Quantifying the Indirect Effects of Haemophilus Influenzae type b Vaccination in Children Under 5 Years-Old

Background Haemophilus influenzae type b (Hib) is a significant cause of meningitis and pneumonia among children under 5 years. A conjugate vaccine has been available since the mid-1980s, leading to disease reductions well above what would be expected from direct protection of the vaccine alone. This indicates indirect effects provide substantial protection against Hib disease and are a function of population-level vaccine coverage. Indirect effects are rarely investigated because it requires large, cluster randomized trials; instead we used pre-post vaccine introduction studies to model these effects. Methods Three methods to perform this analysis were identified in the literature. Wolfson, et al. described a method to compare the observed disease reduction to the reduction expected only from direct effects, resulting in an indirect effect multiplier based on vaccine coverage. Samandari, et al. estimated a multiplier for the number of people effectively protected by vaccination using vaccine coverage and incidence rates before and after vaccination. Lastly, Adegbola, et al. used average ages of Hib infection and vaccination to calculate an alternative estimate of direct protection from vaccination. Eleven studies were used for the Wolfson and Samandari methods and three were used for the Adegbola method. Results All three methods suggest a robust indirect effect of Hib vaccine against disease, with > 90% disease reduction predicted at only 70% coverage. Indirect effects were most influential at vaccine coverages below 40%, as vaccinating one child protected anywhere from two to six others. Direct effects dominated at vaccine coverages above 60%. Validating these results against an infectious disease theoretical framework and a study that empirically examined indirect effects on an individual level confirmed the accuracy of our results. Conclusion Predicted protection varied between the methods, but all demonstrated the importance of indirect effects at low vaccine coverage. These results can be used to better estimate the expected disease reduction prior to beginning a vaccine program and can impact policy decisions regarding vaccination. The models used in this analysis can also be applied to other vaccines, such as pneumococcal conjugate vaccine

Diversity and Distribution of Archaea in the Mangrove Sediment of Sundarbans

Mangroves are among the most diverse and productive coastal ecosystems in the tropical and subtropical regions. Environmental conditions particular to this biome make mangroves hotspots for microbial diversity, and the resident microbial communities play essential roles in maintenance of the ecosystem. Recently, there has been increasing interest to understand the composition and contribution of microorganisms in mangroves. In the present study, we have analyzed the diversity and distribution of archaea in the tropical mangrove sediments of Sundarbans using 16S rRNA gene amplicon sequencing. The extraction of DNA from sediment samples and the direct application of 16S rRNA gene amplicon sequencing resulted in approximately 142 Mb of data from three distinct mangrove areas (Godkhali, Bonnie camp, and Dhulibhashani). The taxonomic analysis revealed the dominance of phyla Euryarchaeota and Thaumarchaeota (Marine Group I) within our dataset. The distribution of different archaeal taxa and respective statistical analysis (SIMPER, NMDS) revealed a clear community shift along the sampling stations. The sampling stations (Godkhali and Bonnie camp) with history of higher hydrocarbon/oil pollution showed different archaeal community pattern (dominated by haloarchaea) compared to station (Dhulibhashani) with nearly pristine environment (dominated by methanogens). It is indicated that sediment archaeal community patterns were influenced by environmental conditions

Burden of <i>Streptococcus pneumoniae</i> and <i>Haemophilus influenzae</i> type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15

Background: Pneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine are now used in most countries. To monitor global and regional progress towards improving child health and to inform national policies for disease prevention and treatment, we prepared global, regional, and national disease burden estimates for these pathogens in children from 2000 to 2015. Methods: Using WHO and Maternal and Child Epidemiology Estimation collaboration country-specific estimates of pneumonia and meningitis mortality and pneumonia morbidity from 2000 to 2015, we applied pneumococcal and Hib cause-specific proportions to estimate pathogen-specific deaths and cases. Summary estimates of the proportion of pneumonia deaths and cases attributable to these pathogens were derived from four Hib vaccine and six PCV efficacy and effectiveness study values. The proportion of meningitis deaths due to each pathogen was derived from bacterial meningitis aetiology and adjusted pathogen-specific meningitis case–fatality data. Pneumococcal and Hib meningitis cases were inferred from modelled pathogen-specific meningitis deaths and literature-derived case–fatality estimates. Cases of pneumococcal and Hib syndromes other than pneumonia and meningitis were estimated using the ratio of pathogen-specific non-pneumonia, non-meningitis cases to pathogen-specific meningitis cases from the literature. We accounted for annual HIV infection prevalence, access to care, and vaccine use. Findings: We estimated that there were 294 000 pneumococcal deaths (uncertainty range [UR] 192 000–366 000) and 29 500 Hib deaths (18 400–40 700) in HIV-uninfected children aged 1–59 months in 2015. An additional 23 300 deaths (15 300–28 700) associated with pneumococcus and fewer than 1000 deaths associated Hib were estimated to have occurred in children infected with HIV. We estimate that pneumococcal deaths declined by 51% (7–74) and Hib deaths by 90% (78–96) from 2000 to 2015. Most children who died of pneumococcus (81%) and Hib (76%) presented with pneumonia. Less conservative assumptions result in pneumococcccal death estimates that could be as high as 515 000 deaths (302 000–609 000) in 2015. Approximately 50% of all pneumococcal deaths in 2015 occurred in four countries in Africa and Asia: India (68 700 deaths, UR 44 600–86 100), Nigeria (49 000 deaths, 32 400–59 000), the Democratic Republic of the Congo (14 500 deaths, 9300–18 700), and Pakistan (14 400 deaths, 9700–17 000]). India (15 600 deaths, 9800–21 500), Nigeria (3600 deaths, 2200–5100), China (3400 deaths, 2300–4600), and South Sudan (1000 deaths, 600–1400) had the greatest number of Hib deaths in 2015. We estimated 3·7 million episodes (UR 2·7 million–4·3 million) of severe pneumococcus and 340 000 episodes (196 000–669 000) of severe Hib globally in children in 2015. Interpretation: The widespread use of Hib vaccine and the recent introduction of PCV in countries with high child mortality is associated with reductions in Hib and pneumococcal cases and deaths. Uncertainties in the burden of pneumococcal disease are largely driven by the fraction of pneumonia deaths attributable to pneumococcus. Progress towards further reducing the global burden of Hib and pneumococcal disease burden will depend on the efforts of a few large countries in Africa and Asia

Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activator receptor γ (PPARγ) and zinc finger protein 407 (Zfp407)

Abstract: Although homocysteine (Hcy), a part of the epigenome, contributes to cell death by pyroptosis and decreases PPARγ levels, the mechanisms are unclear. Hcy is found in high concentrations in the sera of obese individuals which can elicit an immune response as well by hypermethylating CpG islands of specific gene promoters, a marker of epigenetics. Hcy has also been established to chelate divalent metal ions like Cu+2 and Zn+2, but this role of Hcy has not been established in relationship with obesity. It has been known for a while that PPARγ dysregulation results in various metabolic disorders including glucose and lipid metabolism. Recently, zinc finger protein 407 (Zfp407) is reported to regulate PPARγ target gene expression without affecting PPARγ transcript and protein levels by synergistically working with PPARγ. However, the mechanism(s) of this synergy, as well as other factors contributing to or inhibiting this synergism have not been proven. This review suggests that Hcy contributes to pyroptosis, changes gut microbiome, alter PPARγ-dependent mechanism(s) via Zfp407 mediated upregulated adipogenesis and misbalanced fatty acid metabolism leading that can predispose to obesity and consequently the obesity-related metabolic disorders.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Evaluation of management practices in rice–wheat cropping system using multicriteria decision-making methods in conservation agriculture

Abstract In this study, we employed two multiple criteria decision-making (MCDM) methods, namely the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) and the Analytic Hierarchic Process (AHP), to determine the best management choice for the cultivation of wheat with a regime of conservation agriculture (CA) practices. By combining alternative tillage approaches, such as reduced tillage and zero tillage, with the quantity of crop residues and fertilizer application, we were able to develop the regime of CA practices. The performance of the regimes compared to the conventional ones was then evaluated using conflicting parameters relating to energy use, economics, agronomy, plant protection, and soil science. TOPSIS assigned a grade to each alternative based on how close it was to the ideal solution and how far away it was from the negative ideal solution. However, employing AHP, we determined the weights of each of the main and sub-parameters used for this study using pairwise comparison. With TOPSIS, we found ZERO1 (0% residue + 100% NPK) followed by ZERO4 (50%residue + 100% NPK), and ZERO2 (100% residue + 50% NPK) were the best performing tillage-based alternatives. To best optimize the performance of wheat crops under various CA regimes, TOPSIS assisted the decision-makers in distinguishing the effects of the parameters on the outcome and identifying the potential for maneuvering the weak links. The outcomes of this investigation could be used to improve management techniques for wheat production with CA practices for upscaling among the farmers

Hydrogen sulfide intervention in cystathionine-β-synthase mutant mouse helps restore ocular homeostasis

AIM: To investigate the applications of hydrogen sulfide (H2S) in eye-specific ailments in mice. METHODS: Heterozygous cystathionine-β-synthase (CBS+/-) and wild-type C57BL/6J (WT) mice fed with or without high methionine diet (HMD) were administered either phosphate buffered saline (PBS) or the slow-release H2S donor: GYY4137. Several analyses were performed to study GYY4137 effects by examining retinal lysates for key protein expressions along with plasma glutamate and glutathione estimations. Intraocular pressure (IOP) was monitored during GYY4137 treatment; barium sulfate and bovine serum albumin conjugated fluorescein isothiocyanate (BSA-FITC) angiographies were performed for examining vasculature and its permeability post-treatment. Vision-guided behavior was also tested employing novel object recognition test (NORT) and light-dark box test (LDBT) recordings. RESULTS: CBS deficiency (CBS+/-) coupled with HMD led disruption of methionine/homocysteine (Hcy) metabolism leading to hyperhomocysteinemia (HHcy) in CBS+/− mice as reflected by increased Hcy, and s-adenosylhomocysteine hydrolase (SAHH) levels. Unlike CBS, cystathionine-γ lyase (CSE), methylenetetrahydrofolate reductase (MTHFR) levels which were reduced but compensated by GYY4137 intervention. Heightened oxidative and endoplasmic reticulum (ER) stress responses were mitigated by GYY4137 effects along with enhanced glutathione (GSH) levels. Increased glutamate levels in CBS+/− strain were prominent than WT mice and these mice also exhibited higher IOP that was lowered by GYY4137 treatment. CBS deficiency also resulted in vision-guided behavioral impairment as revealed by NORT and LDBT findings. Interestingly, GYY4137 was able to improve CBS+/− mice behavior together with lowering their glutamate levels. Blood-retinal barrier (BRB) appeared compromised in CBS+/− with vessels’ leakage that was mitigated in GYY4137 treated group. This corroborated the results for occludin (an integral plasma membrane protein of the cellular tight junctions) stabilization. CONCLUSION: Findings reveal that HHcy-induced glutamate excitotoxicity, oxidative damage, ER-stress and vascular permeability alone or together can compromise ocular health and that GYY4137 could serve as a potential therapeutic agent for treating HHcy induced ocular disorders

CircRNAs constitute an inherent gene-regulatory axis in the mammalian eye and brain

CircRNAs are a new class of covalently closed transcripts that are produced via back-splicing. These molecules have been identified in organisms ranging from worm to plants. Research on circRNAs is an active area because of their diverse roles in health and in diseases. Their circularity makes them resistant to degradation thus they hold great promise as unique biomarkers. We believe that further work on their applications could help in developing them as “first-in-class” diagnostics, therapeutics, and prognostic targets for eye conditions. Many circRNAs play roles in transcriptional regulation by acting as miRNAs sponges. Since retina is an extension of brain and is part of CNS, we highlight the current state of circRNA biogenesis, properties and function and we review the crucial roles they play in the eye and brain. We also discuss their roles as miRNA sponges, regulation of genes or linear mRNAs, translation into micro-peptides/proteins, and responses to cellular stress. We posit that future advances will provide newer insights in the fields of RNA metabolism in general and diseases of the aging eye and brain. Furthermore, in keeping pace with the rapidly evolving discipline of RNA‘omics’-centered metabolism and to achieve uniformity among researchers, we recently introduced the term “cromics”The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author