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).

Neuronal AR Regulates Glucose Homeostasis and Energy Expenditure in Lean Female Mice With Androgen Excess.

Hyperandrogenemia and polycystic ovary syndrome are a result of the imbalance of androgen levels in females. Androgen receptor (Ar) mediates the effect of androgen, and this study examines how neuronal Ar in the central nervous system mediates metabolism under normal and increased androgen conditions in female mice. The neuron-specific ARKO mouse (SynARKO) was created from female (Ar fl/wt; synapsin promoter driven Cre) and male (Ar fl/y) mice.

Eliminating morbidity caused by neglected tropical diseases by 2030.

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.

Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor.

Previous studies in our laboratory have suggested that the increase in stillbirth in pregnancies complicated by chronic maternal stress or hypercortisolemia is associated with cardiac dysfunction in late stages of labor and delivery. Transcriptomics analysis of the overly represented differentially expressed genes in the fetal heart of hypercortisolemic ewes indicated involvement of mitochondrial function. Sodium dichloroacetate (DCA) has been used to improve mitochondrial function in several disease states.

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.

Pharmacokinetic and Biochemical Profiling of Sodium Dichloroacetate in Pregnant Ewes and Fetuses.

Sodium dichloroacetate (DCA) is an investigational drug that shows promise in the treatment of acquired and congenital mitochondrial diseases, including myocardial ischemia and failure. DCA increases glucose utilization and decreases lactate production, so it may also have clinical utility in reducing lactic acidosis during labor. In the current study, we tested the ability of DCA to cross the placenta and be measured in fetal blood after intravenous administration to pregnant ewes during late gestation and labor.

Maternal hypercortisolemia alters placental metabolism: a multiomics view.

Previous studies have suggested that increases in maternal cortisol or maternal stress in late pregnancy increase the risk of stillbirth at term. In an ovine model with increased maternal cortisol over the last 0.20 of gestation, we have previously found evidence of disruption of fetal serum and cardiac metabolomics and altered expression of genes related to mitochondrial function and metabolism in biceps femoris, diaphragm, and cardiac muscle.

Fetal ovine skeletal and cardiac muscle transcriptomics are differentially altered by increased maternal cortisol during gestation.

We have previously found that in utero exposure to excess maternal cortisol (1 mg/kg/day) in late gestation increases the incidence of stillbirth during labor and produces fetal bradycardia at birth. In the interventricular septum, mitochondrial DNA (mt-DNA) was decreased, and transcriptomics and metabolomics were consistent with altered mitochondrial metabolism. The present study uses transcriptomics to model effects of increased maternal cortisol on fetal biceps femoris.

Transcriptomic evidence that cortisol alters perinatal epicardial adipose tissue maturation.

Cortisol administration during late gestation in ewes, modeling maternal stress, resulted in transcriptomic changes suggesting altered maturation and metabolic changes to the offspring heart. This study investigates the effects of cortisol on epicardial adipose tissue (EAT), a visceral fat pad associated with adverse cardiovascular conditions in adults. Pregnant ewes were treated with either 1 mg·kg·day cortisol from 115 days gestation to term and EAT collected from term fetuses (control: = 8, maternal cortisol 1 mg·kg·day: = 6).

Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis.

Background: The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs).

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.

Determinants of time from HIV infection to linkage-to-care in rural KwaZulu-Natal, South Africa.

Objective: To estimate time from HIV infection to linkage-to-care and its determinants. Linkage-to-care is usually assessed using the date of HIV diagnosis as the starting point for exposure time. However, timing of diagnosis is likely endogenous to linkage, leading to bias in linkage estimation.

Adverse Events from a Randomized, Multi-Arm, Placebo-Controlled Trial of Mebendazole in Children 12-24 Months of Age.

Large-scale deworming interventions, using anthelminthic drugs, are recommended in areas where the prevalence of soil-transmitted helminth infection is high. Anthelminthic safety has been established primarily in school-age children. Our objective was to provide evidence on adverse events from anthelminthic use in early childhood.

The effect of deworming on early childhood development in Peru: A randomized controlled trial.

Background: There is a knowledge gap on the effect of early childhood deworming on development in low- and middle-income countries. This evidence is important in the critical window of growth and development before two years of age.

Methods: A randomized controlled trial of the benefit, and optimal timing and frequency, of deworming on development was conducted in Iquitos, Peru.

The Effect of Deworming on Growth in One-Year-Old Children Living in a Soil-Transmitted Helminth-Endemic Area of Peru: A Randomized Controlled Trial.

Background: Appropriate health and nutrition interventions to prevent long-term adverse effects in children are necessary before two years of age. One such intervention may include population-based deworming, recommended as of 12 months of age by the World Health Organization in soil-transmitted helminth (STH)-endemic areas; however, the benefit of deworming has been understudied in early preschool-age children.

Methodology/principal Findings: A randomized, double-blind, placebo-controlled trial was conducted to determine the effect of deworming (500 mg single-dose crushed mebendazole tablet) on growth in one-year-old children in Iquitos, Peru.

Risk factors associated with malnutrition in one-year-old children living in the Peruvian Amazon.

Background: Children under two years of age are in the most critical window for growth and development. As mobility increases, this time period also coincides with first exposure to soil-transmitted helminth (STH) infections in tropical and sub-tropical environments. The association between malnutrition and STH infection, however, has been understudied in this vulnerable age group.

Timing of umbilical cord-clamping and infant anaemia: the role of maternal anaemia.

Background: Evidence from randomized controlled trials has shown that delayed cord-clamping is beneficial to infant iron status. The role of maternal anaemia in this relationship, however, has not been established.

Objective: To determine the effect of maternal anaemia at delivery on the association between timing of umbilical cord-clamping and infant anaemia at 4 and 8 months of age.

A hospital policy change toward delayed cord clamping is effective in improving hemoglobin levels and anemia status of 8-month-old Peruvian infants.

Objective: To assess the effectiveness of a hospital policy change toward delayed cord clamping on infant hemoglobin (Hb) levels and anemia status at 4 and 8 months of age.

Methods: A cohort of Peruvian mothers and infants, originating from a pre/post study investigating a change in hospital policy from early to delayed cord clamping, was followed until 8 months postpartum. Infant hemoglobin levels and anemia status were measured at 4 and 8 months postpartum.

Effect of a two-component intervention to change hospital practice from early to delayed umbilical cord clamping in the Peruvian Amazon.

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.

Stunting and helminth infection in early preschool-age children in a resource-poor community in the Amazon lowlands of Peru.

The World Health Organization recommends deworming of children aged 12-24 months in highly endemic areas. Our research objectives were to: 1) examine prevalence patterns of helminth infection in early childhood; 2) assess the association between helminth infection and socio-demographic characteristics; and 3) examine the effect of the intensity of helminth infection on stunting and anemia. A survey of children (7-9 and 12-14 months) living in Belén (Peru) was undertaken between July 2007 and February 2008.

A comparison of low birth weight among newborns of early adolescents, late adolescents, and adult mothers in the Peruvian Amazon.

To compare low birth weight (LBW: <2,500 g) between infants born to adolescent and adult mothers in Iquitos, Peru. A random sample of 4,467 records of women who delivered at the Hospital Apoyo Iquitos between 2005 and 2007 was collected from hospital birth registries. Multivariate logistic and linear regression analyses were performed to compare LBW in newborns of adolescents (10-14, 15-19 years) and adults (≥20 years) and then for primiparous mothers with a normal gestational age, adjusting for newborn sex, antenatal care, and location of the mother's residence.

Comparison of prenatal care coverage in early adolescents, late adolescents, and adult pregnant women in the Peruvian Amazon.

Objective: To compare prenatal care coverage between adolescent (early and late) and adult pregnant women in Iquitos, Peru.

Methods: A random sample of 4467 birth records was collected. Multivariate analyses were performed to compare prenatal care coverage in all adolescent (10-14 years, 15-19 years) and adult (>or=20 years) age groups and then for primiparous women only.

Progress towards the Millennium Development Goals in a community of extreme poverty: local vs. national disparities in Peru.

Objectives: Standard indicators are being used worldwide to track progress towards achieving the Millennium Development Goals (MDGs). These are usually at country level and do not accurately reflect within-country variability of progress towards the targets. This may lead to lack of attention and under-resourcing of the most vulnerable populations.