搜索结果：Hormones (Athens, Greece)

Three-dimensional printing has emerged as a novel technology to produce vaginal rings (VRs). However, the inherent high flexibility demanded by VRs poses a challenge when using filaments during the printing process. Here, we introduce a new approach for continuous 3D printing that eradicates the dependence on filaments and their printability for the fabrication of highly flexible VRs. Herein, Hot Melt Extrusion (HME) was used to create progesterone (PGR)-loaded thermoplastic polyurethane (TPU) pellets that were used as feedstock for 3D printing material extrusion of VRs. The TPU-based VRs presented excellent printability performance. Further physicochemical characterization indicated the presence of high amorphous PGR content while mechanical tests revealed that the VRs were consistently manufactured without significant deformation under prolonged compression and their performance was comparable to that of commercial VRs. The printed rings presented sustained release of clinically relevant quantities of progesterone over 28 days. Ex vivo studies showed that PGR permeated the porcine mucosa in a sustained manner for at least seven days. Finally, no cytotoxicity was observed in murine fibroblasts for the plain and progesterone-loaded pellets. This study demonstrates the potential of coupling HME and direct extrusion to produce 3D-printed VRs, aligning with the characteristics of traditional devices.

The association between serum vitamins and sex hormones has gained considerable research interest; however, studies focusing specifically on adolescent males remain limited. To analyze associations between key serum vitamins and sex hormone levels in adolescent males. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) (2001-2004). Weighted generalized linear regression models were employed to examine associations between serum vitamins (D, B12, folate, A, and E) and sex hormones, namely, total testosterone (TT), sex hormone-binding globulin (SHBG), and estradiol (E2). The Bayesian kernel machine regression (BKMR) model was employed to account for the combined effects of vitamins, nonlinear exposure-outcome relationships, and interactions among vitamins. A total of 231 participants aged 12-18 years were included. In the generalized linear model, vitamin A was positively correlated with TT (&#x3b2;&#x2009;=&#x2009;0.421; 95% CI: 0.013, 0.829; P&#x2009;=&#x2009;0.028) and negatively correlated with SHBG (&#x3b2;=-0.372; 95% CI: -0.549, -0.195; P&#x2009;<&#x2009;0.001); folate was negatively correlated with both TT (&#x3b2;=-0.017; P&#x2009;<&#x2009;0.001) and E2 (&#x3b2;=-0.012; P&#x2009;<&#x2009;0.001). In the BKMR model, the combined effects of serum vitamins on TT and E2 showed a non-significant weak negative trend; no clear pattern was observed for SHBG. Folate was identified as the most important factor influencing all three sex hormones. Bivariate exposure-response functions indicated potential interactions of folate with vitamin B12 on TT and with vitamin D on E2; no vitamin interactions were observed for SHBG. Complex effects of vitamins on sex hormones in adolescent males were revealed. The mechanism(s) underlying the regulation and long-term health implications will be explored in the future.

The oxidative balance score (OBS) was developed to reflect the overall exposure of the body to antioxidants and pro-oxidants in the individual's lifestyle and diet. The research aims to explore the relationship between OBS and sex hormones, including total testosterone (TT) and estradiol (E2), as well as indices including sex hormone-binding globulin (SHBG), testosterone deficiency (TD), free testosterone, and the ratio of TT to E2. A total of 2464 male participants were enrolled in the study during the period 2013 to 2016. Multivariable regression analyses were performed to investigate the association between OBS and sex hormones. Stratified analysis was conducted in participants of different age, body mass index (BMI), poverty income ratio, smoking status, alcohol consumption, and diabetes mellitus (DM). We found that OBS (&#x3b2;&#x2009;=&#x2009;2.13, 95% CI: 0.17&#x2009;~&#x2009;4.09, P&#x2009;=&#x2009;0.030) and lifestyle OBS (&#x3b2;&#x2009;=&#x2009;21.09, 95% CI: 9.27&#x2009;~&#x2009;32.90, P&#x2009;=&#x2009;0.004) were significantly correlated with TT with full adjustment. We also found noteworthy relationships between lifestyle OBS and SHBG (&#x3b2;&#x2009;=&#x2009;2.55, 95% CI: 0.77&#x2009;~&#x2009;4.33, P&#x2009;=&#x2009;0.010), TD (OR&#x2009;=&#x2009;0.76, 95% CI: 0.58&#x2009;~&#x2009;1.00, P&#x2009;=&#x2009;0.045), and ratio of TT to E2 (&#x3b2;&#x2009;=&#x2009;1.10, 95% CI: 0.71&#x2009;~&#x2009;1.50, P&#x2009;<&#x2009;0.001). Stratified analyses by many covariates revealed that the results were basically stable across populations. The results showed that males who lead an antioxidant-rich lifestyle had increased serum TT levels and were less likely to develop TD. This suggests that antioxidant-rich lifestyle choices may additionally help to prevent disorders related to sex hormone imbalance.

Periodontal disease (PD) is associated with type 2 diabetes mellitus (T2DM), while periodontal treatment (PT) improves glycemic control in T2DM patients. Leptin and adiponectin belong to the adipokines family and have almost antagonistic functions in inflammatory processes and insulin sensitivity modulation. Hence, these hormones have been linked with both PD severity and glycemic control. This systematic review aims to assess the effect of PT on serum levels of leptin and adiponectin in patients with T2DM. PubMed, Cochrane Library, and Google Scholar databases and ClinicalTrials.gov website were searched up to January 5th, 2025. Randomized and non-randomized controlled clinical trials (RCTs and CCTs) including patients with T2DM and PD who underwent PT and evaluated serum levels of leptin and adiponectin were included. Assessments of risk of bias and of certainty of evidence were performed. Seven trials were eligible for qualitative synthesis. A statistically significant increase in serum adiponectin levels was observed across most studies, while no such consistency was observed for leptin. The overall level of certainty of evidence was judged low in the RCTs and very low in the CCTs. Meta-analysis could not be performed due to significant methodological heterogeneity. Preliminary findings suggest a potential increase in adiponectin levels in T2DM patients, with possible implications for glycemic control. However, these results should be interpreted with caution due to the small number of studies and important methodological limitations. Well-designed studies with larger sample sizes and adequate adjustment for confounders are necessary to verify this observation. People with type 2 diabetes often also have periodontitis, an inflammatory gum disease, which may affect their overall health. The aim of this study was to investigate whether treating periodontitis could help improve certain substances in the blood-called adiponectin and leptin-that are linked to blood sugar control and inflammation. Several studies that tested this in people with both diabetes and periodontitis were included and most of them showed that, after periodontal treatment, levels of adiponectin (which helps reduce inflammation and improve insulin sensitivity) increased. However, results for leptin were less clear. This suggests that taking care of gum health might support better diabetes management. The overall strength of evidence was low due to methodological limitations and heterogeneity among studies. Current findings should be interpreted cautiously, as available data remain preliminary. Still, more high-quality research is needed to fully understand how treating periodontitis may benefit people with diabetes.

Oocyte competency is a crucial determinant of fertilisation success and the initial development of embryos in assisted reproductive technologies. The metabolic and biochemical environment of the ovarian follicle is crucial for determining oocyte developmental potential, alongside genetic integrity. The follicular microenvironment includes a complex network of signalling chemicals that regulate mitochondrial activity, steroidogenesis, oxidative balance, and cellular energy metabolism. Recently, metabolic hormones originating from adipose tissue and skeletal muscle, namely, adipokines and myokines, have received considerable focus as crucial regulators of ovarian physiology. Adiponectin, irisin, and the recently identified hormone asprosin have emerged as crucial metabolic regulators influencing granulosa cell activity, mitochondrial bioenergetics, insulin signalling pathways, and redox homeostasis inside the follicular niche. Adiponectin mostly provides metabolic protection by activating AMP-activated protein kinase (AMPK) and improving insulin sensitivity, which in turn enhances mitochondrial efficiency and steroidogenic function in granulosa cells. Irisin, derived from the breakdown of fibronectin type III domain-containing protein 5 (FNDC5), aids the developing oocyte by facilitating mitochondrial biogenesis, augmenting oxidative phosphorylation, and altering cellular defence mechanisms against oxidative stress. Conversely, asprosin has been associated with glucogenic signalling, metabolic stress, and probable mitochondrial malfunction, suggesting a possible relationship between systemic metabolic problems and negative reproductive consequences. Clinical and experimental research indicate that the levels of these metabolic regulators in follicular fluid may correlate with ovarian response, oocyte quality, fertilisation rates, and embryo development during in vitro fertilisation cycles. This review consolidates current molecular, cellular, and clinical information, clarifying the pathways by which adipokines and myokines influence follicular metabolism and impact oocyte competency. Understanding the metabolic connections between systemic endocrine signals and the follicular milieu may provide novel indicators for reproductive prognosis and provide new treatment targets to improve assisted reproduction outcomes.

Thyroid hormones play an important role in regulating the cardiovascular system. Thyroid dysfunction, which encompasses hypothyroidism and hyperthyroidism, is relatively common and has been linked to a range of cardiovascular manifestations, including dyslipidaemia, abnormal blood pressure regulation, endothelial dysfunction, impaired cardiac function, and arrhythmias. The effects of levothyroxine replacement therapy on cardiovascular endpoints in subclinical hypothyroidism remain uncertain. The largest randomized controlled trial (TRUST) to date was underpowered to assess cardiovascular outcomes, although the results demonstrated a pattern towards a beneficial effect of levothyroxine. The aim of this review was to provide a summary of current knowledge on the relationship between thyroid dysfunction and cardiovascular health, with a focus on molecular and pathophysiological mechanisms underlying thyroid dysfunction and cardiovascular disease. Evidence from recent omics and Mendelian randomization studies is discussed, alongside an overview of the epidemiology of thyroid diseases and the impact of levothyroxine treatment on cardiovascular outcomes in subclinical hypothyroidism.

Kisspeptin stimulates gonadotropin-releasing hormone (GnRH) release and, by extension, gonadotropin secretion. Although continuous kisspeptin administration has been shown to dampen kisspeptin-induced GnRH release in non-human primates [1, 2], this has not been replicated in the limited human studies reported to date. The objective of this study was to examine the effects of continuous kisspeptin administration on luteinizing hormone (LH) secretion in healthy men. Three healthy adult men received a continuous intravenous infusion of kisspeptin-10 at a dose of 12.5 mcg/kg/h for 24&#xa0;h and underwent frequent blood sampling to characterize the effect on reproductive hormones. Continuous administration of kisspeptin resulted in an immediate increase in LH concentrations, from a baseline of 2.8-3.8 mIU/mL to the highest values of 17.5-30.6 mIU/mL (5- to eightfold above baseline), reached within 12-20&#xa0;h of infusion onset. LH concentrations subsequently declined by 13-47% from max to end of the infusion, settling at 10.7-22.8 mIU/mL. FSH and testosterone rose modestly in parallel. While kisspeptin boluses have been employed to probe GnRH pulse generation, continuous infusion of kisspeptin is a complementary physiologic tool used to study dynamic changes in GnRH-induced LH secretion. Further studies are warranted to further elucidate the physiologic response of the kisspeptin receptor to non-pulsatile ligand administration. NCT01438073 (August 24, 2011).

Roux-en-Y gastric bypass (RYGB) improves glucose homeostasis beyond weight loss, but the underlying mechanisms remain incompletely understood. Counter-regulatory hormones such as glucagon, ACTH, and cortisol are key components of glucose regulation. The aim of this study was to characterize alterations in glucagon, ACTH, and cortisol regulation before and after RYGB using nonlinear mixed-effects (NLME) population modeling, and to explore potential mediators of these changes. Post-hoc analysis of one cross-sectional and two prospective cohort studies. Clinical research unit. In total, 62 individuals without diabetes from three previous clamp studies were included: 39 from a cross-sectional cohort covering a wide range of BMI and insulin sensitivity (cohort 1, utilized for model development only), and 23 participants examined both before and approximately four months after RYGB (cohort 2). Hyperinsulinemic-euglycemic-hypoglycemic (both cohorts) and hyperglycemic (cohort 1 only) clamps. Glucose-dependent secretion dynamics of glucagon, ACTH, and cortisol quantified through NLME modeling and the impact of RYGB and metabolic characteristics on corresponding model parameters. According to models developed using presurgical data from both cohorts, glucagon and ACTH turnover rates and baseline concentrations decreased post-RYGB in cohort 2. Insulin-mediated glucagon suppression and the glucose deficit required for ACTH stimulation increased, while cortisol dynamics remained stable. Higher insulin sensitivity was associated with lower baseline glucagon levels. RYGB induces reductions in glucagon and ACTH responsiveness to hypoglycemia, partially indicative of central nervous system-mediated resetting of glucose regulation. These adaptations may contribute to improved metabolic control following bariatric surgery.

In ethnopharmacology, historical texts provide crucial insights by revealing the continuity of traditional medicines, while also serving as valuable sources for the discovery of bioactive natural products and potential new therapeutics. From 1828 to 2009, five official editions of the Greek Pharmacopoeia (Ph. Gr.) were published, prior to full alignment with the European Pharmacopoeia (Ph. Eur.). Despite this rich history, the content and significance of Greece's officinal herbal products remain largely unexplored. This study aims to investigate the inclusion of natural products, especially herbal products, in the official Greek Pharmacopoeias and to compare them with those listed in the European Pharmacopoeia 11. The analysis examined Ph. Gr. I (1868), II (1924), III (1974), IV (1989; with Addenda, 1990-1994), and V (2009), alongside the Bavarian Pharmacopoeia (1822) and Ph. Eur. 11. A total of 298 herbal drug aggregates were identified across 94 botanical families. Herbal monographs reached their highest count in Ph. Gr. I, declined in the following editions, and increased again in Ph. Gr. V. Comparative analysis with Ph. Eur. 11 showed that 86 were previously listed in Ph. Gr. I, 59 in II, 55 in III, 44 in IV, and 142 in V. Notably, 74 herbal monographs introduced in Ph. Gr. I are still present in Ph. Eur. 11. Additional entries include natural metabolites, animal-derived products, antibiotics, enzymes, hormones, vaccines, and vitamins. This is the first systematic review of natural product inclusion in the Greek Pharmacopoeias. The enduring inclusion of many herbal products in Ph. Eur. underscores their significant value in pharmaceutical science.

Background: Altered gut microbiota and gut-derived inflammation impair glucose regulation and promote metabolic endotoxemia, yet evidence on probiotic effects across combined glycaemic, inflammatory and short-chain fatty acid (SCFA) outcomes remains limited. This study investigated the effects of a 12-week multi-species probiotic on glucose homeostasis, incretin hormones, inflammatory biomarkers and circulating SCFAs in adults with subthreshold depression. Methods: In a 12-week double-blind, randomised, placebo-controlled trial, 39 adults with subthreshold depression were allocated to either a probiotic supplement containing Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01 and Bifidobacterium longum 04 (n = 19) or placebo (n = 20). Fasting glucose, insulin, HOMA-IR, glucose-dependent insulinotropic peptide (GIP), high-sensitivity C-reactive protein (hs-CRP), lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14) and SCFAs were evaluated at three time points: baseline, week 6 and week 12. Between-group and treatment &#xd7; time effects were analysed using general linear models. Results: Probiotic supplementation significantly reduced fasting glucose at 12 weeks compared with placebo (-1.8 vs. 0.1 mmol/L; p = 0.036). In the probiotic group, greater reductions in GIP (p = 0.012; p = 0.037), LBP (p < 0.001), sCD14 (p = 0.002; p = 0.001) and hs-CRP (p = 0.047) were also observed compared with placebo. Plasma SCFA concentrations remained largely unchanged, with no significant treatment &#xd7; time interactions, except for higher valerate levels at 12 weeks in the probiotic group (p = 0.019). Conclusions: Twelve weeks of multi-species probiotic supplementation improved fasting glucose, reduced incretin and inflammatory biomarkers and attenuated metabolic endotoxemia, without alterations in circulating SCFAs. These findings support beneficial modulation of metabolic-immune pathways and highlight the promising role of probiotics to enhance glucose regulation and systemic inflammatory tone in adults with subthreshold depression.

BACKGROUND: Migraine burden is over twice as high among females than males. Although sex differences are recognized in migraine, robust sex-specific guidance for management remains limited. OBJECTIVE: To systematically review and synthesize current evidence on sex-related clinical differences in migraine, including treatment outcomes and reproductive management, and to provide evidence-based or expert consensus recommendations where high-quality data are lacking. METHODS: A systematic literature review using the PICO framework addressed 24 sex-specific questions across three domains: (1) biological sex differences across the lifespan, (2) sex-specific variations in treatment outcomes, and (3) fertility and reproduction-related management. To address anticipated evidence gaps, a structured Delphi consensus process complemented the review. The protocol was registered in PROSPERO (CRD420251058438). RESULTS: Thirty-seven studies informed 10 evidence summaries. Acute and preventive anti-CGRP therapies seem to show similar efficacy between sexes. For menstrual-related migraine attacks (MM), triptans and lasmiditan are effective, with frovatriptan being recommended for short-term prevention; long-term prevention include topiramate and anti-CGRP mAbs. In pregnancy triptans, greater occipital nerve (GON) blocks, and onabotulinumtoxinA are safe, with GON blocks showing potential efficacy. During breastfeeding, triptans appear to be safe. Anti-CGRP mAbs are equally effective in pre and postmenopausal women. Expert consensus emphasizes the influence of hormonal transitions on migraine expression across sexes and supports the use of acetaminophen, antiemetics, magnesium, NSAIDs, steroids, beta-blockers, amitriptyline, and calcium channel blockers as generally safe in WOCBP and during pregnancy, although some agents have trimester-specific limitations. Efficacy was noted for acetaminophen, sumatriptan, antiemetics, magnesium, propranolol, amitriptyline, and onabotulinumtoxinA. During breastfeeding, acetaminophen, NSAIDs, domperidone, prochlorperazine, magnesium, caffeine, beta-blockers, tricyclics, onabotulinumtoxinA, and GON blocks were considered safe. CONCLUSIONS: Evidence is limited, but sex (likely mediated by sex hormones) influence the clinical course of migraine, and likely treatment response. Limitations include absence of sex-specific analyses in older trials, underrepresentation of men, and scarce reproductive safety data. Integrating sex-based analyses and broadening trial inclusion and more reproductive safety evidence are essential for personalized, equitable migraine care.

Diabetes mellitus (DM) is a growing public health concern that is affecting a significant proportion of older adults aged&#x2009;&#x2265;&#x2009;65 years. Diabetes-related complications often lead to other comorbidities necessitating the use of multiple medications. Consequently, polypharmacy, defined as the concurrent use of five or more medications, is highly prevalent among older adults with DM. While sometimes necessary, greater medication counts increase the risk of medication nonadherence, potentially inappropriate medication use, drug-drug interactions, and adverse drug reactions. Thus, polypharmacy is considered a significant clinical challenge that also contributes to other geriatric syndromes such as falls, delirium, dementia, frailty, and functional decline, leading to increased healthcare utilization, hospitalization, and mortality. Older adults with DM are also heterogeneous, with two main groups, namely, sarcopenic-obesity (low muscle mass, high visceral adiposity, and high insulin resistance) and anorexic-malnourished (low nutritional intake and proneness to hypoglycemia), each patient requiring distinct therapeutic priorities and strategies. This review summarizes the prevalence, causes, and consequences of polypharmacy in older adults with DM, and outlines management strategies centered on comprehensive geriatric assessment.

PURPOSE: Multiple endocrine neoplasia type 2 (MEN2) is caused by germline pathogenic variants (PVs) in the RET proto-oncogene, leading to medullary thyroid carcinoma (MTC), pheochromocytoma, and primary hyperparathyroidism (PHPT). RET p.Lys666Asn is a rare PV, but its clinical significance remains incompletely understood. The purpose of this study is to expand the clinical understanding of the RET Lys666Asn variant. METHODS: Index patients carrying the RET Lys666Asn variant were identified through clinical genetic testing in two referral medical centers. Comprehensive clinical evaluation, biochemical screening, and imaging studies were performed to assess the presence of MTC, pheochromocytoma, and PHPT of the index patients and carrier family members. We performed a literature search on Lys666Asn carriers and their clinical manifestations. RESULTS: Ten individuals from five families were identified as carriers of the RET Lys666Asn variant. The median age at diagnosis was 43.7&#xa0;years (range 2&#x2013;75&#xa0;years). Only one individual presented with pheochromocytoma, diagnosed at age 54. The rate of MTC, pheochromocytoma, and PHPT was 0 (0&#x2013;0.26), 0.1 (0.01&#x2013;0.39), and 0 (0&#x2013;0.26), respectively. In a pooled analysis of cases reported in the literature, MTC, pheochromocytoma, and PHPT rate are 0.42 (0.28&#x2013;0.57), 0.11 (0.04&#x2013;0.22), and 0.03 (0&#x2013;0.12), respectively. MTC had a wide age range at presentation (20&#x2013;70&#xa0;years). CONCLUSION: The RET Lys666Asn variant is associated with lower event rate of MEN2-related tumors compared to classical MEN2 variants, particularly MTC and pheochromocytoma. Despite its rarity, pheochromocytoma cannot be excluded in carriers, underscoring the need for individualized screening protocols based on specific RET variants.

PURPOSE: Adrenocortical insufficiency (AI), one of the most common hormonal deficiencies, is associated with significant mortality due to acute precipitation of adrenal crisis. This study aims to assess trends and disparities in mortality due to AI in the United States of America (US) from 1999 to 2020. METHODS: Death certificate data pertaining to AI-related mortality were retrieved from the CDC WONDER database. Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) were calculated per 1,000,000 population. Annual percentage change (APC) and average APC were used to assess temporal trends using Joinpoint regression. RESULTS: A total of 26,791 deaths occurred due to AI in the US from 1999 to 2020, with an increasing overall trend (average APC: 1.68). Males (5.89) had a higher AAMR than females (5.52). Non-Hispanic (NH) American Indians (9.62) had the highest AAMR and Hispanics (4.11) had the lowest. CMRs in older adults (19.81) aged 65&#x2009;+&#x2009;years were ten times higher than those of young adults (2.37) aged 25&#x2013;64 years. Rural areas (6.72) had higher mortality than urban areas (5.43). The Midwest (6.27) reported the highest mortality among the census regions, and the Northeast (4.91) the least. The states with the highest AAMRs were North Dakota (11.25) and Oklahoma (9.54), while Florida (3.32) and Nevada (2.99) had the lowest. CONCLUSION: Adults in the US have shown increasing mortality burden due to AI, with men, NH American Indians, older adults and rural populations being the most high-risk. Targeted strategies need to be developed to curb the rise in mortality rates.

Diabetes technology has transformed substantially over the past two decades, becoming central to modern diabetes management. Continuous glucose monitoring (CGM), automated insulin delivery (AID) systems, and smart insulin pens have reshaped both the assessment of glycemic control and diabetes treatment, particularly in people with type 1 diabetes (T1D) and selected individuals with insulin-treated type 2 diabetes (T2D). Among these technologies, CGM represents a major paradigm shift, providing continuous insight into glucose trends, variability, and time spent within clinically meaningful glycemic ranges, thereby complementing-and in many cases replacing-traditional self-monitoring of blood glucose. This narrative review summarizes evidence from randomized controlled trials and real-world studies regarding the evolution of CGM technology, insulin delivery strategies-including conventional insulin pumps, sensor-augmented pumps, and hybrid closed-loop systems-and the application of these technologies in specific clinical contexts, such as pregnancy, gestational diabetes, and perioperative and inpatient settings. While these systems offer clear metabolic and psychosocial benefits, important limitations remain, particularly those related to delayed insulin pharmacokinetics, sensor lag during rapid glucose changes, and user-dependent factors. Emerging developments, including fully closed-loop and dual-hormone systems as well as the growing role of artificial intelligence in CGM data analysis and risk prediction are also explored. Future development is expected to focus on improved personalization, tighter integration of technologies, and a transition toward more predictive and proactive diabetes care.

Steatotic liver disease encompasses a wide range of disease states, from steatosis to steatohepatitis and ultimately cirrhosis. As these stages progress, several severe hepatic and non-hepatic issues are triggered. Patients with diabetes exhibit accelerated progression through the MASLD spectrum, with increased liver-related mortality. To recognize the close association between MASLD and type 2 diabetes (T2D), it must be understood that lipid and glucose metabolism are closely intertwined. Insulin resistance and obesity are central features of both MASLD and T2D and stem from multifactorial etiologies related to lifestyle, environmental, genetic, and epigenetic factors. Due to the shared physiopathological routes and the higher risk of disease progression attributed to MASLD and T2D, hepatic steatosis should be suspected and screened for in patients with T2D. Once the diagnosis of MASLD is established, lifestyle interventions, with close follow-up and strict metabolic control must be implemented. The presence of clinically significant fibrosis warrants management by an interdisciplinary team, including a gastroenterologist or hepatologist. Current pharmacotherapies that target metabolic dysfunction aim to prevent cardiovascular disease and MASH cirrhosis. This review discusses drugs approved for T2D treatment with liver-related benefits, as well as ongoing research for dual treatment strategies.

The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines aim to improve the reporting of observational studies, including cohort, case-control, and cross-sectional designs, relevant to assessing associations, risks, and outcomes in real-world clinical settings. They are conceived to optimize the meaningfulness of epidemiological and clinical studies, aligning them with the Aristotelian "mesotes" curve, namely, the principle of achieving balance and avoiding extremes to best reflect the most truthful approximation of reality. This commentary addresses situations where strict adherence to STROBE guidelines may be impossible or inappropriate, potentially distorting results, and shows how statistical tools can mitigate these issues. Specific challenges arise in real-life randomization scenarios, situations lacking placebo arms, and in correcting for multiple comparisons. We discuss these challenges, examine the role of Bonferroni and similar corrections, and propose alternative approaches such as false discovery rate (FDR) and Bayesian hierarchical models. We illustrate these points with examples from the literature and a simulation study evaluating p-value adjustments in multiple hypothesis testing. This work provides a framework for researchers to navigate STROBE guidelines thoughtfully, ensuring that observational studies are both rigorous and relevant.

BACKGROUND: Osteoporosis is a metabolic bone disease prevalent in postmenopausal women due to estrogen deficiency, leading to impaired bone homeostasis. Bone marrow mesenchymal stem cells (BMSCs) play a crucial role in bone formation and microRNA-613 (miR-613) has been implicated in bone metabolism, but its role in osteoporosis remains unclear. This study explores the expression of miR-613 in postmenopausal osteoporosis (PMOP) and its diagnostic value. METHODS: miR-613 levels in 84 PMOP patients and 71 healthy controls were analyzed by qRT-PCR. Receiver operating characteristic (ROC) curve analysis was used to assess its diagnostic potential. In vitro, hBMSCs were induced to differentiate into osteoblasts by &#x3b2;-glycerophosphate and miR-613 inhibition was used to evaluate its role in osteogenesis, cell proliferation, apoptosis, and osteogenic marker expression. The interaction between miR-613 and TIMP3 was confirmed using dual-luciferase assays. RESULTS: miR-613 expression was significantly lower in PMOP patients compared to healthy controls (P&#x2009;<&#x2009;0.0001), and ROC analysis showed its potential as a diagnostic biomarker (AUC&#x2009;=&#x2009;0.843, 95% CI&#x2009;=&#x2009;0.783&#x2013;0.904). Inhibition of miR-613 suppressed osteogenic differentiation, decreased cell proliferation, and increased apoptosis. TIMP3 was identified as a direct target of miR-613 and its expression inversely correlated with miR-613 levels in PMOP patients. Silencing TIMP3 partially reversed the suppressive effects of miR-613 inhibition on osteogenesis. CONCLUSION: miR-613 promotes osteogenic differentiation of BMSCs by targeting TIMP3. Its downregulation in PMOP patients points to its potential as a diagnostic biomarker and therapeutic target.

Esophageal involvement in Crohn's disease is rare and poorly understood, presenting with nonspecific symptoms that contribute to delayed diagnosis and inconsistent management. This systematic review aims to characterize the clinical presentation, diagnostic pathways, and treatment approaches for adult patients with esophageal Crohn's disease. A systematic search of PubMed and Scopus was conducted through May 2025 to identify studies reporting on adult patients with esophageal Crohn's disease. Descriptive statistics, univariate comparisons, and post hoc pairwise testing with Bonferroni correction were performed. Ninety studies, involving 100 adult patients (54% women; median age, 38 years), were included. The most common primary location was ileocolic (31%), and 20% of the study population had isolated upper gastrointestinal involvement. Dysphagia was the most frequent symptom (41%). Endoscopic diagnosis was made in 98% of patients, with predominant findings of ulcers (70%) and strictures (37%). Granulomas were identified in 29% of biopsy specimens. First-line treatments varied, with corticosteroids (29.6%) and surgery (14.3%) used most frequently. Biologic agents were used in 15.4% of patients, as most studies were published before the biologics era. Four deaths were reported due to postoperative complications. Significant associations were found between the primary site of Crohn's disease and both esophageal behavior and endoscopic findings. Esophageal Crohn's disease is a rare entity with diagnostic delays and inconsistent treatment. The variability in clinical features, diagnostic findings, and treatment approaches reported in adult patients, as well as the lack of consensus definitions and standardized management, is reflected in high rates of surgical intervention and morbidity in the past. Improved awareness and collaborative research are needed to establish evidence-based guidelines and improve patient outcomes.