The Effects of Elevated Testosterone on the Outcome of ma2009 H1N1 Influenza A Virus infection in Old Male Mice

Testosterone (T) has anti-inflammatory properties, and has been shown to play a role in the pathogenesis of infectious and autoimmune diseases. Disease pathology from influenza A virus (IAV) infection is caused by an excessive pro-inflammatory response, and severe disease is especially common among elderly men, who have lower T levels. We tested the hypothesis that T will protect against IAV pathogenesis in young adult (8-10 weeks) and old (17-18 months) male mice. To study the effects of T in young adult male mice, the mice were gonadectomized, treated with T or placebo capsules, infected with a sub-lethal dose of H1N1, and monitored for morbidity and mortality. In old male mice, serum T is naturally low, therefore gonadectomies are not required before the subsequent steps. In addition, we attempted to elevate testosterone levels endogenously in old male mice through steroidogenic drugs called TSPO ligands. However, two different drugs tested did not significantly raise serum testosterone levels. T-treated young adult males experienced lower morbidity, and had lower IgG antibody titers compared to placebo-treated young adult males. In old males, while the same dose of T was not protective against morbidity from IAV infection, treatment with a higher dose of T resulted in improved recovery from influenza disease. Protection from morbidity by testosterone treatment is not reflected in the expression of Ki67, which is a marker for proliferation, in the lungs at 21 days after infection. This suggests that either the improved recovery from disease is not associated with improved repair, or day 21, which is after peak disease and viral clearance, is too late a time point to detect any difference. We hypothesize that old males require a higher dose of T in order to mitigate the chronic pro-inflammatory state brought about by aging

Ancestral Polymorphisms Shape the Adaptive Radiation of Metrosideros across the Hawaiian Islands

Some of the most spectacular adaptive radiations begin with founder populations on remote islands. How genetically limited founder populations give rise to the striking phenotypic and ecological diversity characteristic of adaptive radiations is a paradox of evolutionary biology. We conducted an evolutionary genomics analysis of genus Metrosideros, a landscape-dominant, incipient adaptive radiation of woody plants that spans a striking range of phenotypes and environments across the Hawaiian Islands. Using nanopore-sequencing, we created a chromosome-level genome assembly for Metrosideros polymorpha var. incana and analyzed whole-genome sequences of 131 individuals from 11 taxa sampled across the islands. Demographic modeling and population genomics analyses suggested that Hawaiian Metrosideros originated from a single colonization event and subsequently spread across the archipelago following the formation of new islands. The evolutionary history of Hawaiian Metrosideros shows evidence of extensive reticulation associated with significant sharing of ancestral variation between taxa and secondarily with admixture. Taking advantage of the highly contiguous genome assembly, we investigated the genomic architecture underlying the adaptive radiation and discovered that divergent selection drove the formation of differentiation outliers in paired taxa representing early stages of speciation/divergence. Analysis of the evolutionary origins of the outlier single nucleotide polymorphisms (SNPs) showed enrichment for ancestral variations under divergent selection. Our findings suggest that Hawaiian Metrosideros possesses an unexpectedly rich pool of ancestral genetic variation, and the reassortment of these variations has fueled the island adaptive radiation

Pharmacies in informal settlements : a retrospective, cross-sectional household and health facility survey in four countries

Background Slums or informal settlements characterize most large cities in LMIC. Previous evidence suggests pharmacies may be the most frequently used source of primary care in LMICs but that pharmacy services are of variable quality. However, evidence on pharmacy use and availability is very limited for slum populations. Methods We conducted household, individual, and healthcare provider surveys and qualitative observations on pharmacies and pharmacy use in seven slum sites in four countries (Nigeria, Kenya, Pakistan, and Bangladesh). All pharmacies and up to 1200 households in each site were sampled. Adults and children were surveyed about their use of healthcare services and pharmacies were observed and their services, equipment, and stock documented. Results We completed 7692 household and 7451 individual adults, 2633 individual child surveys, and 157 surveys of pharmacies located within the seven sites. Visit rates to pharmacies and drug sellers varied from 0.1 (Nigeria) to 3.0 (Bangladesh) visits per person-year, almost all of which were for new conditions. We found highly variable conditions in what constituted a “pharmacy” across the sites and most pharmacies did not employ a qualified pharmacist. Analgesics and antibiotics were widely available but other categories of medications, particularly those for chronic illness were often not available anywhere. The majority of pharmacies lacked basic equipment such as a thermometer and weighing scales. Conclusions Pharmacies are locally and widely available to residents of slums. However, the conditions of the facilities and availability of medicines were poor and prices relatively high. Pharmacies may represent a large untapped resource to improving access to primary care for the urban poor

Pharmacies in informal settlements : a retrospective, cross-sectional household and health facility survey in four countries

Background Slums or informal settlements characterize most large cities in LMIC. Previous evidence suggests pharmacies may be the most frequently used source of primary care in LMICs but that pharmacy services are of variable quality. However, evidence on pharmacy use and availability is very limited for slum populations. Methods We conducted household, individual, and healthcare provider surveys and qualitative observations on pharmacies and pharmacy use in seven slum sites in four countries (Nigeria, Kenya, Pakistan, and Bangladesh). All pharmacies and up to 1200 households in each site were sampled. Adults and children were surveyed about their use of healthcare services and pharmacies were observed and their services, equipment, and stock documented. Results We completed 7692 household and 7451 individual adults, 2633 individual child surveys, and 157 surveys of pharmacies located within the seven sites. Visit rates to pharmacies and drug sellers varied from 0.1 (Nigeria) to 3.0 (Bangladesh) visits per person-year, almost all of which were for new conditions. We found highly variable conditions in what constituted a “pharmacy” across the sites and most pharmacies did not employ a qualified pharmacist. Analgesics and antibiotics were widely available but other categories of medications, particularly those for chronic illness were often not available anywhere. The majority of pharmacies lacked basic equipment such as a thermometer and weighing scales. Conclusions Pharmacies are locally and widely available to residents of slums. However, the conditions of the facilities and availability of medicines were poor and prices relatively high. Pharmacies may represent a large untapped resource to improving access to primary care for the urban poor

The prevalence and socio-demographic associations of household food insecurity in seven slum sites across Nigeria, Kenya, Pakistan, and Bangladesh. A cross-sectional study

Although the proportion of people living in slums is increasing in low- and middle-income countries and food insecurity is considered a severe hazard for health, there is little research on this topic. This study investigated and compared the prevalence and socio-demographic associations of household food insecurity in seven slum settings across Nigeria, Kenya, Pakistan, and Bangladesh. Data were taken from a cross-sectional, household-based, spatially referenced survey conducted between December 2018 and June 2020. Household characteristics and the extent and distribution of food insecurity across sites was established using descriptive statistics. Multivariable logistic regression of data in a pooled model including all slums (adjusting for slum site) and site-specific analyses were conducted. In total, a sample of 6,111 households were included. Forty-one per cent (2,671) of all households reported food insecurity, with varying levels between the different slums (9-69%). Household head working status and national wealth quintiles were consistently found to be associated with household food security in the pooled analysis (OR: 0·82; CI: 0·69-0·98 & OR: 0·65; CI: 0·57-0·75) and in the individual sites. Households which owned agricultural land (OR: 0·80; CI: 0·69-0·94) were less likely to report food insecurity. The association of the household head's migration status with food insecurity varied considerably between sites. We found a high prevalence of household food insecurity which varied across slum sites and household characteristics. Food security in slum settings needs context-specific interventions and further causal clarification

Analysis of OpenStreetMap data quality at different stages of a participatory mapping process : evidence from slums in Africa and Asia

This paper examines OpenStreetMap data quality at different stages of a participatory mapping process in seven slums in Africa and Asia. Data were drawn from an OpenStreetMap-based participatory mapping process developed as part of a research project focusing on understanding inequalities in healthcare access of slum residents in the Global South. Descriptive statistics and qualitative analysis were employed to examine the following research question: What is the spatial data quality of collaborative remote mapping achieved by volunteer mappers in morphologically complex urban areas? Findings show that the completeness achieved by remote mapping largely depends on the morphology and characteristics of slums such as building density and rooftop architecture, varying from 84 in the best case, to zero in the most difficult site. The major scientific contribution of this study is to provide evidence on the spatial data quality of remotely mapped data through volunteer mapping efforts in morphologically complex urban areas such as slums; the results could provide insights into how much fieldwork would be needed in what level of complexity and to what extent the involvement of local volunteers in these efforts is required

Genome analysis traces regional dispersal of rice in Taiwan and Southeast Asia.

The dispersal of rice (Oryza sativa) following domestication influenced massive social and cultural changes across South, East, and Southeast Asia. The history of dispersal across islands of Southeast Asia, and the role of Taiwan and the Austronesian expansion in this process remain largely unresolved. Here, we reconstructed the routes of dispersal of O. sativa ssp. japonica rice through Taiwan and the northern Philippines using whole-genome re-sequencing of indigenous rice landraces coupled with archaeological and paleoclimate data. Our results indicate that japonica rice found in the northern Philippines diverged from Indonesian landraces as early as 3500 BP. In contrast, rice cultivated by the indigenous peoples of the Taiwanese mountains has complex origins. It comprises two distinct populations, each best explained as a result of admixture between temperate japonica that presumably came from northeast Asia, and tropical japonica from the northern Philippines and mainland Southeast Asia respectively. We find that the temperate japonica component of these indigenous Taiwan populations diverged from northeast Asia subpopulations at about 2600 BP, while gene flow from the northern Philippines occurred before ∼1300 years BP. This coincides with a period of intensified trade established across the South China Sea. Finally, we find evidence for positive selection acting on distinct genomic regions in different rice subpopulations, indicating local adaptation associated with the spread of japonica rice

A protocol for a multi-site, spatially-referenced household survey in slum settings : methods for access, sampling frame construction, sampling, and field data collection

Background Household surveys are a key epidemiological, medical, and social research method. In poor urban environments, such as slums, censuses can often be out-of-date or fail to record transient residents, maps may be incomplete, and access to sites can be limit, all of which prohibits obtaining an accurate sampling frame. This article describes a method to conduct a survey in slum settings in the context of the NIHR Global Health Research Unit on Improving Health in Slums project. Methods We identify four key steps: obtaining site access, generation of a sampling frame, sampling, and field data collection. Stakeholder identification and engagement is required to negotiate access. A spatially-referenced sampling frame can be generated by: remote participatory mapping from satellite imagery; local participatory mapping and ground-truthing; and identification of all residents of each structure. We propose to use a spatially-regulated sampling method to ensure spatial coverage across the site. Finally, data collection using tablet devices and open-source software can be conducted using the generated sample and maps. Discussion Slums are home to a growing population who face some of the highest burdens of disease yet who remain relatively understudied. Difficulties conducting surveys in these locations may explain this disparity. We propose a generalisable, scientifically valid method that is sustainable and ensures community engagement