Cyclic vomiting syndrome (CVS) with acetonemia is a representative psychosomatic disorder triggered by psychological stress. In most cases, patients experience symptoms of ketoacidosis, including vomiting during childhood, which typically resolve by approximately 10 years of age. Although abnormal activation of the glucose metabolic response associated with stress has been suggested to be involved in its onset, the underlying mechanisms remain unclear. In this study, we established a mouse model of stress-induced glycogen depletion and ketosis observed in CVS with acetonemia. We compared the glucose metabolic responses to stress between young (4-week-old) and adult (8-week-old) mice. After 8 h of restraint stress (RS), liver glycogen levels decreased in both age groups. At 16 h post-stress, liver glycogen levels recovered to the baseline level in adult mice, but did not recover in young mice. This difference was attributed to a significant reduction in food intake in young mice owing to stress. Furthermore, young mice exhibited a marked elevation in blood ketone levels during RS, suggesting that an immature stress response induced lipolysis. This experimental model may help to elucidate how immature stress responses contribute to metabolic dysregulation. This study is a step toward understanding the pathology of CVS with acetonemia.

Prader- Willi Syndrome (PWS) is a complex neuroendocrine disorder that presents with hyperphagia, obesity, and social and cognitive impairment. The cognitive impairment is comparatively under-researched in PWS and in the Magel2-null mouse model. Cognitive function is commonly trained and tested in mice after the manipulation of metabolic state to induce motivation, yet physiologic function in the Magel2-null mouse model is most commonly assessed in the fed state. This project evaluates Magel2-null mouse physiology in ad libitum, acute fast, and chronic restriction settings to establish a baseline prior to examining cognitive function in operant conditioning paradigms. As in prior work, when maintained on ad lib diet or fasted acutely overnight, there is no difference in food intake or body weight between the null and control mice. However, in the context of chronic restriction, the Magel2-null mice are resistant to weight loss and maintain elevated fat stores. In this state of chronic restriction, Magel2-null mice demonstrate a latency to form initial cue associations, reduced motivation to perform an operant task, and a preference for low effort responses. This decreased motivation and preference for low-effort responses suggest Magel2-null mice undervalue food rewards compared to littermate controls, likely due to their altered fat storage and corresponding metabolic state. Together this data shows that the Magel2-null mouse is a useful model for assessing cognitive function relative to metabolic physiologic changes that may be helpful to further understanding and treating the constellation of symptoms in people with PWS.

This systematic review and meta-analysis compared reproductive, perinatal and neonatal outcomes between letrozole-based endometrial preparation, with or without adjuvant gonadotrophins, and programmed-cycle endometrial preparation for frozen embryo transfer (FET) in women with polyendocrine metabolic ovarian syndrome (PMOS), including only randomized controlled trials (RCTs). MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched from inception through September 10, 2025. Four RCTs met inclusion criteria (n = 891). Random-effects models were used to pool risk ratios, risk of bias was assessed with RoB-2 and certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations. No significant difference in live birth rate was observed between the two protocols (RR 0.92, 95% CI 0.79 to 1.07). Similarly, no significant differences were observed in clinical pregnancy, miscarriage, hypertensive disorders of pregnancy or cycle cancellation rates. A lower risk of gestational diabetes mellitus (GDM) was observed with programmed-cycle FET in a meta-analysis of two RCTs (RR 0.33, 95% CI 0.14 to 0.82, P = 0.02); however, this hypothesis-generating finding should be interpreted cautiously because of the unexpectedly high GDM rates and requires confirmation in larger studies. Other perinatal and neonatal outcomes did not differ significantly, although evidence was underpowered. In contrast to observational studies, current RCT evidence does not demonstrate superiority of letrozole-based over programmed-cycle endometrial preparation for reproductive outcomes in women with PMOS.

Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder caused by germline mutations in the FLCN gene. It is characterized by pulmonary cysts with recurrent pneumothorax, renal tumors, and cutaneous lesions, with marked phenotypic variability. This review summarizes current evidence on the molecular basis and clinical manifestations of BHD, highlighting the role of folliculin in cellular metabolism through the AMPK-mTOR signaling pathway and related mechanisms involved in tumorigenesis. From a clinical perspective, diagnosis is often challenging and relies on combined genetic and phenotypic criteria. Management is currently based on surveillance strategies, particularly for early detection of renal cancer. Emerging therapeutic approaches targeting mTOR signaling, metabolic pathways, and transcriptional regulators show promising results in preclinical models, although their clinical impact remains to be established.

Catecholamines such as epinephrine and norepinephrine regulate white adipose tissue lipolysis through β-adrenergic receptors (β-AR). In metabolic syndrome, adipose tissue downregulates β-AR and becomes catecholamine resistant, a finding recapitulated under high-fat diet. In many receptor-ligand systems, chronic stimulation induces desensitization, but limited data explores whether this relationship holds true for adipose tissue catecholamine resistance. Catecholamine signaling in adipose tissue is also regulated by clearance through monoamine oxidases and catechol-O-methyltransferases, but almost no data have examined the products of these pathways in adipose tissue. We show that plasma catecholamines are elevated under short term high fat diet in male mice prior to onset of catecholamine resistance at two weeks of HFD. At eight weeks of HFD, circulating catecholamines remain elevated and correlate with visceral mesenteric and subcutaneous fat mass accrual. Catecholamine elevations co-occur with catecholamine resistance in both fat pads, which we demonstrate is receptor dependent and is alleviated by bypassing β-AR using forskolin. We also observe elevated adipose tissue norepinephrine turnover without any change in its downstream metabolites, dihydroxyphenylglycol (DHPG) or 3-Methoxy-4-hydroxyphenylglycol (MHPG), suggestive of unchanged neurotransmitter clearance and increased norepinephrine availability driven by increased secretion. Inhibiting monoamine oxidase A mediated norepinephrine clearance using moclobemide blunted energy expenditure responses to Cl314,243, the β3-AR agonist. Taken together, these data suggest that elevated catecholamines could be causally related to catecholamine resistance and suggest a novel approach to reversing catecholamine resistance by increasing clearance or decreasing receptor stimulation.

Polycystic ovarian syndrome, also known by the newly proposed term polyendocrine metabolic ovarian syndrome (PMOS), is an understudied and underfunded condition, despite its health burden and the urgent need for more effective treatment. In this News and Perspectives article, JMIR Correspondent Bharath Thampi reports on the factors affecting PMOS treatment in India-especially rural regions-and on a new digital twin treatment initiative.

Polyendocrine metabolic ovarian syndrome (PMOS) is the most common reproductive and cardiometabolic disorder in women of reproductive age. Once viewed as primarily an ovarian disease, it is now recognized as a neuroendocrine-metabolic disorder driven by dysregulation of the hypothalamic-pituitary-gonadal axis. A central feature of the syndrome is increased gonadotropin releasing hormone (GnRH) pulsatility, which drives excess luteinizing hormone (LH) secretion, disrupts the LH/follicle stimulating hormone (FSH) balance, and promotes ovarian androgen excess and anovulation. Hypothalamic Kisspeptin neurons, the principal regulators of GnRH pulse generation, show altered activity and impaired steroid feedback sensitivity. Anti-Müllerian hormone (AMH) has emerged as an ovary-to-brain signal that directly stimulates GnRH neurons and remodels the neuroendocrine interface, amplifying LH secretion and perpetuating reproductive dysfunction. Developmental programming, through interactions among genetic, environmental, and epigenetic factors, may durably alter the organization and function of hypothalamic circuits, predisposing to neuroendocrine dysfunction later in life. In parallel, metabolic dysfunction, including insulin resistance and adipose tissue dysfunction, can interact bidirectionally with reproductive and neuroendocrine pathways, reinforcing hyperandrogenism and perturbing both reproductive and energy homeostasis. This review summarizes current knowledge of the neuroendocrine mechanisms underlying PMOS and discusses emerging targeted therapies that may offer disease-modifying approaches for this prevalent and heterogeneous disorder.

Vacuolar protein sorting 16 (VPS16) functions in endolysosomal trafficking. Biallelic VPS16 variants cause a mucopolysaccharidosis-like syndrome reported in only four patients, with neurological involvement ranging from mild developmental delay to severe impairment with epilepsy and pyramidal signs. We report an additional patient biallelic for VPS16 NM_022575.4:c.2272-18 C > A, with profound developmental delay, early-onset epilepsy, and spasticity. Multisystem involvement included recurrent infections, neutropenia, serosal effusions, and tubular proteinuria. Brain MRI showed white-matter abnormalities, progressive cerebral and cerebellar atrophy, and symmetric signal changes in the globus pallidus and substantia nigra, suggestive of iron deposition, further expanding the neurological spectrum of this disorder.

History An asymptomatic 45-year-old man with sickle cell disease and coinherited α-thalassemia was referred to the hepatology department for workup of an indeterminate hepatic mass discovered incidentally at screening cardiac MRI. The patient was diagnosed with sickle cell disease in childhood and required several hospitalizations with blood transfusions. During adulthood, disease management was suboptimal, with infrequent transfusion therapy and undertreated chronic hemolytic anemia. There was no history of malignancy, hepatitis B or C infection, alcohol consumption, metabolic syndrome, diabetes, or fatty liver disease. There was no evidence of tuberous sclerosis, glycogen storage disease, or anabolic steroid use. Laboratory investigations demonstrated chronic hemolytic anemia, with a hemoglobin level of 98-109 g/L (reference range, 135-175 g/L) and markedly elevated reticulocyte count (207.9 × 10[9]/L to 247.8 × 10[9]/L; reference range, 25 × 10[9]/L to 75 × 10[9]/L). Peripheral blood smear showed sickle cells, target cells, and Howell-Jolly bodies. Liver enzymes, synthetic liver function, and tumor markers (α-fetoprotein, carbohydrate antigen 19-9, and carcinoembryonic antigen) were within normal limits. There was no evidence of systemic iron overload. Abdominal US (Fig 1), abdominal MRI (Figs 2, 3), and chest CT (Fig 4) were performed.