should be examined and clarified for the better definition and classification of snow and ice masses on the earth.

Introduction

There is a variety of snow and ice masses on the globe. Some of them have been regarded as the glacier. However, the definition and classification of the glacier is not clearly understood even in researchers of related sciences. In Figures 1-3 some typical glaciers, which should be understood generally as the valley glacier, mountain glacier, and ice sheet with an outlet glacier are given.

fig 1

Figure 1: Aretsch Glacier in the Swiss Alps, view of the middle reaches. Far above, uppermost cirques are seen (Photo provided by R. Naruse, taken in July 2018).

fig 2

Figure 2: West side view of Arakam tse, Everest area, with typical mountain glaciers on the west slope. A small valley glacier is seen on southeast of the peak and a large Nojumba Glacier is seen on the bottom of the picture. (Photo taken in October 2007).

fig 3

Figure 3: Antarctic ice sheet in eastern Queen Maud Land and Skallen outlet glacier, February. 1970

In 2012, 3 perennial snow patches in Tateyama-Tsurugi range of Hida Mountains in north-central Japan were identified as active glaciers by Fukui and Iida (2012) [1]. About one hundred glaciologists in Japan assembled and discussed on the report at an open symposium [Perennial snow patches and glaciers in Japan – past studies and future researches organized by the Data Center for Glacier Research of the Japanese Society of Snow and Ice (JSSI) [2]. The summary of the symposium is that the participants of the symposium do not object to call these 3 snow patches as the glacier.

The present author has had some experiences of observing glaciers worldwide as a geologist and a mountaineer since the 1960s, and has been interested in the active glaciers reported by Fukui and Iida. It is found that there are some vagueness to be clarified on the definition and classification of glaciers. The present author proposed in 2019 (Yoshida, 2019-2020) [3,4] to call the above kind of snow patches as the “snow patch glacier” (abbreviated as SPG from here onwards in this paper). Recent researches in Japan on SPGs are considered useful to contribute the understanding of similar SPGs, which are distributed widely in some areas of the earth.

Glaciological Research on Perennial Snow Patches in Japan

The beginning of glaciological studies on perennial snow patches in Japan was the report by Ohzeki (1917) [5] on a perennial snow patch (designated as PSP below onwards) in Mt. Gassan in Northeast Japan. Ohzeki showed the shape, structure, and size of the ice mass within a large perennial snow patch known as “Ohyukijiro” (big snow castle, in Japanese meaning), and pointed out a possibility that the snow patch is similar with the glacieret distributed at several places in European Alps.

Since then several glaciological studies on snow patches in Japan including the report of identification of glaciers or glacierets were conducted [1,6-31] in mountains in Hokkaido, Northeast Japan and north central Japan, etc.

After around 1970, a systematic study project of snow patches in Japan started led by Prof. K. Higuchi of Nagoya University. The study project was related with the International Hydrological Decade (IHD, 1963-1974) and Intergovernmental Hydrological Programme (IHP, 1975-) that aimed to clarify the actual situation of water resources and to contribute to the examination of their relationship with climatic changes. Due to the studies of the above Japanese project, the outline of perennial snow patches distributed throughout Japan was clarified and detailed studies of several snow patches were also conducted. All these studies contributed to the IHD-IHP projects for the formation of the world glacier inventory.

The glaciological researches in Japan had been influenced by the general idea of Japanese geomorphologists that there should be no glaciers in Japan referring the suggestion of Hoshiai and Kobayashi (1957) [32] that the equilibrium line altitude (snow line) in Japan is 4000 meters, which is nearly one thousand meters higher than the Japanese highest mountain range. Several glaciological researches in Japan, however, have been conducted even after 1957. It is first because field evidence of glaciologic characteristics of some snow patches were noticed, and second because the idea that the snow line might change locally due to differences in local climate and topography, which affect in large differences in the amount of snow accumulation and melting. The above idea was further clearly pointed out recently by Ono [33].

In 2012, Fukui and Iida [1] reported 3 PSPs in Tateyama-Tsurugi range in the Hida Mountains (Japanese North Alps) in north-central Japan are identified as active glaciers. These PSPs are several hundred to over one km in length, have a thick (25 – 45 meters thick) ice bodies in the lower horizons, and are flowing downwards some meters per year. They showed mesoscopic and microscopic inner structure of the ice mass and figured out the mechanism of ductile flow of the mass. Fukui and Iida (2012) [1] pointed out that the above signatures are conformable with the definition of glaciers.

An open symposium [Perennial snow patches and glaciers in Japan- past studies and future researches] was held in 2012 at the Data Center for Glacier Research of JSSI to discuss on the report of Fukui and Iida (2012) [1], and about 100 members of the society assembled.

During the symposium, several lectures and discussions were presented in relation to the report of Fukui and Iida (2012) [1]. At the end of the symposium, the chairman summarized that all the participants did not deny that 3 PSPs reported by Fukui and Iida could be called as the glacier, but one PSP has to be further examined, because the flow of the PSP is not clear [34]. In the symposium, however, there appeared to have been no discussion on the criteria of definition and classification of glaciers, and further, no discussion referring those by international organizations such as the International Glaciological Society (IGS), ICSI, etc. Almost all participants of the symposium appeared to have had the understanding on the definition of glaciers as that given in the so far published dictionaries of JSSI [35].

Fukui and others [29] and Arie and others (2019) [30] further reported additional 4 PSPs in the Hida Mountains with the conclusion that they also have signatures to be identified as glaciers. Similar PSPs in the Hida Mountains are under the survey by the same authors and will shortly be reported. The distribution of these snow patches are shown on topographic maps in Figures 4-6. In these maps, all large snow patches shown on the 1:25000 topographic map of the Geospacial Information Authority of Japan (2018) [36] are delineated by the present author. Snow patches, which were so far reported [1,29-31] that they have or should have an ice mass are shown as SPG. Field photos of some of the above SPGs are given in Figures 7-9. A detailed topographic sketch and a cross section of one of the SPGs are shown in Figure 10a and 10b, citing after Fukui et al. [29].

fig 4

Figure 4: Distribution of SPGs and a PSP surrounding Mt. Tateyama in the northwestern Hida Mountains. A: Ikenotani SPG, B: Komado SPG, C: San-no-mado SPG, D: Tsurugisawa PSP, E: Bessanzawa PSP, F: Hamaguriyuki SPG, G: Kuranosukesawa SPG, H: Gozensawa SPG.

fig 5

Figure 5: Distribution of SPGs and PSPs on the eastern slope of Mts.Shiroumadake-Karamatsudake in theNortheastern Hida Mountains. A: Hakubasawa migimata PSP, B: Hakubasawa SPG, C: Daisekkei PSP, D: Shakushizawa SPG, E: Tengusawa PSP, F: Kaerazusawa SPG, G: Karamatsuzawa SPG.

fig 6

Figure 6: Distribution of SPGs and PSPs in eastern slopes of Mts.Karamatsudake-Kashimayarigatake, northeastern Hida Mountains.A: Karamatsuzawa SPG, B: Ohgurozawa-migimatamigi PSP, C.

fig 7

Figure 7: San-no-mado SPG and Komado SPG on the eastern slope of Mt. Tsurugidake (Aerial Photo Provided by J. Akabane)

fig 8

Figure 8: Karamatsuzawa SPG and Kaerazuawa SPG on the eastern slope of the north ridge of Mt.

fig 9

Figure 9: Kakunezato SPG on the north- east slope of Mt. Kashimayarigatake, northeastern Hida Mountains

fig 10a

Figure 10a: Horizontal sketch of Kakunezato SPG in October 2015 (after Fukui et al., 2018)

fig 10b

Figure 10b: Cross section of the Kakunezato SPG (Referred to Fukui et al., 2018)

Commentary on the Definition and Classification of Glaciers

There is so far no definition or criteria of recognition of glaciers officially decided by international as well as Japanese academic societies of related sciences. Merrian-Webster Dictionary [37] gives the definition of the glacier as “large ice body flowing slowly on the slope or along a valley, or large ice body on a large gentle land and flows outside from the land”, and a Japanese dictionary of earth science [38] describes “ice body existing on the surface of the earth and flowing continuously”. These descriptions may give a general understating of a glacier to people. However, we have to examine the correct definition, which is acceptable by scientists of related fields from the cryospheric academic point of view.

In the cryospheric world of Japan, explanations given by Ageta [35] and Shiraiwa [39] appeared in dictionaries of snow and ice convened by JSSI could generally be accepted by Japanese researchers of related fields, although Naruse [40], citing the definition of Flint [41], gives the explanation of a glacier as 1) large mass composed of snow and ice, and 2) existing on land and flows presently or flowed in the past.

The definition given by Flint [41] in his book Glacial and Quaternary Geology, “a large mass of snow and ice accumulated naturally and is mostly existing on the land, and is flowing presently or flowed in the past” is often referred to internationally. Reisco [42] pointed out that the International Association of Cryospheric Sciences and Intergovernmental Panel on Climate Change (IPCC) also show the similar definition.

In contrast, the IGS [43] has declared the agreement upon the Standard Practice Guide used by the Argentine Institute of Nivology, Glaciology and Environmental Sciences for making the National Glacier Inventory of Argentine, ① “a snow and ice mass with the dimension of less than 0.01 km2 is not included in the inventory, and ② definition of glaciers as “glacier is a perennial ice mass either stable or flowing” that appeared in the Argentinean Glacial Law. Raup [44] showed a candidate definition of the glacier related with the GLIMS (Global Land Ice Measurements from Space) Project of NSIDC (National Snow and Ice Data Center of US) [45] as “an ice mass existing over several years and has the dimension of more than 0.01km2 after the melting in summer”, and no description on the flow of the ice mass is given. The amount and thickness of ice mass within the snow and ice mass are considered to be critical for the recognition of a glacier, however, are not referred to in any descriptions of definition of glaciers so far disclosed. This point will be discussed in a later section.

Thus, there are two different ideas on the definition of glaciers regarding its flow signature, i.e., either “an ice mass stable or flowing” or “an ice mass flowing presently or flowed in the past”. The author prefers the former, because it is often almost impossible to clarify either an ice mass is a remnant of a past glacier or not. Since an ice mass has existed in a snow patch during this warm interglacial stage, it is possible that the ice mass of a past glacier of the glacial epoch have not disappeared and existed continuously throughout the interglacial stage. In such a case, it does not matter whether ice crystals forming the mass might have renewed time to time and no old crystals formed during the glacier epoch might have survived or not.

The principal classification of glaciers is based on temperature conditions (e.g., Ahlmann [46]; Journal of Glaciology, 1957) [47]. However, for snow and ice masses occurring in a restricted area, the above classification has almost no importance and instead, classifications based on the topographic characteristics are generally adopted (e.g., United Stage Geological Survey, 2004).

The International Committee on Snow and Ice (ICSI) planned under the International Hydrologic Decade (IHD, 1965-1974), with the objective to outline all snow and ice masses of the earth, and disclosed in 1967 a table of classification of glaciers (Table 1, UNESCO-IASH, 1970, described as ICSI table below) as the standard practice guide for making a world catalogue of snow and ice masses (the world glacier inventory) on the surface and sub-ground of the earth. The program of making the world inventory of glaciers has been succeeded to the IHP (1975), and in 1995 NSIDC started the renewal of the world glacier inventory project (GLIPS Project) [48], and the first report was delivered in 2014. In all the above international projects, the ICSI table has actively been used.

Table 1: Classification of snow and ice masses (UNESCO/IASH, 1970)

 

Digit 1 Primary classification

Digit 1 Form

Digit 3 Frontal characteristics

Digit 4

Longitudinal profile

 

Digit 5

Major source of nourishment

 

Digit 6

Activity of tongue

 

0 Uncertain or misc.

Uncertain or misc.

Normal or misc.

Uncertain or misc.

Uncertain or misc.

Uncertain or misc.

1 Continental ice sheet

Compound basins

Piedmont

Even; regular

Snow and/or drift snow.

 

Marked retreat

 

2 Ice-field

Compound basin

Expanded foot

Hanging

Avalanche ice and/ or avalanche snow

Slight retreat

3 Ice cap

Simeple basin

Lobed

 

Cascading

 

Superimposed ice

Stationary

4 Outlet glacier

Cirque

Calving

Ice-fall

Slight advance

5 Valley glacier

Niche

Coalescing, non-contributing

Interrupted

 

Marked advance

6 Mountain glacier

Crater

Possible surge

7 Glaieiret & Snow field

Ice apron

Known surge

8 Ice shelf

Group of small unites

Oscilating

9 Rock glacier

Remnant

The ICSI table has been used widely in the snow and ice academic world (e.g., Rau et al., [49]; JSSI, 2019). This table, however, was principally prepared to include all masses of snow and ice of the earth. That means that it includes not only all kinds of glaciers but also snow and ice masses such as snowfield, snow patch, ice shelf, etc., which are obviously not glaciers, and is thus practically the table for perennial snow and ice masses. The GLIMS Project disclosed a table principally same as the ICSI table, however, is supplemented by detailed explanations for each kind of snow and ice masses, and thus enables to give common and detailed classification of snow and ice masses in the world.

The constitution of the ICSI table, as shown on the Table 1 is briefly explained below. The table consists of 6 digits. In digit 1, all snow and ice masses on the earth are classified into 9 primary classes. Digits 2 to digit 6 are composed of characteristics of frontal shape, longitudinal profile, major source of nourishment, and activity of tongue of the 9 classes above, such as existence/absence, strength, size, etc. in 4 to 10 levels. Simple sketches and explanations are given for each class. Some explanations of the classes, which appear to be related with PSPs and SPGs of Japan mentioned above, are given below extracted from the explanations attached with the ICSI table.

Valley glacier: The glaciers of this class flow in the valley, and have clear nourishment area. Both side slopes of the valley are generally not covered by ice.

Mountain glacier: This class includes cirque, niche, and crater glaciers as major kinds, and apron, hanging and group glaciers also belong the same class. The topography of these glaciers does not show the development into the valley shape, however, the distinction between the valley and mountain glaciers are sometimes not easy.

Glacieret and snowfield: This class includes small masses of snow and ice with a variety of shapes that resist existing over 2 years. They are formed by drift, avalanche, or unusual precipitation on depressions, valley floor, or sun or window shades. They generally have no indication of flow. It is difficult to clearly distinguish between the glacieret and snow patch. Nourishment and ablation areas are sometimes not identified.

The explanation of ICSI table given on the glacieret appears difficult to understand because the table explains altogether with glacieret and snowfield. The Cryosphere Glossary given by NSIDC, which is considered to be intimately related with the GLIMS Project describes the glacieret as “a very small glacier”. To examine altogether the above, we understand that the glacieret and snowfield given in the ICSI table is composed of two groups, i.e., the glacieret, which is a very small glacier, and the snowfield, which includes snowfield, snow patch, and snow deposit. There is no clear evidence of flow in both of the above groups.

The ICSI table is, as mentioned above, completely different from proper dictionaries cited above. It classifies all kinds of snow and ice masses and gives detailed explanations. Further the manual of glacier classification by GLIMS cited above gives further detailed explanations on many kinds of glaciers of the table. In this classification, all snow and ice masses except snowfield, snow patch, ice field and ice field are identified as glaciers. That means that a snow and ice mass which is classed into either one of the classes 1, 3, 4, 5, 6, 9, and glacieret of 7 of the ICSI table is identified internationally as a class of the glaciers. In conclusion, the ICSI table is further useful and clear than ordinary dictionaries of related science world to define either a snow and ice mass is the glacier or not, and in what class of the glacier it belongs.

To avoid confusion on the definition and classification of glaciers, the usage of the international definition of glaciers (IGS, 2017) [43] and ICSI table is preferable. Actually in Japan, JSSI discloses the same table (with Japanese translation by G. Wakahama – [50]) as the model for the world inventory of snow and ice masses.

In the above ICSI table including detailed explanations of GLIMS, indexes on the size of the snow and ice mass and speed of flow are not shown, and thus, a variety of snow and ice masses with no flow and with a variety of sizes are included. There is no description on the flow signature for the mountain glacier, and for the glacieret, a description “no obvious flow is recognized” is given. For other glaciers, for which the flow of the mass is mentioned, there is no constraint on the speed and mechanism of the flow and the inner structure of the mass, and even on what part of the snow and ice mass flows is not given. Further for all snow and ice masses, no description on the past or future flow is given.

It may be reasonable that the description on the flow is not necessary in the ICSI table, since the table was principally made with the objective (UNESCO/IAASH, 1970) [51] of clarifying the amount and the income and outcome of snow and ice of the earth. However, since the table is to be used now, to cover all snow and ice masses of the earth and to show their major signatures apart from its original objective, existence/absence of and speed of the flow, size, and amount of ice mass of a snow and ice mass are expected to be added to the ICSI table as the 7th-9th digits.

UNESCO/IASH (1970) [51] disclosed examples of usage of the ICSI table for making the world glacier inventory for snow and ice masses, in the North Polar region, Rocky Mountains and Himalaya in pilot field studies, showed general examples of field evidence of dimensions and ice thicknesses for some classes of glaciers as follows.

Valley glaciers: 1-100 km2 in dimension and 30-120 m in ice thickness.

Mountain glaciers: 0-20 km2 in dimension and 20-120 m in ice thickness.

Glacierets: 0-2 km2 in dimension and 10-25 m in ice thickness.

As mentioned above, the critical smallest limit for the dimension of a snow and ice mass as 0.01km2 is considered to have become used worldwide for making the world inventory (e.g., Paul et al. [52]; IGS, 2017) [43]. The Journal of Glaciology [47] once showed the idea that an ice mass of less than 15m in thickness could not be included in the inventory. However after that, the ice thickness of 15 meters appears not become common for the registration in the inventory. Muller (1970) [53-56] in his pilot study in the Himalaya showed several glaciers with the ice thickness of 8 meters, although the thickness was not practically measured.

Muller [53] in his study of glaciers in the Everest area of eastern Himalaya as the pilot study of UNESCO/IASH (1970) [41], showed many examples of signature (length, width, ice thickness, etc.) of glaciers. Some examples of his description are given in Figures 11, 12 and Table 2. In his study, the valley glaciers develop generally in a large, long and gentle valley and the snow and ice mass is very large, thus, the distinction from mountain glaciers are generally clear. However, there are found some exceptional cases that a short glacier developed on a steep mountain slope is also classed as the valley glacier. Almost all mountain glaciers are classed as the cirque glacier or unclassed, and only 2 glaciers among 121 mountain glaciers are classed as the niche glacier. Only 2 glacierets are shown in the report and they develop on steep mountain slopes and the distinction from the mountain glacier is not clear.

fig 11

Figure 11: Glaciers surrounding Kyajo Ri, west of Dudhu Koshi, Everest area. Numbers show glacier numbers and locations reported by Muller, 1970.

fig 12

Figure 12: The western slope of Kyajo Ri, with glaciers (numbered) described by Muller (1970)

Table 2: Description of glaciers in the area of Fig. 10 (surrounding Kyajo Ri) by Muller (1970). The classification numerical numbers are given by Muller following the Table 1.

Glacier No.

 

Classification

 

Length km

 

Dims km2

 

Ice thick m

 

NEA45C-55

600011

1

0.29

13

NEA45C-56

600011

1.1

0.36

14

NEA45C-57

602311

1.4

0.52

18

NEA45C-58

600210

0.8

0.06

10

NEA45C-59

640020

0.4

0.06

10

NEA45C-60

640021

1

0.24

20

NEA45C-61

700210

0.9

0.11

10

NEA45C-62

600210

0.5

0.13

12

NEA45C-63

600210

0.2

0.06

10

NEA45C-64

600310

1.1

0.06

10

NEA45C-65

640022

0.4

0.15

12

Referring all the above, SPGs of Japan developed in small valleys and have been identified as glaciers are considered to belong the mountain glacier, glacieret, or valley glacier. Fukui et al. [29] classed all 6 SPGs they reported to belong the mountain glacier, among which 4 glaciers as the niche, and 2 as the cirque glaciers. The author, however, prefers to classify most of those glaciers as the valley glacier, since these SPGs develop in deep and clear valley topography, which are different from niche.

The cirque glacier is considered to be the glacier that contributed principally to form the cirque topography. Two glaciers classed as the cirque glacier by Fukui et al. [29] are not clear either they contributed to the formation of the concerned cirque topography or not, and therefore they could be provisionally classed as the valley glacier or glacieret.

Summary and Discussion

  1. The glaciological study on perennial snow patches (PSPs) in Japan has been conducted continuously since around 1917. Since 1970, glaciologic data were summarized by K. Higuchi and others for wide areas in Japan. In 2012, 3 PSPs in the Hida Mountains were identified as the active glacier, and the Data Center for Glacier Research of JSSI had an open symposium to examine the above identification. The symposium positively recognized it, appreciating the existence of distinct flow of the ice mass as the important criterion for the identification of the glacier.
  2. The definition and classification of glaciers are examined referring various references. There are two different ideas on the definition of glaciers regarding its flow signature, i.e., either “an ice mass stable or flowing” or “an ice mass flowing presently or flowed in the past”. The author prefers the former, because it is often almost impossible to clarify either an ice mass is a remnant of a past glacier or not. Regarding the dimension, 0.01 km2 is also the widely accepted criterion as the smallest limit, and there is no constraint on the dimension and thickness of the ice mass within a snow and ice mass.
  3. The definition of a glacier given in common dictionaries gives only a general signature of glaciers and does not include all kinds of glaciers. The glacier classification table by ICSI, in contrast, includes all kinds of glaciers and provides detailed characterization of them, and therefore useful to define, identify and classify all kinds of glaciers and snow and ice masses, although the table includes snow and ice masses such as snowfield and iceshelf, which do not clearly belong the glacier.
  4. The international glacier classification table of ICSI has been used widely in international bodies and projects. This table, however, was made with the objective of classifying all kinds of snow and ice masses of the earth, and therefore includes all kinds of glaciers as well as snowfield, snow patch, ice shelf etc., which are obviously not the glacier.
  5. Large (larger than 0.01km2 in dimension) perennial snow patches in Japan with considerable size of ice mass within it are classified as glacieret, mountain glacier or valley glacier. The distinction among the above three kinds of glaciers, however, includes some uncertainties, and ideas of classification is not definite at present.
  6. Judgement criteria to identify a snow and ice mass as the glacier is simple following the international definition. Size of the ice mass within a snow and ice mass, identification of flow, speed of flow, inner structure, and mechanism of flow of the ice mass are important to understand the glaciological signature of the ice mass, but not necessary for the identification of the glacier.
  7. The present international classification table of glaciers (ICSI table) includes some uncertainties and needs to include some components in the criterial signatures such as: existence/absence of flow of ice, and size of the ice mass. Further, some more characterizations for the discriminations among valley glacier and mountain glacier, mountain glacier and glacieret, niche glacier, glacieret and snow patch are considered necessary. The present nomenclature of one of the principal classes of the ICSI table, the mountain glacier, is confusing, because it is generally understood as glacier developed in mountains. An appropriate name such as the mountain slope glacier proposed by G. Wakahama (in JSSI, 1970) may be worth consideration. These points are important to clearly classify a snow and ice mass and requested to be examined in the related science world.

Acknowledgement

The present author is indebted to Dr. Renji Naruse of the Glacier and Cryospheric Environment Research Laboratory in Japan, who gave important advices at the beginning of the precursory Japanese manuscript and also provided a photo of the Aretch Glacier, and Mr. Jinyu Akabane and Dr. Chiyuki Narama who provided photos of snow patch glaciers of the Hida Mountains.

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Person-Centred Care Should Be Visible in Stem Cell Transplantation According to Patient’s Subjective Experiences – A Qualitative Study

DOI: 10.31038/CHBT.2023211

Abstract

Background: The hematopoietic stem cell transplant affected the patients’ physical, mental, and spiritual well-being. Taking patients’ needs into account can improve the care experience and alleviate the impact of difficulties during the transplant period. According to the Swedish Patient Act (2014: 821), patients have the right to be involved in their care

Purpose: To describe patients’ subjective experiences, reported in a study specific questionnaire with open-ended questions, when being treated and cared for during autologous hematopoietic stem cell transplantation and to further discuss the importance of person-centred care in a clinical context.

Methods: Sixty-four patients were asked to participate in the study and chose to take part. Fifty-two patients fulfilled the study specific questionnaire (81%). A thematic analysis, was performed with the support of Braun and Clarke, including both inductive and semantic approaches. This is secondary data, part of a larger project evaluating patient experience of safety and security in care during autologous hematopoietic stem cell transplantation regardless of inpatient or outpatient care. The study has a qualitative, pragmatic, comparative design.

Results: Three themes emerged from the analysed data: subjectively perceived positive information and support; subjectively perceived negative information and support; subjective desired increased possibility of person-centred care.

Conclusions: The results of the upcoming study can design new functional tools to support person-centred care in the care of patients undergoing hematopoietic stem cell transplantation or cared for in the haematology department. The results revealed, despite unequally distributed groups, similar subjective experiences of care.

Keywords

Patient, Hematopoietic stem cell transplantation, Person-centred care, Subjective experiences

Introduction

Illnesses requiring hematopoietic stem cell transplantation (hSCT) such as myeloma or lymphoma, require a long-lasting relationship with caregivers. Until now, most high-dose therapy and supportive care while awaiting hematopoietic recovery has been performed entirely in hospital, with a stay of approximately 14 days for autologous hSCT and 30 days for allogeneic hSCT. This can cause a reduction in the patient’s functional capacity and an increased risk of nosocomial infections, particularly relevant for allogeneic transplant patients when they are immunosuppressed [1,2].

Background

The hematopoietic stem cell transplant affected the patients’ physical, mental, and spiritual well-being. Transplantation also had an impact on the patients’ outlook on life and way of thinking. Taking patients’ needs into account can improve the care experience and alleviate the impact of difficulties during the transplant period, thereby improving the experience [3]. Evidence is found on improved health outcomes and quality of life, on enhanced safety and effectiveness and on reduced overall costs and hospital stays, with similar results on overall survival rates comparing both models for autologous and allogeneic patients. It is also stated that the outpatient Hematopoietic Stem Cell Transplantation is a safe practice as well as less costly, it requires fewer days of hospital stay both for autologous and allogeneic transplantations. Incorporating outpatient models could improve the quality of care for people requiring Hematopoietic Stem Cell Transplantation programs [4]. A study showed that most patients treated in hospital in connection with stem cell transplantation were alone during the period of care, no relatives or friends stayed with them, compared to patients who were at home in connection with stem cell transplantation where the majority lived together with close relatives or friends. Almost all patients who were cared for in hospital and who responded to the study-specific questionnaire experienced anxiety during the care period compared to patients who were cared for in the home environment, where the vast majority did not experience any anxiety during the care period [5]. According to the Swedish Patient Act (2014: 821) [6], patients have the right to be involved in their care. Autologous and allogeneic HCT patients are usually grouped in studies, but patients’ experiences and recovery abilities are different [7-10]. Deficiencies in caregivers to focus on patients’ specific psychological, social, and emotional concerns has emerged [11-14].

In a Swedish context, person-centred care is defined as a partnership between patients/relatives and professionals in health care. The starting point is to listen to the patient’s stories, which together with other examinations form the basis for a health plan (https://www.gu.se/gpcc) [15]. In 2020, a European standard for person-centred care was added to ensure patient participation in quality indicators and improvement work in all operational and strategic levels within healthcare (BS EN 17398) [16]. To facilitate and understand the use of person-centred care in a clinical context, the eight principles of patient-centred care is highlighted in research conducted by the Picker Institute and Harvard Medical School (Institute of Medicine (US) Committee on Quality of Health Care in America) [17].

The aim of this study was to describe patients’ subjective experiences, reported in a study specific questionnaire with open-ended questions, when being treated and cared for during SCT and to further discuss the importance of PCC in a clinical context.

Methods

Design

This secondary analysis is part of a larger study [5] and regards patient’s perceived experience of care during autologous hematopoietic stem cell transplantation (SCT) regardless of inpatient (IP) care or outpatient (OP) care. The study has a pragmatic, comparative design.

Theoretical Framework

The practice of caring for patients and their families, Patient-centered care (PCC), includes listening to, informing and involving patients in their care, in ways that are meaningful and valuable to the individual patient. The Institute of Medicine (IOM) defines PCC as: “Providing care that is respectful of, and responsive to, individual patient preferences, needs and values, and ensuring that patient values guide all clinical decisions” (Institute of Medicine (US) Committee on Quality of Health Care in America) [17].

With the support of focus groups (patients, family members, physicians, and health professionals) and relevant literature, researchers defined eight principles of PCC. Based on the eight principles, the researchers developed the instrument, Picker’s Eight Principles of Patient-Centered care to help and support in care to apply PCC (Institute of Medicine (US) Committee on Quality of Health Care in America) [17] (Figure 1).

FIG 1

Figure 1: Picker`s Eight Principles of Patient-Centered Care

How to Practise Person-centred Care (PCC)?

A useful framework for how to practise person-centred care (PCC) is Ekman’s conceptual framework, including the three domains of initiate, integrate and safeguard to establish PCC in daily clinical practice to ensure that PCC is systematically and consistently practiced [18]. The framework in this article will be used for a discussion of the study’s results, and therefore further explained here. Initiate – initiating the partnership: patient narratives which means that the patient’s story is the sick one the person’s personal account of his/her illness, symptoms, and its impact on her/his life. It captures the person’s suffering in an everyday context, as opposed to medical narratives such as reflects the process of diagnosing and treating the disease. Our experience is that the patient story is the start for PCC and lays the foundation for a partnership in healthcare. Integrate – Considering the nature of the diseases and the need for overall disease management, it is important that the profession and patients (often also relatives) develop a collaboration to reach jointly agreed goals. At the time of diagnosis, the care team, including the patient, should present and evaluate all aspects of care, considering treatment options tailored to the patient’s lifestyle, preference, beliefs, values, and health concerns. Safeguard – Documenting the patient’s preferences, beliefs, and values as well as his involvement in care and treatment decisions in patient records gives strong legitimacy to the patient perspective. Makes the interaction between patient and caregiver transparent and facilitates continuity of care. Documenting such information must be considered as mandatory as clinical and laboratory findings [18].

Study Setting and Recruitment

Patients diagnosed with myeloma or lymphoma, scheduled for autologous hSCT at a University Hospital in Sweden between February 2017 and February 2019, were consecutively asked to participate. Sixty-four patients were asked to participate in the study and chose to take part. Fifty-two patients fulfilled the study specific questionnaire (81%) (Table 1).

Table 1: Patient characteristics, diagnosis, outpatient and inpatient care

Diagnosis

Myeloma

Lymphoma

Total (n=64)

Women

14

8

22

Men

30

12

42

Age, under 60 yrs of age (range 44-60)

15

12

27

Age, over 50 yrs of (range 61-71)

29

8

37

Outpatient care

32

10

42

Inpatient care

12

10

22

Inclusion and-or Exclusion

Inclusion criteria were age ≥18 years and diagnosed with myeloma or lymphoma and planned for hSCT. The patients would also understand the Swedish language in speech, reading and writing. Exclusion criteria were whether the patient did not meet the requirements for OP care during hSCT.

Data Collection

Data were collected from a previous study published in Journal of Nursing & Care. An invitation to participate in the study was given to the patients when they were enrolled in the University hospital in Sweden, for autologous hSCT during the period February 2017 to February 2019. Information about the study was received at enrollment and the patients had the opportunity to ask questions about the content of the study. The patients who chose to join the study gave their consent in writing. The patients answered the study specific questionnaire at discharge [5].

Data Analysis

For demographic data descriptive statistics were used (Table 1). The answers from the open-ended questions were transcribed verbatim by the two authors. Guided by the aim of the study, the authors independently read all the material several times. A thematic analysis, was performed with the support of Braun and Clarke, including both inductive and semantic approaches [19]. First, with the support of the study’s aim the authors independently read all the study questionnaires several times. Second, all substantial features in the text were assigned a code, with all relevant data collected under the same code. Third, codes were deployed into tentative themes. Before entering the fourth step, data from questionnaires were added into the analysis by performing steps 1 to 3. Fourth, themes were evaluated by going back to the codes and the transcribed text. A thematic map was produced to visualise the analysis. Fifth, themes were defined and labelled, i.e. continued analysis and refinement of the specific content and definitions of each theme (Figure 1). Finally, the result report was written, with quotes exemplifying the raw data (Figure 2).

FIG 2

Figure 2: Final thematic map, showing final three themes and six subthemes

Ethical Consideration

The study rests on the ethical principles; World medical association declaration of Helsinki [20]. The study was approved by the regional Research Ethics Committee, Uppsala, D no; 2016/521.

Results

Three themes emerged from the analysed data: subjectively perceived positive information and support; subjectively perceived negative information and support; subjective desired increased possibility of PCC.

Subjectively Perceived Positive Information and Support

Patients (IP and OP) reported that they were satisfied with information in connection with their planned hSCT. The information was given early and frequently both orally and in writing. Patients expressed it important to have time to understand and prepare any accompanying relatives for a long-term stay in an apartment if the care environment was outside the hospital. The perceived support of caring by nursing staff and relatives regarding daily life, for example nutrition and activity, was assessed as safe and secure.

“Positive experience of information by post with the summons and upon admission”. (IP)

“Good with both oral and written information because you forget a lot with oral information” (IP)

Good to have time to understand the information and prepare any accompanying relatives for a long-term stay in an apartment” (OP)

I had close relatives with me who cooked and made sure I ate even when it was problematic” (OP)

“I received all the support I needed by nurses, but the illness meant I couldn’t eat. Absolutely nothing wrong with the food”. (IP)

Subjectively Perceived Negative Information and Support

Patients (IP and OP) reported that they were unsatisfied with information in connection with their planned hSCT. The information was sometimes incomplete and incorrect. The patient’s subjective experience of support from healthcare professionals and relatives was sometimes perceived as unsatisfactory both with reference to healthcare hygiene and psychosocial support.

“Got some different information in the written booklet. Got 2 different ones” (OP)

“However, information was lacking” (IP)

“Some nurse was a little too busy. If you can’t eat, you can’t” (IP)

“During the three weeks I was in the ward, no one asked how I was feeling mentally, which is an important part of care. It must not be forgotten” (IP)

“The hardest thing when you were alone was shopping and cooking when you felt sick and nothing tasted good. Then there was no support from the nursing staff” (OP)

Subjective Desired Increased Possibility of Person Centered Care (PCC)

Several wishes regarding care during hSCT were expressed by both patients in IP and OP care to increase the possibility of PCC. Patients indicate that they wish to be listened to and to be informed and involved in their care, in ways that are meaningful and valuable to them. To be able to achieve optimal PCC, there was a request for developed IT support. The patients raised requests for increased physical and psychological support as well as nutrition and physical activity advice about daily life.

“Above all, support from the care staff when walking – a shorter turn – as I was unsure how much I could handle” (IP)

“Opportunity to control wishes around food. For example, change lunch/dinner to yogurt or sour milk” (IP)

“When the needle in the port à cat was to be inserted, no one asked if I wanted pain patches first. I had to tell the nurses all the time”. (IP)

“Using modern technology for communication is great “a department xxx channel” on TV with the possibility to see the person you are talking to can partly replace visits” (OP)

“Better information about how I handle food and exercise when I’m discharged and have to fend for myself” (OP)

I lacked proper information about how weak and tired you would become after the stem cell transplant” (OP)

Discussion

The themes emerged from the analysed data: perceived information and support; desired increased possibility of PCC is in accordance with the Swedish Patient Act (2014: 821) [6] that highlights patients right to be involved in their care. The patients in this study have experienced deficiencies in psychological, social, and emotional concerns, which is in line with previous studies [11-14].

Shared decision-making is based on the trust of the partnership between patient and caregiver. The patient story is the first step in establishing a partnership with the patient. Documentation in patient records not only highlights the value of this story, but also contributes to the continuity and transparency of the partnership between provider and patient [18]. The results show that patients regardless IP or OP care felt a need for developed PCC. It was highlighted that information about diet and activity such as PCC was not paid attention to in hSCT care and that support to independently exercise in daily physical activities and communication around food and drink is not prioritized.

The three domains of initiate, integrate and safeguard to establish PCC in daily clinical practice [18] could be a help to establish PCC in the care of patients undergoing hSCT. This initially requires an effort by nursing staff and care planners, which in the long run can give the patient an experience of security and to feel supported by the care staff in being at home during a large part of the care period. Initiation captures the patient’s own story about the perceived condition and the subjective suffering in an everyday context, unlike the medical story that describes the diagnosis and treatment of illness The patients’ subjective experiences differ on certain points between IP and OP care environments. There is, however, very little difference in how they experience some shortcomings in the desired support from the health care staff. Integration means developing cooperation between the patient and care to achieve jointly agreed goals. The care team should, in collaboration with the patient and any relatives, describe all aspects of the care, considering treatment options adapted to the patient’s lifestyle, preferences, beliefs, values and health problems. It can be a challenge for healthcare to find instruments to facilitate the practice of PCC and a support for patients and healthcare practitioners to follow a thought pattern within PCC. Safeguard includes documenting the patient’s story in the patient record as the beginning of a good PCC and describes the patient’s participation in care and treatment decisions, which gives strong legitimacy to the patient’s own will. This leads to transparency between patient and care provider and facilitates continuity of care. The Institute of Medicine (IOM) defines PCC as: “Providing care that is respectful of, and responsive to, individual patient preferences, needs and values, and ensuring that patient values guide all clinical decisions” (Institute of Medicine (US) Committee on Quality of Health Care in America) [17]. As patients today are often alone when staying in the care unit during hSCT and some patients in home care, planning for PCC is needed to strengthen the patient’s self-care possibilities. To facilitate the introduction and maintenance of PCC by healthcare professionals, the instrument, Picker’s eight principles of patient-centered care to help and support in care, can be used. With respect to quality-of-life results, in the autologous studies, the psychological, physical, social, and financial well-being has been reported with higher scores in the outpatient model [21]. This is in accordance with the previously published study [5] regarding anxiety. It was estimated lower in patients treated in hospital (IP). Thru the introduction of PCC, patients can experience increased security in care regardless of the form of care, which can also lead to improved health economics.

Strength and Limitations of the Work

This is a study where the patient’s own voice comes to the fore. Response participation in the study was high, which may indicate patients’ need to be able to express subjective experiences about care. The study is easy to apply as there is a study-specific questionnaire prepared for the specific patient group undergoing hSCT. The results of the study may be helpful in developing PCC in the care of patients undergoing hSCT

A limitation with this study could be the small sample size and the uneven distribution of the groups where patients treated in hospital (IP) were fewer than in the outpatient group (OP). Another limitation is that only one university hospital out of a possible six was involved in the study.

However, patients in this study shared both positive and negative experiences about their period of care, which may indicate that they provided honest and reflective written input in the study-specific questionnaire. The results can be of importance as it gives an insight into patients’ subjective experience of care.

Recommendations for Further Research

More participating university hospitals is needed for a larger base of patients which may lead to improved PCC for patients undergoing hSCT. Complement the study-specific questionnaires with in-depth interviews to capture more subjective experiences to help strengthen PCC. Interview healthcare professionals to strengthen transparency in conversations when caring for patients undergoing hSCT. Overall, the results of the present study may form the basis for the design of new functional tools to support PCC in the care of patients undergoing hSCT or cared for in the hematology department.

Conclusion

Taken together, the results of the upcoming study can design new functional tools to support PCC in the care of patients undergoing hSCT or cared for in the hematology department. The results revealed, despite unequally distributed groups (IP and OP), generally similar subjective experiences of the care context the patient was in. Patients indicate that they want to be listened to and informed and involved in their care, in a way that is meaningful and valuable to them. To achieve optimal PCC, there was, for example, a desire for developed IT support. Previous experiences of PCC in hSCT care have not been exposed within a care context, which together with the desire for developed transparency between patient and care provider should benefit health care leaders.

Relevance to Clinical Practice

To maintain and ensure the patient’s rights according to the Swedish Patient Act (2014: 821), patients have the right to be involved in their care. Therefore, the results from this study can be a help for health care professionals to gain an insight into how patients subjectively describe experiences of care today when they undergo hSCT at a university hospital in Sweden. This might promote the healthcare provider’s intention to introduce PCC based on the patient’s own qualifications. As a routine during patient enrolment, patient-nurse-physician conversations should include Ekman’s conceptual framework, including the three domains of initiate, integrate, and ensure, to guarantee that PCC is practiced systematically and consistently. Caring for patients undergoing hSCT is and should be a team effort in which dietitians and physiotherapists have an obvious place. Using an instrument such as Picker’s eight principles of patient-centered care can facilitate the team.

Statements and Declarations

Authorship

Design: ACS, AEW; Data collection and drafting the manuscript: ACS, AEW; Data analysis: ACS, AEW; Critical reviewing the manuscript: ACS, AEW. All authors approved the final version of the manuscript.

Funding

The authors declare that no funds, grants, or other supports were received during the preparation of this manuscript.

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Ethical Consideration

The study rests on the ethical principles; World medical association declaration of Helsinki [20]. The study was approved by the regional Research Ethics Committee, Uppsala, D no; 2016/521

Consent to Participate

Written informed consent was obtained from all individual participants included in the study.

Consent to Publish

A statement confirming that consent to publish has been received from all participants.

Conflict of Interest

The authors declare no conflict of interest.

References

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Findings Associated with Detection of H-Pylori in Egyptian Patients Recruited for Liver Transplantation

DOI: 10.31038/IMROJ.2023822

Abstract

Helicobacter pylori is considered one of major carcinogens organisms which cause gastric, pancreatic and lung cancers. Arising studies are still to understand about relationship between H-pylori and tumor markers. Patients undergoing liver transplantation are put under a full investigation protocol for exclusion criteria, yet H-pylori infection is not well considered.

Objectives: To study findings associated with detection of H-pylori in Egyptian patients recruited for liver transplantation and taking into consideration their prognostic value.

Material and methods: a retrospective study of 40 cases of patients recruited for liver transplantation at the National Hepatology and Tropical Medicine Research Institute (NHTMRI). Data include patient Age and sex, Blood group, Hepatitis viral markers, Tumor markers (CA125, CA19.9, CEA, and AFP), Bilharzial Ag/Ab and Autoimmune profile (ASMA, ANA and AMA). Histopathologic and immunohistochemical assessment of H-Pylori expression in hepatic tissue and pre hepatic lymph nodes.

Results: there was a significant relation between Anti-H-pylori Antibody expression in lymph node tissue to the tumor marker (CA 19.9) in studied cases with significant (P value 0.046). More than 80% of studied cases that showed dysplasia in liver tissue express Anti-H-pylori antibody in liver tissue. The relation between Anti-H-pylori Antibody expression in lymph nodes and dysplasia in liver tissue of studied cases was statistically significant (p value=0.037).

Conclusion: H-pylori infection should be considered among the causes of CA 19-9 elevation so that needless interventions and health expenses can be prevented. While in case of transplantation, presence of H-pylori as a carcinogen should be fully evaluated with consideration to other tumor markers and serological markers with new scoring formulation strategies.

Abbreviations: AFP: Alpha Feto Protein; AMA: Anti-Mitochondrial Antibody; ANA: Anti-Nuclear Antibody; ASMA: Anti-Smooth Muscle Antibody; CA: Carbohydrate Antigen; CEA: Carcino-Embryonic Antigen; CMV: Cytomegalovirus; EBV: Epstein-Barr Virus; HBV: Hepatitis B Virus; HCC: Hepatocellular Carcinoma; HCV: Hepatitis C Virus; IgG: Immunoglobulin G; LN: Lymph Nodes; MALT: Mucosa Associated Lymphoid Tissue Lymphoma; AILD: Autoimmune Liver Disease; TGFB: Transforming Growth factor B1

Introduction

As Liver transplantation survival rates frequency has been increased, postoperative management of recipients requires more attention. Increasing reports about de novo gastric cancer after transplantation and there are many studies about critical role of H-pylori infection as a gastric carcinogen. Chronic inflammation, Immune stimulation and cellular proliferation have been always implicated in tumors pathogenesis, thus this pathogenesis progression should always be investigated and monitored in post transplantation patients [1-3].

Other long-term complications of H-pylori should also be well investigated, studying serological findings associated with detection of H-pylori in Egyptian patients recruited for liver transplantation is a key step to predict and prevent complications and their pathogenesis.

Material and Methods

A retrospective study of 40 cases of cirrhotic patients with decompensated end stage liver disease recruited for liver transplantation collected from the National Hepatology and Tropical Medicine Research Institute (NHTMRI). The study protocol was approved by The Research Ethics committee (REC) GOTHI on 13 -1- 2021. Data were collected from reports regarding personal data (age and sex), clinical, laboratory and pathological data. data were collected and tabulated. The following data and investigations were collected and done at NHTMRI: – Age and sex of patient. – Blood group. – Hepatitis viral markers. – Tumor markers (CA125, CA19.9, CEA and AFP). – Bilharzial Ag/Ab. – Autoimmune profile (ASMA, ANA and AMA). – Histopathological findings in the liver (Cholestasis, Dysplasia and HCC). – Etiology of cirrhosis. Histopathologic, Staining and Immunohistochemical Assessment of Anti-H-pylori antibody expression in hepatic tissue and enlarged prehepatic LNs.

Statistical Method

The collected data was revised, coded tabulated and introduced to a PC using Statistical package for Social Science (SPSS 25)

Results

Demographic Data

Results showed that the majority (36 cases) of studied liver cirrhotic cases were male patients. As for age in our study ranges between 20 and 60 years old with mean age about 44years. With 70% of them above the age of 40 years.

Blood Group

Blood groups are shown in the below Graph 1.

graph 1

Graph 1: Distribution of cases according to the blood group of studied cases: 40% of cases were blood group B.

Virology Profile

More than half of cases were HCV positive.

  • All patients were EBV IgG (Epstein-Barr virus) CMV (Cytomegalovirus) IgG positive (Graph 2).

graph 2

Graph 2: Distribution of cases according to viral markers (HBV and HCV) of studied cases.

Bilharziasis

More than 70% of cases were negative bilharzial Ag/Ab.

Etiology of Cirrhosis

Regarding etiology of cirrhosis, more than 50% of cases were HCV related cirrhosis.

Tumor Markers

  • Tumor markers showed average values at time of transplantation; cases showed normal level of CA125 (50%), AFP level (62%), CEA level (92%) and CA19.9 (72%) (Table 1).

Table 1: Tumor markers of total studied group at time of transplantation.

tab 1

Autoimmune Profile

Regarding autoimmune profile, more than half of studied cases were positive for ASMA (Anti smooth muscle antibody) and > 72% were negative for ANA (Antinuclear antibody). All patients were AMA negative.

Pathological Data

Regarding to histopathological findings in liver tissue, more than 50% of studied cases were positive cholestasis, 40% of them were positive dysplasia while 25% were positive for hepatocellular carcinoma (Graph 3).

graph 3

Graph 3: Distribution of cases according to liver findings (cholestasis, dysplasia, and HCC) in studied cases.

Anti H-pylori Antibodies

85% of studied cases were positive for anti H-pylori antibodies in liver tissue while 70% of studied cases were positive for anti H-pylori antibodies in the LN tissue (Graph 4).

graph 4

Graph 4: Distribution of cases according to Anti-H. Antibody expression in liver and LN tissues of studied cases.

Expression of Anti H-pylori Antibodies with Age

The relation between age groups and Anti-H. Antibody expression in liver of studied cases was statistically significant (p value=0.006). About 80% of cases with positive anti H antibodies in liver were above age of forty (Graph 5).

graph 5

Graph 5: Relation between age group and Anti-H. Antibody expression in liver of studied cases.

Expression of Anti H-pylori Antibodies with Blood Groups

  • All blood group A and O cases express Anti-H antibody in liver tissue, while less than forty percent of blood group B cases didn’t express Anti-H antibody in liver tissue.

A statistically significant relationship was obtained between Anti-H. Antibody expression in liver and (O) blood group in studied cases (p value=0.006) while the relation between Anti-H. Antibody expression in lymph nodes and (O) blood group in studied cases was statistically insignificant (p value=0.908) (Graph 6).

graph 6

Graph 6: Relation between Anti-H. Antibody expression in liver and blood groups in studied cases.

Expression of Anti H-pylori Antibodies with Tumor Markers

Relation between Anti-H-pylori Antibody expression in lymph node tissue to the tumor marker (CA 19.9) in studied cases was significant (P value 0.046) (Table 2).

Table 2: Relation of Anti-H. Antibody expression in lymph node to age group and tumor markers in studied cases.

tab 2

Relation of Anti-H

Antibody expression in liver to age group: mean age positive cases was 47 years with ±13 in contrast with 30 years with SD ±14 negative cases with significant P value (0.007). Relation of Anti-H. Antibody expression in liver to tumor markers in studied cases was Insignificant (Table 3).

Table 3: Relation of Anti-H. Antibody expression in liver to age group and tumor markers in studied cases.

tab 3

Pathological Findings

Expression of anti H-pylori Antibodies with Dysplasia

50% of studied cases that showed dysplasia in liver tissue expressed Anti-H. Pylori antibody in the lymph nodes. The relation between Anti-H. Pylori Antibody expression in lymph nodes and dysplasia in liver tissue of studied cases was statistically significant (p value=0.037).

More than 80% of studied cases that showed dysplasia in liver tissue express Anti-H. Pylori antibody in liver tissue. 17% of studied cases that were negative for dysplasia in liver tissue didn’t express Anti-H. Pylori antibody in liver tissue (Graph 7).

graph 7

Graph 7: Relation between Anti-H. Antibody expression in lymph nodes and dysplasia in studied cases.

Expression of anti H-pylori antibodies with HCC

60% of cases that were positive HCC in liver expressed Anti-H. antibody in lymph nodes. A statistically significant relationship was obtained between Anti H-pylori antibody expression in lymph nodes and HCC in liver of studied cases (p value=0.041).

All cases that showed HCC in liver tissue express Anti-H. Pylori antibody in the liver tissue while 29% of the cases that were negative for HCC in liver tissue didn’t express Anti-H. Pylori antibody in the lymph nodes. A statistically insignificant relationship was obtained between Anti-H. Pylori Antibody expression in lymph nodes and HCC in liver tissue of studied cases (p value=0.307) (Graph 8).

graph 8

Graph 8: Relation between Anti-H. Antibody expression in lymph nodes and presence of HCC in liver of studied cases.

Discussion

This study, alongside earlier investigations, showed that H. pylori is a liver carcinogen and plays a crucial role in the genesis of several liver diseases. Because it increases the risk of developing hepatocellular carcinoma (HCC), which has a high mortality and morbidity rate, hepatic cirrhosis is particularly significant [4]. Mekonnen et al. [5] state that H. pylori infection should be viewed as a liver oncogenic organism similar to HCV because it is more prevalent in HCC patients than in controls. Another study that identified H-pylori and its related groups in hepatic tissue samples from patients with cholangiocarcinoma and HCC agreed with that [6]. H-pylori infection increased HCC development passing through increased vascular mediators and inflammatory markers. Furthermore, eliminating it might lower the likelihood of these side effects [7]. CA 19-9 is also produced by ductal cells in the pancreatic and biliary system, as well as epithelial cells in the stomach, colon, uterus, and salivary glands. Although high amounts of CA 19-9 can be found in a number of gastrointestinal and gynaecological cancers, it is particularly useful as a marker for pancreaticobiliary tumours [8]. CA 19-9 is utilised to monitor pancreatic cancer patients since it is elevated in various gastrointestinal malignancies, such as colorectal, hepatic, and esophageal cancers.

Awama et al. [9] found that the relationship between Helicobacter pylori infection and levels of CA 19-9 showed no significance in patients with benign gastrointestinal diseases, another study agreed [10] and concluded that CA19.9 was unable to predict the presence of HP. In our study, CA19.9 showed unexplained significant relationship with Anti-H-pylori Ab expression in LN tissue. Anti-H. pylori Antibody Expression in Lymph Nodes and HCC in the Liver Tissue of Studied Cases were Found to Be Statistically Insignificantly Associated in This Study (p value=0.307). A study mentioned that in some conditions of benign cases of pancreatic and gastric disorders there is a notable high increase in CA 19-9 serum level that returns normal after effective treatment which may result in rapid serum CA 19-9 levels normalization. The proliferation of epithelial cells under those circumstances may explain this elevation, and that H-pylori infection-related inflammatory cytokines are a significant contributor to this elevation., specially it was noted that CA 19-9 returns to normal levels after eradication of H-pylori infection. It is challenging to detect the precise cause of the CA 19-9 elevation whether due to benign versus malignant conditions. So that CA19-9 is not considered a sensitive tumor marker on its own and combined use of other tumor markers as CEA and CA125 is recommended to overcome the confusion caused by CA19-9 elevation. But this suggestion is not widely accepted yet.

Another case report study found a significant rise of CA19.9 in a 68-year man infected with H-pylori suis [11], they mentioned that in cases of high CA19.9, in addition to H-pylori, infection with non-human H-pylori species should be considered. Its implication in carcinogenesis is also patent. While more data is required to confirm a direct relationship, this CA 19-9 elevation is assumed to be related to the same factors: gastric epithelial cells proliferation and inflammatory cytokines. After treatment and condition improvement, the biological follow-up showed CA 19-9 levels normalization.

The development of gastric mucosa associated lymphoid tissue (MALT) lymphoma is a multistep process as H. pylori infection is followed by the recruitment of immune cells to the stomach mucosa. [12]. Due to the presence of H. pylori, persistent inflammation is frequently linked to gastric MALT lymphoma. The pathophysiology of non-gastric MALT lymphomas is likewise thought to include chronic immunological activation, therefore autoimmune diseases are frequently present. Neoplastic cells present in epithelial structures and subsequent damage to the glandular architecture, resulting in lymphoepithelial lesions, are distinguishing characteristics of MALT lymphoma [13]. In the same scope, antibodies as AMA, ANA and ASMA have been associated with range of diseases that respond to these autoantibodies leading to inflammation and initiation of the hepatic tissue injury in autoimmune liver disease (AILD) patients. Earlier studies found that positive rates of ANA, AMA and SMA were higher in H-pylori infected patients than in patients with negative H-pylori infection [14]. Such findings suggest that immunological disturbances could be associated with future risk of pathogenesis and development of lymphomatous neoplasms, AILD and possible graft rejection.

In the current study, the lymph nodes of 70% of cases were having anti-H. pylori antibodies. Ito et al. [15] found that macrophages in 85% of patients’ lamina propria and in 63% of patients’ paracortical regions of their gastric LNs

Conclusion

In developing countries as Egypt, H-pylori infection is a common health problem with many well-known sequences and other undetermined ones. H-pylori must be considered as a cause of elevation of ca19-9 and ASMA titre elevation. And so, a lot of needless investigations and health care expenses could be saved. While in case of transplantation, presence of H-pylori as a carcinogen should be fully evaluated with consideration to other tumor markers and serological markers with new scoring formulation strategies.

References

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Analysis of C-section Rates Using Robson’s Ten Group Classification System (RTGCS) in Pakistan: A Review

DOI: 10.31038/AWHC.2023634

Introduction

For a long period of time, cesarean sections were primarily performed in situations where they were medically necessary to safeguard the lives of both mothers and infants. However, over the past few decades, the prevalence of this surgical procedure has notably increased. According to the Lancet series on Cesarean section, there were approximately 141 million babies born around the world in 2015 – 29 million of them (21%) were delivered through a Cesarean section [1]. The escalation in cesarean section rates is attributable to a complex interplay of factors, which vary widely between and within countries. The World Health Organization highlights the importance of conducting research to identify and define the specific drivers of rising cesarean section rates in distinct settings. This research should also explore the local factors influencing cesarean births and consider the perspectives and cultural norms of both women and healthcare providers [2].

The proportion of caesarean sections at the population level is a measure of assessing progress in maternal and infant health and in monitoring emergency obstetric care. It is however challenging to determine the optimal or adequate rate of caesarean sections in a country [3].

WHO conducted a systematic review of studies to find this rate, and recommended that no more than 10-15 percent deliveries are justifiable by C section in any population [1,4]. The advice emphasized performing Cesarean sections solely when medically required and refrained from suggesting a specific population-level target rate. This was due to the potential for debate regarding the definition of underuse and overuse rates [5]. Still countries have used certain cut-off levels to show high or low C section rates in any population. Less than 5 percent of C section in any population indicates low antenatal and maternal care and hence account for delivery complications and even maternal mortality [6]. For nearly 30 years, the international healthcare community considered the ideal rate for caesarean sections to be between 10% and 15% based on the World Health Organization recommendation of 1985. However, with the changing demographics of the world population, especially in high- and middle-income countries the 10% to 15% rates don’t seem optimal [7]. Studies have shown that until now there is no evidence of benefit for the health of mothers and babies in populations with values of CS above 15%, regarding the lower limit, it has been argued that CS rates of 5% could achieve major improvement on maternal outcomes. However, for neonatal health, rates between 5% and 10% have been reported to attain better outcomes [5].

Pakistan presents a similar picture and the CS rates have increased from 3.1% to 22.3% in the last two decades [7] with reported rural and urban CS rates as 18% and 32% respectively. Equity analysis showed that women in the highest wealth quintile were more likely to be delivered by CS (46%) compared to women in the lowest quintile (8%). Further, more developed, and urban provinces like Punjab have higher CS rates (29%) than the less developed province like Baluchistan (4%). Private health facilities (38%) report higher CS rates as compared to public health facilities (25%) [8]. The factors contributing to the rise in CS rate are complex and identifying interventions to reduce this rate is challenging. One of the main referred difficulties was the lack of a classification tool that would be feasible to be used internationally, to allow audit feedback and setting an optimal CS rate over countries. Till the end of 2010, there was no standard classification system for caesarean section that would allow the comparison of caesarean section rates across different facilities, cities, countries, or regions in a useful and action-oriented manner. In 2011 the World Health Organization (WHO) conducted a systematic review that identified 27 different systems to classify CS. These classifications looked at “who” (woman-based), “why” (indication-based), “when” (urgency-based), as well as “where”, “how” and “by whom” a CS was performed [1]. This systematic review of system concluded the Robson classification is the most appropriate system to fulfil current international and local needs [5].

Based on the review WHO recommended the “Robson’s Ten Group Classification System” (RTGCS) for comparing CS rates for the purpose of audit and monitoring interventions needed to reduce the Cesarean section rates globally [9]. The classification is simple, robust, reproducible, clinically relevant, and prospective – which means that every woman admitted for delivery can be immediately classified into one of the 10 groups based on the following basic characteristics: parity (nulliparous, multiparous with and without previous caesarean section); onset of labor (spontaneous, induced or pre-labor caesarean section); gestational age (preterm or term); fetal presentation (cephalic, breech or transverse); and number of fetuses (single or multiple). This allows a comparison and analysis of caesarean section rates within and across these groups. Unlike classifications based on indications for CS, the Robson Classification is for “all women” who deliver at a specific setting (e.g., a maternity or a region) and not only for the women who deliver by CS. It is a complete perinatal classification [6].

Robson Classification Data Collection and Implementation

For implementation of Robson group classification in institutions the simplest way is:

i) Collect data on the six variables as shown in Robson Classification Manual(World Health Organization, 2017) [6], from obstetrical history or from case sheet of client.

ii) Classify each woman into one of the 10 groups. This can be done manually or recording the core variables in electronic client record using a software application that automatically assigns the specific Robson group shown in Table 1 based on pre-established formulas.

iii) Data collection then is conducted on the information of mode of delivery, vaginal or Cesarean section. The 10-group classification could be used to create the Robson report Table 1 and assess the C/section rate in each group and then possibly bring about changes in management that may alter the caesarean section rate.

The implementation of this classification is simple and helped healthcare facilities to: Identify and analyze the groups of women which contribute most and least to overall caesarean section rates; Compare practice in these groups of women with other units who have more desirable results and consider changes in practice; Assess the effectiveness of strategies or interventions targeted at optimizing the use of caesarean section; Assess the quality of care and of clinical management practices by analyzing outcomes by groups of women [10].

Despite of WHO’s recommendation that all health care facilities should use the Robson classification system for women admitted to give birth and to monitor the rates of caesarean sections there is little done in this regard. To ensure the adoption of the key recommendations in Pakistan, and to prevent cases of unnecessary caesarean section, there is little published experience on the practical utilization of the WHO Robson classification and no concrete experience reported so far on how to use and implement Robson classification in an action-oriented manner in health facilities.

We conducted a literature review to identify and appraise the studies that included Robson Classification as a system for categorizing and analyzing the data in clinical audits, as interventions to help reduce and optimize CS rates.

Methodology

This review of literature was conducted using two data bases; PubMed, Google Scholar, and grey literature, it was then reported according to recommendations of PRISMA framework.

Types of Studies

Any study that used the Robson classification within clinical audit or as an intervention to reduce or optimize CS rate, were eligible for inclusion. CS rate had to be part as one of the outcomes in each study. We included studies regardless of study design, sample size, duration of study, and type of setting for example, nationwide or facility-based etc.

Type of Participants

Studies presenting the use of the Robson classification in any group of women were eligible for inclusion regardless of obstetric characteristics, level of risk, socio-economic status.

Type of Implementation of the Robson Classification

We considered studies demonstrating the use of the Robson classification including any number of patients, study duration, in a group of women regardless of the women’s obstetric characteristics, level of risk or socio-economic status. Studies using variations of Robson Classification like (splitting or combining groups e.g., 2a, 2b etc.). Only those studies were incorporated which used Robson classification for clinical audit or to assess trends and outcomes (CS rate, group size, group CS rates etc.)

Exclusion Criteria

We excluded studies that were not conducted in Pakistan and did not provide any quantitative data on the effects of the use of Robson Classification in clinical audit or intervention to optimize CS rates. Studies that had unclear definitions or groups categorization were also excluded.

Search Strategy

An electronic search was conducted using two electronic databases; PubMed and Google Scholar for studies published between January 2010 and January 2023. Only studies in English language were included. The electronic search was complemented by screening the references of all articles chosen for full-text evaluation.

Screening, Data Extraction Template

All citations identified from the electronic searches were downloaded into Reference Manager and duplicates were deleted. Relevant citations for full text readings were then selected. The selected articles were then independently read by two reviewers and those fulfilling the aforementioned selection criteria were included in the review. A standardized data extraction template was designed for this review and data was extracted by two reviewers.

Information recorded for each article included: (1) study design; (2) study objectives; (3) place of study, year, setting, type of institution, time duration; (4) number of women or deliveries included; (5) source of data; (6) description of the intervention; (7) CS rates pre and post intervention(s); (8) conclusions according to the author; (9) observations, comments for using the classification system.

WHO recommends the adoption of updated Robson classification including its 10 groups and ensures its implementation at health facility as a tool to facilitate the classification system to monitor and compare CS rates at facility level in a standardized, reliable, consistent, and action-oriented manner.

Table 1: Studies in Pakistan using Robson Classification included in review

SN

Study Site

Deliveries

Use of Robson

1 Abbasi Shaheed Hospital Karachi (ASH-KHI) (Imtiaz, Husain, & Izhar, 2018) [17]

1960

To compare the rate at health facility for 2013 and then in 2016 after simple interventions
  Abbasi Shaheed Hospital Karachi (ASH-KHI) (Imtiaz, Husain, & Izhar, 2018) [17]

1560

2 CMH Abbottabad, (CMH-AB) (Tahir N, 2018) [18]

2340

 To see what proportion of CS cases fall into each group, from Sep 2016 to Mar 2017
3 Pakistan Institute of Medical Sciences, Islamabad (PIMS-ISB) (Gilani, Mazhar, Zafar, & Mazhar, 2020) [19]

6155

To identify and analyze the groups of women which contribute most and least to overall CS rates, from October,2016, to September 2017
4 Pak Emirates Military Hospital Rawalpindi (PEMH, RWP) (Ansari A, 2019) [20]

7206

To assess the effectiveness of strategies. The audit cycle was completed from Jan to June 2017 by identifying the problem areas, and devising & implementing recommendations. A re-audit was conducted after 6 months to analyze the changes from July to Dec 2017
5 Khan Research Laboratories (KRL-ISB) (Khan, Sohail, & Habib, 2020) [21]

964

To analyze the trends of cesarean sections from Nov 2017 to April 2018
6 Holy Family Hospital – Unit 1, Rawalpindi, (HFH-UI)

1458

To compare rate in ten groups of women with other units and health facilities in 2019
Holy Family Hospital – Unit 1, Rawalpindi, (HFH-U2)

1521

Benazir Bhutto Hospital, Rawalpindi (BBH-RWP)

1528

District Head Quarter, Rawalpindi (DHQ-RWP) (Chaudri, et al., 2019) [22]

1096

 7  Unit B Mchc, Ath Abbottabad (Afridi SA, 2022) [23]

 352

The analysis of unjustified C/S rate is done by Using Robson’s Ten Group Classification system

August 2021-jan 2022

8 Lahore General Hospital (Sabir, et al., 2020) [24]

3660

A Retrospective descriptive study is carried out in gynecology unit 2 of Lahore General Hospital Lahore. Records of all patients who delivered in gynecology unit two over a period of one year from 1st January 2021 to 31st December2021 are collected and analyzed.
9 Hayatabad Medical Complex (Ali, Khattak, Sadaf, Begum, & Kishwar, 2021) [25]

5611

Retrospective study done in the Department of Obstetrics and Gynecology Hayatabad Medical Complex

Hospital Peshawar, a tertiary care hospital, from a period of 1

st January 2019 till 31

st December 2019.

10 Allama Iqbal Memorial Teaching Hospital, Sialkot (Bano, et al., 2022) [26]

5787

It is a retrospective study conductedatKhawaja Muhammad Safdar Medical College, Allama Iqbal Memorial Teaching Hospital Sialkot,from January 2022 to June 2022
11 Jinnah postgraduate medical center Karachi (JPMC) (Majid E, 2022) [27]

1242

To determine the frequency of caesarean section with its indication by grouping according to Modified Robson’s Criteria at JPMC.

1st Jan to 30th June 2018

12 MTI, LRH Peshawar (Fatima SS, 2022) [28]

1679

To analyze CS rate in Department of Obstetrics and Gynecology MTI, LRH, Peshawar; according to RTGCS. This will help understand the major contributory groups to the overall CS rate and to formulate strategies to optimize the escalating rates

Jan 2021-Dec 2021

 

13 Hayatabad medical complex Peshawar-Unit B (Akhtar R, 2021) [29]

1258

To determine the caesarean section rate and frequency of different indications of caesarian section (CS) in a tertiary care hospital.

1st January2019 to 31st December2019

14 Holy Family Hospital, Karachi, Pakistan. (Abidi SM, 2023) [30]

1464

To identify areas for improvement in obstetric care practices and facilitate the development of strategies to optimize obstetric care and reduce CS rates, thereby improving maternal and neonatal outcomes.

January 1st, 2022, to December 31st, 2022

15

 

CMH Quetta (Khanum F, 2021) [31]

714

To find out the incidence of C-Section rate and reducing it after auditing by use of Modified Robson Criteria

January 2020-June 2020

853

To find out the incidence of C-Section rate and reducing it after auditing by use of Modified Robson Criteria

August 2020-January 2021

16 Khyber teaching hospital Peshawar (Afridi F, 2022) [32]

330

To determine the frequency of various groups of patients undergoing C-section in a tertiary care hospital in Peshawar, using WHO Ten Group ROBSON Classification of C section. January-March 2019

Results

An electronic search yielded 597 studies using two Databases. After screening of records, 35 studies fulfilled the inclusion criteria and all other studies that were either not conducted in Pakistan or did not use Robson Classification system for clinical audit were excluded. After reading full-texts 16 studies were included in our review. Our review also highlights the limited number of studies published in Pakistan using the RTGCS Figure 1.

fig 1

Figure 1: Study Flowchart.
*Reasons for exclusion include duplication, not including Pakistan, not using Robson Classification.

Two-third of the studies included more than 1000 women and were hospital record data. Majority of the studies (2/3rd) were cross sectional study designs while were three studies each used trend analysis and audit. The figure below, Figure 2, shows the studies that are included in the review of C-Section rates in Pakistan. All these studies showed the utility of Robson’s ten group classification system for caesarean section as an auditing tool. Most of the studies were cross-sectional designs and audits, two were a trend-analysis. All the studies are single center/facility studies. It helped in identifying the groups which are contributing to high cesarean rates. Effort then directed towards those groups, strategies devised, and policies and practices modified to help reduce the LSCS rate.

fig 2

Figure 2: A review of results from various studies on RTGCS in Pakistan

The bars in the above graph represent the upper proportion limit of CS rates in each of the Robson groups (except for groups 6 &7). It was based on the source developed by Michael Robson, based on his international experience since 1990. It was used merely to interpret range of CS rates in Robson report table, rather than recommendations. Each colored dot represents the proportion of Cesarean section reported by each reviewed study. In above mentioned sites, over all primary caesarean delivery rates in group 1, 2, 3 and 4 were higher than the recommended Robson’s guidelines, except in two hospitals for group 1 and group 2 and in one hospital for group 3. In group 5 (had previous one or more sections) all studies reported a very high rate that ranged from 57% to 98%. In all sites almost 75% of women in group 6 and 7 (women with breech presentations) had Cesarean sections. Group 9 (transverse lie) which is recommended to be 100% and shows quality of data and understanding of Robson Classification leading to misclassification of women. CS rates in each group will vary in different hospitals and settings depending on their capacity level of complexity, the epidemiological characteristics of the population served and the local clinical management guidelines, among other factors Figure 3.

fig 3

Figure 3: Overall CS rates in each health facility

Results show that the overall C/S rate in all targeted health facilities ranged between 26.4% to 64% which is many points higher than the recommended 5 to 15% CS rate by Robson Guidelines. Studies that were clinical audits showed decrease in overall CS rates, for example, a study in CMH Quetta showed a 12% decrease in overall CS rates and a similar trend was observed in a tertiary care facility in Karachi. We, however, know that c/section rates higher than 10-15% are not associated with reductions in maternal and neonatal mortality rates.

Discussion

This review included 16 studies from Pakistan presenting the experiences of users for adoption, interpretation, and implementation of Robson classification in their health facility. The findings of our review suggests that despite lack of official endorsement from the government of Pakistan, the use of Robosn Classification is increasing rapidly globally and in Pakistan for optimization of CS rates. All the studies in our review include experiences from tertiary care facilities. The Robson classification system classifies every woman who is admitted for delivery into 10 groups to identify and categorize women to understand the underlying factors for the increased CS deliveries, to design interventions according to groups, in turn optimizing the overall CS rates [9].

WHO has proposed health facilities to use the Robson classification system as a gold standard to assess the Cesarean section rates in a country [6]. Despite WHO’s recommendation that all health care facilities should use the Robson classification system for women admitted giving birth, to monitor the rates of caesarean sections there is little done in this regard. To ensure the adoption of the key recommendations in Pakistan, and to prevent cases of unnecessary caesarean section, there is little published experience on the practical utilization of the WHO Robson classification and no concrete experience reported so far on how to use and implement Robson classification in an action-oriented manner in health facilities.

In studies included, over all primary caesarean delivery rates in group 1, 2, 3 and 4 were higher than the recommended Robson’s guidelines, except in two hospitals for group 1 and group 2 and in one hospital for group 3 [11]. The primary caesarean delivery for these groups in targeted health facilities raised a specific concern. In Group 1 and 3 (women admitted in spontaneous labor) primary Cesarean sections can be explained by inappropriate indication to Cesarean section (CTG misinterpretation or suspected fetal distress). An area needing improvement was thus brought to light. High rates in group 1 and 3 for primary caesarean section can be lowered by the presence of senior consultants [12]. Cesarean section rates in groups 2 and 4 (women who had induction of labor or pre labor C/S) were higher in all sites than Robson except at only one site for group 2 . This may be possibly due to poor choice of women to induce or poor success rates for induction or inappropriate indications to Cesarean section in IOL and pre-labor Cesarean section. Absence of consensus on what constitutes a failed induction, the standard inducing agent, duration of induction and improper counselling regarding expectation of the women is a reason quoted for failed inductions [13].

In group 5 (had previous one or more sections) all studies reported a very high rate that ranged between 57% and 98%. It needs to be mentioned that the recommended rate of CS in this group is between 50-60%. The high rate in this group has been a matter of discussion and has attracted a lot of criticism towards the community regarding the promotion of vaginal birth after caesarean section. The vaginal birth after caesarean section (VBAC) is a valid option for women with nonrecurring indications and is safe if a delivery is conducted at a hospital [14].

In all studies almost 75% of women in group 6 and 7 (women with breech presentations) had Cesarean sections. By identifying the high rate in these groups clinical interventions, such as external cephalic version for breech delivery at term, vaginal breech delivery in appropriately selected women could reduce the frequency of CS use.

Variations in group 8 (had multiple pregnancy) depends on the type of twin pregnancy and ratio of nulliparous/multiparous with or without a previous scar. In Group 9 (women with transverse lie) should be 100% as showed in studies. In group 10, the rates had a huge variation and ranged between 6.6% and 56.9%. The recommended rate in this group is 5%, thus a very high rate in this group is seen.

In addition to the studies mentioned above, an intervention study was conducted in Abbasi Shaheed Hospital, Karachi. Two sets of data were collected each in year 2013 and 2016. The CS rates of both years were compared in terms of RTGCS. After the initial audit in 2013, three interventions were implemented, and the audit cycle repeated. The overall C/S rate fell from 30.7% to 26.4% and C/S rate in each group also reduced in three years just by implementing simple measures such as 24-hour senior registrar presence; structured counselling for women with previous caesarean delivery during the antenatal visits regarding vaginal birth after caesarean and review of all women with failed induction by a senior obstetrician [15].

In this context, WHO conducted a systematic review in 2014 which included 73 studies from 31 countries that reported on the use of Robson Classification between 2000-2013 [16]. The review assessed the challenges faced by countries in the adoption, implementation and interpretation of the Robson’s classification and identified various barriers and facilitators of its adaptation and implementation. The main strengths of this classification reported are its simplicity, robustness, reliability, and flexibility. An inherent advantage of the classification is that it allows self-validation since some groups can act as controls. For instance, group 9 (women with a fetus in a transverse or oblique lie) is expected to represent less than 1% of all women admitted for delivery and to have a CS rate of close to 100%. The resources, software and variables needed to implement the classification are considered minimal, making it suitable for low resource settings. In addition, ‘‘not requiring indications for CS’’ is an advantage because of the variability and potential subjectivity when using indications to classify CS, and because these are insufficiently registered in some settings. Some of the limitations included focus of more than two third of these studies in developed regions (Europe, North America, and Oceania). The classification also does not consider other maternal and fetal factors that significantly influence the rate of CS (e.g., maternal age, pre-existing conditions such as BMI or complications) and therefore additional statistical methods (e.g., adjusting) are necessary to account for these factors.

These multiple global reviews suggest that the basic Robson classification identifies the contributors to the CS rate but does not provide insight into the reasons (indications) or explanations for the differences observed. Several suggested modifications could be useful to help facilities and countries as they work towards its implementation. If used on a continuous basis, some studies suggest that this classification system can provide critical assessment of care at delivery and be used to change.

The RTGCS can also be used to monitor and compare caesarean section rates within provinces, states as well as assess the progress within selected health care facilities over time. However, there is a constant debate about the usefulness of the Robson’s CD rates especially because it is difficult to conclude that much progress has been made or consensus on its effectiveness.

Conclusion

To conclude all studies reviewed showed exceptionally high rates of Cesarean sections, overall as well as across all different groups. However, it is important to realize that all these studies were conducted in tertiary care hospitals, receiving referral of high-risk obstetric population.

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Anti-inflammatory Metabolites and Allergenic Proteins from Green Lipped Mussel (Perna canaliculus)

DOI: 10.31038/IJVB.2023711

Abstract

Lipophilic extracts from the green-lipped mussel (Perna canaliculus) are known to have anti-inflammatory capacity, but allergenic proteins from Perna canaliculus were identified recently. This raises the question of the safety of the anti-inflammatory products of Perna canaliculus. The anti-inflammatory effects on symptoms of arthritis are reported for a lipid fraction, comprising inhibitors of cyclooxygenases (cox1 and cox2), histamine blockers and omega-3 fatty acids. The lipid fractions can be obtained by extracting mussel tissue using supercritical CO2 or organic solvents. To produce glycosaminoglycan-rich extracts, homogenates are delipidated, and the proteins are digested by proteases, leading to an enrichment of the carbohydrate fraction consisting primarily of glycosaminoglycans. Products for animal health care can also be prepared more cost-efficiently by simply homogenising mussel tissue and subsequent freeze-drying. These products are mainly applied as dietary supplements. We here review briefly the knowledge on the mode of action of the various supposed anti-inflammatory capacities of Perna canalicus associated with several classes of molecules and focus on the applied extraction protocols because the extraction methods define the potential risk of allergenic proteins, which were recently discovered.

Background

The Green Lipped Mussel (Perna canaliculus) is a bivalve mollusc from the family of Mytilidae and is found endemically in the sea around New Zealand. The mussels have been cultivated since the 1960s in large capacities by aqua farming and exported worldwide. P. canaliculus products are available as dietary supplements. They are promoted for therapy as well as for prevention of bone problems in humans as well as in animals.

Anti-inflammatory Activity of Lipid Fractions from Perna canaliculus

The anti-inflammatory potential of Perna canalicus was first reported about four decades ago [1]. The study by Couch et al. reported a positive effect in managing inflammatory joint disease [2], and Caughey et al. described a positive impact on treating rheumatoid arthritis [2]. The anti-inflammatory effects of Perna canaliculus were hypothesised to be caused by three different modes of action. First, there is evidence that Perna canaliculus extracts contain inhibitors of prostaglandin synthase, also known as cox-1 and cox-2 [3]; second, the histamine inhibitor lysolecithin was found in high abundance in P. canaliculus extracts [4], and thirdly also the relatively high content of Omega-3 fatty acids might exert an additional anti-inflammatory effect [5].The association of the prostaglandin level with auto-immune diseases is well documented for many auto-immune diseases like rheumatoid arthritis and osteoarthritis [6]. Cox-1 is constitutively expressed in many tissues, but the cox-2 gene is dramatically upregulated after inflammation [7]. Since the formation of prostaglandins is associated with inflammation and pain, many painkillers are cox-1 or cox-2 inhibitors. Due to its induction during inflammation, the cox-2 enzyme is a primary target for the therapy of auto-immune diseases [8-10]. Based on identifying cox-I inhibition by freeze-dried homogenates of P. canaliculus in different studies, the question was raised about the specific mode of action and the actively involved molecules. In the study of McPhee et al., the homogenate was saponified by KOH hydrolysis, which enormously increased the inhibition of cox-enyzmes [3]. The treatment of the homogenate with proteases and lipase also resulted in a substantial increase in the inhibitory capacity compared to the homogenate; please see Figure 1.

fig 1 new

Figure 1: Overview of processes resulting in P. canaliculus products. The lipid fraction, glycosaminoglycans and whole homogenate require different extraction methods and are promoted by commercial providers for applications like inflammation, arthritis, cartilage malfunctions and osteoarthritis. The extracellular matrix comprises a wide range of glycosaminoglycans and collagens as the main protein content and associated proteins.

These results rule out the role of proteins and complex lipids and favour the involvement of the lipid fraction. Such a lipid fraction from P. canaliculus is also produced as the commercially available extract Lyprinol ®(Pharmalink International Ltd.), which is achieved by extracting the lipid fraction from the homogenate by supercritical CO2. Further Lyprinol free fatty acid fraction tests revealed that purified polyunsaturated fatty acids (PUFA) extracts seem to be competitive substrate inhibitors of prostaglandin synthase [11]. The effects of different types of molecules were summarised in the review of Grienke et al. [1]. Besides the inhibition of prostaglandin synthase, the blocking of histamine by lysolecithin might contribute to the anti-inflammatory effects of extracts from P. canaliculus. Lysolecithin was isolated from a methanol-based extraction from Perna homogenate by liquid-liquid extractions, further silica-based chromatography, and size-exclusion chromatography. The molecular analysis of a single spot from thin-layer chromatography by NMR and mass spectrometry yielded the identification of lysolecithin [4]. Because phosphatidylcholine is relatively small, it is soluble in methanol and assumingly also in CO2, which explains the enrichment by these extraction methods. The third potential anti-inflammatory activity within lipid extracts is omega-3 fatty acids, which have been found to inhibit cox-2 [12]. In the case of osteoarthritis, both the lipid fraction and whole extracts of Perna canaliculus have yielded therapeutic benefits for the included patients [13].

Effects of Glycosaminoglycans

Besides the anti-inflammatory capacity of Perna extracts, there is also experimental evidence for the effects of Perna extracts on cartilage function in the case of osteoarthritis [13,14]. In this disease, inflammation is supposed to be the primary starting point with secondary effects on the cartilage function. Here, the high content of sulphated glycosaminoglycans in Perna canaliculus extracts [15] might play a role since they first replace a disease-induced lack of glycosaminoglycans in affected joints and secondly interact with proteins involved in regulating the inflammatory processes [16]. The main cartilage components are proteoglycans, consisting of a protein core with covalently bound glycosaminoglycans (GAGs). The high content of chondroitin-sulfate (up to 12%) in Perna canaliculus [15] might supply the chondrocytes in the cartilage to synthesise an increased amount of proteoglycans. The increase in proteoglycans in the cartilage might also affect the binding of cytokines that control the inflammation processes and contribute to the healing process.

Application of Whole Homogenates in Animals and Detection of Allergens Therein

Perna canaliculus extracts have been used in studies on animals like dogs with a focus on osteoarthritis [17]. Besides osteoarthritis in dogs, studies about the effects of feline degenerative joint disease and lameness and joint pain in horses have been reviewed earlier [18]. For most of the cases, positive results were found. Still, since the more cost-effective whole homogenates were used for animals, there is less information about the effective molecule class or molecule. Recently, proteins from Perna canaliculus were identified as allergenic in humans [19]. The sole case of an allergic reaction to Perna proteins was a dog owner who fed freeze-dried homogenate to her arthritic dog. The affected person had dermal contact with the powder and assumingly inhaled small amounts. Prick tests confirmed the allergic symptoms, and the allergic proteins were identified by IgE-based western blotting with the patient’s serum. The proteins in the IgE-positive bands were identified by mass-spectrometry as actin, tropomyosin, and paramyosin. All these proteins are highly abundant in all cells across the animal kingdoms. Actin is crucial in forming a part of the cytoskeleton, which is key for forming cells. Tropomyosin and paramoysin form fibres that are crucial for muscle contraction. The biggest part of the mussel is the muscle necessary to move the clamps, which leads to a very high abundance of these two proteins in extracts.Although these are the first allergens to be reported, they are closely related to allergens found in other mussels. For example, actin is a significant allergen in Paphia textile and tropomyosin in Haliotis discus [20-22]. Further evidence stems from the free available software AllCatPro which predicts high potential allergenicity for humans [23-25]. The prediction is primarily based on the degree of homology distance to human proteins because the more significant the difference, the higher the allergenicity prediction. The same principle also applies to the potential allergenic reactions in pet animals like dogs. However, much less is known about allergic reactions in dogs than in humans, which raises concerns about protein-containing Perna canaliculus extracts for treating arthritis in dogs. However, reports also describe a strong antioxidant and ACE inhibitory activity of peptides derived from a proteolytic digest of the mussel proteome [2].

Conclusions

Despite a lack of successful clinical studies on the therapeutic efficiency of Perna canaliculus in humans, there is plenty of experimental evidence for an anti-inflammatory capacity of both the lipid fraction and the glycosaminoglycan fraction. These purified extracts lack the protein content and thus do not suppose a threat of any protein-based allergenicity for humans or pet animals.

References

  1. Miller TE, Ormrod D The anti-inflammatory activity of Perna canaliculus (N.Z. green lipped mussel). N Z Med J [crossref]
  2. Caughey DE, et al. Perna canaliculus in the treatment of rheumatoid arthritis. Eur J Rheumatol Inflamm [crossref]
  3. McPhee S, et al. Anti-cyclooxygenase effects of lipid extracts from the New Zealand green-lipped mussel, Perna canaliculus. Comp Biochem Physiol B Biochem Mol Biol [crossref]
  4. Kosuge T, et al. Isolation of an anti-histaminic substance from green-lipped mussel (Perna canaliculus). Chem Pharm Bull (Tokyo) [crossref]
  5. Mickleborough TD, et al. Marine lipid fraction PCSO-524 (lyprinol/omega XL) of the New Zealand green lipped mussel attenuates hyperpnea-induced bronchoconstriction in asthma. Respir Med [crossref]
  6. Robinson DR, Dayer JM, Krane SM, Prostaglandins and their regulation in rheumatoid inflammation. Ann N Y Acad Sci [crossref]
  7. Crofford LJ, COX-1 and COX-2 tissue expression: implications and predictions. J Rheumatol Suppl [crossref]
  8. Ichikawa A [Molecular biology of prostaglandin E receptors–expression of multi-function by PGE receptor subtypes and isoforms]. Nihon Rinsho [crossref]
  9. Park JY, Pillinger MH, Abramson SB, Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol [crossref]
  10. Ferrer MD, et al. Cyclooxygenase-2 Inhibitors as a Therapeutic Target in Inflammatory Diseases. Curr Med Chem [crossref]
  11. Whitehouse MW, et al. Anti-inflammatory activity of a lipid fraction (lyprinol) from the N.Z. green-lipped mussel. Inflammopharmacology [crossref]
  12. Calder PC, Omega-3 fatty acids and inflammatory processes. Nutrients [crossref]
  13. Abshirini M, et al. Green-lipped (greenshell) mussel (Perna canaliculus) extract supplementation in treatment of osteoarthritis: a systematic review. Inflammopharmacology, [crossref]
  14. Miller TE, et al. Anti-inflammatory activity of glycogen extracted from Perna canaliculus (N.Z. green-lipped mussel). Agents Actions [crossref]
  15. Mubuchi A, et al. Isolation and structural characterization of bioactive glycosaminoglycans from the green-lipped mussel Perna canaliculus. Biochem Biophys Res Commun [crossref]
  16. Crijns HV, Vanheule, and P. Proost, Targeting Chemokine-Glycosaminoglycan Interactions to Inhibit Inflammation Front Immunol [crossref]
  17. Bui LM, Bierer RL Influence of green lipped mussels (Perna canaliculus) in alleviating signs of arthritis in dogs. Vet Ther [crossref]
  18. Eason CT, et al. Greenshell Mussels: A Review of Veterinary Trials and Future Research Directions. Vet Sci [crossref]
  19. Kage, P, et al. Identification of New Potential Allergens from Green-lipped Mussel (Perna Canaliculus). Iran J Allergy Asthma Immunol [crossref]
  20. Mohamad Yadzir ZH, et al. Tropomyosin and Actin Identified as Major Allergens of the Carpet Clam (Paphia textile) and the Effect of Cooking on Their Allergenicity. Biomed Res Int [crossref]
  21. Naz S, et al. Characterization of Sarcoptes scabiei Tropomyosin and Paramyosin: Immunoreactive Allergens in Scabies. Am J Trop Med Hyg [crossref]
  22. Ji NR, et al. Analysis of Immunoreactivity of alpha/alpha(2)-Tropomyosin from Haliotis discus hannai, Based on IgE Epitopes and Structural Characteristics. J Agric Food Chem
  23. Maurer-Stroh S, et al. AllerCatPro-prediction of protein allergenicity potential from the protein sequence. Bioinformatics [crossref]
  24. Grienke UJ. Silke, and D. Tasdemir, Bioactive compounds from marine mussels and their effects on human health. Food Chem [crossref]
  25. Jayaprakash, R. and C.O. Perera, Partial Purification and Characterization of Bioactive Peptides from Cooked New Zealand Green-Lipped Mussel (Perna canaliculus) Protein Hydrolyzates. Foods [crossref]

Hearing from Refugee Adolescent Girls and Their Parents about Sexual Health Programming: Are We Listening?

DOI: 10.31038/AWHC.2023633

 
 

The world is facing a huge voluntary and involuntary migration across continents. In the U.S., more than 6000,00 refugees have been re-settled and more than half of these persons are children, adolescents, and emerging adults (US Dept of State, 2020) [1]. Developmentally, teens and young adults are at a stage where they are developing life skills, establishing social and romantic partnerships, and often experience testing of boundaries and exposure to risk-taking behaviors. Experimentation in the “s” aspects of life – social, sexual, substances, and safety – pose challenges to the health and well-being of both the adolescent and emerging adult as well as their parents and other connected adults.

Females in these age groups, in particular, face threats to their well-being and futures as they are disproportionately impacted by unplanned pregnancies, Sexually-Transmitted Infections (STIs), and HIV. Compounding these issues, diasporic populations – persons who migrated, moved, or been resettled suddenly or involuntarily – can enter a new country and face overwhelming obstacles to the transition. Successful and safe transition for young females includes preventing exposure to, or intervening early, in potential sexual risk situations to avoid pregnancy, STIs or HIV. Often concerning, is their lack of related experiences and exposures needed to build sexual risk prevention knowledge, attitudes, and skills including communication and negotiation competence [2,3] and being able to navigate potential risk situations and identifying triggers to unsafe decision-making (e.g., substance use, depression and anxiety).

We conducted studies with both resettled refugee adolescent girls (ages 15-17) and their parents to learn from them why they (or their daughters) were interested in participating in an evidence-based sexual health promotion program, The Health Improvement Project for Teens (HIP Teens). We also assessed outcomes based on qualitative thematic data analysis from separate interviews to more clearly understand the utility and acceptability of the program. Overall, study participants represented ten different countries providing a broad swath of impressions and feedback.

Recruited from an internationally-recognized refugee resettlement service in the U.S.F that offered this CDC- and DHHS-recognized evidence-based sexual health intervention, interviewers sought to gain an understanding of how the program was received and applied by the participants. Originally developed through extensive formative qualitative and quantitative studies and randomized controlled trial [4], this manualized intervention is theoretically-driven, using trauma-informed care approaches and uses interactive activities, games, and role plays to provide medically-accurate sexual risk reduction information. It enables participants to expand a personal “menu” of healthy behavior choices and reduce risk, while providing skills training in negotiation, assertive communication, risk appraisal, safer behaviors, and goal setting. Following individual interviews with the girls accompanied by interpreters, our qualitative content analysis identified three themes: (1) My cultural norm is not to ask; (2) Groups were a safe way for me to learn and share; and (3) I learned to use my voice [5].

Interviews, again accompanied by interpreters, with mothers (N=8) and fathers (N=5) provided insight into motivations and concerns driving their decision to consent for their daughter’s participation as well as discussions with their daughter during the program and after completion that they may have had that would provide insight on impact . We identified five predominant themes using in-depth qualitative thematic analysis including: (1) Protecting our daughters with knowledge; (2) A different country, a different approach to protection; (3) Consent and understanding can be different; (4) Parents cannot do it all; and (5) My daughter gained a voice [6].

Through the voices of both the girls who participated in the program and the parents who consented for their participation, we heard very clearly about the need for, and desire to learn from, a program tailored for the needs of refugee teens to improve sexual health outcomes. By providing information, increasing motivation, and, most importantly, developing risk-prevention and healthy choices behavioral skills, we addressed their deficits in this area while building on the strengths they brought to the program. Both parents and girls recognized the challenges they might face in a different country with a vast array of potential risk exposures. They were committed to preparing themselves as best they could and this intervention offered a targeted approach conducted within a trusted setting and with facilitators that they had already built relationships.

While refugee populations may enter into a new culture and country with hopes of both acclimating to their new residence while, importantly, maintaining their own mores, traditions, and customs, we still need to work hand-in-hand with them about the many challenges they often face in this transition. Parents may not be ready to address all these challenges solely within their home setting or communities and it was evident in our work that they wanted a guiding partnership with agencies that acknowledged and included them in approaches to meeting the needs of their families. Building upon the strengths that these communities bring to the partnership and integrating members into the organization’s team for programming and services is key to successful results. Identifying multiple approaches to providing opportunities for their voices to not only be heard, but listened to, can help create and grow approaches that are feasible, acceptable, and embraced by these vulnerable communities. Never is this more important than when addressing sexual health programming for girls and young women who continue to bear a disproportionate negative burden for health, education, employment, and social consequences as a result of pregnancy, STIs and HIV around the world.

References

  1. S. Department of State. Refugee admissions report. Refugee Processing Center. 2020.
  2. Kaczkowski W, Swartout KM (2020) Exploring gender differences in sexual and reproductive health literacy among young people from refugee backgrounds. Culture Health & Sexuality 22: 369-384. [crossref]
  3. Tirado V, Chu J, Hanson C, Ekström AM, Kågesten A (2020) Barriers and facilitators for the sexual and reproductive health and rights of young people in refugee contexts globally: A scoping review. PloS one 15: e0236316. [crossref]
  4. Morrison-Beedy D, Jones S, Xia Y, Tu X, Crean H, et al. (2012) Reducing Sexual Risk Behavior in Adolescent Girls: Results from a Randomized Controlled Trial. Journal of Adolescent Health 52: 314-321.
  5. Morrison-Beedy D, Wegener R, Ewart A, Ross S, Spitz A (2023) Reflections from refugee adolescent girls on participation in a US-based sexual health promotion project. Journal of Immigrant and Minority Health 25: 680-684. [crossref]
  6. Morrison-Beedy D, Ewart A, Ross S, Wegener R, Spitz A (2022) Protecting their daughters with knowledge: Understanding refugee parental consent for a US-based teen sexual health program. American Journal of Sexuality Education 17: 474-489.

RGCC Promotes Adipocyte Thermogenesis by Modulating Pgc1α Expression

DOI: 10.31038/CST.2023832

Abstract

Brown and beige adipocytes dissipate energy in a non-shivering thermogenesis manner, exerting beneficial impact on metabolic homeostasis. RGCC (protein regulator of cell cycle) is BAT-enriched protein, while its role in thermogenic adipocytes remains unknown. RGCC is upregulated by acute cold challenge or β3 agonist in BAT and iWAT. Lack of RGCC constrains expression of a set of thermogenic genes in brown and beige adipocytes. Conversely, ectopic expression of RGCC drives a full of program of thermogenesis and promotes browning. Pgc1α knockdown obviously prevents expression of RGCC-elicited thermogenic genes. Together, these findings uncover that physiological role for RGCC-mediated activation of the thermogenic program in adipocytes.

Keywords

RGCC, Pgc1α, Brown adipocytes, Beige adipocytes, Thermogenesis

Introduction

Brown and beige adipocytes have long been well recognized as an organ specialized for energy expenditure by dissipating energy as heat in a process called non-shivering thermogenesis [1]. Beige adipocytes, resided in white adipose tissue (WAT), are induced by chronic cold exposure, exercise, and treatment with other external cues [2]. These adipocytes have a multilocular lipid droplet morphology, specifically expressing a group of thermogenic genes, involving in uncoupling protein 1(Ucp1)-dependent or Ucp1-independent pathway, which contributes to generate heat [3]. Both brown adipose tissue (BAT) and beige adipocytes are found in rodents and humans [4-6]. Recent studies further demonstrate that the BAT-positive group were younger and showed lower metabolism-related parameters such as the body mass index (BMI), body fat mass, glycated hemoglobin (HbA1c), glucose, total cholesterol and the LDL-cholesterol [4,7]. These findings lead to the proposal that increasing BAT mass/ activity or beige adipocytes transformation might be a promising therapeutic strategy for metabolic disease. RGCC (protein regulator of cell cycle), also known as RGC-32 (response gene to complement 32 protein), is an ancient and conserved intracellular proteins existed in all eukaryotes. It was found to function as a role in the cell cycle, cell differentiation, fibrosis and cell metabolism in various physiological and pathological states [8-16]. The previous data revealed that RGCC is a unique protein expressed in brown adipocytes, and regulates adipogenesis in the Pdgrfa +/ Thy1 (LP) cells sorted from E14.5 embryos to determine adipocyte fate. Adipocytes, derived from multipotent mesenchymal stem cells, goes through two phases of adipogenesis. The first phase, known as determination, converts the pluripotent stem cell into the adipocyte lineage which lost the potential to differentiate into other cell type. In the second phase, the preadipocytes give rise to mature adipocytes, which is called terminal differentiation [17]. However, the role of RGCC in the terminal differentiation stage of brown adipocytes, especially in the regulation of thermogenesis, had not yet been studied.

In this study, we found that RGCC expression in BAT and iWAT was strongly induced by β3-adrenergic signaling. Depletion of RGCC in brown and beige adipocytes led to defect in maintain of thermogenesis. Consistently, RGCC overexpression strongly promotes expression of BAT-selective gene. Mechanistically, RGCC drives a full program of thermogenesis in part through Pgc1α. Our studies identified RGCC as a major regulator for thermogenesis of brown and beige adipocytes, and may provide a potential therapeutic target for obesity and metabolic diseases.

Results

RGCC is BAT-enriched Protein and Triggered by Cold Exposure

BAT-enriched regulators have the potential function in adaptive thermogenesis. To identify the presumed activators, we analyzed a previously published RNA-Seq datasets of mouse tissues, and found that the RGCC gene was highly expressed in adipose tissues [18]. Similarly, real time-quantitative PCR (RT-PCR) analysis confirmed that RGCC was mostly expressed in the brown fat and white fat of adult mice (Figure 1A). While the protein levels of RGCC were strikingly higher in BAT, and were extremely lower in iWAT and eWAT compared to BAT (Figure 1A). Cold exposure or noradrenergic cascade activate thermogenesis in BAT and recruit beige adipocytes in WAT. RGCC mRNA level and protein level in BAT were evidently provoked upon mice were subjected to acute cold exposure (Figure 1B). Chronic activation of β3-signaling by Cl316,243 agonist certainly induced RGCC expression in BAT and iWAT (Figure 1C and 1D). Moreover, the RGCC messenger levels were progressively inducted during adipocyte differentiation and peaked at late stage in immortalized brown adipocytes and C3H10T1/2 cells (a beige-like adipocyte model) (Figure 1E and 1F). These data suggested RGCC may be participated in maintaining thermogenesis of brown adipocytes and browning process of white adipocytes.

fig 1

Figure 1: RGCC is a BAT-enriched protein and induced by cold challenge.
(A) RGCC mRNA levels in several tissues (top) (n=5 each group) and RGCC protein levels in adipose tissues of 8-week-old C57BL/6J mice (bottom).
(B) RGCC mRNA level (top) and protein expression (bottom) in BAT after cold challenge for 6 h (n=4 each group).
(C-D) RGCC mRNA levels (C) and protein levels (D) in adiposes of mice. C57BL/6J mice were intraperitoneally (i.p.) injected Cl316,243 or phosphate-buffered saline at a dose 0.5 ug /g body weight for 1, 2, or 3 days.
(E-F) qPCR analysis of RGCC mRNA expression in differentiating immortalized brown adipocytes (E) and C3H10T1/2 cells (F) (n=3 independent cultures).
Data are expressed as mean ± SEM of biological independent samples. Two-tailed unpaired Student’s t-test was performed. *P<0.05.

RGCC Perturbation in Brown Adipocytes Impairs Thermogenesis

To investigate whether RGCC is responsible for function of brown adipocytes, we knocked down RGCC with lentiviral short hairpin RNAs (shRNAs) in immortalized brown preadipocytes, which then were induced to differentiation. The previous study indicated that RGCC depletion by 80% in the Pdgrfa +/ Thy1 cells isolated from E14.5 embryos obviously hinders adipogenesis [19]. While we knocked down RGCC by 50-60% from preadipocytes which would not affect adipocyte differentiation as indicated by picture during differentiation course and similar expression levels of common fat marker genes ap2 and Pparγ (Figure 2A, 2B, 2D and 2E). RGCC-knockdown adipocytes were accumulated more enlarged lipid droplets and triglyceride (TG) content (Figure 2B and 2C), indicating weaker energy metabolism. Knockdown of Rgcc reduced a broad of BAT-selective gene expression, including Ucp1, Cox7a1, Cpt1b, which was further confirmed by western blot analysis (Figure 2D and 2E). Importantly, the effect of Rgcc knockdown is functionally relevant, as basal and uncoupled oxygen consumption rate was greatly reduced (Figure 2F). FCCP-induced maximal respiration was also lower than controls (Figure 2F). Collectively, these data demonstrates that RGCC is required for thermogenesis in brown adipocytes.

fig 2

Figure 2: RGCC modulates the thermogenesis gene program in brown adipocytes.
(A) Representative images of brown adipocytes during differentiation. The immortalized brown preadipocytes were infected with shRGCC or scramble knockdown lentiviruses and differentiated. Scale bar is 200 μm.
(B) Representative Oil-red staining of mature adipocyte generated as in (A). Scale bar is 200 μm.
(C) TG contents in RGCC knockdown cells generated as in (A) (n=3 each group).
(D-E) Gene mRNA levels (D) and protein levels (E) in RGCC knockdown cells from (A) (n=3 each group).
(F) Oxygen consumption rate (OCR) in brown adipocytes generated as in (A) by Oroboros O2K. Oligomycin (Oligo), FCCP and Rotenone (Rot) were added at the time points indicated by the arrows (n=3 independent cultures). Basal respiration, uncoupled respiration, and maximal respiration were showed in the right panel.
Data are expressed as mean ± SEM of biological independent samples. Two-tailed unpaired Student’s t-test was performed. *P<0.05, **P<0.01, ***P<0.001.

RGCC Depletion Restrains Browning of White Adipocytes

We observed that the RGCC protein is triggered in iWAT when subjected to activation of chronic β3-adregenic signaling, denoting it may be involved in white fat browning (Figure 1C and 1D). C3H10T1/2 derived from mesenchymal stem cells were utilized to induce beige adipocytes. Similar to what is observed in brown adipocytes, RGCC knockdown (nearly 50-60%) had no effect on adipogenesis, but clearly increased larger lipid droplets and more intracellular triglyceride TG content (Figure 3A and 3C). At a molecular level, diminishing RGCC expression in beige adipocytes led to systematic decreased expression of adipocyte genes including Ucp1, Cox7a1 and Cpt1b, which basically phenocopied the knockdown brown adipocytes (Figure 3C and 3D). Moreover, Rgcc disruption constrained the basal and FCCP-stimulated OCR of adipocytes (Figure 3E). Together, RGCC deficiency in beige adipocytes inhibits the expression of BAT-specific genes and β-oxidation genes, hinders the function of beige adipocytes.

fig 3

Figure 3: RGCC depletion constrains BAT-selective gene expression in beige cells.
(A) C3H10T1/2 preadipocytes were infected with RGCC knockdown lentiviruses and then subjected to the adipogenic differentiation process. Oil-red staining was performed on day 8.
(B) TG contents were performed in C3H10T1/2 adipocytes generated as in (A) (n=3 each group).
(C-D) mRNA levels (C) and protein levels (D) were analyzed in C3H10T1/2 adipocytes generated as in (A) (n=3 each group).
(E) OCR analysis in C3H10T1/2 adipocytes generated as in (A). Diagram of basal respiration, uncoupled respiration and maximal respiration were showed in the right panel (n=3 each group).
Data are expressed as mean ± SEM of biological independent samples. Two-tailed unpaired Student’s t-test was performed. *P<0.05, **P<0.01, ***P<0.001.

Pgc1α Mediated RGCC-dependent Thermogenesis

To study the gain-of-function of RGCC in adipocytes, we used lentiviruses to stably overexpress RGCC during differentiation of adipocytes. Ectopic expression of RGCC did not affect common fat maker gene Pparγ and Fabp4 expression, while increased Ucp1, Cox7a1 and Cpt1b expression whether in brown adipocytes or in beige adipocytes, indicating that RGCC promotes thermogenesis of adipocytes in cell-autonomous way (Figure 4A-4D). In order to identify the driver for RGCC-mediated thermogenesis, we screened a list of known positive regulators of thermogenesis in RGCC-knockdown brown and beige cells. Figure 4E-4F implied that peroxisome proliferator-activated receptor γ coactivator 1α (Pgc1α) was the only candidate whose expression level fully responses to RGCC changes. Its protein levels were further confirmed in Rgcc-knockdown adipocytes (Figure 4E-4F). Knockdown of Pgc1α did abolish RGCC-elicited strong effect on Ucp1, Cox7a1 and Cpt1b expression, in both brown adipocytes and C3H10T1/2 adipocytes (Figure 4G-4H). Taken together, we conclude that the Pgc1α is responsible for RGCC-mediated thermogenesis.

fig 4

Figure 4: Pgc1α mediates RGCC-dependent thermogenesis.
(A-B) protein levels (A) and mRNA levels (B) expression in mature brown adipocytes. Preadipocytes were infected with RGCC overexpression lentiviruses on day 2 and harvested on day6 (n=3 each group).
(C-D) Protein levels (C) and mRNA levels (D) levels analysis in C3H10T1/2 adipocytes. C3H10T1/2 preadipocytes were infected with lentiviruses expressing RGCC on day 4 and harvested on day 8 (n=3 each group).
(E-F) RT-PCR analysis in mature brown adipocytes (E) and C3H10T1/2 adipocytes (F). Immortalized brown preadipocyte or C3H10T1/2 preadipocytes were infected with shRGCC lentiviruses, differentiated, and harvested for analysis (n=3 each group). Pgc1α protein levels were separately showed in the bottom panel.
(G) Relative mRNA levels in brown adipocytes. lentiviral Pgc1α shRNA was infected with Rgcc-overexpressed cells on differentiation day 4 (n=3 each group).
(H) Relative mRNA levels in C3H10T1/2 adipocytes. Lentiviral Pgc1α shRNA was infected with Rgcc-overexpressed cells on differentiation day 5 (n=3 each group).
Data are expressed as mean ± SEM of biological independent samples. Two-tailed unpaired Student’s t-test was performed. *P<0.05, **P<0.01, ***P<0.001.

Discussion

Here, we found RGCC is induced upon β3-adregenic signaling and modulates the adaptive thermogenesis gene expression. Knockdown of RGCC in cultured brown and beige adipocytes evidently weaken the expression of a broad panel of thermogenic and fatty acid oxidation genes in cell-autonomous way. Consistently, RGCC overexpression strengthens expression of thermogenic marker genes and β-oxidation-related genes. Pgc1α expression is a potential key mechanism for RGCC-mediated thermogenesis. Our results demonstrate that RGCC is crucial for maintaining thermogenesis in brown and beige adipocytes. Previous studies reported that RGCC deficiency had no effect on 3T3-L1 differentiation, but modestly boosted Lipe and Pgc1α expression, which is contrary to our results. It may be because brown, beige and white adipocytes originate from different adipocyte lineage, involving divergent regulation mechanisms. Several regulators have been revealed the inconsistent regulation function in different adipocytes. In 3T3-L1 adipocytes, nutlin-3a-mediated activation of p53 or p53 overexpression suppresses adipogenesis [20]. In C3H10T1/2 cells and human adipose-derived stem cells, p53 knockdown enhances differentiation [21]. While in the skeletal muscle myogenic cell line-C2, as the brown preadipocyte, p53 abrogation substantially impaired differentiation [21]. RGCC-/- mice exhibited a lean phenotype and improved systemic inflammation, further alleviative dyslipidemia and insulin resistance upon HFD. It should not exclude the contribution of RGCC expressed in nonadipose cells on metabolism using while-body Rgcc KO mice. RGCC-mediated thermogenesis and energy homeostasis in vivo, especially in BAT and iWAT, need to be investigated in next study.Pgc1α is induced early in brown fat differentiation and is preferentially expressed in mature brown adipocytes compared to white adipocytes. Moreover, Pgc1α is highly induced by cold exposure and involved in the adaptive thermogenic program in BAT, including fatty-acid oxidation, mitochondrial biogenesis to increase thermogenic genes and promotes browning [22,23]. Obviously, Pgc1α is not a direct target of RGCC. How RGCC regulates Pgc1α mRNA level needs to be studied in future. In conclusion, our results have revealed that RGCC play a fundamental role in regulating thermogenic gene expression in brown adipocytes and beige adipocytes, which makes RGCC a potential drug target in the therapeutics of obesity.

Experimental Procedures

Animals and Treatment

All mice were housed at room temperature with a 12 h light/ dark cycle and ad libitum access to food and water. All studies involving animal experimentation were approved by the University Committee on Use and Care of Animals at the Zhejiang University. For cold experiment, 8-week-old Male C57BL6/J mice were housed at 4℃ for 6h.

Cell Culture

The immortalized brown preadipocytes are cultured and differentiated to brown adipocytes as previously described [24]. Briefly, upon reaching 70% confluence, brown preadipocytes were maintained in the induction medium (DMEM containing 10% FBS, 20 nM insulin, 1 nM T3) for 2 days. Then the differentiation medium containing 10% FBS, 20 nM insulin, 1 nM T3, 0.5 mM dexamethasone, 0.5 mM isobutylmethylxanthine, 0.125 mM indomethacin were changed for another 2 days. Next cells were cultured into induction medium and changed every other day until day 6 waiting for experiments.

The mesenchymal stem cell derived C3H10T1/2 were maintained in DMEM containing 10% CS (designed day-2) for 2 days and induced to differentiate into beige adipocytes with differentiation medium (DMEM containing 10% FBS, 1 μg/ml insulin, 1 mM dexamethasone, 0.5 mM isobutylmethylxanthine, 1 μm rosiglitazone). Two days after induction, cells were switched to maintenance medium containing 10% FBS, 1 μg/ml insulin and 1μm rosiglitazone for another 2 days. Then cells were cultured in DMEM containing 10% FBS every other day until day 8.

Plasmids and Viruses

The sequences of short hairpin RNA (shRNA) were as follows: shRGCC-1: 5’-CTCGAAGACTTCATTGCCGAT-3’; shRGCC-2: 5’-GCAGCATATT

CAACAGAGAAT-3’; shPgc1α-1: 5’-GGTGGATTGAAGTGGTG-TAGC-3’; shPgc1α-2: 5’-CCTCCTCATAAAGCCAACCAA-3’. All above of shRNA oligos were respectively subcloned into lentivirus vector Psp108 (addgene). The vectors were transfected into HEK 293T cells along with packaging plasmids (Pmd2.G, psPAX2 from addgene). Full-length Rgcc cDNAs was amplified by reverse transcription and constructed into lentiviral pENTR1A (addgene) system.

Lentivirus Infection

Overexpression plasmid and packaging plasmid (pLP1, pLP2, pVSVG) were together transfected in HEK 293T cells. The viral supernatant was harvested after 48 h post-transfection. The brown and C3H10T1/2 preadipocytes were infected with lentiviruses using polybrene of 5 μg/ ml, were selected with puromycin (3 μg/ ml) and were differentiated to mature adipocytes following the standard induction protocol. Lentiviruses bearing shPgc1α infected overexpressed-RGCC adipocytes on differentiation day 2 in brown adipocytes and day 4 in C4H10T1/2 adipocytes. The mature brown adipocytes were harvested for gene and protein analysis on day 6, and mature C3H10T1/2 were harvested on day 8.

Oil-red O staining

Differentiated cells were washed with PBS twice, fixed with 4% paraformaldehyde for 10 min at room temperature, and stained with oil-red O working solution (byotime C0158M) for 30 min. Then cells were washed with PBS for several times and waited for scan using a microscope.

Oxygen Consumption Measurement

Real-time measurements of oxygen consumption rates (OCR) were performed using a O2K (Oroboros). The mature brown and C3H10T1/2 adipocytes were washed twice by PBS, trypsinized and suspended in DMEM. The OCR were measured under basal conditions and after addition of oligomycin (2.5 μM), FCCP (1 μM), and rotenone (1 μM).

Antibodies

The following primary antibodies were used: anti-Ucp1 (Ucp11-A) from alpha diagnostic; anti-Pgc1α (66369-1-Ig), anti-Fabp4 (12802-1-AP) from Proteintech; anti-Pparγ1/2 (2443S) from Cell Signaling Technology; anti-Rgcc (A17689), anti-β-actin (AC026), anti-Cox7a1 (A21240), anti-Cpt1b (A6796), anti-β-Tubulin (AC008) from Abclonal.

Real-time qPCR

Total RNA from tissues were extracted using TRIzol (Vazyme R701) and an equal amount of RNA was reverse transcribed by HiSciptÒ QRT SuperMix with gDNA wiper (Vazyme R222). Quantitative real-time PCR was performed following the protocols of chamQ qPCR Master Mix (Vazyme Q711) with ViiA 7 Real-Time PCR system (Applied biosystems).

Western Blot

Mature adipocytes were harvested with cell lysis buffer (100 mM NaCl, 0.5% Triton-X-100, 5% glycerol, 50 mM Tris-HCl (pH 7.5), 1 mM PMSF and protease inhibitor mixture cocktail). Cell supernatants were collected by centrifugation at 16,000 g for 10 minutes at 4 ℃ and quantified for protein content using BCA kit (YEASEN, 20201ES86). The equal protein content of cells lysates was separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and revealed with chemiluminescence (ECL) system.

Statistical Analysis

Data are presented as mean ± standard error of the means. Differences between two groups were estimated using the unpaired two-tailed Student’s t-test. Statistical significance was showed as *P<0.05, **P<0.01, ***P<0.001.

Acknowledgements

This research was supported by Zhejiang Provincial Natural Science Foundation of China (LQ23C070004 to Q.Z., LQ21C110001 to S.H.), China Postdoctoral Science Foundation (2020M680053 to Q.Z), the Construction Fund of Key Medical Disciplines of Hangzhou (OO20200055 to Y.G.), and the National Natural Science Foundation of China (82100904 to S.H.).

Conflict of Interest

The authors declare that they have no conflict of interest.

Author Contributions

Q.Z. designed the project, performed most experiments, analyzed data and wrote the manuscript. Q.W., B.L., S.H., X.W., Y.Z., Y.Y., and Z.L. aided in some experiments. Y.G. supervised the study.

Data Availability

All study data, method, and results of statistical analyses are reported in this paper. We welcome any specific inquiries.

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