Divergent membrane properties of mouse cochlear glial cells around hearing onset

Spiral ganglion neurons (SGNs) are the primary afferent neurons of the auditory system, and together with their attendant glia, form the auditory nerve. Within the cochlea, satellite glial cells (SGCs) encapsulate the cell body of SGNs, whereas Schwann cells (SCs) wrap their peripherally- and centrally-directed neurites. Despite their likely importance in auditory nerve function and homeostasis, the physiological properties of auditory glial cells have evaded description. Here, we characterized the voltage-activated membrane currents of glial cells from the mouse cochlea. We identified a prominent weak inwardly rectifying current in SGCs within cochlear slice preparations (postnatal day P5-P6), which was also present in presumptive SGCs within dissociated cultures prepared from the cochleae of hearing mice (P14-P15). Pharmacological block by Ba2+ and desipramine suggested that channels belonging to the Kir4 family mediated the weak inwardly rectifying current, and post hoc immunofluorescence implicated the involvement of Kir4.1 subunits. Additional electrophysiological profiles were identified for glial cells within dissociated cultures, suggesting that glial subtypes may have specific membrane properties to support distinct physiological roles. Immunofluorescence using fixed cochlear sections revealed that although Kir4.1 is restricted to SGCs after the onset of hearing, these channels are more widely distributed within the glial population earlier in postnatal development (i.e., within both SGCs and SCs). The decrease in Kir4.1 immunofluorescence during SC maturation was coincident with a reduction of Sox2 expression and advancing neurite myelination. The data suggest a diversification of glial properties occurs in preparation for sound-driven activity in the auditory nerve

Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing.

Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice

Markets, marketing and production issues for aquaculture in East Africa: the case of Uganda

Aquaculture is currently responsible for an insignificant proportion of total fish production in Uganda. However, given the increasing demand for fresh fish in urban and peri-urban araes, and threats to the supply of fish from natural catch fisheries, the potential exists for a strong market in aquaculture. Small-scale fish farmers located relatively close to markets or all-season roads, and who can supply consistent and high quality produce, will have the widest range of marketing opportunities, and will likely be within the area of operation of potential traders and intermediaries that deliver fish to markets. Fish farmers that are not close to roads, or produce unreliable quantities and variable quality products may face high transaction costs of marketing their product, and decreasing net returns to production. The authors found that significant on-farm labor, and access to input markets are important factors leading to positive net returns to fish production. Areas with high population density and relatively low wages will be well suited to labor intensive aquaculture. The authors concluded that aquaculture development has good potential in certain areas of Uganda and should therefore be pursued as a potential development pathway. However, policy makers should consider the importance of the price of fresh fish relative to the cost of labor, as well as other factors including the importance of smallholder credit and access to extension services, when directing investments in aquaculture technology

The influence of smoking, sedentary lifestyle and obesity on cognitive impairment-free life expectancy

BACKGROUND Smoking, sedentary lifestyle and obesity are risk factors for mortality and dementia. However, their impact on cognitive impairment-free life expectancy (CIFLE)has not previously been estimated. METHODS Data were drawn from the DYNOPTA dataset which was derived by harmonizing and pooling common measures from five longitudinal ageing studies. Participants for whom the Mini-Mental State Examination was available were included (N¼8111,48.6% men). Data on education, sex, body mass index, smoking and sedentary lifestyle were collected and mortality data were obtained from Government Records via data linkage.Total life expectancy (LE), CIFLE and years spent with cognitive impairment (CILE)were estimated for each risk factor and total burden of risk factors. RESULTS CILE was approximately 2 years for men and 3 years for women, regardless of age. For men and women respectively, reduced LE associated with smoking was 3.82and 5.88 years, associated with obesity was 0.62 and 1.72 years and associated with being sedentary was 2.50 and 2.89 years. Absence of each risk factor was associated with longer LE and CIFLE, but also longer CILE for smoking in women and being sedentary in both sexes. Compared with participants with no risk factors, those with 2þ had shorter CIFLE of up to 3.5 years depending on gender and education level. CONCLUSIONS Population level reductions in smoking, sedentary lifestyle and obesity increase longevity and number of years lived without cognitive impairment. Years lived with cognitive impairment may also increase.This work was supported by a National Health and Medical Research Council grant # 410215 and by the Australian Research Council Centre of Excellence in Population Ageing Research (CE110001029). K.J.A is funded by NHMRC Fellowship #1002560. C.J. is funded by the AXA Research Fund

Therapeutic efficacy of favipiravir against Bourbon virus in mice

Bourbon virus (BRBV) is an emerging tick-borne RNA virus in the orthomyxoviridae family that was discovered in 2014. Although fatal human cases of BRBV have been described, little is known about its pathogenesis, and no antiviral therapies or vaccines exist. We obtained serum from a fatal case in 2017 and successfully recovered the second human infectious isolate of BRBV. Next-generation sequencing of the St. Louis isolate of BRBV (BRBV-STL) showed >99% nucleotide identity to the original reference isolate. Using BRBV-STL, we developed a small animal model to study BRBV-STL tropism in vivo and evaluated the prophylactic and therapeutic efficacy of the experimental antiviral drug favipiravir against BRBV-induced disease. Infection of Ifnar1-/- mice lacking the type I interferon receptor, but not congenic wild-type animals, resulted in uniformly fatal disease 6 to 10 days after infection. RNA in situ hybridization and viral yield assays demonstrated a broad tropism of BRBV-STL with highest levels detected in liver and spleen. In vitro replication and polymerase activity of BRBV-STL were inhibited by favipiravir. Moreover, administration of favipiravir as a prophylaxis or as post-exposure therapy three days after infection prevented BRBV-STL-induced mortality in immunocompromised Ifnar1-/- mice. These results suggest that favipiravir may be a candidate treatment for humans who become infected with BRBV

Curcumin-based photosensitization inactivates Aspergillus flavus and reduces aflatoxin B1 in maize kernels

Different methods have been applied in controlling contamination of foods and feeds by the carcinogenic fungal toxin, aflatoxin, but nevertheless the problem remains pervasive in developing countries. Curcumin is a natural polyphenolic compound from the spice turmeric (Curcuma longa L.) that has been identified as an efficient photosensitiser for inactivation of Aspergillus flavus conidia. Curcumin mediated photoinactivation of A. flavus has revealed the potential of this technology to be an effective method for reducing population density of the aflatoxin-producing fungus in foods. This study demonstrates the influence of pH and temperature on efficiency of photoinactivation of the fungus and how treating spore-contaminated maize kernels affects aflatoxin production. The results show the efficiency of curcumin mediated photoinactivation of fungal conidia and hyphae were not affected by temperatures between 15 and 35 °C or pH range of 1.5–9.0. The production of aflatoxin B was significantly lower (p < 0.05), with an average of 82.4 μg/kg as compared to up to 305.9 μg/kg observed in untreated maize kept under similar conditions. The results of this study indicate that curcumin mediated photosensitization can potentially be applied under simple environmental conditions to achieve significant reduction of post-harvest contamination of aflatoxin B in maize

Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS)

Background: Little is known about how the proportions of dependency states have changed between generational cohorts of older people. We aimed to estimate years lived in different dependency states at age 65 years in 1991 and 2011, and new projections of future demand for care. Methods: In this population-based study, we compared two Cognitive Function and Ageing Studies (CFAS I and CFAS II) of older people (aged ≥65 years) who were permanently registered with a general practice in three defined geographical areas (Cambridgeshire, Newcastle, and Nottingham; UK). These studies were done two decades apart (1991 and 2011). General practices provided lists of individuals to be contacted and were asked to exclude those who had died or might die over the next month. Baseline interviews were done in the community and care homes. Participants were stratified by age, and interviews occurred only after written informed consent was obtained. Information collected included basic sociodemographics, cognitive status, urinary incontinence, and self-reported ability to do activities of daily living. CFAS I was assigned as the 1991 cohort and CFAS II as the 2011 cohort, and both studies provided prevalence estimates of dependency in four states: high dependency (24-h care), medium dependency (daily care), low dependency (less than daily), and independent. Years in each dependency state were calculated by Sullivan's method. To project future demands for social care, the proportions in each dependency state (by age group and sex) were applied to the 2014 England population projections. Findings: Between 1991 and 2011, there were significant increases in years lived from age 65 years with low dependency (1·7 years [95% CI 1·0-2·4] for men and 2·4 years [1·8-3·1] for women) and increases with high dependency (0·9 years [0·2-1·7] for men and 1·3 years [0·5-2·1] for women). The majority of men's extra years of life were spent independent (36·3%) or with low dependency (36·3%) whereas for women the majority were spent with low dependency (58·0%), and only 4·8% were independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71 215 care home places by 2025. Interpretation: On average older men now spend 2·4 years and women 3·0 years with substantial care needs, and most will live in the community. These findings have considerable implications for families of older people who provide the majority of unpaid care, but the findings also provide valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations. Funding: Medical Research Council (G9901400) and (G06010220), with support from the National Institute for Health Research Comprehensive Local research networks in West Anglia and Trent, UK, and Neurodegenerative Disease Research Network in Newcastle, UK

The Peterborough Exemplar: a protocol to evaluate the impact and implementation of a new patient-centred, system-wide community mental healthcare model in England.

BACKGROUND: Community mental healthcare has significantly grown since de-institutionalization. Despite progress, service fragmentation and gaps in service provision remain key barriers to effective community care in England. Recent mental healthcare policies highlighted the need to transform service provision by developing patient-centred, joined-up community mental healthcare. In response to policy guidance, a system-wide community mental healthcare model was developed in Peterborough (England). The "Peterborough Exemplar" is based on two main pillars: (1) the creation of knowledge exchange pathways to strengthen interorganizational relationships, and (2) the development of new, accessible community services addressing existing service gaps. This paper presents the protocol developed to evaluate the Peterborough Exemplar. METHODS: A quasi-experimental design with an intervention group and a nonequivalent comparator group has been developed to compare service provision provided in Peterborough pre- and post-intervention with services provided in Fenland, a neighbouring area where service users access usual care. Two evaluation methods will be employed to compare service provision between the two groups: (1) outcome measures completed by service users and carers will be analysed to assess quality of life and service satisfaction, and (2) service activity data will be analysed to assess service usage. In addition, qualitative interviews will be conducted with staff members of participating organizations to explore the implementation of the Exemplar in Peterborough and evaluate knowledge exchange processes among local service providers. A matched control approach will be used to compare outcome measures between the two areas. Descriptive and inferential statistics, including chi-square tests, will be used to analyse service activity data and examine differences between the two areas. A thematic analysis will be adopted to analyse qualitative data. DISCUSSION: Outcomes of the evaluation will contribute to understanding the contribution of the Peterborough Exemplar on mental health service provision locally. Evaluation findings and intermediate reporting will be shared with organizations involved in the implementation of the Peterborough Exemplar and with local decision-makers to inform the Exemplar delivery. As the Peterborough Exemplar is an Early Implementer (EI) site funded by NHS England, findings will be shared with policy-makers to inform national policy on community mental healthcare and integrated care

Early Adoption of an Improved Household Energy System in Urban Rwanda

Cooking with solid fuels and inefficient cookstoves has adverse consequences for health, environment, and human well-being. Despite the promise of improved cookstoves to reduce these impacts, adoption rates are relatively low. Using a 2-wave sample of 144 households from the baseline and first midline of an ongoing 4-year randomized controlled trial in Rwanda, we analyze the drivers and associations of early adoption of a household energy intervention marketed by a private sector firm. Households sign an annual contract to purchase sustainably produced biomass pellets and lease a fan micro-gasification cookstove with verified emissions reductions in laboratory settings. Using difference-in-differences and fixed effects estimation techniques, we examine the association between take-up of the improved cooking system and household fuel expenditures, health outcomes, and time use for primary cooks. Thirty percent of households adopted the pellet and improved cookstove system. Adopting households had more assets, lower per capita total expenditures and cooking fuel expenditures, and higher per capita hygiene expenditures. Households with married household heads and female cooks were significantly more likely to adopt. Adjusting for confounders, we find significant reduction in primary cooks’ systolic blood pressure, self-reported prevalence of shortness of breath, an indicator of respiratory illness, time spent cooking, and household expenditures on charcoal. Our findings have implications for marketing of future clean fuel and improved cookstove programs in urban settings or where stoves and fuel are purchased. Analysis of follow-up surveys will allow for estimation of long-term impacts of adoption of interventions involving pellets and fan micro-gasification cookstoves