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Background: During the surge of COVID-19 pandemic, the mechanism of reporting and documentation of deaths was inadequate. It is crucial to establish the mechanism for measuring the actual events of COVID-19 and associated mortalities as well during this pandemic situation. This is the first instance of application of different rapid methods for death estimation during the pandemic situation. If found to be valid, these methods may be useful for other countries with limited resources and less developed death registration system. Objective: To find out the feasibility, acceptability of different rapid method for estimating the cause of deaths among the general population & healthcare workers and also to estimate the number of deaths among allopathic doctors. Methodology: The study was conducted from September 2022 to October 2023. Target population being adult deceased person between 1st April 2020 to 30th November 2022 among general population, health care worker and allopathic doctor. For the general population, the study was conducted in one urban municipal area and two sub-centres of Habra Block I under North 24 Parganas district with WHO Verbal Autopsy (VA) tool for adult. Complete enumeration with snowballing, compartmental and capture-recapture method was adopted for general population, health care worker and allopathic doctor respectively. Results: Overall, 300 VA could be performed (121 urban & 179 rural) among general population. There were challenges related to both feasibility & acceptability in terms of data access, permission and cooperation. Research team employed a combination of persistence, local collaboration, and strategic decision-making to successfully collect data. Acceptability was more in rural area. Total number of deceased doctors was estimated to be 246 from two different lists. Conclusion: Rapid methods may be employed as a part of response systems during pandemic or any future disasters if adequate governmental support and assistance is obtained along with aid from the local people.

B7-H4 is a negative regulatory B7 family member. We investigated the role of host and donor B7-H4 in regulating acute graft-versus-host disease (GVHD). Allogeneic donor T cells infused into B7-H4-/- versus WT recipients markedly accelerated GVHD-induced lethality. Chimera studies pointed toward B7-H4 expression on host hematopoietic cells as more critical than parenchymal cells in controlling GVHD. Rapid mortality in B7-H4-/- recipients was associated with increased donor T cell expansion, gut T cell homing and loss of intestinal epithelial integrity, increased T effector function (proliferation, proinflammatory cytokines, cytolytic molecules), and reduced apoptosis. Higher metabolic demands of rapidly proliferating donor T cells in B7-H4-/- versus WT recipients required multiple metabolic pathways, increased extracellular acidification rates (ECARs) and oxygen consumption rates (OCRs), and increased expression of fuel substrate transporters. During GVHD, B7-H4 expression was upregulated on allogeneic WT donor T cells. B7-H4-/- donor T cells given to WT recipients increased GVHD mortality and had function and biological properties similar to WT T cells from allogeneic B7-H4-/- recipients. Graft-versus-leukemia responses were intact regardless as to whether B7-H4-/- mice were used as hosts or donors. Taken together, these data provide new insights into the negative regulatory processes that control GVHD and provide support for developing therapeutic strategies directed toward the B7-H4 pathway.

The recent successes of immunotherapy have shifted the paradigm in cancer treatment, but because only a percentage of patients are responsive to immunotherapy, it is imperative to identify factors impacting outcome. Obesity is reaching pandemic proportions and is a major risk factor for certain malignancies, but the impact of obesity on immune responses, in general and in cancer immunotherapy, is poorly understood. Here, we demonstrate, across multiple species and tumor models, that obesity results in increased immune aging, tumor progression and PD-1-mediated T cell dysfunction which is driven, at least in part, by leptin. However, obesity is also associated with increased efficacy of PD-1/PD-L1 blockade in both tumor-bearing mice and clinical cancer patients. These findings advance our understanding of obesity-induced immune dysfunction and its consequences in cancer and highlight obesity as a biomarker for some cancer immunotherapies. These data indicate a paradoxical impact of obesity on cancer. There is heightened immune dysfunction and tumor progression but also greater anti-tumor efficacy and survival after checkpoint blockade which directly targets some of the pathways activated in obesity.

Background: Exposure to extreme weatherly events potentially develops mental disorders among affected individuals. Aim: To synthesize the burden of mental disorders following impact of extreme weather events in South-east Asian (SEA) countries. Methods: Proposal was registered in PROSPERO register [CRD42023469788] and reported as per PRISMA-2020 guidelines. Studies reporting prevalence of mental health disorders following extreme weather events from SEA countries during 1990 and 2023 were searched on Embase, PubMed, and Scopus databases. Study quality was assessed using Appraisal tool for Cross-Sectional Studies. Overall pooled prevalence was computed using DerSimonian-Laird method for random-effects model and reported as 95% confidence intervals. Results: On screening 12,046 records, we included 155 studies (2,04,474 participants) for analysis. Overall burden of mental disorders was 35.31% (95%CI: 30.42%-40.21%). In subgroup analysis, studies on cyclones, India, local residents, children and adolescents, rural settings, and community settings reported higher burden of mental disorders. Depression (28.58%; 95%CI: 24.05%-33.1%) and PTSD (29.36%; 95%CI: 26.26%-32.46%) had similar prevalence. Visiting tourists to SEA region experienced fear, fear of recurrence of tsunami, nightmares, and sense of helplessness. Mental health outcomes were relatively higher in studies conducted within 1 year of events. Heterogeneity and possibility of publication bias exists among the reported studies. Conclusion: With the significant rise in episodes of extreme weather events in SEA region over the last three decades, mental disorders are documented in different proportions. We suggest prioritizing well-informed policies to formulate inclusive and resilient strategies on effectively identifying and treating mental health concerns among victims of extreme weather events. [ABSTRACT FROM AUTHOR]

Programmed death ligand-1 (PD-L1) interaction with PD-1 induces T cell exhaustion and is a therapeutic target to enhance immune responses against cancer and chronic infections. In murine bone marrow transplant models, PD-L1 expression on host target tissues reduces the incidence of graft-versus-host disease (GVHD). PD-L1 is also expressed on T cells; however, it is unclear whether PD-L1 on this population influences immune function. Here, we examined the effects of PD-L1 modulation of T cell function in GVHD. In patients with severe GVHD, PD-L1 expression was increased on donor T cells. Compared with mice that received WT T cells, GVHD was reduced in animals that received T cells from Pdl1-/- donors. PD-L1-deficient T cells had reduced expression of gut homing receptors, diminished production of inflammatory cytokines, and enhanced rates of apoptosis. Moreover, multiple bioenergetic pathways, including aerobic glycolysis, oxidative phosphorylation, and fatty acid metabolism, were also reduced in T cells lacking PD-L1. Finally, the reduction of acute GVHD lethality in mice that received Pdl1-/- donor cells did not affect graft-versus-leukemia responses. These data demonstrate that PD-L1 selectively enhances T cell-mediated immune responses, suggesting a context-dependent function of the PD-1/PD-L1 axis, and suggest selective inhibition of PD-L1 on donor T cells as a potential strategy to prevent or ameliorate GVHD.

Background: Coal mining in India has a long history of nearly 200 years. Coal mining can also increase the risk of coal workers' pneumoconiosis, asthma, and chronic obstructive pulmonary diseases such as emphysema and chronic bronchitis. Objectives: This study was conducted with the objective of knowing the health effects of coal mining workers. Material and Methods: A cross-sectional study was conducted in an open-cast mine in Eastern India. Two hundred and fifty coal mine workers were included in the study. A questionnaire survey followed by a health examination of the study subjects was carried out. Workers actively involved in mining activity were included in this study. Results: The most common symptom complained by study subjects was musculoskeletal pain (16.8%). As far as the pulmonary function status of study subjects is concerned, about 7% of subjects had a restrictive type of abnormality. Obstructive type of abnormality was also present in a similar number of subjects. Conclusion: The current study has shown a higher prevalence of musculoskeletal pain than the national prevalence. Morbidity is more than the normal population. Health education was imparted among workers regarding chronic diseases and their risk factors. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis. However, current Treg immunotherapies do not optimally treat inflammatory diseases in patients. Understanding the cellular processes that control Treg function may allow for the augmentation of therapeutic efficacy. In contrast to activated conventional T cells, in which protein kinase C-6 (PKC-O) localizes to the contact point between T cells and antigen- presenting cells, in human and mouse Tregs, PKC-6 localizes to the opposite end of the cell in the distal pole complex (DPC). Here, using a phosphoproteomic screen, we identified the intermediate filament vimentin as a PKC-6 phospho target and show that vimentin forms a DPC superstructure on which PKC-6 accumulates. Treatment of mouse Tregs with either a clinically relevant PKC-6 inhibitor or vimentin siRNA disrupted vimentin and enhanced Treg metabolic and suppressive activity. Moreover, vimentin-disrupted mouse Tregs were significantly better than controls at suppressing alloreactive T cell priming in graft-versus-host disease (GVHD) and GVHD lethality, using a complete MHC-mismatch mouse model of acute GVHD (C57BL/6 donor into BALB/c host). Interestingly, vimentin disruption augmented the suppressor function of PKC-[theta]-deficient mouse Tregs. This suggests that enhanced Treg activity after PKC-6 inhibition is secondary to effects on vimentin, not just PKC-6 kinase activity inhibition. Our data demonstrate that vimentin is a key metabolic and functional controller of Treg activity and provide proof of principle that disruption of vimentin is a feasible, translationally relevant method to enhance Treg potency., Introduction Regulatory T cells (Tregs) are critical for maintaining immune homeostasis and preventing autoimmune and inflammatory disorders (1, 2). However, they also support cancer progression by suppressing antitumor immunity (3). [...]

Byline: Asim. Saha, Anirban. Das, Bhaskar. Chattopadhyay, Jane. Alam, Tilak. DasguptaBackground: Byssinosis is an acute respiratory difficulty that is caused usually following exposure to cotton and hemp dust. Occurrence of [...]