Reproductive Profile of Neuronal Androgen Receptor Knockout Female Mice With a Low Dose of DHT.

Hyperandrogenism and polycystic ovarian syndrome result from the imbalance or increase of androgen levels in females. Androgen receptor (AR) mediates the effects of androgens, and this study examines whether neuronal AR plays a role in reproduction under normal and increased androgen conditions in female mice. The neuron-specific AR knockout (KO) mouse (SynARKO) was generated from a female mouse (synapsin promoter driven Cre) and a male mouse (Ar fl/y). Puberty onset and the levels of reproductive hormones such as LH, FSH, testosterone, and estradiol were comparable between the control and the SynARKO mice. There were no differences in cyclicity and fertility between the control and SynARKO mice, with similar impairment in both groups on DHT treatment. Neuronal AR KO, as in this SynARKO mouse model, did not alleviate the infertility associated with DHT treatment. These studies suggest that neuronal AR KO neither altered reproductive function under physiological androgen levels, nor restored fertility under hyperandrogenic conditions.

Eliminating morbidity caused by neglected tropical diseases by 2030 / Eliminar la morbilidad causada por las enfermedades tropicales desatendidas para el 2030 / Eliminação até 2030 da morbidade causada pelas doenças tropicais negligenciadas

ABSTRACT The objective of this manuscript is to provide selective examples of the work of the Pan American Health Organization/World Health Organization (PAHO/WHO) Collaborating Centre for Research and Training in Parasite Epidemiology and Control which contribute to the WHO goal of eliminating neglected tropical diseases by 2030. This PAHO/WHO CC specifically aligns its activities with the Sustainable Development Goals and with the goals outlined in the WHO Road Map for Neglected Tropical Diseases 2021-2030. Its role is to contribute to advancing global action on NTDs, primarily through policy development and knowledge translation. Three important projects have recently been completed: 1. Finalizing the Monitoring and Evaluation Framework for the NTD Road Map (published May 2021; this PAHO/WHO CC was a member of the working group); 2. Developing new guidelines for the preventive chemotherapy of Taenia solium taeniasis (published September 2021; this PAHO/WHO CC was co-Chair; and 3. Formulating a policy brief on deworming for adolescent girls and women of reproductive age (published January 2022; this PAHO/WHO CC is co-lead). These projects are the result of the integration of expertise and experience from multiple partners, including from PAHO and WHO (where both organizations provided key leadership), this PAHO/WHO CC, government ministries, civil society organizations and universities, among others. In conclusion, this PAHO/WHO CC contributes timely guidance to country-led evidence-informed public health policy, to cost-effective program implementation and to the identification of priority research topics - all focused, ultimately, on eliminating NTD-attributable morbidity by 2030.

RESUMEN El objetivo de este artículo es proporcionar ejemplos seleccionados de la labor del centro colaborador de investigación y capacitación en epidemiología y control de parásitos de la Organización Panamericana de la Salud/Organización Mundial de la Salud (OPS/OMS), que contribuye al objetivo de la OMS de eliminar las enfermedades tropicales desatendidas para el 2030. Este centro colaborador de la OPS/OMS alinea sus actividades específicamente con los Objetivos de Desarrollo Sostenible y con los objetivos descritos en la Hoja de ruta sobre enfermedades tropicales desatendidas 2021-2030 de la OMS. Su función es contribuir al avance de las medidas mundiales sobre las enfermedades tropicales desatendidas, principalmente mediante la elaboración de políticas y la traducción de conocimiento. Recientemente se han completado tres proyectos importantes: 1) finalización del marco de seguimiento y evaluación de la Hoja de ruta sobre enfermedades tropicales desatendidas (publicado en mayo del 2021; este centro colaborador de la OPS/OMS formó parte del grupo de trabajo); 2) elaboración de nuevas directrices para la quimioterapia preventiva de la teniasis por Taenia solium (publicado en septiembre del 2021; este centro colaborador fue copresidente); y 3) formulación de un informe de políticas sobre la desparasitación de las adolescentes y las mujeres en edad reproductiva (publicado en enero del 2022; este centro colaborador fue coautor). Estos proyectos son el resultado de la integración del conocimiento y la experiencia de múltiples asociados, como la OPS y la OMS (ambas organizaciones ofrecieron un liderazgo clave), este centro colaborador de la OPS/OMS, así como varios ministerios gubernamentales, organizaciones de la sociedad civil y universidades, entre otros. En conclusión, este centro colaborador de la OPS/OMS ofrece orientaciones oportunas para las políticas de salud pública basadas en la evidencia lideradas por los países, la ejecución de programas costo-efectivos y la determinación de los temas de investigación prioritarios, todo ello destinado, en última instancia, a eliminar la morbilidad atribuible a las enfermedades tropicales desatendidas para el 2030.

RESUMO O objetivo deste manuscrito é fornecer exemplos seletivos do trabalho do Centro Colaborador de Pesquisa e Treinamento em Epidemiologia e Controle de Parasitos da Organização Pan-Americana da Saúde/Organização Mundial da Saúde (OPAS/OMS) que contribuem para a meta da OMS de eliminar até 2030 as doenças tropicais negligenciadas. Este CC da OPAS/OMS alinha especificamente suas atividades com os Objetivos de Desenvolvimento Sustentável e com as metas delineadas no Roteiro da OMS para Doenças Tropicais Negligenciadas 2021-2030. Seu papel é contribuir para o avanço da ação global contra doenças tropicais negligenciadas, principalmente por meio do desenvolvimento de políticas e da tradução de conhecimentos. Três importantes projetos foram concluídos recentemente: 1. Finalização da Estrutura de Monitoramento e Avaliação do Roteiro para as DTN (publicada em maio de 2021 - este CC da OPAS/OMS foi membro do grupo de trabalho); 2. Desenvolvimento de novas diretrizes para a quimioprofilaxia da teníase por Taenia solium (publicado em setembro de 2021 - este CC da OPAS/OMS foi copresidente); e 3. Formulação de orientação para políticas de desparasitação para adolescentes e mulheres em idade reprodutiva (publicado em janeiro de 2022 - este CC da OPAS/OMS foi cogestor). Esses projetos são o resultado da integração de conhecimentos e experiência de múltiplos parceiros, incluindo a OPAS e a OMS (onde ambas as organizações forneceram liderança essencial), este CC da OPAS/OMS, ministérios governamentais, organizações da sociedade civil e universidades, entre outros. Em suma, este CC da OPAS/OMS contribui com orientações oportunas para uma política de saúde pública liderada pelos países e informada com base em evidências, para a implementação de programas com boa relação custo-benefício e para a identificação de tópicos prioritários de pesquisa - todos focados, em última análise, na eliminação da morbidade atribuível às DTN até 2030.

Androgen-induced insulin resistance is ameliorated by deletion of hepatic androgen receptor in females.

Androgen excess is one of the most common endocrine disorders of reproductive-aged women, affecting up to 20% of this population. Women with elevated androgens often exhibit hyperinsulinemia and insulin resistance. The mechanisms of how elevated androgens affect metabolic function are not clear. Hyperandrogenemia in a dihydrotestosterone (DHT)-treated female mouse model induces whole body insulin resistance possibly through activation of the hepatic androgen receptor (AR). We investigated the role of hepatocyte AR in hyperandrogenemia-induced metabolic dysfunction by using several approaches to delete hepatic AR via animal-, cell-, and clinical-based methodologies. We conditionally disrupted hepatocyte AR in female mice developmentally (LivARKO) or acutely by tail vein injection of an adeno-associated virus with a liver-specific promoter for Cre expression in ARfl/fl mice (adLivARKO). We observed normal metabolic function in littermate female Control (ARfl/fl ) and LivARKO (ARfl/fl ; Cre+/- ) mice. Following chronic DHT treatment, female Control mice treated with DHT (Con-DHT) developed impaired glucose tolerance, pyruvate tolerance, and insulin tolerance, not observed in LivARKO mice treated with DHT (LivARKO-DHT). Furthermore, during an euglycemic hyperinsulinemic clamp, the glucose infusion rate was improved in LivARKO-DHT mice compared to Con-DHT mice. Liver from LivARKO, and primary hepatocytes derived from LivARKO, and adLivARKO mice were protected from DHT-induced insulin resistance and increased gluconeogenesis. These data support a paradigm in which elevated androgens in females disrupt metabolic function via hepatic AR and insulin sensitivity was restored by deletion of hepatic AR.

Preventive chemotherapy in one year reduces by over 80% the number of individuals with soil-transmitted helminthiases causing morbidity: results from meta-analysis.

The morbidity due to Ascaris lumbricoides and Trichuris trichiura is caused by infections of moderate and heavy intensity while hookworm infections of all intensities are recognized to cause morbidity. This study aims to evaluate the effect of repeated rounds of preventive chemotherapy on the proportion of soil-transmitted helminth (STH) infections causing morbidity. We identified studies from 17 countries, reporting changes in the proportion of STH infection causing morbidity between baseline and follow-up. In the studies identified, the average proportion of individuals with STH infections of moderate and heavy intensity was of 14% at baseline and was on average reduced to 2% by the intervention (i.e., 85% reduction). There was an average reduction of 73% after the first year of treatment, which reached almost 80% after 5 years and over 95% in 10 years of deworming interventions. The reduction in hookworm prevalence was 57% after 12 months reaching 78% after 5 years. We consider the results presented in this study especially useful for decision makers as it demonstrates the effectiveness of preventive chemotherapy in reducing STH prevalence and morbidity. We encourage the implementation of deworming programs to achieve the goal, set by WHO for 2020, to eliminate STH morbidity in children.

Effect of a two-component intervention to change hospital practice from early to delayed umbilical cord clamping in the Peruvian Amazon / Efecto de una intervención de dos componentes para modificar la práctica hospitalaria de pinzamiento del cordón umbilical de precoz a tardío en la Amazonia peruana

OBJECTIVE: To investigate the effect of a two-component intervention to change hospital practice with regard to the timing of umbilical cord clamping. METHODS: A pre-/post-study design was used to measure the effect of a two-component intervention on mean time to clamp the umbilical cord. The study took place at Hospital Iquitos "César Garayar García" in Iquitos, Peru. A total of 224 women were recruited from the hospital labor room: 112 pre-intervention, from 18 May-3 June 2009, and 112 post-intervention, from 6-20 July 2009. The intervention consisted of 1) a "best practice" three-day training workshop on birthing, and 2) a hospital directive. All deliveries were observed and the time between delivery of the first shoulder and clamping of the umbilical cord was measured with a digital stopwatch. RESULTS: The mean time between delivery and cord clamping before the intervention was 56.8 seconds (95 percent confidence interval [CI]: 51.0, 62.7). This increased to 169.8 seconds (95 percent CI: 153.8, 185.8) following the intervention. The difference in mean time to clamp remained significant in multivariate analyses (βadjusted = 113.2 seconds, 95 percent CI: 96.6, 129.9). CONCLUSIONS: Hospital policy and practice can be successfully changed from early to delayed umbilical cord clamping using a simple, two-component intervention.

OBJETIVO: Investigar el efecto de una intervención de dos componentes para modificar la práctica hospitalaria respecto del momento en que se practica el pinzamiento del cordón umbilical. MÉTODOS: Se empleó un estudio con diseño antes-después para medir el efecto de una intervención de dos componentes sobre el tiempo medio de pinzamiento del cordón umbilical. El estudio se llevó a cabo en el Hospital Iquitos "César Garayar Gar-cía" en Iquitos (Perú). Se incluyeron en total 224 mujeres atendidas en la sala de trabajo de parto del hospital: 112 antes de la intervención, entre el 18 de mayo y el 3 de junio del 2009, y 112 después de la intervención, entre el 6 y el 20 de julio del 2009. La intervención consistió en: 1) un taller de capacitación sobre las "mejores prácticas" en la atención del parto, de 3 días de duración y 2) una directiva del hospital. Se observaron todos los partos y se midió el tiempo entre la salida del hombro anterior y el pinzamiento del cordón umbilical con un cronómetro digital. RESULTADOS: El tiempo medio entre el parto y el pinzamiento del cordón antes de la intervención fue de 56,8 segundos (intervalo de confianza [IC] de 95 por cento: 51,0-62,7), y aumentó a 169,8 segundos (IC 95 por cento: 153,8-185,8) después de la intervención. La diferencia en el tiempo medio hasta el pinzamiento siguió siendo significativa en los análisis multivariados (βajustado = 113,2 segundos, IC 95 por cento: 96,6-129,9). CONCLUSIONES: Es posible cambiar las normas y las prácticas hospitalarias de pinzamiento del cordón umbilical de precoz a tardío mediante una intervención sencilla de dos componentes.

Multidisciplinary and participatory workshops with stakeholders in a community of extreme poverty in the Peruvian Amazon: development of priority concerns and potential health, nutrition and education interventions.

BACKGROUND: Communities of extreme poverty suffer disproportionately from a wide range of adverse outcomes, but are often neglected or underserved by organized services and research attention. In order to target the first Millennium Development Goal of eradicating extreme poverty, thereby reducing health inequalities, participatory research in these communities is needed. Therefore, the purpose of this study was to determine the priority problems and respective potential cost-effective interventions in Belen, a community of extreme poverty in the Peruvian Amazon, using a multidisciplinary and participatory focus. METHODS: Two multidisciplinary and participatory workshops were conducted with important stakeholders from government, non-government and community organizations, national institutes and academic institutions. In Workshop 1, participants prioritized the main health and health-related problems in the community of Belen. Problem trees were developed to show perceived causes and effects for the top six problems. In Workshop 2, following presentations describing data from recently completed field research in school and household populations of Belen, participants listed potential interventions for the priority problems, including associated barriers, enabling factors, costs and benefits. RESULTS: The top ten priority problems in Belen were identified as: 1) infant malnutrition; 2) adolescent pregnancy; 3) diarrhoea; 4) anaemia; 5) parasites; 6) lack of basic sanitation; 7) low level of education; 8) sexually transmitted diseases; 9) domestic violence; and 10) delayed school entry. Causes and effects for the top six problems, proposed interventions, and factors relating to the implementation of interventions were multidisciplinary in nature and included health, nutrition, education, social and environmental issues. CONCLUSION: The two workshops provided valuable insight into the main health and health-related problems facing the community of Belen. The participatory focus of the workshops ensured the active involvement of important stakeholders from Belen. Based on the results of the workshops, effective and essential interventions are now being planned which will contribute to reducing health inequalities in the community.