Seerupcaldwell1397

Patient-derived xenografts (PDXs) are tools of the trade for many researchers from all disciplines and medical specialties. Most endocrinologists, and especially those working in oncology, commonly use PDXs for preclinical drug testing and development, and over the last decade large collections of PDXs have emerged across all tumor streams. In this review, we examine how the field has evolved to include PDXs as versatile resources for research discoveries, providing evidence for guidelines and changes in clinical practice.Polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility, is associated with altered signaling within the hormone-sensitive neuronal network that regulates gonadotropin-releasing hormone (GnRH) neurons, leading to a pathological increase in GnRH secretion. CPI-613 manufacturer Circuit remodeling is evident between GABAergic neurons in the arcuate nucleus (ARN) and GnRH neurons in a murine model of PCOS. One-third of ARN GABA neurons co-express neuropeptide Y (NPY), which has a known yet complex role in regulating GnRH neurons and reproductive function. Here, we investigated whether the NPY-expressing subpopulation (NPYARN) of ARN GABA neurons (GABAARN) is also affected in prenatally androgenized (PNA) PCOS-like NPYARN reporter mice [Agouti-related protein (AgRP)-Cre;τGFP]. PCOS-like mice and controls were generated by exposure to di-hydrotestosterone or vehicle (VEH) in late gestation. τGFP-expressing NPYARN neuron fiber appositions with GnRH neurons and gonadal steroid hormone receptor expression in τGFP-expressing NPYARN neurons were assessed using confocal microscopy. Although GnRH neurons received abundant close contacts from τGFP-expressing NPYARN neuron fibers, the number and density of putative inputs was not affected by prenatal androgen excess. NPYARN neurons did not co-express progesterone receptor or estrogen receptor α in either PNA or VEH mice. However, the proportion of NPYARN neurons co-expressing the androgen receptor was significantly elevated in PNA mice. Therefore, NPYARN neurons are not remodeled by prenatal androgen excess like the wider GABAARN population, indicating GABA-to-GnRH neuron circuit remodeling occurs in a presently unidentified non-NPY/AgRP population of GABAARN neurons. NPYARN neurons do, however, show independent changes in the form of elevated androgen sensitivity.Neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington disease, are characterized by the loss of neurons as well as neuronal function in multiple regions of the central and peripheral nervous systems. Several studies in animal models have shown that androgens have neuroprotective effects in the brain and stimulate axonal regeneration. The presence of neuronal androgen receptors in the peripheral and central nervous system suggests that androgen therapy might be useful in the treatment of neurodegenerative diseases. To illustrate, androgen therapy reduced inflammation, amyloid-β deposition, and cognitive impairment in patients with AD. As well, improvements in remyelination in MS have been reported; by comparison, only variable results are observed in androgen treatment of PD. In ALS, androgen administration stimulated motoneuron recovery from progressive damage and regenerated both axons and dendrites. Only a few clinical studies are available in human individuals despite the safety and low cost of androgen therapy. Clinical evaluations of the effects of androgen therapy on these devastating diseases using large populations of patients are strongly needed.This study aimed to compare conventional medication management of type 2 diabetes (T2D) to medication management in conjunction with a lifestyle intervention using continuous glucose monitoring to minimize glucose excursions. Thirty adults (63% female; mean age, 53.3 years) who were diagnosed with T2D for less than 11 years (mean, 5.6 years), had glycated A1c (HbA1c) ≥ 7.0% (51 mmol/mol) (mean 8.8%, [73 mmol/mol]), and were not using insulin, were randomly assigned in a 12 ratio to routine care (RC) or 4 group sessions of glycemic excursion minimization plus real-time CGM (GEMCGM). Assessments at baseline and 5 months included a physical exam, metabolic and lipid panels, a review of diabetes medications, and psychological questionnaires. For the week following assessments, participants wore a blinded activity monitor and completed 3 days of 24-hour dietary recall. A subgroup also wore a blinded CGM. GEMCGM participants significantly improved HbA1c (from 8.9% to 7.6% [74-60 mmol/mol] compared with 8.8% to 8.7% [73-72 mmol/mol] for RC (P = .03). Additionally, GEMCGM reduced the need for diabetes medication (P = .01), reduced carbohydrate consumption (P = .009), and improved diabetes knowledge (P = .001), quality of life (P = .01) and diabetes distress (P = .02), and trended to more empowerment (P = .05) without increasing dietary fat, lipids, or hypoglycemia. Confirming our prior research, GEMCGM appears to be a safe, effective lifestyle intervention option for adults with suboptimally controlled T2D who do not take insulin.

Melatonin may play a role in the regulation of the human menstrual cycle and may decline with menopause and/or aging.

The objective of this work is to investigate the relations between melatonin and the menstrual cycle, menopause, and aging.

This was a cross-sectional and longitudinal analysis of 20 participants from the Study of Women's Health Across the Nation (SWAN) Daily Hormone Study (DHS). The outcome measure was first-morning urine assay of 6-sulfatoxymelatonin (aMT6s), a gauge of melatonin. For each participant, aMT6s was measured daily during one premenopausal cycle with evidence of luteal activity (ELA) and one postmenopausal collection with no evidence of luteal activity (NELA).

In addition to the organized patterns of hormone metabolites (estrone conjugates [E1c], and pregnanediol glucuronide [PdG]) and gonadotropins that characterized ovulatory menstrual cycles, there was a late luteal rise in aMT6s. In NELA collections, there was no periodicity of E1c, PdG, gonadotropins, or aMT6s. The sgical aging.Landslides pose a devastating threat to human health, killing thousands of people annually. Human vulnerability is a crucial element of landslide risk reduction, yet up until now, all methods for estimating the human consequences of landslides rely on subjective, expert judgment. Furthermore, these methods do not explore the underlying causes of mortality or inform strategies to reduce landslide risk. In light of these issues, we develop a data-driven tool to estimate an individual's probability of death based on landslide intensity, which can be used directly in landslide risk assessment. We find that between inundation depths of approximately 1-6 m, human behavior is the primary driver of mortality. Landslide vulnerability is strongly correlated with the economic development of a region, but landslide losses are not stratified by gender and age to the degree of other natural hazards. We observe that relatively simple actions, such as moving to an upper floor or a prepared refuge space, increase the odds of survival by up to a factor of 12. Additionally, community-scale hazard awareness programs and training for citizen first responders offer a potent means to maximize survival rates in landslides.Vehicle electrification is a common climate change mitigation strategy, with policymakers invoking co-beneficial reductions in carbon dioxide (CO2) and air pollutant emissions. However, while previous studies of U.S. electric vehicle (EV) adoption consistently predict CO2 mitigation benefits, air quality outcomes are equivocal and depend on policies assessed and experimental parameters. We analyze climate and health co-benefits and trade-offs of six U.S. EV adoption scenarios 25% or 75% replacement of conventional internal combustion engine vehicles, each under three different EV-charging energy generation scenarios. We transfer emissions from tailpipe to power generation plant, simulate interactions of atmospheric chemistry and meteorology using the GFDL-AM4 chemistry climate model, and assess health consequences and uncertainties using the U.S. Environmental Protection Agency Benefits Mapping Analysis Program Community Edition (BenMAP-CE). We find that 25% U.S. EV adoption, with added energy demand sourced from the present-day electric grid, annually results in a ~242 M ton reduction in CO2 emissions, 437 deaths avoided due to PM2.5 reductions (95% CI 295, 578), and 98 deaths avoided due to lesser ozone formation (95% CI 33, 162). Despite some regions experiencing adverse health outcomes, ~$16.8B in damages avoided are predicted. Peak CO2 reductions and health benefits occur with 75% EV adoption and increased emission-free energy sources (~$70B in damages avoided). When charging-electricity from aggressive EV adoption is combustion-only, adverse health outcomes increase substantially, highlighting the importance of low-to-zero emission power generation for greater realization of health co-benefits. Our results provide a more nuanced understanding of the transportation sector's climate change mitigation-health impact relationship.Gene flow between sympatric congeneric plants is thought to be very common and may pose serious threats to endangered species. In the present study, we evaluate the genetic diversity and divergence of three sympatric Rhododendron species in Jiaozi Mountain using newly developed microsatellites through the Illumina MiSeq sequencing approach. Genetic diversity of all three Rhododendron species studied was moderate in comparison to genetic parameters previously reported from species of this genus. Interestingly, genetic structure analysis of the three species identified a possible hybrid origin of the threatened Rh. pubicostatum. This sympatry should be considered a unimodal hybrid zone, since Rh. pubicostatum is predominant here. Unimodal hybrid zones are uncommon in Rhododendron, despite the fact that hybridization frequently occurs in the genus. Issues pertaining to the conservation of Rh. pubicostatum resulting from admixture of genetic material from its parental species are discussed.Ethiopia is land of geographical contrasts with elevations that range from 125 m below sea level in the Danakil Depression to 4533 m above sea level in the Semien Mountains, a world heritage site. The diverse climate of various ecological regions of the country has driven the establishment of diverse vegetation, which range from Afroalpine vegetation in the mountains to the arid and semi-arid vegetation type in the lowlands. The formation of Ethiopian vegetation is highly connected to the climate and geological history of the country. Highland uplift and rift formation due to volcanic forces formed novel habitats with different topography and climatic conditions that have ultimately become drivers for vegetation diversification. Due to Ethiopia's connection with the temperate biome in the north and the Arabian Peninsula during the dry glacial period, the biotic assemblage of Ethiopian highlands consists of both Afrotropical and palearctic biota. In general, eight distinct vegetation types have been identified in Ethiopia, based mainly on elevation and climate gradients.