POMC neurons control fertility through differential signaling of MC4R in Kisspeptin neurons.

Inactivating mutations in the melanocortin 4 receptor () gene cause monogenic obesity. Interestingly, female patients also display various degrees of reproductive disorders, in line with the subfertile phenotype of MC4RKO female mice. However, the cellular mechanisms by which MC4R regulates reproduction are unknown.

Sex-specific pubertal and metabolic regulation of Kiss1 neurons via Nhlh2.

Hypothalamic Kiss1 neurons control gonadotropin-releasing hormone release through the secretion of kisspeptin. Kiss1 neurons serve as a nodal center that conveys essential regulatory cues for the attainment and maintenance of reproductive function. Despite this critical role, the mechanisms that control kisspeptin synthesis and release remain largely unknown.

Extracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus.

Background: Gestational diabetes mellitus (GDM) is a serious public health issue affecting 9-15% of all pregnancies worldwide. Recently, it has been suggested that extracellular vesicles (EVs) play a role throughout gestation, including mediating a placental response to hyperglycaemia. Here, we investigated the EV-associated miRNA profile across gestation in GDM, assessed their utility in developing accurate, multivariate classification models, and determined the signaling pathways in skeletal muscle proteome associated with the changes in the EV miRNA profile.

Inhibiting Kiss1 Neurons With Kappa Opioid Receptor Agonists to Treat Polycystic Ovary Syndrome and Vasomotor Symptoms.

Context: Recent evidence suggests that vasomotor symptoms (VMS) or hot flashes in the postmenopausal reproductive state and polycystic ovary syndrome (PCOS) in the premenopausal reproductive state emanate from the hyperactivity of Kiss1 neurons in the hypothalamic infundibular/arcuate nucleus (KNDy neurons).

Objective: We demonstrate in 2 murine models simulating menopause and PCOS that a peripherally restricted kappa receptor agonist (PRKA) inhibits hyperactive KNDy neurons (accessible from outside the blood-brain barrier) and impedes their downstream effects.

Design: Case/control.

Experience with cultured thymus tissue in 105 children.

Background: Currently, there are no approved therapies to treat congenital athymia, a condition of immune deficiency resulting in high early mortality due to infection and immune dysregulation. Multiple syndromic conditions, such as complete DiGeorge syndrome, 22q11.2 deletion syndrome, CHARGE (coloboma, heart defects, choanal atresia, growth or mental retardation, genital hypoplasia, and ear anomalies and/or deafness) syndrome, diabetic embryopathy, other genetic variants, and FOXN1 deficiency, are associated with congenital athymia.

Care of Children with DiGeorge Before and After Cultured Thymus Tissue Implantation.

Background: Children with complete DiGeorge anomaly (cDGA) have congenital athymia plus a myriad of other challenging clinical conditions. The term cDGA encompasses children with congenital athymia secondary to 22q11.2DS, CHARGE syndrome (coloboma, heart defects, choanal atresia, growth or mental retardation, genital abnormalities, and ear abnormalities and/or deafness), and other genetic abnormalities.

Characterization of the Action of Tachykinin Signaling on Pulsatile LH Secretion in Male Mice.

The alternation of the stimulatory action of the tachykinin neurokinin B (NKB) and the inhibitory action of dynorphin within arcuate (ARH) Kiss1 neurons has been proposed as the mechanism behind the generation of gonadotropin-releasing hormone (GnRH) pulses through the pulsatile release of kisspeptin. However, we have recently documented that GnRH pulses still exist in gonadectomized mice in the absence of tachykinin signaling. Here, we document an increase in basal frequency and amplitude of luteinizing hormone (LH) pulses in intact male mice deficient in substance P, neurokinin A (NKA) signaling (Tac1KO), and NKB signaling (Tac2KO and Tacr3KO).

Obstetric and perinatal outcomes for women with pre-existing diabetes in rural compared to metropolitan settings in Victoria, Australia.

Background: Pre-existing diabetes in pregnancy is associated with an increased risk of complications. Likewise, living in rural, regional and remote Victoria, Australia, is also associated with poorer health outcomes. There is a gap in the literature with regard to whether Victorian women with pre-existing diabetes experience a greater risk of adverse pregnancy outcomes compared to their metropolitan counterparts.

Improving the quality of childbirth services in Zambia through introduction of the Safe Childbirth Checklist and systems-focused mentorship.

Although strong evidence exists about the effectiveness of basic childbirth services in reducing maternal and newborn mortality, these services are not provided in every childbirth, even those at health facilities. The WHO Safe Childbirth Checklist (SCC) was developed as a job aide to remind health workers of evidenced-based practices to be provided at specific points in the childbirth process. The Zambian government requested context-specific evidence on the feasibility and outcomes associated with introducing the checklist and related mentorship.

Examining subjective sleep quality in adults with hoarding disorder.

Hoarding disorder (HD), characterized by difficulty parting with possessions and functionally impairing clutter, affects 2-6% of the population. Originally considered part of Obsessive-Compulsive Disorder (OCD), HD became a distinct diagnostic entity in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013. While sleep impacts OCD, little is known about sleep in HD.

The effect of breastfeeding on postpartum glucose tolerance and lipid profiles in women with gestational diabetes mellitus.

Background: We aimed to investigate the association of breastfeeding on postpartum glucose levels and lipid profiles in women diagnosed with gestational diabetes mellitus (GDM) and women without GDM.

Methods: We performed a secondary analysis of a cohort study of 243 women, 159 women with GDM and 84 normally glucose tolerant women between 2012 and 2017. At approximately 6-10 weeks postpartum, we measured fasting blood glucose and plasma lipid levels.

Pregnancy outcomes for women with pre-pregnancy diabetes mellitus in Australian populations, rural and metropolitan: A review.

Background: Historically, pre-pregnancy diabetes (PPDM) is a recognised risk factor for poor pregnancy outcome. Co-existing pathology and adverse social determinants including rural-metropolitan inequities in health and healthcare access may confer additional risks. Multidisciplinary care before, during and after pregnancy can improve outcomes for women with PPDM and their infants.

Impact of the Safe Childbirth Checklist on health worker childbirth practices in Luapula province of Zambia: a pre-post study.

Background: A strong evidence base exists regarding routine and emergency services that can effectively prevent or reduce maternal and new-born mortality. However, even when skilled providers care for women in labour, many of the recommended services are not provided, despite being available. Barriers to the provision of appropriate childbirth services may include lack of availability of supplies, limited health worker knowledge and confidence, or inadequate time.

Impact of passenger engagement through road safety bus stickers in public service vehicles on road traffic crashes in Zambia: a randomized controlled trial.

Background: Road Traffic Crashes (RTCs) are the third highest cause of death in Zambia, claiming about 2000 lives annually, with pedestrians and cyclists being the most vulnerable. Human error accounts for 87.3% of RTCs.

Timing of diagnosis of gestational diabetes and pregnancy outcomes: A retrospective cohort.

Background: Recent guidelines suggest screening high-risk women in early pregnancy for gestational diabetes (GDM); however, there is little evidence to support this.

Aims: To compare pregnancy outcomes associated with diabetes for women with risk factors for GDM according to gestation of diagnosis. Early GDM was defined as a positive test before 20 weeks gestation, late GDM as a positive test at 20 or more weeks and no GDM when both tests were negative.

Effect of Ovarian Hormones and Mating Experience on the Preference of Female Mice to Investigate Male Urinary Pheromones.

In female mice, the expression of receptive lordosis behavior requires estradiol and progesterone actions in the nervous system; however, the contribution of these hormones to females' motivation to seek out male pheromones is less clear. In an initial experiment, sexually naïve ovary-intact female mice preferred to investigate (make nasal contact with) testes-intact male as opposed to estrous female urine, provided they were in vaginal estrus. In a second experiment, groups of sexually naïve and mating-experienced, ovariectomized females were tested for urinary pheromone preference first without and then with ovarian hormone replacement.

Multi-month prescriptions, fast-track refills, and community ART groups: results from a process evaluation in Malawi on using differentiated models of care to achieve national HIV treatment goals.

Introduction: In order to facilitate scale-up of antiretroviral therapy (ART) in Malawi, innovative and pragmatic models have been developed to optimize the efficiency of HIV service delivery. In particular, three models of differentiated care have emerged for stable patients: adjusted appointment spacing through multi-month scripting (MMS); fast-track drug refills (FTRs) on alternating visits; and community ART groups (CAGs) where group members rotate in collecting medications at the facility for all members. This study aimed to assess the extent to which ART patients in Malawi are differentiated based on clinical stability and describe the characteristics and costs associated with the models of differentiated care offered.

DREADD-induced silencing of the medial amygdala reduces the preference for male pheromones and the expression of lordosis in estrous female mice.

Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal-accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females' preference for male pheromones and improvement in receptivity normally seen with repeated testing.

Quality improvement intervention to increase adherence to ART prescription policy at HIV treatment clinics in Lusaka, Zambia: A cluster randomized trial.

Introduction: In urban areas, crowded HIV treatment facilities with long patient wait times can deter patients from attending their clinical appointments and picking up their medications, ultimately disrupting patient care and compromising patient retention and adherence.

Methods: Formative research at eight facilities in Lusaka revealed that only 46% of stable HIV treatment patients were receiving a three-month refill supply of antiretroviral drugs, despite it being national policy for stable adult patients. We designed a quality improvement intervention to improve the operationalization of this policy.

Optogenetic Activation of Accessory Olfactory Bulb Input to the Forebrain Differentially Modulates Investigation of Opposite versus Same-Sex Urinary Chemosignals and Stimulates Mating in Male Mice.

Surgical or genetic disruption of vomeronasal organ (VNO)-accessory olfactory bulb (AOB) function previously eliminated the ability of male mice to processes pheromones that elicit territorial behavior and aggression. By contrast, neither disruption significantly affected mating behaviors, although VNO lesions reduced males' investigation of nonvolatile female pheromones. We explored the contribution of VNO-AOB pheromonal processing to male courtship using optogenetic activation of AOB projections to the forebrain.

A comparison of the effects of male pheromone priming and optogenetic inhibition of accessory olfactory bulb forebrain inputs on the sexual behavior of estrous female mice.

Previous research has shown that repeated testing with a stimulus male is required for ovariectomized, hormone-primed female mice to become sexually receptive (show maximal lordosis quotients; LQs) and that drug-induced, epigenetic enhancement of estradiol receptor function accelerated the improvement in LQs otherwise shown by estrous females with repeated testing. We asked whether pre-exposure to male pheromones ('pheromone priming') would also accelerate the improvement in LQs with repeated tests and whether optogenetic inhibition of accessory olfactory bulb (AOB) projection neurons could inhibit lordosis in sexually experienced estrous female mice. In Experiment 1, repeated priming with soiled male bedding failed to accelerate the progressive improvement in LQs shown by estrous female mice across 5 tests, although the duration of each lordosis response and females' investigation of male body parts during the first test was augmented by such priming.