Rural-urban difference in meeting the need for healthcare and food among older adults: evidence from India.

BACKGROUND: Due to changes in demographic and epidemiological scenarios, and the gradual increase in the older population, India is yet to prepare for rising nutrition and health-related issues among older adults in the coming decades. While the process of ageing and its associated aspect has been found to have an urban-rural divide. Thus, this study examines rural/urban differences in unmet needs for food and healthcare among Indian older adults. METHODS: A sample of 31,464 older adults aged 60 years and above were considered in the study from the Longitudinal and Ageing Survey of India (LASI). The bivariate analysis was done using the sampling weights. Logistic regression and decomposition analysis was used to explain the rural-urban gap in the unmet needs for food and healthcare among Indian older adults. RESULTS: Rural older adults were more vulnerable to meeting the need for health and food than their urban counterparts. While factors that contributed majorly to the difference in unmet need for food between urban and rural were education (34.98%), social group (6.58%), living arrangements (3.34%) and monthly per capita expenditure (MPCE) (2.84%). Similarly, for the unmet need for health, the factors that contributed the most to the rural-urban gap are education (28.2%), household size (2.32%), and MPCE (1.27%). CONCLUSION: The study indicates more vulnerability among rural older adults than compared to urban older individuals. The targeted policy-level efforts should be initiated considering the economic and residential vulnerability identified in the study. There is a need for primary care services that can provide targeted help to older adults in rural communities.

Feasibility and acceptability of home-based neonatal hyperbilirubinemia screening by community health workers using transcutaneous bilimeters in Bangladesh.

BACKGROUND: Universal screening for neonatal hyperbilirubinemia risk assessment is recommended by the American Academy of Pediatrics to reduce related morbidity. In Bangladesh and in many low- and middle-income countries, there is no screening for neonatal hyperbilirubinemia. Furthermore, neonatal hyperbilirubinemia may not be recognized as a medically significant condition by caregivers and community members. We aimed to evaluate the acceptability and operational feasibility of community health worker (CHW)-led, home-based, non-invasive neonatal hyperbilirubinemia screening using a transcutaneous bilimeter in Shakhipur, a rural subdistrict in Bangladesh. METHODS: We employed a two-step process. In the formative phase, we conducted eight focus group discussions with parents and grandparents of infants and eight key informant interviews with public and private healthcare providers and managers to explore their current knowledge, perceptions, practices, and challenges regarding identification and management of neonatal hyperbilirubinemia. Next, we piloted a prenatal sensitization intervention and home-based screening by CHWs using transcutaneous bilimeters and evaluated the acceptability and operational feasibility of this approach through focus group discussions and key informant interviews with parents, grandparents and CHWs. RESULTS: Formative findings identified misconceptions regarding neonatal hyperbilirubinemia causes and health risks among caregivers in rural Bangladesh. CHWs were comfortable with adoption, maintenance and use of the device in routine home visits. Transcutaneous bilimeter-based screening was also widely accepted by caregivers and family members due to its noninvasive technique and immediate display of findings at home. Prenatal sensitization of caregivers and family members helped to create a supportive environment in the family and empowered mothers as primary caregivers. CONCLUSION: Adopting household neonatal hyperbilirubinemia screening in the postnatal period by CHWs using a transcutaneous bilimeter is an acceptable approach by both CHWs and families and may increase rates of screening to prevent morbidity and mortality.

Implementing a group-based multi-component early child development intervention through the government health system in rural Bangladesh: A feasibility study.

Children in low- and middle-income countries face an increased risk of impaired cognitive development due to contaminated environments, poor nutrition, and inadequate responsive stimulation from caregivers. Implementing multi-component, community-level interventions may reduce these risks; however, there is little evidence supporting implementation of these interventions at scale. We assessed the feasibility of implementing a group-based intervention that included responsive stimulation, maternal and child nutrition, water and sanitation, and childhood lead exposure prevention through the government health system in Chatmohar, Bangladesh. After implementation, we conducted 17 in-depth interviews with frontline health service providers and 12 key informant interviews with their supervisors and managers to explore the facilitators and difficulties implementing such a complex programme within the health system. Factors facilitating implementation included: high quality training and skill level of providers, support from community members, family, and supervisors, positive relationships between providers and participants, and provision of children's toys and books free of cost. Difficulties included increased workload of the providers, complicated group-based yet stage-specific delivery where providers had to manage a large group of mother-child dyads representing many different child age-groups at once, and logistics difficulties in providing toys and books through a centralised health system process. Key informants made suggestions to ensure effective government-level scale-up including engaging relevant NGOs as partners, identifying feasible ways to make toys available, and offering providers meaningful even if non-monetary rewards. These findings can be used to shape the design and delivery of multi-component child development interventions to be delivered through the health system.

A comprehensive study of epitopes and immune reactivity among Plasmodium species.

BACKGROUND: Malaria is a life-threatening disease caused by protozoan parasite of genus Plasmodium. Various antigenic proteins of Plasmodium are considered as the major targets for the development of an effective vaccine. The aim of the current study was a comprehensive analysis of the experimentally validated epitopes of Plasmodium obtained from various immunoassays. METHODS: Plasmodium species epitopes were prefetched from Immune Epitope Database (IEDB). Species specific classification of available epitopes was done for both human and murine malaria parasites. Further, these T cell and B cell epitopes along with MHC I/II binders of different Plasmodium species were examined to find out their capability to induce IFN-γ and IL-10 using IFNepitope and IL-10 Pred, respectively. RESULTS: The species-specific classification of 6874 unique epitopes resulted in the selection of predominant human and murine Plasmodium species. Further, the attempt was made to analyse the immune reactivity of these epitopes for their ability to induce cytokines namely IFN-γ and IL-10. Total, 2775 epitopes were predicted to possess IFN-γ inducing ability, whereas 1275 epitopes were found to be involved in the induction of IL-10. CONCLUSIONS: This study facilitates the assessment of Plasmodium epitopes and associated proteins as a potential approach to design and develop an epitope-based vaccine. Moreover, the results highlight the epitope-based immunization in malaria to induce a protective immune response.

CD4+ICOS+Foxp3+: a sub-population of regulatory T cells contribute to malaria pathogenesis.

BACKGROUND: Regulatory T cells are known to play a key role to counter balance the protective immune response and immune mediated pathology. However, the role of naturally occurring regulatory cells CD4+CD25+Foxp3+ in malaria infection during the disease pathogenesis is controversial. Beside this, ICOS molecule has been shown to be involved in the development and function of regulatory T cell enhance IL-10 production. Therefore, possible involvement of the ICOS dependent regulatory CD4+ICOS+Foxp3+ T cells in resistance/susceptibility during malaria parasite is explored in this study. METHODS: 5 × 105 red blood cells infected with non-lethal and lethal parasites were inoculated in female Balb/c mice by intra-peritoneal injection. Infected or uninfected mice were sacrificed at early (3rd day post infection) and later stage (10th day post infection) of infection. Harvested cells were analysed by using flow cytometer and serum cytokine by Bioplex assay. RESULTS: Thin blood films show that percentages of parasitaemia increases with disease progression in infections with the lethal malaria parasite and mice eventually die by day 14th post-infection. Whereas in case of non-lethal malaria parasite, parasitaemia goes down by 7th day post infection and gets cleared within 13th day. The number of CD4+ ICOS+ T cells increases in lethal infection with disease progression. Surprisingly, in non-lethal parasite, ICOS expression decreases after day 7th post infection as parasitaemia goes down. The frequency of CD4+ICOS+FoxP3+ Tregs was significantly higher in lethal parasitic infection as compared to the non-lethal parasite. The level of IL-12 cytokine was remarkably higher in non-lethal infection compared to the lethal infection. In contrast, the level of IL-10 cytokines was higher in lethal parasite infection compared to the non-lethal parasite. CONCLUSION: Taken together, these data suggest that lethal parasite induce immunosuppressive environment, protecting from host immune responses and help the parasite to survive whereas non-lethal parasite leads to low frequencies of Treg cells seldom impede immune response that allow the parasite to get self-resolved.

Social exclusion and mental health among older adults: cross-sectional evidence from a population-based survey in India.

BACKGROUND: Social exclusion has far-reaching consequences that extend beyond regular activities and access to resources and knowledge; social exclusion is a major social determinant of health. However, there is a lack of evidence on social exclusion and health outcomes among India's older adults. Thus, the current study investigates the association of social exclusion with depressive symptoms among Indian older adults. METHODS: This study used information on 30,366 older adults from Longitudinal Ageing Study in India (LASI) wave-1, 2017-2018. Social exclusion scores were calculated, and two broad domains of social exclusion, i.e., exclusion from civic activity & social relations and exclusion from services, were considered in the study. The depressive symptom was calculated using the CES-D score. Using logistic regression models, the average marginal effects of selected covariates and domains of social exclusion on depressive symptoms were estimated to assess the links between social exclusion and depressive symptoms. RESULTS: With the increase in the social exclusion score in the selected domains, the prevalence of depressive symptoms among older also increased. Elderly persons who do not vote or live alone in the domain of being excluded from civic & social activities and older adults excluded from services were observed to have a higher prevalence of depressive symptoms. Adjusting for sociodemographic factors, the average marginal effects suggested that older with four scores of civic activity & social relation exclusion, two scores of service exclusion and four scores of overall social exclusion were estimated to have a higher prevalence of depressive symptoms, respectively. CONCLUSIONS: This study's findings shed light on social exclusion and its relationship to depressive symptoms among older Indians. Older health care services should be expanded in breadth while also addressing social exclusion, resulting in considerable improvements in older individuals' mental health.

Administration of L-citrulline prevents Plasmodium growth by inhibiting/ modulating T-regulatory cells during malaria pathogenesis.

BACKGROUND & OBJECTIVES: Malaria affects around 228 million people all over the globe. Malaria causing parasite Plasmodium infection leads to activation of immune responses. The growth of parasite and immune activation requires semi essential amino acids like L-arginine. Malaria infection leads to condition of hyperargininemia and low availability of nitric oxide. However, the effect of L-arginine supplementation in malaria infected mice has not been explored in in-vivo studies. In this study we have compared the effect of oral supplementation of nitric oxide donor, L-arginine and L-citrulline, in malaria infected mice Methods: To examine the effect of oral supplementation of L-arginine and L-citrulline, Plasmodium berghei infected mice were divided in different groups and respective groups were fed with L- arginine and L-citrulline, parasitemia was measured on different days. Mice was sacrificed and immunophenotyping was done on 10 days post infection. RESULTS: our results show that supplementation of L-arginine induces conducive environment for Plasmodium growth due to which the infected mice dies earlier than control wild type infected mice whereas L-citrulline supplementation inhibits parasite growth and mice survives for longer period of time. Flow cytometric analysis shows that supplementation of L-arginine increases cTLA-4 on T cell population, increases Treg cells leading to immunosuppression while supplementation of L-citrulline does not have effect on T cells population and number of Treg cell decrease compared to P. berghei infected mice. INTERPRETATION & CONCLUSION: our results show that L-citrulline can be a better alternative than L-arginine because of lower expression of inhibitory molecules and lower parasitemia as well as increased survival of infected mice.

Effects of the COVID-19 pandemic on caregiver mental health and the child caregiving environment in a low-resource, rural context.

Early child development has been influenced directly and indirectly by the COVID-19 pandemic, and these effects are exacerbated in contexts of poverty. This study estimates effects of the pandemic and subsequent population lockdowns on mental health, caregiving practices, and freedom of movement among female caregivers of children 6-27 months (50% female), in rural Bangladesh. A cohort (N = 517) was assessed before and during the pandemic (May-June, 2019 and July-September, 2020). Caregivers who experienced more food insecurity and financial loss during the pandemic reported larger increases in depressive symptoms (0.26 SD, 95% CI 0.08-0.44; 0.21 SD, 0.04-0.40) compared to less affected caregivers. Stimulating caregiving and freedom of movement results were inconsistent. Increases in depressive symptoms during the pandemic may have consequences for child development.

Can Altering Grip Technique and Bag Size Optimize Volume Delivered with Bag-Valve-Mask by Emergency Medical Service Providers?

INTRODUCTION: Emergency Medical Services (EMS) professionals rely on the bag-valve-mask (BVM) to provide life-saving positive-pressure ventilation in the prehospital setting. Multiple emergency medicine and critical care studies have shown that lung-protective ventilation protocols reduce morbidity and mortality. A recent study has shown that the volumes typically delivered by EMS professionals with the adult BVM are often higher than recommended by lung-protective ventilation protocols. Our primary objective was to determine if a group of EMS professionals could reduce the volume delivered by adjusting the way the BVM was held. Secondary objectives included 1) if the adjusted grip allowed for volumes more consistent with lung-protection ventilation strategies and 2) comparing volumes to similar grip strategies used with a smaller BVM. METHODS: A patient simulator of a head and thorax was used to record respiratory rate, tidal volume, peak pressure, and minute volume delivered by participants for 1 minute each across 6 different scenarios: 3 different grips (using the thumb and either 3 fingers, 2 fingers, or one finger) with 2 different sized BVMs (adult and pediatric). Trials were randomized by blindly selecting a paper with the scenario listed. A convenience sample of EMS providers was used based on EMS provider and research staff availability. RESULTS: We enrolled 50 providers from a large, busy, urban hospital-based EMS agency a mean 8.60 (SD = 9.76) years of experience. Median volumes for each scenario were 836.0 mL, 834.5 mL, and 794 mL for the adult BMV (p = 0.003); and 576.0 mL, 571.5 mL, and 547.0 mL for the pediatric BVM (p < 0.001). Across all 3 grips, the pediatric BVM provided more breaths within the recommended volume range for a 70 kg patient (46.4% vs. 0.4%; p < 0.001) with only a 1.1% of breaths below the recommended tidal volume. CONCLUSION: The study suggests that it is possible to alter the volume provided by the BVM by altering the grip on the BVM. The tidal volumes recorded with the pediatric BVM were above recommended range in 2 of the 3 grips. The volumes of the pediatric BVM were overall more consistent with lung-protective ventilation volumes when compared to all 3 finger-grips of the adult BVM.

Effect of L-arginine on the growth of Plasmodium falciparum and immune modulation of host cells.

BACKGROUND & OBJECTIVES: Malaria is a life-threatening disease caused by Plasmodium parasites. The life-cycle of Plasmodium species involves several stages both in mosquito and the vertebrate host. In the erythrocytic stage, Plasmodium resides inside the red blood cells (RBCs), where it meets most of its nutritional requirement by degrad- ing host's haemoglobin. L-arginine is required for growth and division of cells. The present study was aimed to demonstrate the effect of supplementation of different concentrations of L-arginine and L-citrulline on the growth of parasite, and effect of the culture supernatant on the host's peripheral blood mononuclear cells (PBMCs). METHODS: To examine the effect of supplementation of L-arginine and L-citrulline, Plasmodium falciparum (3D7 strain) was cultured in RPMI 1640, L-arginine deficient RPMI 1640, and in different concentrations of L-arginine, and L-citrulline supplemented in arginine deficient RPMI 1640 medium. To have a holistic view of in vivo cell activation, the PBMCs isolated from healthy human host were cultured in the supernatant collected from P. falciparum culture. RESULTS: Growth of the parasite was greatly enhanced in L-arginine supplemented media and was found to be concentration dependent. However, parasite growth was compromised in L-citrulline supplemented and L-arginine deficient media. The supernatant collected from L-arginine supplemented parasite media (sArg) showed increased FOXP3 and interleukin-10 (IL-10) expression as compared to the supernatant collected from L-citrulline supple- mented parasite media (sCit). INTERPRETATION & CONCLUSION: The in vitro culture results showed, decreased parasite growth, and decreased expression of programmed cell death-1 (PD-1) (a coinhibitory molecule) and IL-10 in the L-citrulline supplemented media as compared to L-arginine supplemented media. Hence, it was concluded that L-citrulline supplementation would be a better alternative than L-arginine to inhibit the parasite growth.

Mesenchymal stem cells play an important role in host protective immune responses against malaria by modulating regulatory T cells.

Plasmodium spp. parasites, the causative agents of malaria, survive and replicate in human hosts by modulating host protective immune responses. In a rodent model, malaria manifests as a severe splenomegaly, with infiltration of cells and lympho-proliferation as major contributing factors of the immunopathology. However, the cellular contents and the functions of these cells have not been well studied. Here, we report that Plasmodium berghei infection of mice leads to massive recruitment of mesenchymal stem cells (MSCs) in secondary lymphoid organs. Infusion of these cells into naïve mice was able to confer host resistance against malaria. Furthermore, MSCs augmented interleukin (IL)-12 production but suppressed IL-10 production in recipient animals. In addition, we observed dramatic reductions of regulatory T (Treg) cells in animals that received MSCs. Taken together, our findings have identified recruitment of MSCs as a novel host protective mechanism adopted by the host to combat malaria by modulating Treg-cell responses.

Cerebral malaria pathogenesis: Dissecting the role of CD4+ and CD8+ T-cells as major effectors in disease pathology.

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum (P. falciparum) infection, with complex pathogenesis involving multiple factors, including the host's immunological response. T lymphocytes, specifically CD4+ T helper cells and CD8+ cytotoxic T cells, are crucial in controlling parasite growth and activating cells for parasite clearance via cytokine secretion. Contrary to this, reports also suggest the pathogenic nature of T lymphocytes as they are often involved in disease progression and severity. CD8+ cytotoxic T cells migrate to the host's brain vasculature, disrupting the blood-brain barrier and causing neurological manifestations. CD4+ T helper cells on the other hand play a variety of functions as they differentiate into different subtypes which may function as pro-inflammatory or anti-inflammatory. The excessive pro-inflammatory response in CM can lead to multi-organ failure, necessitating a check mechanism to maintain immune homeostasis. This is achieved by regulatory T cells and their characteristic cytokines, which counterbalance the pro-inflammatory immune response. Maintaining a critical balance between pro and anti-inflammatory responses is crucial for determining disease outcomes in CM. A slight change in this balance may contribute to a disease severity owing to an extreme inflammatory response or unrestricted parasite growth, a potential target for designing immunotherapeutic treatment approaches. The review briefly discusses the pathogenesis of CM and various mechanisms responsible for the disruption of the blood-brain barrier. It also highlights the role of different T cell subsets during infection and emphasizes the importance of balance between pro and anti-inflammatory T cells that ultimately decides the outcome of the disease.

CM is potentially fatal complication of P. falciparum infection that presents with high mortality and morbidity. Vaccines are extensively being developed against the Plasmodium parasite but very few of them are effective. Artemisinin Combination Therapy (ACT) is a major treatment for malaria, but its effectiveness is declining due to Plasmodium sp. developing resistance to it, necessitating the need for development of new drugs and treatments. During infection, the parasite is responsible for causing infected red blood cell (RBC) sequestration and cytoadherence in brain vasculature and extreme pro-inflammatory response that ultimately causes endothelial dysfunction and bloodbrain barrier (BBB) disruption. The host initiates a pro-inflammatory response against the parasite which includes activation of cells of both innate and adaptive immune response. These cells control the parasite growth and aid in parasite clearance from host's body. The inflammatory response generally targets foreign pathogens and provides protection against possible infection but can also cause harm to the self when left unchecked. It has been reported that activated immune cells, mainly T-lymphocytes often migrate to brain vasculature and ultimately results in neuronal damage characteristic CM. To counteract the overwhelming pro-inflammatory response, the host immune system deploys an anti-inflammatory response, which often involves regulatory cells and cytokines that help the body maintain immunological homeostasis. The review briefly highlights the necessity of balancing the pro- and anti-inflammatory responses for successful parasite clearance without the deleterious effects to the host that might increase disease severity in CM.

Maternal health outcomes associated with ambient air pollution: An umbrella review of systematic reviews and meta-analyses.

A growing body of literature demonstrated an association between exposure to ambient air pollution and maternal health outcomes with mixed findings. The objective of this umbrella review was to systematically summarize the global evidence on the effects of air pollutants on maternal health outcomes. We adopted the Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standards for this umbrella review. We conducted a comprehensive search across six major electronic databases and other sources to identify relevant systematic reviews and meta-analyses (SRMAs) published from the inception of these databases up to June 30, 2023. Out of 2399 records, 20 citations matched all pre-determined eligibility criteria that include SRMAs focusing on exposure to air pollution and its impact on maternal health, reported quantitative measures or summary effects, and published in peer-reviewed journals in the English language. The risk of bias of included SRMAs was evaluated based on the JBI critical appraisal checklist. All SRMAs reported significant positive associations between ambient air pollution and several maternal health outcomes. Specifically, particulate matter (PM), SO2, and NO demonstrated positive associations with gestational diabetes mellitus (GDM). Moreover, PM and NO2 showed a consistent positive relationship with hypertensive disorder of pregnancy (HDP) and preeclampsia (PE). Although limited, available evidence highlighted a positive correlation between PM and gestational hypertension (GH) and spontaneous abortion (SAB). Only one meta-analysis reported the effects of air pollution on maternal postpartum depression (PPD) where only PM10 showed a significant positive relationship. Limited studies were identified from low- and middle-income countries (LMICs), suggesting evidence gap from the global south. This review necessitates further research on underrepresented regions and communities to strengthen evidence on this critical issue. Lastly, interdisciplinary policymaking and multilevel interventions are needed to alleviate ambient air pollution and associated maternal health disparities.

Prostanoid receptor 2 signaling protects T helper 2 cells from BALB/c mice against activation-induced cell death.

T helper 2 (Th2) cells play a central role in the progression of many diseases such as allergic airway inflammation, autoimmune diseases, and infections caused by intracellular pathogens. Consequently, animals such as BALB/c mice, which exhibit a propensity for generating Th2 responses, are susceptible to allergic airway inflammation, type-II autoimmune diseases, and various infections induced by intracellular pathogens, namely, Leishmania. In contrast, C3H/OuJ mice have a tendency for generating T helper 1 (Th1) responses and show resistance to these diseases. Here, we show that prostaglandin endoperoxide E(2) selectively inhibits activation-induced cell death of Th2 cells by signaling through its receptor E-prostanoid receptor 2 (EP2). Consequently, Th2 cells derived from BALB/c mice expressed very high levels of EP2. On the other hand, Th2 cells derived from C3H/OuJ mice expressed very low levels of EP2, which failed to support the survival of Th2 cells. Furthermore, we found that this effect of EP2 on Th2 cells from BALB/c mice was executed by a granzyme B-mediated mechanism. EP2 belongs to a group of G-protein-coupled receptors that are amenable to therapeutic targeting. Our findings therefore identify EP2 as a promising target for small molecule-directed immunomodulation.

Transforming growth factor-ß protein inversely regulates in vivo differentiation of interleukin-17 (IL-17)-producing CD4+ and CD8+ T cells.

TGF-ß is a pleiotropic cytokine that predominantly exerts inhibitory functions in the immune system. Unexpectedly, the in vitro differentiation of both Th17 and Tc17 cells requires TGF-ß. However, animals that are impaired in TGF-ß signaling (TGF-ßRIIDN mice) display multiorgan autoimmune disorders. Here we show that CD4(+) T cells from TGF-ßRIIDN mice are resistant to Th17 cell differentiation and, paradoxically, that CD8(+) T cells from these animals spontaneously acquire an IL-17-producing phenotype. Neutralization of IL-17 or depletion of CD8(+) T cells dramatically inhibited inflammation in TGF-ßRIIDN mice. Therefore, the absence of TGF-ß triggers spontaneous differentiation of IL-17-producing CD8(+) T cells, suggesting that the in vivo and in vitro conditions that promote the differentiation of IL-17-producing CD8(+) T cells are distinct.

CD4+ T cell-derived novel peptide Thp5 induces interleukin-4 production in CD4+ T cells to direct T helper 2 cell differentiation.

The differentiation of naïve CD4(+) T cells into T helper 2 (Th2) cells requires production of the cytokine IL-4 in the local microenvironment. It is evident that naïve/quiescently activated CD4(+) T cells produce the IL-4 that drives Th2 cell differentiation. Because early production of IL-4 in naïve T cells leads to preferential Th2 cell differentiation, this process needs to be tightly regulated so as to avoid catastrophic and misdirected Th2 cell differentiation. Here, we show that Thp5, a novel peptide with structural similarity to vasoactive intestinal peptide, regulates production of early IL-4 in newly activated CD4(+) T cells. Induction of IL-4 in CD4(+) T cells by Thp5 is independent of the transcription factor STAT6 but dependent on ERK1/2 signaling. Furthermore, cytokines (IL-12 and TGF-ß) that promote the differentiation of Th1 or Th17 cells inhibit Thp5 induction, thus suppressing Th2 cell differentiation. We further showed that Thp5 enhances Th2 responses and exacerbates allergic airway inflammation in mice. Taken together, our findings reveal that early activated CD4(+) T cells produce Thp5, which plays a critical role as a molecular switch in the differentiation of Th cells, biasing the response toward the Th2 cell phenotype.

Current understanding of the immune potential of B-cell subsets in malarial pathogenesis.

In the past several decades, our understanding of how B cells are generated and what function they perform has continued to advance. It is widely accepted that B-cell subsets play a critical role in mediating immune response. Surprisingly, human and murine malarial infections cause major alterations in the composition of B-cell subsets in both the spleen and periphery. Multiple B-cell subsets are well characterized in murine models following primary and secondary infection, although in human malarial infection, these subsets are not well defined. Furthermore, a rare known function of B cells includes the potential role of regulating the activities of other cells in the body as regulatory cells. Plasmodium infection strongly alters the frequency of these regulatory B cells indicating the immunoregulatory function of B cells in malarial. It is important to note that these subsets, taken together, form the cellular basis of humoral immune responses, allowing protection against a wide array of Plasmodium antigens to be achieved. However, it remains a challenge and an important area of investigation to understand how these B-cell subsets work together to provide protection against Plasmodium infection.

Chemokines: A key driver for inflammation in protozoan infection.

Chemokines belong to the group of small proteins within the cytokine family having strong chemo-attractant properties. In most cases, the strong immuno-modulatory role of chemokines is crucial for generating the immune response against pathogens in various protozoan diseases. In this review, we have given a brief update on the classification, characterization, homeostasis, transcellular migration, and immuno-modulatory role of chemokines. Here we will evaluate the potential role of chemokines and their regulation in various protozoan diseases. There is a significant direct relationship between parasitic infection and the recruitment of effector cells of the immune response. Chemokines play an indispensable role in mediating several defense mechanisms against infection, such as leukocyte recruitment and the generation of innate and cell-mediated immunity that aids in controlling/eliminating the pathogen. This process is controlled by the chemotactic movement of chemokines induced as a primary host immune response. We have also addressed that chemokine expressions during infection are time-dependent and orchestrated in a systematic pattern that ultimately assists in generating a protective immune response. Taken together, this review provides a systematic understanding of the complexity of chemokines profiles during protozoan disease conditions and the rationale of targeting chemokines for the development of therapeutic strategies.

Prevalence of anemia in diabetes mellitus in South Asia: A systematic review and meta-analysis.

OBJECTIVE: Anemia and Diabetes Mellitus (DM) are amongst major clinical and public health challenges in South Asia that influence the progression of chronic health problems in this population. Despite a growing body of research on these problems, there is a lack synthesized evidence on the burden of anemia among people with DM in this region. This meta-analytic review was conducted to estimate the prevalence of anemia among people with DM in South Asia. METHODS: A systematic search of the literature was conducted in five primary databases and additional sources up to July 29, 2022, that reported the prevalence of anemia among DM patients in any of the eight South Asian countries. Observational studies that met pre-determined eligibility criteria according to the protocol registered in PROSPERO (CRD42022348433) were included in this meta-analysis. Random effect models were used to estimate pooled prevalence. RESULTS: Of the 40 eligible studies, 38 underwent meta-analysis representing 14,194 participants with DM. The pooled prevalence of anemia was 45% (95% CI: 37.0-54.0, I2 = 99.28%, p = 0.00) among diabetic people in South Asia. In sub-group analysis, the pooled prevalence of anemia was higher in females (48%, 95% CI: 37.0-60.0, I2 = 98.86%, p = 0.00) compared to males (39%, 95% CI: 29.0-48.0, I2 = 98.18%, p = 0.00). Diabetic patients with older age (≥ 50 years) reported higher pooled estimates of anemia (48%, 95% CI: 38.0-58.0, I2 = 99.07%) than younger age group (< 50 years) (34%, 95% CI: 21.0-47.0, I2 = 98.83%). In addition, we found variation in pooled prevalence estimates of anemia considering the type of DM, such as type 1 reported 2% (95% CI: 0.00-4.00), type-2 reported 48% (95% CI: 40.0-56.0, I2 = 98.94%), and Gestational diabetes mellitus (GDM) reported 6% (95% CI: 3.00-12.0). CONCLUSION: High pooled estimates of anemia among diabetic patients in South Asia, including publication bias, warrants further clinical and public health research following standard research methods to understand the more context-specific epidemiological insights and evidence.

Correction: Prevalence of anemia in diabetes mellitus in South Asia: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0285336.].