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Effects of multistrain probiotic supplementation on hepatic function and anthropometric parameters in patients with metabolic dysfunction-associated steatotic liver disease: a double-blind, randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent on a global scale. The gut microbiota is integral to its pathogenesis, prompting extensive research into microbiota modulation as a potential adjunctive therapeutic strategy. AIM: The study aimed to evaluate the effect of multistrain probiotics supplementation on hepatic function in patients with MASLD in a double-blind, randomized, controlled trial. The primary outcomes were changes in Fibrosis-4 index (FIB-4) and fatty liver index (FLI). Secondary outcomes included changes in anthropometric parameters, selected biochemical markers, and other liver-related indices. METHODS: A total of 64 patients with MASLD were randomly assigned to two groups receiving either placebo (C) or a probiotic mixture (PRO) containing the following bacterial strains: 50% Lactococcus lactis Rosell-1058, 25% Lacticaseibacillus casei Rosell-215, 12.5% Lactobacillus helveticus Rosell-52, 12.5% Bifidobacterium bifidum Rosell-71 for 12 wk. RESULTS: Significant group &#xd7; time interactions were observed for FIB-4 (Q = 0.007), with reduction in the PRO group and increase in the C group (-0.05 vs. 0.10; P = 0.002). No significant interaction was found for FLI (Q = 0.942). Significant group &#xd7; time interactions were also observed for aspartate aminotransferase (-2.87 vs. 1.87 U/L; Q = 0.003) and APRI (-0.03 vs. 0.02; Q = 0.001), favoring the PRO group (P < 0.001 for both). No significant changes were observed in anthropometric parameters, glucose levels, or lipid profile. CONCLUSIONS: In patients with MASLD, the 12-wk probiotic supplementation had a modest but statistically significant effect on FIB-4, aspartate aminotransferase, and APRI, with no significant effect on FLI or anthropometric and metabolic parameters. These findings suggest that this probiotic formulation may have potential benefits for liver function in MASLD. However, long-term studies incorporating imaging-based and histological endpoints are required to determine the clinical significance of these findings.

Humans

Effects of continuous isomaltulose-containing gummy intake on interstitial glucose and salivary hormones during an 18-hole golf round: a randomized, double-blind controlled pilot study.

BACKGROUND: Golf is a prolonged, moderate-intensity sport requiring sustained physiological stability to manage cumulative stress and maintain performance. Although carbohydrate intake is commonly used to reduce fatigue, rapidly absorbed sugar-induced rapid blood glucose fluctuations may induce volatile arousal and latent metabolic stress. Isomaltulose, a slow-digesting disaccharide, provides a steadier glucose supply compared with sucrose. This exploratory pilot study examined the effects of isomaltulose intake on physiological stress markers, glycemic dynamics, and subjective responses during a competitive 18-hole golf round. METHODS: Twenty-three male collegiate golfers were randomized to either the isomaltulose group (ISO; n&#x2009;=&#x2009;12) or the sucrose group (CON; n&#x2009;=&#x2009;11) in a double-blind controlled trial. Participants consumed gummies containing isomaltulose or sucrose immediately after each hole (12.1 g carbohydrate per hole; total carbohydrate intake: 217.5 g). Primary outcomes were salivary stress markers [cortisol, testosterone, and dehydroepiandrosterone sulfate (DHEAS)] levels. Secondary outcomes included interstitial glucose concentration measured via continuous glucose monitoring, subjective assessments (i.e. sleepiness, relaxation, and concentration), and golf performance (18-hole score). Between-group comparisons at each time point were conducted using planned Welch's t-tests. RESULTS: No significant between-group differences were observed for 18-hole score (p&#x2009;=&#x2009;0.38) or mean interstitial glucose concentration (p&#x2009;=&#x2009;0.20). However, exploratory analyses revealed distinct hormonal variations; salivary DHEAS and testosterone levels were higher in the ISO group during the latter half of the round (p&#x2009;<&#x2009;0.05), whereas both declined in the CON group. Regarding glycemic variability, the ISO group demonstrated a more stable glucose profile with a medium effect size for lower standard deviation (ISO: 14.7&#x2009;&#xb1;&#x2009;1.9 vs. CON: 16.7&#x2009;&#xb1;&#x2009;4.6 mg/dL; d&#x2009;=&#x2009;0.58), although this difference was not significant. Conversely, subjective outcomes diverged; the CON group reported significantly greater subjective arousal (wakefulness and relaxation) (p&#x2009;<&#x2009;0.01) relative to the ISO group. CONCLUSIONS: In conclusion, continuous intake of isomaltulose-containing gummies during an 18-hole golf round was associated with differences in selected physiological markers, including DHEAS and testosterone concentrations. However, these findings were not accompanied by improvements in objective golf performance outcomes compared with sucrose-containing gummies. Isomaltulose may influence glycemic dynamics and hormonal responses during prolonged golf play; however, the practical significance of these effects remains exploratory. Further studies with larger sample sizes and appropriate repeated-measures frameworks are needed to determine whether such physiological changes translate into meaningful performance or recovery benefits.

Humans

Corneal Epithelial Alterations Associated With Cyclin-Dependent Kinase 4/6 Inhibitor Therapy in Hormone Receptor-Positive Breast Cancer.

IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renewal of the corneal epithelium. No controlled study has systematically evaluated corneal epithelial changes in patients receiving CDK4/6 inhibitors. OBJECTIVE: To determine whether CDK4/6 inhibitor-based therapy is associated with cornealepithelial alterations independent of aromatase inhibitor exposure and tear film dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective comparative cross-sectional study at a tertiary ophthalmology center. A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor (CDKAI group), 44 receiving aromatase inhibitor monotherapy (AI group), and 43 age-matched postmenopausal controls without systemic oncologic therapy. EXPOSURES: CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) combined with an aromatase inhibitor; aromatase inhibitor alone; or no systemic oncologic therapy. MAIN OUTCOMES AND MEASURES: Prevalence and severity of punctate epitheliopathy and vortex keratopathy, assessed by a masked ophthalmologist. Secondary outcomes included Schirmer I test, tear film break-up time, and Ocular Surface Disease Index (OSDI). RESULTS: PE was present in 44.4% of eyes in the CDKAI group vs 4.7% in the AI group and 2.3% in controls (&#x3c7;&#xb2; = 34.31; P < .001). All moderate (13.3%) and severe/complicated (8.9%) PE cases occurred exclusively in the CDKAI group. Vortex keratopathy was observed in 13.3% of CDKAI patients and in none of the other groups (P = .025). Schirmer values, tear film break-up time, and OSDI scores did not differ among groups (all P > .05). Within the CDKAI group, PE was not associated with treatment duration (P = .963) or tear film parameters. CONCLUSIONS AND RELEVANCE: In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of PE and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Symptom scores were low, although OSDI interpretation was limited by incomplete responses. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

Humans

Delayed maturation of the milk microbiome in women with type 1 diabetes.

AIMS/HYPOTHESIS: The breastmilk microbiome plays a crucial role in gut microbial colonisation and immune development, but little is known about how it is influenced by type 1 diabetes. METHODS: We conducted a longitudinal 16S rRNA gene sequencing study of milk from women with type 1 diabetes (n=69 pregnancies; 174 samples) and women who did not have type 1 diabetes (n=49 pregnancies; 123 samples), collected at seven timepoints from birth to 15 months postpartum. Alpha diversity (richness, inverse Simpson evenness) was analysed by generalised linear mixed models, beta diversity was analysed by Bray-Curtis dissimilarities and PERMANOVA, and differential abundance was analysed by limma. Additionally, we examined associations with maternal genetic risk score (GRS), maternal HLA type, glycaemic management (HbA1c) and breastmilk secretory IgA (sIgA), and performed a parallel analysis for the infant stool microbiome. RESULTS: A significant interaction between type 1 diabetes status and timepoint was observed for alpha diversity, both richness (p=0.01) and inverse Simpson diversity (p=0.003), indicating distinct temporal trajectories between women with and without type 1 diabetes. In those without type 1 diabetes, richness increased significantly between birth and 1&#xa0;week postpartum, but this early increase was delayed in women with type 1 diabetes to between 1&#xa0;week and 3&#xa0;months postpartum (p=0.002). Beta diversity analysis revealed earlier and more extensive compositional shifts in women without type 1 diabetes compared to those with type 1 diabetes. These differences persisted after adjusting for Caesarean delivery, BMI, parity and infant sex, and were not attributable to a delay in initiating breastfeeding. Taxa with delayed enrichment in women with type 1 diabetes included Streptococcus spp. and Rothia mucilaginosa, which metabolise human milk oligosaccharides to short-chain fatty acids to promote development of the infant's gut barrier and immune system. Maternal GRS, HLA, HbA1c or sIgA were not associated with milk microbiota diversity trajectories. In infant stool samples, alpha diversity did not differ between exposure groups, and showed no evidence of delayed maturation. Beta diversity revealed an early compositional shift between birth and 1&#xa0;week postpartum only in infants born to women without type 1 diabetes. Similarly, significant taxonomic changes between birth and 1&#xa0;week postpartum were detected only in infants born to women without type 1 diabetes, but with some taxa differing between exposure groups at 1&#xa0;week. CONCLUSIONS/INTERPRETATION: Maternal type 1 diabetes is associated with delayed early maturation of the breastmilk microbiome. Early compositional differences in microbiota restructuring were also observed in the infant gut, partially mirroring the pattern in the milk microbiome; however, sustained differences in infant gut microbiota diversity were not detected. Further investigation could determine whether these changes affect development of the infant's gut and immune system.

Humans

Fourteen-Day Amoxicillin- or Tetracycline-Containing Bismuth Quadruple Therapy versus 14-Day Metronidazole-Based Triple Therapy as the Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial.

BACKGROUND/AIMS: Combination therapy comprising a proton pump inhibitor (PPI), amoxicillin, and metronidazole (PAM) is used to treat clarithromycin-resistant Helicobacter pylori in the Republic of Korea, but eradication rates are decreasing due to an increasing incidence of clarithromycin resistance. We compared PAM, bismuth compounds plus PAM (PAM-B), and the combination of PPI, bismuth compounds, metronidazole, and tetracycline (PBMT) to determine whether PAM-B can achieve an eradication rate higher than that of PAM and comparable to that of PBMT. METHODS: This prospective multicenter study enrolled patients with clarithromycin-resistant H. pylori infections in the Busan and Gyeongsangnam-do of the Republic of Korea between December 2022 and February 2024. RESULTS: In the intention-to-treat (ITT) analysis, the eradication rate was significantly lower in the PAM group (68.2%) than in the PAM-B group (84.8%, p=0.024), whereas the difference from the PBMT group (81.8%) was not significant (p=0.070). The rate remained lowest in the PAM group (75.4%) in the per-protocol (PP) analysis (PAM-B, 96.5%, p=0.001; PBMT, 94.6%, p=0.004). Eradication rates were comparable between the PAM-B and PBMT groups in both the ITT (p=0.640) and PP analyses (p=0.633). Nausea and vomiting were significantly less frequent in the PAM-B group than in the PBMT group (6.8% vs 25.0%; p=0.007). Severe adverse events were rare, and all symptoms resolved after treatment discontinuation. CONCLUSIONS: PAM-B yielded eradication rates higher than those of PAM and comparable to those of PBMT, with no significant increase in the incidence of adverse events, suggesting the potential of PAM-B as a first-line treatment for clarithromycin-resistant H. pylori infection. Further large-scale studies are needed to validate these results. Registered retrospectively with the Clinical Research Information Service (CRIS; KCT0012265).

Humans

Molecular mechanisms of neuroendocrine regulation of molting in the Chinese mitten crab (Eriocheir sinensis): A transcriptomic analysis based on eyestalk ablation model.

Molting disability severely restricts the sustainable aquaculture of the Chinese mitten crab, yet the neuroendocrine mechanisms coordinating physiological responses remain poorly understood. Using unilateral eyestalk ablation to remove the primary source of molt-inhibiting hormone (MIH), we performed time-resolved transcriptomic profiling of the thoracic ganglion at 24&#xa0;h (early premolt) and 48&#xa0;h (ecdysis) post-ablation. We identified 2825 differentially expressed genes and uncovered a biphasic molecular response. At 24&#xa0;h, the thoracic ganglion activates pathways associated with neuromuscular adaptation, oxidative stress, and cardiac muscle contraction. Notably, the arachidonic acid metabolism pathway is selectively rewired: cytochrome P450 &#x3c9;-hydroxylases (CYP2J2, CYP4V2) are upregulated, while competing branches (epoxide hydrolase, cyclooxygenase) are suppressed, promoting local synthesis of the potent vasoconstrictor 20-HETE within the thoracic ganglion. This enzymatic switch provides a mechanistic link between MIH withdrawal and the local generation of elevated hemolymph pressure required for molting. By 48&#xa0;h, the transcriptional program shifts toward chitin-based extracellular matrix remodeling, glycosphingolipid biosynthesis, and synaptic reorganization. Collectively, our findings redefine the thoracic ganglion as an active neuroendocrine integrator that translates reduced MIH signaling into phased physiological outputs, revealing a "neuro-endocrine-hemolymph pressure" regulatory axis. This study provides novel molecular targets (e.g., CYP2J2, CHS1, UGCG) for mitigating molting disability in E. sinensis aquaculture.

Animals

Genome-wide identification, structural characterization, and evolutionary analysis of growth-related gene families in African catfish (Clarias gariepinus).

The somatotropic axis encompassing growth hormone (GH), insulin-like growth factor (IGF), myostatin (MSTN), and prolactin (PRL) signalling cascades is the master regulator of somatic growth, metabolism, and development in vertebrates. African catfish (Clarias gariepinus), a commercially pivotal aquaculture species, now possesses a chromosome-level reference genome (CGAR_prim_01v2); however, a systematic, genome-wide characterization spanning all five interconnected growth-related gene families has not previously been undertaken in this species. Here, we identified and characterized 15 growth-related genes spanning gh1, ghra, ghrb, Igf1, Igf2a, Igf2b, igf1ra, Igf1rb, Igf2r, Mstna, Mstnb, prl, prlra, prlrb, and smtlb distributed across 13 chromosomes. Complete one-to-one orthology with zebrafish confirmed strong dosage-balance conservation across >120 million years of teleost divergence. Physicochemical analysis resolved a clear biochemical dichotomy between compact, basic secreted ligands (19.88-45.81&#xa0;kDa; pI up to 10.02) and large, acidic, heavily glycosylated membrane receptors (56.82-270.80&#xa0;kDa; pI 4.85-5.97). Phylogenetic analysis confirmed 3R whole-genome duplication origins for all paralog pairs, while synteny analysis revealed a disruption of the ancestral gh1-prl chromosomal block in C. gariepinus, a finding that warrants further comparative and functional investigation. This genomic atlas provides the sequence and structural information including exon-intron boundaries, domain architecture, and chromosomal coordinates needed as a prerequisite for future marker-assisted selection and CRISPR-based myostatin-editing efforts in African catfish aquaculture, though translation into applied breeding outcomes will require subsequent functional and expression studies.

Animals

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female

Treatment of Hot Flashes in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

Humans

Reproductive Intentions and Fertility Preservation Among Transgender and Nonbinary Individuals: A Cross-Sectional Study in Brazil.

PURPOSE: This study evaluated reproductive intentions, fertility-related knowledge, prior fertility counseling, and factors associated with reproductive intentions among transgender and nonbinary individuals receiving care at a Brazilian public reference center. METHODS: This cross-sectional study with a qualitative component was conducted between July and November 2025 in a specialized gender-affirming care clinic in Brazil. Quantitative data included sociodemographic characteristics, reproductive history, gender-affirming hormone therapy (GAHT), and fertility-related variables. Logistic regression was used to assess factors associated with desire for future parenthood. Responses to a single open-ended question regarding perceived effects of GAHT on fertility were analyzed using thematic content analysis. RESULTS: Eighty-two participants were included (mean age 27.5 &#xb1; 7.4 years). Most identified as transgender men (65.9%), followed by transgender women (26.8%) and nonbinary individuals (7.3%); 79.3% were receiving GAHT. Although 63.4% expressed a desire for future parenthood, only 7.3% had children. Current interest in fertility preservation was reported by 20.8% (15/72). Having children (adjusted odds ratio [aOR] = 0.03; 95% confidence interval [CI]: 0.001-0.62; p = 0.023) and each additional year of GAHT duration (aOR = 0.83; 95% CI: 0.70-0.99; p = 0.038) were associated with lower odds of desiring future parenthood. Sex assigned at birth was not independently associated with reproductive intentions. Qualitative analysis revealed misconceptions, uncertainty, and conditional beliefs regarding fertility. CONCLUSIONS: Desire for future parenthood was common among transgender and nonbinary individuals, whereas engagement with fertility preservation remained limited. These findings highlight the need for longitudinal, patient-centered reproductive counseling integrated into gender-affirming care.

fertility preservation

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans

Efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis: a multicenter, randomized, open-label, active-controlled, phase III trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). METHODS: In this phase III, multicenter, randomized, open-label, non-inferiority trial, patients with hyperphosphatemia on maintenance hemodialysis were randomly assigned to receive either ferric citrate or sevelamer carbonate tablets for 12&#x2009;weeks. The primary endpoint was the change in serum phosphorus levels from baseline to week 12, with a non-inferiority margin of 0.32&#x2009;mmol/L. Secondary endpoints included changes in serum calcium, intact parathyroid hormone, and safety assessments. RESULTS: A total of 239 patients were randomized to the ferric citrate group (n&#x2009;=&#x2009;119) or the sevelamer carbonate group (n&#x2009;=&#x2009;120). The mean change in serum phosphorus levels was -0.70&#x2009;&#xb1;&#x2009;0.50&#x2009;mmol/L in the ferric citrate group and -0.61&#x2009;&#xb1;&#x2009;0.59&#x2009;mmol/L in the sevelamer carbonate group (least squares mean difference, -0.09&#x2009;mmol/L; 95% CI, -0.24 to 0.05&#x2009;mmol/L; non-inferiority margin, 0.32&#x2009;mmol/L). No significant inter-group differences were found in the percentage of patients achieving target phosphorus levels (49.09% vs. 48.28%, p&#x2009;=&#x2009;0.902). Ferric citrate significantly improved iron-related parameters and hemoglobin levels. Most treatment-emergent adverse events were mild, with gastrointestinal disorders being the most common. CONCLUSIONS: Ferric citrate tablets were non-inferior to sevelamer carbonate in reducing serum phosphorus levels in hyperphosphatemia patients on maintenance hemodialysis, with the added benefit of improving iron-related anemia and a favorable safety profile.

Adult

Clinical and endocrine correlates of genetic etiologies in severe hypospadias: Study from 34 patients.

OBJECTIVE: Hypospadias is a prevalent congenital anomaly (0.3%-1.0%); however, severe hypospadias (defined as proximal cases with the meatus at the penoscrotal junction, scrotum, or perineum) is a rare and clinically challenging entity with a multifactorial etiology. This study aimed to characterize the interrelationships among the clinical, endocrine, and genetic profiles in children with severe hypospadias. MATERIALS AND METHODS: We conducted a comprehensive analysis of 34 male patients with severe hypospadias. Preoperative hormone levels were measured using two methods: chemiluminescent immunoassay for luteinizing hormone and follicle-stimulating hormone, and liquid chromatography-tandem mass spectrometry for testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17&#x3b1;-hydroxyprogesterone (17&#x3b1;-OHP), and other steroids. Genetic analysis was conducted via whole exome sequencing. RESULTS: The diagnostic yield of clinically relevant genetic variants (including pathogenic and likely pathogenic, and variants of uncertain significance) in our cohort was 41.2% (14/34) of patients. Patients carrying these variants exhibited a more complex phenotypic profile compared to non-carriers, including a significantly higher rate of patients with &#x2265;3 associated malformations and a greater prevalence of cryptorchidism. Furthermore, the group with clinically relevant variants showed selective elevations in adrenal-derived precursors, specifically 17&#x3b1;-OHP and DHEA. Correlation analysis revealed significant positive associations of both 17&#x3b1;-OHP levels and the T/DHT ratio with the number of associated malformations. CONCLUSION: This study reveals significant genetic heterogeneity in patients with severe hypospadias. Those carrying genetic variants was associated with more severe clinical phenotypes, while certain endocrine variations, including the elevation of adrenal-derived hormones, were also observed in this cohort.

Humans

Serum Copeptin Rises After Tolvaptan for Hyponatraemia, but Does Not Predict Risk of Rapid Sodium Rise: Pre-Specified Secondary Analysis of the TVFR Trial.

OBJECTIVE: Hyponatraemia is a common electrolyte disorder often driven by excess arginine vasopressin (AVP). Copeptin is a stable surrogate marker co-secreted with AVP. It is unclear whether treatment of hyponatraemia with tolvaptan, an AVP-V2 receptor antagonist, impacts copeptin. We aimed to assess the effects of tolvaptan on serum copeptin, compared to fluid restriction. DESIGN: Pre-specified secondary analysis of an open-label randomised trial comparing tolvaptan or fluid restriction for 3 days. PATIENTS: Hospitalised patients with plasma sodium (pNa) 115-130&#x2009;mmol/L at a single-centre tertiary hospital in Melbourne, Australia. MEASUREMENTS: Copeptin measured at baseline and completion (Day 4, or discharge if sooner). RESULTS: Copeptin results were available in 45/54 participants, randomised to tolvaptan (n&#x2009;=&#x2009;25) or FR (n&#x2009;=&#x2009;20). Mean baseline copeptin was 10.4&#x2009;pmol/L. pNa increased in both groups, significantly more with tolvaptan as previously reported. Copeptin remained stable after FR, but significantly increased after tolvaptan (mean adjusted difference between groups over 3 days 8.4&#x2009;pmol/L, 95% CI 2.1-14.6, p&#x2009;=&#x2009;0.01). Baseline copeptin did not predict rapid sodium rise. The rise in copeptin after tolvaptan may represent an exaggerated response to osmolality rise in these patients ('reset osmostat'), or feedback mechanisms from AVP blockade. CONCLUSION: Tolvaptan increased serum copeptin compared to fluid restriction. Further research is required to determine if there is clinical utility for measuring copeptin in hyponatraemia before it is adopted into practice. TRIAL REGISTRATION: ACTRN12619001683123.

Humans

Acute Stevia Consumption does not Alter Endocrine Responses in Individuals with Normal Weight, Overweight, and Type 2 Diabetes Mellitus.

BACKGROUND: Stevia is a plant-based non-nutritive sweetener. Acute effects of stevia ingestion on glycemia and hormonal responses have not been fully investigated. OBJECTIVE: This objective of this study was to evaluate the acute effects of beverages containing stevia alone and in combination with glucose on glycemic, hormonal, and appetite responses. METHODS: This study evaluated three cohorts of n=23 individuals with either normal weight (NW), overweight (OW), or type 2 diabetes mellitus (T2DM) for which each individual completed four test conditions in a randomized sequence crossover study design. The four test conditions were beverages containing stevia (75.6 mg steviol equivalents), water, glucose (30 g), and stevia+glucose (30 g glucose+75.6 mg steviol equivalents). Blood samples were collected before and for 180 min after beverage consumption. Assessments included net area under the curve (niAUC) and incremental maximal concentration values for plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, and PYY. Appetite was assessed with visual-analog scale questions and energy consumption during an ad libitum meal. RESULTS: Responses to the stevia beverage did not differ significantly from those for water alone, and stevia + glucose did not differ significantly from glucose alone for any of the three groups. CONCLUSION: Acute stevia consumption did not materially alter responses for glycemia or hormones involved in glucose and appetite regulation, appetite ratings, or energy intake at a subsequent meal. Clinical Trial Registry number and website where it was obtained: Clinical Trials.gov Identifier: NCT05287906. Study Details | NCT05287906 | A Trial to Assess Steviol Glycosides on Acute Appetite Hormone Release | ClinicalTrials.gov.

Appetite

Hypothalamic-Pituitary Axis Involvement in Primary Central Nervous System Lymphoma.

CONTEXT: Primary central nervous system lymphoma (PCNSL) is a rare malignancy that may involve the hypothalamic-pituitary axis (HPA), leading to underrecognized but clinically significant endocrine dysfunction. OBJECTIVE: This work aims to characterize the spectrum and patterns of HPA-related endocrine disturbances in patients with PCNSL. DATA SOURCES: A systematic search was conducted in PubMed, EMBASE, Scopus, and Web of Science, supplemented by gray literature. The search concluded in February 2025. STUDY SELECTION: We included studies reporting adult PCNSL cases with documented dysfunction of at least one hormonal axis. Exclusion criteria were preexisting hypopituitarism or lack of endocrine data. DATA EXTRACTION: Data on demographics, tumor localization, hormonal axes affected, radiological findings, treatment, and outcomes were extracted. Risk of bias was assessed using JBI tools. RESULTS: Ninety-nine cases met the inclusion criteria. Diffuse large B-cell lymphoma accounted for 84% of cases. Endocrine dysfunction included isolated adenohypophyseal involvement (46%), neurohypophyseal (8%), and combined (45%). The most affected pituitary axes were the gonadal and thyroid axes, with 89.7% and 89.2% involvement, respectively. Hypothalamic tumors were strongly associated with combined dysfunction (odds ratio = 9.47; 95% CI, 3.76-23.86; P < .001). Persistent endocrinopathy was more frequent in progressive disease. No direct association was found between endocrine dysfunction and mortality. CONCLUSION: HPA dysfunction in PCNSL is frequent and often underdiagnosed. Hypothalamic involvement is associated broader hormonal impairment. Routine hormonal screening and multidisciplinary management should be standard in PCNSL care to minimize complications and improve outcomes.

Humans

Insights into specific and nonspecific butyrate-producing pathways during the in vitro fecal fermentation of butyrylated starch.

Butyrylated starch is a special type-4 resistant starch with butyrate-carrying attribute. In this study, the unique butyrate-producing capability of butyrylated starch was deeply investigated by focusing on its specific and nonspecific butyrate-producing pathways, respectively, using specially designed substrates as controls. In vitro fermentation studies revealed that butyrylated and isobutyrylated starches generated high levels of butyrate and isobutyrate, respectively, highlighting the role of butyryl group metabolism in the specificity of butyrate production. Carboxylesterase assays have demonstrated that butyryl group metabolism is primarily facilitated by carbohydrate esterases expressed in the gut microbiota. Combined with 16S rRNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it was found that butyrylated starch fermentation did not significantly enhance traditional butyrate synthesis pathways but modified the balance between the butyryl-CoA:acetyl-CoA transferase and butyrate kinase pathways by altering the gut microbiota composition, specifically by upregulating the relative abundance of indicator species such as Bacteroides, the Lachnospiraceae_NK4A136_group, and Parabacteroides. These insights offer theoretical guidance for designing butyrylated starch structures and regulating intestinal health.

Starch

Association of ERBB4 and SHBG gene polymorphisms with polycystic ovarian syndrome in South Indian women: a case-control genetic analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinological disorder with a substantial genetic component. However, the role of genes involved in follicular development and androgen regulation remains incompletely understood, particularly in South Indian populations. This study aimed to evaluate how variations in the ERBB4 and SHBG genes affect PCOS risk. METHODOLOGY: A hospital-based case-control study was conducted among 400 South Indian women, comprising 200 women with PCOS and 200 age-matched healthy controls. Genomic DNA was extracted to study SNPs at ERBB4 (rs2178575 and rs1351592) and SHBG (rs1799941 and rs727428) using ARMS-PCR genotyping. The study compared genotype and allele frequencies between cases and controls while assessing their associations with allelic, homozygous, heterozygous, dominant, recessive, and over-dominant genetic models. Genotyping accuracy was confirmed by re-genotyping and Sanger sequencing of a subset of samples. RESULTS: The ERBB4 rs2178575 polymorphism demonstrated a significant association with PCOS, as the AA genotype and A allele combination increased risk across all three genetic models, including homozygous, recessive, and allelic models. The ERBB4 rs1351592 variant was associated with 3-fold higher risk of PCOS in heterozygous and GC carriers. The SHBG rs1799941 polymorphism showed a significant link to PCOS through its effects on heterozygous and allelic states, whereas rs727428 displayed no significant connection due to its monomorphic distribution. CONCLUSION: These findings suggest that polymorphisms in ERBB4 and SHBG may contribute to PCOS susceptibility in South Indian women in a locus- and model-specific manner, revealing the intricate genetic structure that defines this medical condition.

Humans