Following the High-Risk Patient: Breast Cancer Risk-Based Screening.

Breast cancer (BC) is the most common cancer occurring in women in the USA today, and accounts for more than 40,000 deaths annually (Giaquinto in CA Cancer J Clin 72: 524-541, 2022). While breast cancer survival has improved over the past decades, incidence has increased, and diagnoses are being made at younger ages. This emphasizes the importance of risk evaluation, accurate prediction, and effective mitigation and risk reduction strategies.

Imaging of Fontan-Associated Liver Disease.

The Fontan procedure is the definitive treatment for patients with single-ventricle physiology. Surgical advances have led to a growing number of patients surviving into adulthood. Fontan-associated liver disease (FALD) encompasses a spectrum of pathologic liver changes that occur secondary to altered physiology including congestion, fibrosis, and the development of liver masses.

Post-COVID-19 syndrome: persistent neuroimaging changes and symptoms 9 months after initial infection.

A previously healthy and active middle-aged woman acquired COVID-19 as an occupational exposure with subsequent persistent post-COVID-19 symptoms including headache, dyspnoea on exertion, chest pressure, tachycardia, anosmia, parosmia, persistent myalgia, vertigo, cognitive decline and fatigue. She presented to a tertiary medical centre for further evaluation after 9 months of persistent symptoms and had a largely unremarkable workup with the exception of a persistently elevated monocyte chemoattractant protein 1, blunted cardiovagal response and non-specific scattered areas of low-level hypometabolism at the bilateral frontal, left precuneus, occipital and parietal regions on PET scan.

Circadian rhythms of 11-oxygenated C19 steroids and ∆5-steroid sulfates in healthy men.

Background: Many hormones display distinct circadian rhythms, driven by central regulators, hormonal bioavailability, and half-life. A set of 11-oxygenated C19 steroids (11-oxyandrogens) and pregnenolone sulfate (PregS) are elevated in congenital adrenal hyperplasia and other disorders, but their circadian patterns have not been characterized.

Participants And Methods: Peripheral blood was collected every 2 h over 24 h from healthy volunteer men (10 young, 18-30 years, and 10 older, 60-80 years).

Suppression of hyperinsulinemia restores growth hormone secretion and metabolism in obese mice.

The well-balanced secretion between insulin and growth hormone (GH) is essential in regulating substrate metabolism, energy metabolism, and body composition. High insulin and low GH levels are often observed in obesity, contributing to reduced energy expenditure and further fat accumulation. Although suppression of hyperinsulinemia is proposed as a treatment for obesity, changes in GH secretion and energy metabolism following this treatment are not thoroughly studied.

Clamping Cortisol and Testosterone Mitigates the Development of Insulin Resistance during Sleep Restriction in Men.

Context: Sleep loss in men increases cortisol and decreases testosterone, and sleep restriction by 3 to 4 hours/night induces insulin resistance.

Objective: We clamped cortisol and testosterone and determined the effect on insulin resistance.

Methods: This was a randomized double-blind, in-laboratory crossover study in which 34 healthy young men underwent 4 nights of sleep restriction of 4 hours/night under 2 treatment conditions in random order: dual hormone clamp (cortisol and testosterone fixed), or matching placebo (cortisol and testosterone not fixed).

Effect of Growth Hormone Secretagogue Receptor Deletion on Growth, Pulsatile Growth Hormone Secretion, and Meal Pattern in Male and Female Mice.

Introduction: While the vast majority of research investigating the role of ghrelin or its receptor, GHS-R1a, in growth, feeding, and metabolism has been conducted in male rodents, very little is known about sex differences in this system. Furthermore, the role of GHS-R1a signaling in the control of pulsatile GH secretion and its link with growth or metabolic parameters has never been characterized.

Methods: We assessed the sex-specific contribution of GHS-R1a signaling in the activity of the GH/IGF-1 axis, metabolic parameters, and feeding behavior in adolescent (5-6 weeks old) or adult (10-19 weeks old) GHS-R KO (Ghsr-/-) and WT (Ghsr+/+) male and female mice.

Stimulation of endogenous pulsatile growth hormone secretion by activation of growth hormone secretagogue receptor reduces the fat accumulation and improves the insulin sensitivity in obese mice.

Obese individuals often show low growth hormone (GH) secretion, which leads to reduced lipid mobilization and further fat accumulation. Pharmacological approaches to increase GH levels in obese individuals by GH injection or GH-releasing hormone receptor agonist showed promising effects on fat reduction. However, side effects on glucose metabolism and the heavy costs on making large peptides hindered their clinical application.

Characterization of novel neutralizing mouse monoclonal antibody JM1-24-3 developed against MUC18 in metastatic melanoma.

Background: MUC18 is a glycoprotein highly expressed on the surface of melanoma and other cancers which promotes tumor progression and metastasis. However, its mechanism of action and suitability as a therapeutic target are unknown.

Methods: A monoclonal antibody (mAb) (JM1-24-3) was generated from metastatic melanoma tumor live cell immunization, and high-throughput screening identified MUC18 as the target.

Pregnancy, but not dietary octanoic acid supplementation, stimulates the ghrelin-pituitary growth hormone axis in mice.

Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue ghrelin increase during pregnancy, or in response to dietary octanoic acid supplementation, is unclear. We therefore measured circulating GH profiles in late pregnant C57BL/6J mice and in aged-matched non-pregnant females fed with standard laboratory chow supplemented with 5% octanoic or palmitic (control) acid (n = 4-13/group).

Age and time-of-day differences in the hypothalamo-pituitary-testicular, and adrenal, response to total overnight sleep deprivation.

Study Objectives: In young men, sleep restriction decreases testosterone (Te) and increases afternoon cortisol (F), leading to anabolic-catabolic imbalance, insulin resistance, and other andrological health consequences. Age-related differences in the hypothalamo-pituitary-testicular/adrenal response to sleep restriction could expose older individuals to greater or lesser risk. We aimed to evaluate and compare the 24-h and time-of-day effect of sleep restriction on F, luteinizing hormone (LH), and Te in young and older men.

Dapagliflozin restores insulin and growth hormone secretion in obese mice.

The well-documented hormonal disturbance in a general obese population is characterised by an increase in insulin secretion and a decrease in growth hormone (GH) secretion. Such hormonal disturbance promotes an increase in fat mass, which deteriorates obesity and accelerates the development of insulin resistance and type 2 diabetes. While the pathological consequence is alarming, the pharmaceutical approach attempting to correct such hormonal disturbance remains limited.

Dynamic Interactions Between LH and Testosterone in Healthy Community-Dwelling Men: Impact of Age and Body Composition.

Background: Aging is associated with diminished testosterone (Te) secretion, which may be attributed to Leydig cell dysfunction, decreased pituitary stimulation, and altered Te feedback.

Objective: To study all regulatory nodes-gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and Leydig cell-in the same cohort of healthy men.

Study Design: This was a placebo-controlled, blinded, prospectively randomized cross-over study in 40 men, age range 19 to 73 years, and body mass index (BMI) range 20 to 34.

Association between allelic variants in the glucagon-like peptide 1 and cholecystokinin receptor genes with gastric emptying and glucose tolerance.

Background: Nutrient-mediated release of cholecystokinin and glucagon-like peptide-1 (GLP-1) regulates gastric emptying (GE) via duodenogastric feedback mechanisms; GLP-1 also regulates postprandial insulin secretion. Some patients with functional upper gastrointestinal symptoms have impaired glucose tolerance during enteral dextrose infusion. Our hypothesis was that variants in CCK, GLP-1, and TCF7L2 (transcription factor 7-like 2 locus), which is associated with greatest genetic risk for development of type 2 diabetes mellitus, are associated with GE and independently with glucose tolerance.

Is a single set of negative blood cultures sufficient to ensure clearance of bloodstream infection in patients with Staphylococcus aureus bacteremia? The skip phenomenon.

Background: The most recent version of the Infectious Diseases Society of America guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections states that a single set of negative blood cultures is sufficient to demonstrate clearance of bacteremia. However, S. aureus might exhibit fluctuating blood culture positivity, labeled as "the skip phenomenon".

Anorectal pressures measured with high-resolution manometry in healthy people-Normal values and asymptomatic pelvic floor dysfunction.

Background: High-resolution manometry (HRM) is used to measure rectoanal pressures in defecatory disorders and fecal incontinence. This study sought to define normal values for rectoanal HRM, ascertain the effects of age and BMI on rectoanal pressures, and compare pressures in asymptomatic women with normal and prolonged balloon expulsion time (BET).

Methods: High-resolution manometry pressures and BET were measured in 163 asymptomatic healthy participants.

A novel measure of glucose homeostasis (or loss thereof) comprising the joint dynamics of glucose, insulin, glucagon, and cortisol.

Quantification of disturbances in glucose-insulin homeostasis has been the cornerstone of appraising insulin resistance and detecting early-stage diabetes. Metabolic homeostasis arises from feedback and feed-forward interactions among (at least) all four of glucose, insulin, glucagon, and cortisol. Quantifying such tetrapartite interactions in the fasting (endogenously regulated) state overnight could elucidate very early regulatory disruption.

Measuring luteinising hormone pulsatility with a robotic aptamer-enabled electrochemical reader.

Normal reproductive functioning is critically dependent on pulsatile secretion of luteinising hormone (LH). Assessment of LH pulsatility is important for the clinical diagnosis of reproductive disorders, but current methods are hampered by frequent blood sampling coupled to expensive serial immunochemical analysis. Here, we report the development and application of a Robotic APTamer-enabled Electrochemical Reader (RAPTER) electrochemical analysis system to determine LH pulsatility.

Modulating Effects of Progesterone on Spontaneous Nocturnal and Ghrelin-Induced GH Secretion in Postmenopausal Women.

Background: Oral administration of estradiol (E2) generally increases GH secretion in postmenopausal women. Oral administration of E2 is associated with a decrease in IGF-1, whereas parenteral or transdermally administered E2 may have no effect on GH. The effect of progesterone (P4) on GH secretion has rarely been studied.

Feedback on LH in Testosterone-Clamped Men Depends on the Mode of Testosterone Administration and Body Composition.

Context: Quantitative studies of the short-term feedback of testosterone (T) on luteinizing hormone (LH) secretion in healthy men are relatively rare. Such studies require the shutting down of endogenous T secretion and the imposition of experimentally controlled IV T addback.

Objective: To evaluate whether pulsatile and continuous T delivery confers equivalent negative feedback on LH secretion.