Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in Caenorhabditis elegans through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic, and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate’s body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour

A direct glia-to-neuron natural transdifferentiation ensures nimble sensory-motor coordination of male mating behaviour

The coordinated execution of innate, stereotyped sexual behaviours, such as courtship and mating, requires sexually dimorphic sensory-motor circuits that are genetically specified during development (reviewed in [1-3]). Studies in the nematode Caenorhabditis elegans, in which the development and function of neural circuits can be interrogated with single cell resolution, have revealed two general developmental mechanisms underlying sexual dimorphism in the nervous system. The first involves the acquisition of sexually dimorphic features in sex-shared neurons during sexual maturation, which include changes in terminal gene expression, such as odorant receptors, neurotransmitters and synaptic regulators [4-10]. The second mechanism involves the generation of sex-specific neurons [11-13]. This requires sex-specific cell death [14] or neurogenesis events resulting from extensive sex differences in the cell division patterns and neurodevelopmental programmes of post-embryonic cell lineages (reviewed in [3]). Here we identify a third, novel way to generate sexual dimorphism in the nervous system. We find that during sexual maturation (L4 stage), a class of sex-shared glial cells acquires sexually dimorphic function by undergoing a direct glia-to-neuron transdifferentiation that results in the production of male-specific neurons. This plasticity is regulated cell-intrinsically by the sex-determination pathway. These previously unnoticed neurons, which we term PHDs, are putative proprioceptors that regulate male locomotion during specific steps of mating. One of these steps is a novel readjustment movement performed when intromission becomes difficult to achieve. Our results reveal sex-specific direct transdifferentiation as a novel mechanism for generating sex-specific neurons and also show the importance of proprioceptive feedback during the complex steps of mating for successful reproduction

Re-interpreting conventional interval estimates taking into account bias and extra-variation

BACKGROUND: The study design with the smallest bias for causal inference is a perfect randomized clinical trial. Since this design is often not feasible in epidemiologic studies, an important challenge is to model bias properly and take random and systematic variation properly into account. A value for a target parameter might be said to be "incompatible" with the data (under the model used) if the parameter's confidence interval excludes it. However, this "incompatibility" may be due to bias and/or extra-variation. DISCUSSION: We propose the following way of re-interpreting conventional results. Given a specified focal value for a target parameter (typically the null value, but possibly a non-null value like that representing a twofold risk), the difference between the focal value and the nearest boundary of the confidence interval for the parameter is calculated. This represents the maximum correction of the interval boundary, for bias and extra-variation, that would still leave the focal value outside the interval, so that the focal value remained "incompatible" with the data. We describe a short example application concerning a meta analysis of air versus pure oxygen resuscitation treatment in newborn infants. Some general guidelines are provided for how to assess the probability that the appropriate correction for a particular study would be greater than this maximum (e.g. using knowledge of the general effects of bias and extra-variation from published bias-adjusted results). SUMMARY: Although this approach does not yet provide a method, because the latter probability can not be objectively assessed, this paper aims to stimulate the re-interpretation of conventional confidence intervals, and more and better studies of the effects of different biases

Community based intervention to optimize osteoporosis management: randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoporosis-related fractures are a significant public health concern. Interventions that increase detection and treatment of osteoporosis are underutilized. This pragmatic randomised study was done to evaluate the impact of a multifaceted community-based care program aimed at optimizing evidence-based management in patients at risk for osteoporosis and fractures.</p> <p>Methods</p> <p>This was a 12-month randomized trial performed in Ontario, Canada. Eligible patients were community-dwelling, aged ≥55 years, and identified to be at risk for osteoporosis-related fractures. Two hundred and one patients were allocated to the intervention group or to usual care. Components of the intervention were directed towards primary care physicians and patients and included facilitated bone mineral density testing, patient education and patient-specific recommendations for osteoporosis treatment. The primary outcome was the implementation of appropriate osteoporosis management.</p> <p>Results</p> <p>101 patients were allocated to intervention and 100 to control. Mean age of participants was 71.9 ± 7.2 years and 94% were women. Pharmacological treatment (alendronate, risedronate, or raloxifene) for osteoporosis was increased by 29% compared to usual care (56% [29/52] vs. 27% [16/60]; relative risk [RR] 2.09, 95% confidence interval [CI] 1.29 to 3.40). More individuals in the intervention group were taking calcium (54% [54/101] vs. 20% [20/100]; RR 2.67, 95% CI 1.74 to 4.12) and vitamin D (33% [33/101] vs. 20% [20/100]; RR 1.63, 95% CI 1.01 to 2.65).</p> <p>Conclusions</p> <p>A multi-faceted community-based intervention improved management of osteoporosis in high risk patients compared with usual care.</p> <p>Trial Registration</p> <p>This trial has been registered with clinicaltrials.gov (ID: NCT00465387)</p

Geographic and ecologic heterogeneity in elimination thresholds for the major vector-borne helminthic disease, lymphatic filariasis

<p>Abstract</p> <p>Background</p> <p>Large-scale intervention programmes to control or eliminate several infectious diseases are currently underway worldwide. However, a major unresolved question remains: what are reasonable stopping points for these programmes? Recent theoretical work has highlighted how the ecological complexity and heterogeneity inherent in the transmission dynamics of macroparasites can result in elimination thresholds that vary between local communities. Here, we examine the empirical evidence for this hypothesis and its implications for the global elimination of the major macroparasitic disease, lymphatic filariasis, by applying a novel Bayesian computer simulation procedure to fit a dynamic model of the transmission of this parasitic disease to field data from nine villages with different ecological and geographical characteristics. Baseline lymphatic filariasis microfilarial age-prevalence data from three geographically distinct endemic regions, across which the major vector populations implicated in parasite transmission also differed, were used to fit and calibrate the relevant vector-specific filariasis transmission models. Ensembles of parasite elimination thresholds, generated using the Bayesian fitting procedure, were then examined in order to evaluate site-specific heterogeneity in the values of these thresholds and investigate the ecological factors that may underlie such variability</p> <p>Results</p> <p>We show that parameters of density-dependent functions relating to immunity, parasite establishment, as well as parasite aggregation, varied significantly between the nine different settings, contributing to locally varying filarial elimination thresholds. Parasite elimination thresholds predicted for the settings in which the mosquito vector is anopheline were, however, found to be higher than those in which the mosquito is culicine, substantiating our previous theoretical findings. The results also indicate that the probability that the parasite will be eliminated following six rounds of Mass Drug Administration with diethylcarbamazine and albendazole decreases markedly but non-linearly as the annual biting rate and parasite reproduction number increases.</p> <p>Conclusions</p> <p>This paper shows that specific ecological conditions in a community can lead to significant local differences in population dynamics and, consequently, elimination threshold estimates for lymphatic filariasis. These findings, and the difficulty of measuring the key local parameters (infection aggregation and acquired immunity) governing differences in transmission thresholds between communities, mean that it is necessary for us to rethink the utility of the current anticipatory approaches for achieving the elimination of filariasis both locally and globally.</p

Occupational stress, work-home interference and burnout among Belgian veterinary practitioners

There have been few formal studies on stress in veterinary surgeons and, in the rare studies available, stress is not examined jointly through the levels of job strain and job engagement, the sources of stress in the issue of work environment and the work-home interference. The authors' goal in this study was to analyse job engagement, job strain, burnout, work-home interference and job stress factors among 216 Belgian veterinary surgeons. Rural practice was compared to small animal and mixed activity. The mean job strain and job engagement level in veterinary surgeons was not higher than what we found in other working populations. However, 15.6% of the group were found to be suffering from high burnout. Rural practitioners had a lower level of job engagement than small animal veterinary surgeons. These small animal practitioners had a lower level of job strain than the mixed practitioners. The level of burnout did not differ significantly across the three types of activity. In comparison to other Belgian and Dutch workers, veterinary surgeons perceived more negative work-home interference. Bovine and mixed practitioners were the most concerned with this problem. The two most important sources of stress reported by bovine practitioners were relations to farmers and working time management (including emergencies and availability)

What is the Role of Community Capabilities for Maternal Health? An Exploration of Community Capabilities as Determinants to Institutional Deliveries in Bangladesh, India, and Uganda

Background: While community capabilities are recognized as important factors in developing resilient health systems and communities, appropriate metrics for these have not yet been developed. Furthermore, the role of community capabilities on access to maternal health services has been underexplored. In this paper, we summarize the development of a community capability score based on the Future Health System (FHS) project’s experience in Bangladesh, India, and Uganda, and, examine the role of community capabilities as determinants of institutional delivery in these three contexts. Methods: We developed a community capability score using a pooled dataset containing cross-sectional household survey data from Bangladesh, India, and Uganda. Our main outcome of interest was whether the woman delivered in an institution. Our predictor variables included the community capability score, as well as a series of previously identified determinants of maternal health. We calculate both population-averaged effects (using GEE logistic regression), as well as sub-national level effects (using a mixed effects model). Results: Our final sample for analysis included 2775 women, of which 1238 were from Bangladesh, 1199 from India, and 338 from Uganda. We found that individual-level determinants of institutional deliveries, such as maternal education, parity, and ante-natal care access were significant in our analysis and had a strong impact on a woman’s odds of delivering in an institution. We also found that, in addition to individual-level determinants, greater community capability was significantly associated with higher odds of institutional delivery. For every additional capability, the odds of institutional delivery would increase by up to almost 6 %. Conclusion: Individual-level characteristics are strong determinants of whether a woman delivered in an institution. However, we found that community capability also plays an important role, and should be taken into account when designing programs and interventions to support institutional deliveries. Consideration of individual factors and the capabilities of the communities in which people live would contribute to the vision of supporting people-centered approaches to health

Socioeconomic status and the incidence of non-central nervous system childhood embryonic tumours in Brazil

<p>Abstract</p> <p>Background</p> <p>Childhood cancer differs from most common adult cancers, suggesting a distinct aetiology for some types of childhood cancer. Our objective in this study was to test the difference in incidence rates of 4 non-CNS embryonic tumours and their correlation with socioeconomic status (SES) in Brazil.</p> <p>Methods</p> <p>Data was obtained from 13 Brazilian population-based cancer registries (PBCRs) of neuroblastoma (NB), Wilms'tumour (WT), retinoblastoma (RB), and hepatoblastoma (HB). Incidence rates by tumour type, age, and gender were calculated per one million children. Correlations between social exclusion index (SEI) as an indicator of socioeconomic status (SES) and incidence rates was investigated using the Spearman's test.</p> <p>Results</p> <p>WT, RB, and HB presented with the highest age-adjusted incidence rates (AAIRs) in 1 to 4 year old of both genders, whereas NB presented the highest AAIR in ≤11 month-olds. However, differences in the incidence rates among PBCRs were observed. Higher incidence rates were found for WT and RB, whereas lower incidence rates were observed for NB. Higher SEI was correlated with higher incidences of NB (0.731; p = 0.0117), whereas no SEI correlation was observed between incidence rates for WT, RB, and HB. In two Brazilian cities, the incidence rates of NB and RB were directly correlated with SEI; NB had the highest incidence rates (14.2, 95% CI, 8.6-19.7), and RB the lowest (3.5, 95% CI, 0.7-6.3) in Curitiba (SEI, 0.730). In Natal (SEI, 0.595), we observed just the opposite; the highest incidence rate was for RB and the lowest was for NB (4.6, 95% CI, 0.1-9.1).</p> <p>Conclusion</p> <p>Regional variations of SES and the incidence of embryonal tumours were observed, particularly incidence rates for NB and RB. Further studies are necessary to investigate risk factors for embryonic tumours in Brazil.</p