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.

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).

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.

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.

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.

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.

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.

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.

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.

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Gender-affirming hormone therapy (GAHT) alters sex-steroid exposure, raising important questions about skeletal health in transgender and gender-diverse populations. Evidence remains fragmented and centred on areal bone mineral density (BMD), with sparse fracture data and little integration of other parameters such as muscle. This narrative review synthesises evidence on skeletal health in transgender individuals, bone density, fracture risk and the muscle-bone unit, bone health screening, and effects of gonadotropin-releasing hormone (GnRH) agonists during adolescence. We performed a narrative review of clinical studies and guidelines addressing BMD, fractures, puberty suppression, and GAHT in transgender populations, prioritising clinically relevant data. Multiple cohorts report low pre-GAHT BMD, particularly in individuals assigned-male-at-birth (AMAB), likely reflecting minority stress, low physical activity, suboptimal vitamin D status, and sedentary lifestyles. Adequately dosed GAHT generally maintains or modestly improves BMD, especially in individuals assigned-female-at-birth (AFAB) on testosterone, while modest lumbar spine deficits may persist in some AMAB individuals. Fracture data are limited but reassuring. In adolescents, GnRH-agonists predictably reduce BMD Z-scores during hormonal suppression, with partial recovery after GAHT-initiation. However, implications for peak bone mass remain uncertain. Emerging evidence favours risk-stratified rather than universal dual-energy X-ray absorptiometry (DXA) screening, alongside optimisation of GAHT, nutrition, and physical activity. Current evidence does not indicate an increased skeletal risk when GAHT is appropriately managed. Pre-existing vulnerabilities appear central to bone health risk stratification, underscoring the need for risk-based care that integrates bone parameters alongside non-skeletal factors, such as muscle.

This article presents a comprehensive historical analysis of thyroid gland pathology as described by Professor Petros S. Kokkalis (1896&#x2013;1962), drawing on original early 20th century clinical observations and the foundational Greek medical literature of the era. It explores the transformation in medical understanding from viewing thyroid disorders as localized organ dysfunctions to recognizing their systemic nature, particularly in the context of hyperthyroidism and Basedow&#x2019;s (Graves&#x2019;) disease. The review synthesizes Kokkalis&#x2019;s meticulous clinical classifications, pathophysiological insights, and pioneering therapeutic protocols, including the adoption of iodine-based therapies and advances in surgical technique. It further contextualizes his work within the broader international landscape by comparing his findings and approaches to those of contemporaneous European and American researchers, such as Neisser, Plummer, Marine, and Mayo, who collectively advanced the field of endocrinology. The article demonstrates that Kokkalis&#x2019;s contributions were not only consistent with but also emblematic of the most progressive medical thought of his time. This historical perspective underscores the enduring importance of detailed clinical observation, systematic documentation, and international collaboration in shaping the scientific foundations of modern thyroid disease management.

Allergic rhinitis (AR) is the most common chronic condition from childhood to adulthood and remains a major, often underestimated, contributor to impaired quality of life, school performance, and healthcare use. Although symptoms frequently begin early in life, pediatric AR is still underdiagnosed and inadequately treated, with important consequences for physical, emotional, and cognitive development. In this narrative review, we summarize recent evidence on the treatment of AR in children, highlighting age-specific challenges and evolving treatment concepts. International recommendations, particularly those from ARIA, support a stepwise, patient-centred approach focused on symptom control, safety, and long-term outcomes. Intranasal corticosteroids remain the cornerstone of therapy for moderate-to-severe disease, while second-generation antihistamines and intranasal antihistamines provide effective options for milder or intermittent symptoms. Fixed-dose intranasal steroid-antihistamine combinations are highly effective, providing options for children with more severe or uncontrolled AR. Allergen immunotherapy is the only disease-modifying intervention. Emerging strategies, including biologics and novel immunotherapy approaches, are promising but currently limited to specific contexts. Alongside pharmacotherapy, education, adherence support, and pragmatic environmental measures are essential to achieve sustained disease control. Ongoing gaps in the pediatric evidence-base highlight the need for age-adapted algorithms and long-term studies focusing on early intervention and disease modification.

Long COVID (LC), a complex syndrome affecting approximately 6-12&#xa0;% of individuals post infection, is characterized by persistent, fluctuating, or progressive symptoms lasting at least three months. Its pathogenic mechanisms involve viral persistence, chronic inflammation, immune dysregulation, endothelial dysfunction, and endocrine/metabolic abnormalities. Currently, no specific diagnostic tests exist for LC, highlighting the need for reliable biomarkers. This review synthesizes current evidence on hormonal, metabolic, and metabolite biomarkers in LC. While vitamin D deficiency is prevalent in LC, being associated with neurocognitive symptoms, delayed recovery and poor physical performance, particularly in older adults, its lack of specificity reduces diagnostic utility. Insulin resistance markers consistently correlate with fatigue, mood disturbances, and myalgia, suggesting a distinct metabolic LC phenotype. Lower cortisol frequently correlates with fatigue, sensory disturbances, and neurocognitive symptoms. Alterations in cortisol/adrenocorticotropic hormone, growth hormone, prolactin, and gonadotropins suggest a potential hypothalamic-pituitary axis involvement; however, these abnormalities are often transient, dynamic or nonsignificant. While some patients may exhibit low free triiodothyronine associated with fatigue, no significant incidence of thyroid dysfunction and autoimmunity was associated with LC. Despite the absence of a distinct and consistent metabolomic signature, LC is characterized by the activation of the kynurenine pathway, including increased kynurenine and quinolinic acid, being associated with fatigue, neurocognitive and depressive symptoms. Emerging metabolites of mitochondrial dysfunction and lipid metabolism alterations require further validation. Despite promising findings, evidence remains scattered, hindered by small sample sizes and methodological limitations. Future research should prioritize standardization of biomarker assessment, validation in diverse populations, and exploration of targeted therapeutic interventions.

Type 1 diabetes mellitus (T1DM) is associated with the levels of interleukin-18 (IL-18). However, the effect of exogenous IL-18 and the immune mechanisms involved in this process have not yet been fully elucidated. This study aimed to explore the effects of exogenous IL-18 and immune mechanisms in T1DM. A T1DM mouse model was established using a single intraperitoneal injection of freshly prepared STZ 180&#xa0;mg per body weight. All mice were all separated into three groups, as follows: diabetic mice treated with recombinant IL-18 (1&#xa0;&#xb5;g/mouse) every other day (D&#x2009;+&#x2009;IL-18 group); diabetic mice treated with phosphate-buffered saline (D group); and a control group with non-diabetic mice receiving no treatment. Fasting blood glucose levels were measured throughout the treatment period. At the end of the 10 days' treatment, an intraperitoneal glucose tolerance test was performed. To evaluate the treatment effect, a linear mixed model was applied. To assess islet morphology and apoptosis, hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence staining (insulin and elevated caspase 3 co-localization) were conducted. Flow cytometry was used to explore immune mechanisms of islet injury. The T1DM model was successfully established. During the first 7 days of recombinant IL-18 treatment, the D&#x2009;+&#x2009;IL-18 group of mice were observed to have significantly lower fasting blood glucose levels than the D group of mice (q&#x2009;<&#x2009;0.012); however, glucose levels were observed to increase thereafter (q&#x2009;<&#x2009;0.010). The intraperitoneal glucose tolerance test showed a larger area under the curve in the D&#x2009;+&#x2009;IL-18 group than in the D group, suggesting impaired glucose tolerance. Histological evaluation suggested a disruption in islet architecture and a potential increase in elevated caspase 3 expression, which may be indicative of islet dysfunction. Flow cytometry further revealed a trend toward elevated proportions of CD11b&#x207a;F4/80&#x207a; macrophages and CD3&#x207b;NK1.1&#x207a; natural killer cells in the pancreas of IL-18-treated mice (p&#x2009;=&#x2009;0.016). Exogenous IL-18 was observed to temporarily ameliorate fasting blood glucose in T1DM mice, but this effect was not sustained beyond day 7, with subsequent impairment of islet function. The latter deterioration may be associated with enhanced infiltration of CD11b&#x207a;F4/80&#x207a; macrophages and CD3&#x207b;NK1.1&#x207a; natural killer cells.

Medication availability and costs can be highly variable across countries and in different time periods. We aimed to conduct a survey among local experts to obtain information on the availability and costs of allergic rhinitis medications in different countries. We sent a survey to members of the Allergic Rhinitis and its Impact on Asthma (ARIA) group, asking for the availability and the lowest cost of specific allergic rhinitis medications in their respective countries. Data in local currencies were converted to 2024 US Dollars adjusted for Purchasing Power Parity (PPP). We compared the costs of different medication classes, assuming, for each class, the least expensive drug in each country, as well as full treatment adherence. We received responses from ARIA experts in 51 different countries. Intranasal corticosteroids (INCS) and oral antihistamines (OAH) were available in all countries, but this was not observed for intranasal antihistamines (INAH) or for INAH+INCS. In most countries, OAH was the least costly drug class, while INAH+INCS was the most expensive. Among INCS, beclomethasone was the medication most frequently identified as the cheapest, while cetirizine and loratadine were the OAH most frequently reported as the least expensive. Among INAH+INCS, azelastine-fluticasone was more frequently identified as less costly than olopatadine-mometasone. There is an important across-country and across-class variability in terms of costs of allergic rhinitis medications. The results of this study will inform the ARIA-EAACI 2024-2025 guidelines.

PURPOSE: Many women suffer from hyperandrogenic conditions during their lifespan. The most prevalent is polycystic ovary syndrome (PCOS), which is characterized by hormonal, metabolic, and reproductive derangements in women of reproductive age. Endometrial cancer of epithelial origin (EC) is among the most common malignancies affecting women&#x2019;s reproductive systems. It has been suggested that androgens are involved in the development of endometrial hyperplasia and EC. Our narrative review aims to analyze the possible relationship between hyperandrogenic states in women and EC onset through risk assessment providing possible pathophysiological explanations. METHODS: A MEDLINE and PubMed search for the years 1990&#x2013;2024 was performed using a combination of keywords. Scientific articles on EC in patients with PCOS, hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN), and non-classical congenital adrenal hyperplasia (NCAH) were analyzed. RESULTS: There is controversy regarding the relationship between the role of androgens associated with the EC. Despite the fact that most of the epidemiological research linked PCOS to the onset of EC, it has been proposed that various androgen types have varying impacts on the development of EC, both prooncogenic and antioncogenic. Furthermore, elevated androgen levels are not the sole cause of EC in hyperandrogenic states; EC may be associated with metabolic pathway dysfunction and microbiota alteration related to hyperandrogenism. CONCLUSION: The hyperandrogenic milieu may represent a risk factor for the development of EC. Thus, investigation into potential biomarkers for EC in PCOS women and women with other hyperandrogenic states as well as routine examination of these patients for endometrial hyperplasia and cancer are vital to effectively shape the future of EC screening and treatment.