NS4A protein as a marker of HCV history suggests that different HCV genotypes originally evolved from genotype 1b

<p>Abstract</p> <p>Background</p> <p>The 9.6 kb long RNA genome of Hepatitis C virus (HCV) is under the control of RNA dependent RNA polymerase, an error-prone enzyme, for its transcription and replication. A high rate of mutation has been found to be associated with RNA viruses like HCV. Based on genetic variability, HCV has been classified into 6 different major genotypes and 11 different subtypes. However this classification system does not provide significant information about the origin of the virus, primarily due to high mutation rate at nucleotide level. HCV genome codes for a single polyprotein of about 3011 amino acids which is processed into structural and non-structural proteins inside host cell by viral and cellular proteases.</p> <p>Results</p> <p>We have identified a conserved NS4A protein sequence for HCV genotype 3a reported from four different continents of the world i.e. Europe, America, Australia and Asia. We investigated 346 sequences and compared amino acid composition of NS4A protein of different HCV genotypes through Multiple Sequence Alignment and observed amino acid substitutions C₂₂, V₂₉, V₃₀, V₃₈, Q₄₆and Q₄₇in NS4A protein of genotype 1b. Furthermore, we observed C₂₂and V₃₀as more consistent members of NS4A protein of genotype 1a. Similarly Q₄₆and Q₄₇in genotype 5, V₂₉, V₃₀, Q₄₆and Q₄₇in genotype 4, C₂₂, Q₄₆and Q₄₇in genotype 6, C₂₂, V₃₈, Q₄₆and Q₄₇in genotype 3 and C₂₂in genotype 2 as more consistent members of NS4A protein of these genotypes. So the different amino acids that were introduced as substitutions in NS4A protein of genotype 1 subtype 1b have been retained as consistent members of the NS4A protein of other known genotypes.</p> <p>Conclusion</p> <p>These observations indicate that NS4A protein of different HCV genotypes originally evolved from NS4A protein of genotype 1 subtype 1b, which in turn indicate that HCV genotype 1 subtype 1b established itself earlier in human population and all other known genotypes evolved later as a result of mutations in HCV genotype 1b. These results were further confirmed through phylogenetic analysis by constructing phylogenetic tree using NS4A protein as a phylogenetic marker.</p

Wealth, household heterogeneity and livelihood diversification of Fulani pastoralists in the Kachia Grazing Reserve, northern Nigeria, during a period of social transition

A mixed methods study was undertaken in the Kachia Grazing Reserve of northern Nigeria. Surveys in March, June and October 2011 included focus group discussions, key informant and in-depth household interviews, concerning livelihood practices, animal health, ownership, and productivity. In May 2011, 249 Fulani families fleeing post-election violence entered the reserve with their livestock, increasing the number of households by one third.Despite being settled within a grazing reserve, over half of households sent all their cattle away on seasonal transhumance and another third sent some away. Cattle accounted for 96% of total tropical livestock units (TLU), of which 26% were cattle kept permanently outside the reserve. While all households cited livestock as their main source of income, 90% grew crops and 55% derived income from off-farm activities. A multiple correspondence analysis showed that for each extra member of a household its TLU value increased by 2.0 [95% CI, 1.4-2.7], while for each additional marriage its TLU increased by 15.7 [95% CI, 7.1-24.3]. A strong association was also observed between small herds, small households with only one wife, alongside marked geographical wealth differences within the reserve. New immigrant families had larger household sizes (33) and livestock holdings (122 TLU) than old settlers (22 people and 67 TLU). Prior to the mass immigration, the distribution of TLU per person was unimodal: 41% of households were classified as 'poor' and 27% as 'medium', whereas post-immigration it was bi-modal, with 26% classified as 'very poor' and 28% as 'medium'.While cattle remain the principal source of Fulani income and wealth, the inhabitants of Kachia Grazing Reserve have diversified their livelihood strategies to respond to changing circumstances and stress, especially the limited availability of grazing within the reserve and political insecurity outside, resulting in continued transhumance, the maintenance of smaller livestock holdings and pushing households into poverty

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men