Immunopathogenesis of multiple sclerosis: molecular and cellular mechanisms and new immunotherapeutic approaches.

Background: Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating autoimmune disease with increasing global prevalence. It predominantly affects females, especially those of European descent. The interplay between environmental factors and genetic predisposition plays a crucial role in MS etiopathogenesis.Methods: We searched recent relevant literature on reputable databases, which include, PubMed, Embase, Web of Science, Scopus, and ScienceDirect using the following keywords: multiple sclerosis, pathogenesis, autoimmunity, demyelination, therapy, and immunotherapy.Results: Various animal models have been employed to investigate the MS etiopathogenesis and therapeutics. Autoreactive T cells within the CNS recruit myeloid cells through chemokine expression, leading to the secretion of inflammatory cytokines driving the MS pathogenesis, resulting in demyelination, gliosis, and axonal loss. Key players include T cell lymphocytes (CD4+ and CD8+), B cells, and neutrophils. Signaling dysregulation in inflammatory pathways and the immunogenetic basis of MS are essential considerations for any successful therapy to MS. Data indicates that B cells and neutrophils also have significant roles in MS, despite the common belief that T cells are essential. High neutrophil-to-lymphocyte ratios correlate with MS severity, indicating their contribution to disease progression. Dysregulated signaling pathways further exacerbate MS progression.Conclusion: MS remains incurable, but disease-modifying therapies, monoclonal antibodies, and immunomodulatory drugs offer hope for patients. Research on the immunogenetics and immunoregulatory functions of gut microbiota is continuing to provide light on possible treatment avenues. Understanding the complex interplay between genetic predisposition, environmental factors, and immune dysregulation is critical for developing effective treatments for MS.

Pneumococcal vaccination and primary care presentations for acute respiratory tract infection and antibiotic prescribing in older adults.

BACKGROUND: While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care. METHODS: Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures. RESULTS: A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]). CONCLUSION: PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.

Uptake of pneumococcal vaccines in older Australian adults before and after universal public funding of PCV13.

BACKGROUND: In 2020 Australia changed the funded universal older adult pneumococcal vaccination program from use of the 23-valent pneumococcal polysaccharide vaccine (PPV23) at age 65 to the 13-valent pneumococcal conjugate vaccine (PCV13) at age 70 years. We investigated uptake of both PCV13 and PPV23 in older adults before and after the program change. METHODS: We analysed a national dataset of records of patients attending general practices (GPs). We included regular attendees aged 65 or above in 2020. Cumulative uptake of PCV13 and monthly uptake of PPV23 was compared for the two periods before (January 2019 to June 2020) and after (July 2020 to May 2021) the program change on 1 July 2020, by age groups and presence of comorbid conditions. RESULTS: Our study included data from 192,508 patients (mean age in 2020: 75.1 years, 54.2 % female, 46.1 % with at least one comorbidity). Before July 2020, for all adults regardless of underlying comorbidities, the cumulative uptake of PCV13 was < 1 % but by May 2021, eleven months after the program changes, cumulative uptake of PCV13 had increased among those aged 70-79 years (without comorbidity: 16.3 %; with comorbidity: 21.1 %) and 80 + years (without comorbidity: 13.5 %; with comorbidity: 17.7 %), but not among those aged 65-69 years (without comorbidity: 1.3 %; with comorbidity: 3 %). Monthly uptake of PPV23 dropped following the program change across all age groups. CONCLUSIONS: Changes in uptake of PCV13 and PPV23 among those aged 70 + years were consistent with program changes. However, PCV13 uptake was still substantially lower in individuals aged 65-69 years overall and in those with comorbidities.

Associations of Parents-Adolescent Relationship with Adolescent Sexual Risk Behaviors: A Global Analysis Based on 156,649 School-Going Adolescents from 50 Countries.

Our study, examining the Global School-Based Student Health Survey data from 50 countries across four WHO regions, found boys have higher sexual exposure (33.5 vs 17.7%) and risk behaviors - early sexual initiation (55.0 vs. 40.1%), multiple partners (45.2 vs. 26.2%), and condom nonuse (29.2 vs. 26.8%) - than girls. We found that adolescents with parents who understood their problems, monitored academic and leisure-time activities, and respected privacy were less likely to be engaged in sexual activities and risk behaviors. This study highlights the importance of parental involvement and advocates for gender-specific, family-focused interventions to mitigate adolescent sexual risks.

Role of women empowerment on mental health problems and care-seeking behavior among married women in Nepal: secondary analysis of nationally representative data.

PURPOSE: This study investigates the associations between women empowerment and the prevalence of mental health symptoms and care-seeking behavior among ever-married Nepalese women aged 15-49 years. METHODS: We utilized 2022 Nepal Demographic and Health Survey data to measure women empowerment, employing the Survey-Based Women's Empowerment (SWPER) index. The index focuses on the domains of social independence, decision-making, and attitudes towards violence. Symptoms of anxiety and depression were measured using the Generalized Anxiety Disorder-7 scale (GAD-7) and the Patient Health Questionnaire (PHQ-9), respectively. Multiple logistic regression was performed to estimate adjusted odds ratio (aOR) for associations of women empowerment domains and mental health problems and care-seeking behavior. RESULTS: Among 5556 women, the prevalence of symptoms of anxiety and depression was 23.1% and 6.1%, respectively. Among those with any symptoms of anxiety or depression, 18.3% sought care. Compared to women with low level of empowerment in the "social independence" domain, those with high level of empowerment were less likely to suffer from symptoms of anxiety (aOR = 0.68; 95%CI, 0.57-0.82) and depression (aOR = 0.69; 95%CI, 0.50-0.94). However, high empowerment in "decision-making" domain was associated with higher likelihood of anxiety (aOR = 1.67; 95%CI, 1.33-2.10) and depression (aOR = 1.80; 95%CI, 1.26-2.58). There was evidence of positive association between high empowerment in "decision-making" and care-seeking (aOR = 1.28; 95%CI, 0.96-1.71). CONCLUSIONS: This study underscores important roles of women empowerment on mental health symptoms and care-seeking behavior, suggesting the need to integrate empowerment initiatives into strategies to promote mental health among women in Nepal and similar low- and middle-income settings.

The burden of psychological distress and unhealthy dietary behaviours among 222,401 school-going adolescents from 61 countries.

We aimed to calculate the sex-specific prevalence of psychological distress and unhealthy eating habits among adolescents across countries and regions, and to explore their potential associations. We used data from the Global School-Based Health Survey (GSHS) for 61 countries. Psychological distress was defined based on the existence of ≥ 2 factors from the following: loneliness, anxiety, suicide ideation, suicide planning, and suicide attempt. Four unhealthy dietary behaviours were examined: inadequate fruit intake, inadequate vegetable intake, daily consumption of soft drinks, and weekly fast-food consumption. We used random-effects meta-analysis to estimate the overall and regional pooled prevalence. Mixed-effect multilevel logistic regressions were used to estimate adjusted odds ratios (aORs) of unhealthy dietary behaviours in relation to psychological distress. Among 222,401 school-going adolescents (53.3% girls), the prevalence of psychological distress was 17.9%, with girls reporting higher than boys (20.8% vs. 14.9%). Adolescents in the African region reported the highest prevalence (22.5%), while those in the South-East Asia region reported the lowest (11.3%). The prevalence of inadequate fruit intake, inadequate vegetable intake, daily soft drink consumption, and weekly fast-food consumption was 37.0%, 28.5%, 50.0%, and 57.4% respectively. Psychological distress was associated with inadequate fruit intake (pooled aOR = 1.19, 95% CI 1.17-1.23), inadequate vegetable intake (pooled OR = 1.19, 1.16-1.22), daily consumption of soft drinks (pooled aOR = 1.14, 1.12-1.17), and weekly consumption of fast food (pooled aOR = 1.12, 1.09-1.15). Our findings indicate a substantial variance in the burden of psychological distress and unhealthy dietary behaviours across different regions. Adolescents experiencing psychological distress were more likely to have unhealthy dietary habits.

Exploring the barriers to the antiretroviral therapy adherence among people living with HIV in Bangladesh: A qualitative approach.

INTRODUCTION: Since the evolution of highly active antiretroviral therapy (ART), a near-perfect ART adherence level (>95%) is needed to control viral suppression. Non-adherence to treatment may lead to acquired immunodeficiency syndrome (AIDS) and drug resistance. Though the Bangladesh government provides free treatment and counselling services to people living with human immunodeficiency virus (PLHIV), only 22% of the identified PLHIV continue treatment. Therefore, this study aims to explore the barriers that obstruct the Bangladeshi PLHIV to ensure ART adherence. METHODS: We conducted a qualitative study in Dhaka, Bangladesh, and recruited the sensitive study population following non-probability, mainly purposive sampling from a community-based registered organization for PLHIV. We conducted the in-depth interview using a semi-structured guideline with 15 consented respondents. We transcribed the audio-recorded interviews in the local language (Bangla) and then translated those into English for data analysis. During the data extraction process, the lead and corresponding authors independently extracted raw data to generate different themes and sub-themes and invited other authors to contribute when they could not solve any discrepancies. RESULTS: The study identified three significant categories of barriers at the individual, community, and institutional levels that negatively interfered with ART adherence. The most dominant barriers were discrimination and rejection related to stigma, as almost all participants mentioned these barriers. Stigmatizing attitudes and the discriminatory act of the community people and healthcare providers critically affected their treatment adherence. Other leading barriers were improper inventory management of ART-related medicines and CD4 tests and lack of proper counselling. In addition, we found that a positive approach toward life and family support motivated some respondents to overcome the barriers. CONCLUSIONS: We recommended strengthening Bangladesh's HIV/AIDS prevention, treatment, and management program with a special focus on the improvement of the supply chain of ART-related medicines and CD4 tests and ensuring proper counselling. In addition, we recommended strengthening the behaviour change communication and IEC activities at a large scale to destigmatize health facilities and community levels.

Psychological distress and unhealthy dietary behaviours among adolescents aged 12-15 years in nine South-East Asian countries: a secondary analysis of the Global School-Based Health Survey data.

It is unclear whether there is any association between psychological distress and unhealthy dietary habits among adolescents in low- and middle-income countries. We aimed to estimate the prevalence of these factors in South-East Asia region and investigate their associations. We used data from the Global School-based Health Survey for nine South-East Asian countries. Psychological distress was defined by presence of ≥ 2 factors from loneliness, anxiety, suicide ideation, suicide planning and suicide attempt. We assessed inadequate fruit intake, inadequate vegetable intake, daily soft drink and weekly fast-food consumption. We used random-effects meta-analysis to estimate pooled prevalence. Logistic regressions were used to estimate OR of unhealthy dietary behaviours for psychological distress. Among 30 013 adolescents (56 % girls) aged 12-15 years, the prevalence of psychological distress was 11·0 %, with girls reporting slightly higher than boys (11·8 % v. 10·1 %). The prevalence of inadequate fruit intake, inadequate vegetable intake, daily soft drink consumption and weekly fast-food consumption was 42 %, 26 %, 40 % and 57 %, respectively. Psychological distress was associated with inadequate fruit intake (pooled OR = 1·20, 95 % CI 1·03, 1·40), inadequate vegetable intake (pooled OR = 1·17, 1·05, 1·31) and daily soft drink consumption (pooled OR = 1·14, 1·03, 1·26); but not with weekly fast-food consumption (pooled OR = 1·13, 0·96, 1·31). We observed substantial cross-country variations in prevalence and OR estimates. In conclusion, South-East Asian adolescents have significant burden of psychological distress and unhealthy dietary behaviours, with those having psychological distress are more likely to have unhealthy dietary behaviours. Our findings will guide preventative interventions and inform relevant policies around adolescent nutrition in the region.

Regional and Sex Differences in the Prevalence and Correlates of Early Sexual Initiation Among Adolescents Aged 12-15 Years in 50 Countries.

PURPOSE: This study aimed to investigate the regional and sex differences in the prevalence of early sexual initiation and its correlates among school-going adolescents in 50 countries. METHODS: We used data from the Global School-based Health Survey from 50 countries in 2009-2015 for 124,091 adolescents (53.5% girls) aged 12-15 years. Using meta-analysis with random effects, we estimated the prevalence of early sexual initiation (i.e., having first sexual intercourse at ≤14 years) by sex, region, and country income classification. Multilevel mixed-effect logistic regressions including a random intercept for countries were used to investigate the correlates of early sexual initiation. RESULTS: Overall, 14.2% (95% confidence interval: 12.1-16.2) of adolescents aged 12-15 years had early sexual initiation, with boys reporting much higher than girls (19.7%, 16.9-22.5 vs. 8.9%, 7.6-10.3). The prevalence of early sexual initiation was the highest in the region of the Americas (18.4%, 15.2-21.5) and the lowest in the South-east Asia region (5.3%, 2.6-8.0). Adolescents from high-income and lower middle-income countries had the highest (19.5%, 13.5-25.5) and the lowest (7.3%, 5.5-9.0) prevalence, respectively. Older age, anxiety, loneliness, suicidal ideation, being bullied, physical fight, school truancy, smoking, drinking alcohol, illicit drug use, physical activity, and being overweight were associated with higher odds of early sexual initiation, whereas female sex, parental monitoring, and peer support were protective. There was little or no evidence of heterogeneity by sex and across regions for these associations. CONCLUSIONS: Substantial differences in the prevalence are observed by sex and across regions for early sexual initiation among adolescents, whereas its correlates remain relatively similar when examined separately by these characteristics.

Double burden of malnutrition in children aged 24 to 59 months by socioeconomic status in five South Asian countries: evidence from demographic and health surveys.

OBJECTIVES: We aimed to investigate the socioeconomic inequalities in the burden of underweight and overweight among children in South Asia. We also examined other factors that were associated with these outcomes independently of household's socioeconomic status. DESIGN: Nationally-representative surveys. SETTINGS: Demographic and Health Surveys from Bangladesh, India, Pakistan, Maldives and Nepal, which were conducted between 2009 and 2016. PARTICIPANTS: Children aged 24 to 59 months with valid measurement for height and weight (n=146 996). PRIMARY EXPOSURE AND OUTCOME MEASURES: Primary exposures were household's wealth index and level of education. Underweight and overweight were defined according to the WHO and International Obesity Task Force definitions, respectively. RESULTS: Underweight prevalence was 37% in Bangladesh, 38% in India, 19% in Maldives, 29% in Nepal and 28% in Pakistan. Bangladesh, India and Nepal had similar overweight prevalence (between 2% and 4%) whereas Pakistan (7%) and Maldives (9%) had higher prevalence. Households with higher wealth index or education had lower odds of having underweight children. Adjusted ORs of underweight for richest versus poorest households were 0.4 (95% CI: 0.3 to 0.5), 0.5 (95% CI: 0.5 to 0.6), 0.5 (95% CI: 0.2 to 1.4), 0.5 (95% CI: 0.3 to 0.8) and 0.7 (95% CI: 0.5 to 1.1) for Bangladesh, India, Maldives, Nepal and Pakistan, respectively. Compared with poorest households, richest households were more likely to have overweight children in all countries except Pakistan, but such associations were not significant after adjustment for other factors. There were higher odds of having overweight children in households with higher education in Bangladesh (OR 2.1 (95% CI: 1.3 to 3.5)), India (OR 1.2 (95% CI: 1.2 to 1.3)) and Pakistan (OR 1.8 (95% CI: 1.1 to 2.9)) when compared with households with no education. Maternal nutritional status was consistently associated with children's nutritional outcomes after adjustments for socioeconomic status. CONCLUSIONS: Our study provides evidence for socioeconomic inequalities for childhood underweight and overweight in South Asian countries, although the directions of associations for underweight and overweight might be different.

Trends in the prevalence of overweight among Bangladeshi children aged 24-59 months (2004-2014) by sex and socioeconomic status.

BACKGROUND: While recent evidence suggests that the overall prevalence of overweight in young children in Bangladesh is low, little is known about variation in trends by sex, socioeconomic status, urbanicity, and region. We investigated the trends in overweight among children aged 24-59 months by these factors, using nationally representative samples from Bangladesh Demographic and Health Surveys (BDHS) between 2004 and 2014. METHODS: Data from four BDHS surveys conducted between 2004 and 2014, with valid height and weight measurements of children, were included in this study (n = 15,648). BMI was calculated and the prevalence of overweight (including obesity) was reported using the International Obesity Taskforce (IOTF) classification system. To explore the association between socioeconomic status and childhood overweight, we used multivariable logistic regression. RESULTS: The overall prevalence of overweight among children aged 24-59 months increased from 1.60% (95% CI: 1.20-2.05%) in 2004 to 2.33% (95% CI: 1.82-2.76%) in 2014. Among girls, the overweight trend increased significantly (adjusted odds ratio (OR) comparing 2014 vs. 2004: 2.02 95% CI: 1.52-2.68), whereas among boys the trend remained steady. When compared with households with the poorest wealth index, households with richest wealth index had higher odds of childhood overweight among both boys (OR 2.39, 95% CI: 1.76-3.25) and girls (OR 1.86, 95% CI: 1.35-2.55). Higher household education level was also associated with childhood overweight. Subgroup analyses showed that relative inequalities by these factors increased between 2004 and 2014 when adjusted for potential confounders. CONCLUSIONS: There is a rising trend in overweight prevalence exclusively among girls aged 24-59 months in Bangladesh. Childhood overweight is associated with higher household education and wealth index, and the relative disparity by these factors appears to be increasing over time. These unmet inequalities should be considered while developing national public health programs and strategies.

Association between body mass index (BMI) and hypertension in south Asian population: evidence from nationally-representative surveys.

BACKGROUND: Although there has been a well-established association between overweight-obesity and hypertension, whether such associations are heterogeneous for South Asian populations, or for different socioeconomic groups is not well-known. We explored the associations of overweight and obesity using South Asian cut-offs with hypertension, and also examined the relationships between body mass index (BMI) and hypertension in various socioeconomic subgroups. METHODS: We analysed the recent Demographic and Health Survey (DHS) data from Bangladesh, India, and Nepal, with a total of 821,040 men and women. Hypertension was defined by 2017 ACC/AHA cut-offs and by Joint National Committee 7 (JNC7) cut-offs for measured blood pressure and overweight and obesity were defined by measured height and weight. We used multiple logistic regressions to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) of hypertension for overweight and obesity as well as for each 5-unit increase in BMI. RESULTS: The prevalence of hypertension using JNC7 cut-offs among participants increased by age in all three countries. The prevalence ranged from 17.4% in 35-44 years to 34.9% in ≥55 years in Bangladesh, from 4.6% in 18-24 years to 28.6% in 45-54 years in India, and from 3.8% in 18-24 years to 39.2% in ≥55 years in Nepal. Men were more likely to be hypertensive than women in India and Nepal, but not in Bangladesh. Overweight and obesity using both WHO and South Asian cut-offs were associated with higher odds of hypertension in all countries. For each 5 kg/m2 increase in BMI, the ORs for hypertension were 1.79 (95% CI: 1.65-1.93), 1.59 (95% CI: 1.58-1.61), and 2.03 (95% CI: 1.90-2.16) in Bangladesh, India, and Nepal, respectively. The associations between BMI and hypertension were consistent across various subgroups defined by sex, age, urbanicity, educational attainment and household's wealth index. CONCLUSIONS: Our study shows that the association of BMI with hypertension is stronger for South Asian populations at even lower cut-offs points for overweight and obesity. Therefore, public health measures to reduce population-level reduction in BMI in all population groups would also help in lowering the burden of hypertension.

Attitude towards diabetes and social and family support among type 2 diabetes patients attending a tertiary-care hospital in Bangladesh: a cross-sectional study.

BACKGROUND: Bangladesh has been suffering from an epidemiological transition from infectious and maternal diseases to non-communicable lifestyle-related diseases like diabetes, cardiovascular diseases, cancers etc. The burden of diabetes has been increasing rapidly due to high incidence as well as poor glycemic control leading to various macro and micro-vascular complications. In this study, we aim to assess the attitude towards diabetes and social and family support among the Bangladeshi type 2 diabetic mellitus (T2DM) patients. METHODS: This was a cross-sectional study among 144 patients with T2DM at the medicine outpatient department of Dhaka Medical College Hospital (DMCH) in Dhaka, Bangladesh between 1 July and 31 July 2014. Data collection was done by interviewing patients using structured questionnaire. Understanding diabetes, education/advice received, attitude towards diabetes, family and friend support were measured by validated scales adapted from diabetes care profile. RESULTS: This study includes a total of 144 patients (101 males and 43 females) with type 2 diabetes aged between 20 and 84 years. 87 % of the patients had inadequate blood glucose control (fasting blood sugar >7.2 mmol/L or >130 mg/dl). Statistically significant differences were observed in the mean scores of various attitude scales (i.e. positive, negative, care ability and self-care adherence scale) among patients with adequate and inadequate blood glucose control (p < 0.05). Statistically significant positive correlations were found between these three categories of social and family support. Self-satisfaction with diabetic care was significantly associated with adequate blood glucose control (p = 0.05). CONCLUSIONS: Positive attitude towards diabetes management and support from friends and family were associated with adequate diabetes management. Appropriate public health interventions should be designed to educate and motivate the family members to offer greater support to the diabetes patients.