What are the barriers and facilitators to polio vaccination and eradication programs? A systematic review.

Global efforts to eradicate polio by the Global Polio Eradication Initiative agency partners and country-level stakeholders have led to the implementation of global polio vaccination programs. This study presents the findings of existing studies regarding the barriers and facilitators that countries face when implementing polio interventions. A comprehensive search was conducted in OVID Medline, OVID Embase, EBSCO CINAHL Plus, and Web of Science. Eligible studies underwent quality assessment. A qualitative evidence synthesis approach was conducted and aligned to the Consolidated Framework for Implementation Research (CFIR). The search identified 4147 citations, and following the removal of duplicates and screening according to our inclusion/exclusion criteria, 20 articles were eligible for inclusion in the review. Twelve countries were represented in this review, with India, Nigeria, Pakistan, Ethiopia, and Afghanistan having the most representation of available studies. We identified 36 barriers and 16 facilitators. Seven themes emerged from these barriers and facilitators: fear, community trust, infrastructure, beliefs about the intervention, influential opinions, intervention design, and geo-politics. The most frequently cited CFIR constructs for the facilitators and barriers were knowledge and beliefs about the intervention, followed by available resources. This study identified a wide range of barriers and facilitators to polio vaccination implementation across the globe, adding to the scarce body of literature on these barriers and facilitators from an implementation perspective and using a determinant framework. The diversity of factors among different groups of people or countries highlights the relevance of contexts. Implementers should be conversant with the contexts within which polio eradication programs boost intervention coverage and capacity. This study provides policymakers, practitioners, and researchers with a tool for planning and designing polio immunization programs. Trial registration: A protocol for this systematic review was developed and uploaded onto the PROSPERO international prospective register of systematic reviews database (Registration number: CRD42020222115).

COVID-19 pandemic containment in the Caribbean Region: A review of case-management and public health strategies.

COVID-19 emerged initially from Wuhan, Hubei province, China, in late December 2019, and since then, it has spread globally to be declared a pandemic by the World Health Organization. The Caribbean region started reporting COVID-19 cases in early March 2020, triggering new regional public health crises. The initial suspects and confirmed cases across the Caribbean countries were mainly imported cases and from cruise ships. The clinical manifestations varied from fever, cough, and malaise in mild cases to acute respiratory distress syndrome (ARDS) and shock in severe cases. The Caribbean Public Health Agency has provided frequent updates on the preventive strategies and quarantine measures across the Caribbean member states. COVID-19 has had a serious impact on the Caribbean region's health system, economy, and psychology. This review presents the Caribbean perspective of COVID-19, detailing the epidemiology, clinical manifestations, diagnosis, management, and preventive and surveillance measures. Vaccine hesitancy was found to be a major challenge that needs appropriate health education strategies to address the public. Strong leadership and regional collaboration among the Caribbean member states are necessary to provide optimal real-time data to the public and implement appropriate and effective guidelines in the island states.

Dissecting Long-Term Glucose Metabolism Identifies New Susceptibility Period for Metabolic Dysfunction in Aged Mice.

Metabolic disorders, like diabetes and obesity, are pathogenic outcomes of imbalance in glucose metabolism. Nutrient excess and mitochondrial imbalance are implicated in dysfunctional glucose metabolism with age. We used conplastic mouse strains with defined mitochondrial DNA (mtDNA) mutations on a common nuclear genomic background, and administered a high-fat diet up to 18 months of age. The conplastic mouse strain B6-mtFVB, with a mutation in the mt-Atp8 gene, conferred ß-cell dysfunction and impaired glucose tolerance after high-fat diet. To our surprise, despite of this functional deficit, blood glucose levels adapted to perturbations with age. Blood glucose levels were particularly sensitive to perturbations at the early age of 3 to 6 months. Overall the dynamics consisted of a peak between 3-6 months followed by adaptation by 12 months of age. With the help of mathematical modeling we delineate how body weight, insulin and leptin regulate this non-linear blood glucose dynamics. The model predicted a second rise in glucose between 15 and 21 months, which could be experimentally confirmed as a secondary peak. We therefore hypothesize that these two peaks correspond to two sensitive periods of life, where perturbations to the basal metabolism can mark the system for vulnerability to pathologies at later age. Further mathematical modeling may perspectively allow the design of targeted periods for therapeutic interventions and could predict effects on weight loss and insulin levels under conditions of pre-diabetic obesity.

Systems biology approaches in aging research.

Aging is a systemic process which progressively manifests itself at multiple levels of structural and functional organization from molecular reactions and cell-cell interactions in tissues to the physiology of an entire organ. There is ever increasing data on biomedical relevant network interactions for the aging process at different scales of time and space. To connect the aging process at different structural, temporal and spatial scales, extensive systems biological approaches need to be deployed. Systems biological approaches can not only systematically handle the large-scale datasets (like high-throughput data) and the complexity of interactions (feedback loops, cross talk), but also can delve into nonlinear behaviors exhibited by several biological processes which are beyond intuitive reasoning. Several public-funded agencies have identified the synergistic role of systems biology in aging research. Using one of the notable public-funded programs (GERONTOSYS), we discuss how systems biological approaches are helping the scientists to find new frontiers in aging research. We elaborate on some systems biological approaches deployed in one of the projects of the consortium (ROSage). The systems biology field in aging research is at its infancy. It is open to adapt existing systems biological methodologies from other research fields and devise new aging-specific systems biological methodologies.

Occupational hazard exposure and general health profile of welders in rural Delhi.

BACKGROUND: Welding is a common industrial process associated with various health hazards. The aspect of duration of hazard exposure among welders at their workplace has been studied to limited extent in India. OBJECTIVE: To assess the duration of occupational hazard exposure and its association with symptoms among the welders. MATERIALS AND METHODS: A cross-sectional study was conducted amongst 106 welders in North Delhi. Data was collected using a questionnaire containing items to assess the socio-demographic profile, their medical history and individual hazard exposure. RESULTS: Majority of them were involved in skilled/semi-skilled job (n = 99; 93%). The predominant nature of work for majority was manual. More than half reported their work to be physically hard (n = 56; 53%), involves much lifting of weight (n = 61; 57%), and is dangerous (n = 59; 56%). Dust/smoke followed by noise was reported to be most common hazards at the workplace by them. Most of them were suffering from eye related symptoms (n = 63; 59%) followed by skin conditions (n = 28; 26%). Skin diseases were reported to be significantly common among group of welders who were exposed to dust and radiation for ≥4 hours in a day (P < 0.05). CONCLUSIONS: Nearly half of the welders found their job to be dangerous and were being exposed to at least one hazardous substance at their workplace. Majority of them complained of eye symptoms. There is a need for health and safety training of this economically productive group.

The systems biology of mitochondrial fission and fusion and implications for disease and aging.

Mitochondria organize themselves as dynamic populations within a cell, by undergoing continuous cycles of fission and fusion. The spatio-temporal distribution and abundance of mitochondria determines the cell's energy budget and is thus intimately linked to the cell's response to environmental stimuli during aging. The dynamic balance of mitochondrial fission and fusion can be studied in terms of antagonistic subpopulations that regulate the mitochondrial responses in space and time. The dynamic nature of these processes motivates mathematical modelling and the simulation of such complex process. In several neurodegenerative and metabolic diseases the dynamic balance of fission and fusion is disturbed. However, how this dynamics plays a role in the progression of diseases is largely unclear. Fission and fusion help mitochondria to regulate cellular energy (ATP) levels, and minimize accumulation of harmful oxidized material called reactive oxygen species which accelerate mutations in mitochondrial DNA (mtDNA) during aging. We discuss how systems biology approaches can be used to investigate the mechanisms controlling the fission­fusion dynamics under two categories: dissecting the design of its molecular regulatory motifs, and understanding complex mitochondrial responses through their population level interactions. This will help us to understand how different regulatory mechanisms regulate the ATP and mutation (mtDNA) landscape of mitochondria to a variety of environmental stimuli in order to maintain their function during aging.

Regulation of mammalian cell cycle progression in the regenerating liver.

The process of cell division in mammalian cells is orchestrated by cell-cycle-dependent oscillations of cyclin protein levels. Cyclin levels are controlled by redundant transcriptional, post-translational and degradation feedback loops. How each of these separate loops contributes to the regulation of the key cell cycle events and to the connection between the G1-S transition and the subsequent mitotic events is under investigation. Here, we present an integrated computational model of the mammalian cell cycle based on the sequential activation of cyclins. We validate the model against experimental data on liver cells (hepatocytes), which undergo one or two rounds of synchronous circadian-clock gated cell divisions during liver regeneration, after partial hepatectomy (PH). The model exhibits bandpass filter properties that allow the system to ignore strong but transient, or sustained but weak damages after PH. Bifurcation analysis of the model suggests two different threshold mechanisms for the progression of the cell through mitosis. These results are coherent with the notion that the mitotic exit in mammalian cells is bistable, and suggests that Cdc20 homologue 1 (Cdh1) is an important regulator of mitosis. Regulation by Cdh1 also explains the observed G2/M phase prolongation after hepatocyte growth factor (HGF) stimulation during S phase.

A mesoscale model of G1/S phase transition in liver regeneration.

The liver regenerates and maintains its function and size after injury by counterbalancing cell death with compensatory cell division. During liver regeneration, injured sites release cytokines, which stimulate normally quiescent hepatocytes to re-enter cell division cycle. Using a mesoscale approach, we have implemented the first mathematical model that describes cytokine-induced dedifferentiation of hepatocytes and the subsequent initiation of DNA synthesis (G0/G1 and G1/S phase transitions of the cell cycle). The model accurately reproduces experimentally measured kinetics of various signaling intermediates and DNA synthesis in hepatocytes for varying degrees of liver damage, in both wild type and knockout backgrounds. Liver regeneration is known to be a robust process, as liver mass reconstitution still occurs in various knockout mice (albeit with different kinetics). We analyze the robustness of the model using methods of control analysis. Moreover, we discuss the system's bandpass filtering properties and delays, which arise from feedbacks and nested feed-forward loops.