Endocrinology Research Articles

Molecular Mechanisms of Methylglyoxal in Diabetes-related Macrovascular Complications

Diabetes mellitus (DM) is a chronic endocrine and metabolic disease indicated by the presence of hyperglycemia. It has been known that hyperglycemia and oxidative stress are the main culprit of all DM complications, including macrovascular complications. As a byproduct of lipid, protein, and carbohydrate metabolism, methylglyoxal (MGO) is a highly reactive substance which plays a positive signaling role in helping cells regain redox balance under oxidative stress circumstances. DM-related problems lead to an excess of mitochondrial superoxide in the heart and big and small vascular endothelial cells. Elevated intracellular reactive oxygen species induce impaired angiogenesis in reaction to ischemia, trigger several proinflammatory pathways, and result in enduring epigenetic modifications that propel the continuous expression of proinflammatory genes even after glucose levels return to normal. Over time, the significance of the extremely quick advanced glycation end-products (AGE) production caused by the extremely reactive MGO has been clarified. It is now evident that MGO causes vascular tissue to react maladaptively. Glyoxalase 1 (GLO1) is the primary enzyme in an organism's enzymatic glyoxalase defense mechanism, which converts MGO to D-lactate in order to counteract the harmful effects of MGO. Understanding the role of the MGO–GLO1 pathway in the etiology of vascular disease in diabetes has advanced significantly. Therefore, it can be summarized that vascular damage are linked to diabetes. The AGE precursor MGO are important in determining the connection between diabetes and vascular damage. MGO and AGEs play a role in several phases of the development of diabetes complications. MGO and AGEs may be useful therapeutic targets for diabetes's macrovascular problems.KEYWORDS: hyperglycemia, AGE, methylglyoxal, glyoxalase, D-lactate, gluthatione, oxidative stress.

Ketogenic Diet and Endocrine and Metabolic Diseases: A Bibliometric Study and Visualization Analysis.

The ketogenic diet, known for its high-fat, low-carbohydrate composition, has been extensively studied in endocrine and metabolic diseases. This study carried out bibliometric analysis to examine the research trends in this field over the past 20 years, aiming to provide insights for future studies. We searched the Web of Science Core Collection for all relevant papers. VOSviewer was used for network visualization, the bibliometrix package of R software (version 4.3.0) was utilized for data analysis, and CiteSpace was employed for mapping and trend analysis. This study encompassed 508 relevant articles spanning from 2003 to 2023, authored by 2827 researchers from 887 institutions across 57 countries/regions. The total number of publications increased from 3 in 2003 to 508 in 2023, showing a steady growth trend. The United States emerged as the predominant contributor in this field, followed by Italy and China. Notably, SAJOUX I consistently exhibited high activity in this field, according to the analysis, with an h-index of 13. The journal Nutrients has consistently made substantial contributions to this field, accounting for 19% of all publications. The keywords "obesity," "ketogenic diet," and "weight loss" appeared most frequently, with "obesity" occurring 163 times. This study used a bibliometric method to analyze the impact of the ketogenic diet on the endocrine metabolic system. The research identifies recent frontiers and trending directions, providing valuable references for scholars in this field.

Polycystic ovary syndrome and labor market attachment in Swedish women

Abstract Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of fertile age and is associated with several burdensome comorbidities. We use Swedish longitudinal register data to identify and compare clusters of employment trajectories among working age women, in order to investigate how PCOS affects labor market attachment. Data and Methods A cohort of 157,356 women born in 1975-1977 were followed annually between the ages of 30 and 39. Labor market states were constructed by combining detailed data on various types of earned income. PCOS was identified through national inpatient and outpatient registers. Sociodemographic covariates (civil status, region of origin, highest attained education, number of children) were measured at the age of 29 years. Sequence analysis was used to identify clusters of typical labor market trajectories. Multinomial logistic regression was employed to assess the associations between being diagnosed with PCOS and belonging to the identified clusters. Results Women with PCOS spent less time in employment and were more dependent on sickness benefits during the follow-up time than those without PCOS. Five clusters of trajectories were identified: stable employment, education into employment, labor market exclusion, continuous unstable position, long-term sickness. Compared to being in stable employment cluster, women diagnosed with PCOS were 97% more likely to experience long-term sickness (RRR (relative risk ratio): 1.97 [CI: 1.90-2.05]), and had 11% higher risk of belonging to education into employment (RRR: 1.11 [CI: 1.07-1.15]) and a 4% higher risk (RRR: 1.04 [CI: 1.00-1.09]) of experiencing labor market exclusion. The magnitude of the association increased for education into employment and labor market exclusion after adjusting for covariates. Conclusions PCOS can lead to disadvantaged labor market outcomes and better strategies are needed in order to prevent economic exclusion among women diagnosed with the condition. Key messages • PCOS leads to disadvantaged labor market outcomes. • Women with PCOS may experience economic exclusion.

Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.

NKX2-1, a crucial transcription factor in thyroid, lung, and brain development, is associated with rare disorders featuring thyroid dysfunction, neurological abnormalities, and respiratory symptoms. The primary challenge in managing NKX2-1-related disorders (NKX2-1-RD) is early diagnosis of the genetic defect and treating specific endocrine disorders. Levothyroxine (LT4) serves as the standard hypothyroidism treatment, with required dosages influenced by the severity of the individual's disorder, which varies widely among affected individuals. This systematic review aims to assess the effectiveness of LT4 treatment in NKX2-1-RD and explore optimal dosing strategies. The primary focus is on the challenges associated with the prompt diagnosis of genetic defects, rather than the established treatment protocols for individual endocrine failures. Adhering to PRISMA guidelines, the review includes 42 studies involving 110 genetically confirmed NKX2-1-RD patients with hypothyroidism. The study investigates congenital hypothyroidism as the most prevalent endocrine alteration, along with gestational and overt hypothyroidism. The administration of LT4 treatment, dosages, and patient responses are analyzed. Among the findings, congenital hypothyroidism emerges as the predominant endocrine alteration in 41% of patients. Notably, LT4 treatment is administered in only 10% of cases, with a mean dose of 52 μg/day. The variability in initiation and dosage is likely influenced by the age at diagnosis. Positive responses, characterized by TSH adjustments within normal ranges, are observed in 11 monitored patients. Early detection of congenital hypothyroidism is emphasized for timely LT4 initiation. Challenges in standardization are highlighted due to the variability in clinical manifestations and diagnostic procedures across NKX2-1-RD cases. While this review provides valuable insights into thyroid and pituitary disease treatment, limited details on LT4 treatment represent a significant study limitation. Key reporting points for future case studies are proposed to enhance the understanding and management of NKX2-1-RD hypothyroidism.

The effects of MIND diet on depression, anxiety, quality of life and metabolic and hormonal status in obese or overweight women with polycystic ovary syndrome: a randomised clinical trial.

Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women of reproductive age, associated with increased risks of metabolic disorders, depression and reduced quality of life. This study examined the impact of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet on mental health, PCOS-related quality of life (PCOSQ), anthropometric indices, hirsutism, and metabolic/hormonal parameters in women with PCOS. Total of 52 women with PCOS, aged between 18 and 45 years, were randomly assigned to either the low calorie MIND diet group or the control group. Anthropometric data, depression and anxiety scores, serum levels of gonadotropins (luteinizing hormone [LH], follicle-stimulating hormone [FSH]), PCOSQ, and Ferriman-Gallwey score were evaluated before and after the intervention. Outcomes were assessed at baseline and at the end of the 8-week follow-up period. After 8 weeks, the MIND diet significantly reduced depression (β -3·03; 95 % CI: [-5·36, -0·70]; P = 0·011) and anxiety (β -3·54; 95 % CI: [-6·60, -0·49]; P = 0·024) scores compared with the control group. The MIND diet group exhibited significant increases in the emotion (β 0·63; 95 % CI: [0·18, 1·08]; P = 0·007) and body hair (β 0·65; 95 % CI: [0·03, 1·28]; P = 0·04) domains of the PCOSQ compared to the control group. The changes in other parameters did not show significant differences between the two groups. Both the MIND diet and control groups showed improvements in weight and BMI, with a slight advantage for the MIND diet group. These findings suggest that the MIND diet may be beneficial for improving mental health and some aspects of PCOSQ in women with PCOS.

Understanding barriers and facilitators to lifestyle management in people with polycystic ovary syndrome: A mixed method systematic review.

Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 10-13% of reproductive-aged women. Lifestyle management through diet and physical activity changes can improve reproductive, metabolic, and psychological comorbidities. The aim of this systematic review is to understand the barriers and facilitators to lifestyle changes from the perspective of people with PCOS and health care professionals (HCP) using the theoretical domains framework and capability, opportunity, motivation, and behavior model. Six databases were systematically searched for qualitative, quantitative, and mixed-methods studies to 22nd September 2022. Quantitative outcomes from quantitative and mixed-methods studies were narratively synthesized and all studies were thematically analyzed. Sixty-eight papers met the eligibility criteria. HCP education on lifestyle management in PCOS was viewed by all to be inadequate, impacting the quality of care and health outcomes. Lifestyle advice delivered by a multidisciplinary team, including dietitians, was identified as a key component for change. All agreed that there was a need for individualized and PCOS-specific lifestyle advice. Weight stigma was identified as negatively impacting both those in larger and smaller bodies with PCOS, reducing the quality of care and affecting self-perception and mental health. People with PCOS perceived that lifestyle management was overly focused on weight loss and fertility, independent of their own personal motivations and goals. Systemic changes, including increasing HCP education on lifestyle management and multidisciplinary collaboration, focusing on lifestyle advice that meets individual needs, and reducing the use of weight-centric care are necessary for long-term sustainable changes and improvements in health outcomes in people with PCOS.

Characterizing clinical and hormonal profiles of acne in north African women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the leading endocrine disorder in young women of childbearing age. Dermatological issues, particularly acne, are a major reason for medical consultations. The aim of this study is to determine the prevalence of PCOS in patients presenting with acne as their main dermatological complaint and to compare the metabolic and hormonal clinical characteristics of acne patients with PCOS to those with isolated acne. This was a prospective study with analytical aims, carried out in the Endocrinology Department and the Dermatology Department of Farhat Hached University Hospital in Sousse. The study included patients seeking treatment for acne from January 2023 to January 2024, divided into two groups: those with confirmed PCOS (G1) and those with isolated acne (G2). All patients underwent hormonal assessment and ovarian ultrasound. We conducted a study involving 212 patients. We found that 65.6% of acne patients had been diagnosed with PCOS. Nodular lesions were significantly more frequent in 'PCOS' (p = 0.02). Acne was linked with hirsutism, which was more prevalent in 'PCOS' (94.2% 'PCOS' vs. 67.1% 'isolated acne'), as well as androgenic alopecia (51% 'PCOS' vs. 21.9% 'isolated acne') (p < 10- 3). 'PCOS' showed evidence of biological hyperandrogenism, with a mean testosterone level of 0.72 ± 0.27 ng/mL, significantly higher than in 'isolated acne'. The LH/FSH ratio was greater than 1 in 72.7% of cases in 'PCOS', demonstrating a significant difference compared to 'isolated acne', where it was greater than 1 in 24.7% of cases (p < 10- 3). In our study, acne in 'PCOS' appeared to be more severe and was associated with hypertestosteronemia (p = 0.041) and hyperprolactinemia (p = 0.008). According to our results, phenotype A was the most likely to cause severe acne (p = 0.043). Our work is unique in that it brings to light this hidden aspect of the dermatological impact of PCOS, prompting physicians to screen for this endocrine disorder in all adult women seeking acne treatment.

Association of SOGPI in mediating the effect of Phosphatidylcholine on polycystic Ovary Syndrome

Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, marked by hormonal imbalances and disruptions in glucose and lipid metabolism. Emerging research has indicated a correlation between lipids and PCOS, yet the specific lipid profiles or associated genes identified in various studies vary, and observational data alone cannot establish causation. Therefore, our study seeks to establish a causal association between lipidome and PCOS. Methods Data from genome-wide association studies, liposomes, metabolites, and PCOS-related information were collected. Four rounds of double-sample bidirectional intermediate Mendelian Randomization analyses including liposomes to disease, liposomes to metabolites, metabolites to disease, and reverse Mendelian Randomization analysis of lipids, total effect values and intermediary effect values were calculated. The proportion mediated by the intermediary effect was determined by dividing the intermediary effect value by the total effect value. Results The analyses revealed that three liposomes and nine metabolites were causally associated with PCOS. Specifically, phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol were identified as independent risk factors for PCOS through further Mendelian Randomization analysis. The risk of developing PCOS increased by 32% for every one standard deviation increase in phosphatidylcholine and by 17% for every one standard deviation increase in 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol. Furthermore, the study revealed that phosphatidylcholine can influence the development of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol acting as a mediator, explaining 4.97% of the effect. Conclusions This study confirmed a causal relationship between phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol with PCOS, where phosphatidylcholine can influence the occurrence of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol as a mediator.

Z-Scores for Assessing Ovarian Reserve in Young Patients Undergoing Fertility Preservation.

Women are born with a non-renewable pool of ovarian follicles, referred to as the ovarian reserve. This reserve consists of primordial follicles in the ovaries and can be affected by many factors, such as genetic and endocrine disorders, medical interventions, and endocrine disruptors. Fertility preservation is recommended when gonadotoxic treatments are necessary. The preferred options for women are oocyte and embryo cryopreservation. However, in very young, sexually immature patients, ovarian tissue cryopreservation is the only option. Knowing the follicular density of cryopreserved tissue samples is essential in fertility counseling for young patients. This protocol demonstrates the use of Z-scores for cortical follicle density as a tool to evaluate the quality of ovarian tissue in girls and young women aged 25 years and below who are undergoing fertility preservation. Follicle density in patient samples is compared to age-normalized reference standards, developed by Hassan et al. to estimate possible deviations from the standard. The follicle density is measured through histological quantification. For this, a small piece of ovarian cortical tissue (~2 mm x 2 mm x 2 mm) is fixed in either Bouin's or formaldehyde solution, embedded in paraffin, sectioned at 4 µm thickness, stained with hematoxylin and eosin, and digitized using a slide scanner. Follicular stages present in the cortex range from primordial to primary follicles. The cortical area was 1 mm from the surface epithelium on histological sections. Follicle density is calculated using a modified formula presented by Schmidt et al., and the Z-score is determined using the reference mean and standard deviation. The Z-score indicates how much the measured value deviates from the reference mean, determiningreduced (<-1.7 Z-score) ovarian reserve. With this method, follicle densities can be used as a valuable measure of ovarian reserve for young patients requiring fertility preservation.

Intracranial aneurysm coexisting with pituitary adenoma: A systematic review

Introduction: The simultaneous occurrence of intracranial aneurysms (IA) and primary brain tumors (BT) is frequently reported, with an estimated incidence of 0.5% to 7.4%. Among the tumor types associated with IA, pituitary adenomas (PA) are the most prevalent. Methods: We selected articles, published from 1960 to December 2023, on the Medline, Embase, Scopus, Cochrane Library, and Web of Science databases. The extraction form contains information specific to the aneurysm and tumor, rupture of the aneurysm, treatment proposal for both and order of treatment and outcome. Results: The study evaluated 118 patients from 25 articles. The most frequent types of tumors were Non-Functioning Hormone (NFA) producers, present in 45.8% (n=54) of the cases, and Growth Hormone (GH) secretors, which represent 23.0% (n=27) of the cases. The main treatment used was surgery, with Subtotal Resection (STR) performed in 4.2% (n=5) of cases, Gross Total Resection (GTR) in 3.4% (n=4), and Transsphenoidal Resection (TSR) in 7.6% (n=9). 16.0% (n=19) of patients had two or more aneurysms concomitant with the adenoma. IA treatment was performed before PA surgery in 25 patients (21.2%) and 15 patients received simultaneous treatment to IA and PA (12.7%). Conclusion: Patients with PAs have a considerable prevalence of IAs. Hormonal imbalances and mechanical changes induced by tumor growth, particularly influenced by GH and IGF-1, contribute to this coexistence. Surgical intervention is common, requiring meticulous precautions to avoid complications. More longitudinal studies including close follow-up with a description of outcomes are necessary to guide treatment protocols for this condition.

Decreased Insulin and Interleukin-6 Levels in Rattus Norvegicus Model of Polycystic Ovary Syndrome-Insulin Resistance Treated with a High Protein Diet

Hypercaloric in women of childbearing age is one of the causes of polycystic ovary syndrome (PCOS) with insulin resistance. Increased inflammation (tumor factor necrosis-α (TNF-α) and interleukin-6 (IL-6)) is the impact of endocrine and metabolic disorders involved due to metabolic syndrome, obesity, and diabetes mellitus. This study aims to evaluate whether a high-protein diet can reduce insulin and interleukin-6 levels, which are key indicators of polycystic ovary syndrome, and whether these changes can help in the treatment of the syndrome. This study used a prepost test only control design, true experimental, with a total sample of 6 female Rattus norvegicus rats aged 2–3 years (150–200 g). It consists of 4 groups, namely the negative control group (K-), the positive control group (K+), the treatment group (P), and the group without treatment (P-). The study examined the rat blood serum ELISA measurement of insulin and IL-6 levels. Anova test results of IL-6 levels (p = 0.002). Post-hoc test results of group K- and group P (p = 0.002), group K + and group P (p = 0.037), group K- and group K + (p = 0.437). The Anova test results of insulin levels between groups found a significant difference (p = 0.001). Post-hoc test of insulin levels of group K- and group P (p = 0.002), group K- and group K+ (p = 0.000), and group K+ with group P (p = 0.356). In group K and group P, the results of the ANOVA and post hoc tests on IL-6 levels and insulin levels with the provision of a high-protein diet show significant differences. This study suggests that a high-protein diet may be an effective therapeutic alternative in reducing the symptoms of polycystic ovary syndrome, especially in controlling high insulin and interleukin-6 levels.

Disorders in cytokine synthesis in women with uterine fibroids

In the structure of gynecological diseases, uterine fibroids occupy an “honorable” second place after inflammatory processes of the genital organs, and its share reaches 40%. Uterine fibroids are a benign monoclonal tumor that develops from one abnormal smooth muscle cell of the myometrium, which, as a result of mutation, has the ability to grow unregulated. Common symptoms of the disease include pelvic discomfort or pain, excessive uterine bleeding, secondary anemia, infertility, and bowel and bladder dysfunction. Uterine fibroids can negatively affect the general condition of a woman, causing hormonal, vegetative-vascular and psycho-emotional disorders. Moreover, about 80% of patients with uterine fibroids undergo radical surgical treatment. The mechanisms of development and growth of this benign tumor have not been fully established and remain controversial. The role of immune disorders in the pathogenesis of fibroids is currently being discussed. It has been proven that the growth of fibroids is accompanied by a weakening of immune defense against the background of an increase in the level of proinflammatory cytokines, which are regulators of the processes of proliferation and apoptosis, mediators of the action of sex steroids. The aim of the study was to study the level of some pro-inflammatory cytokines (IL-1β, IL-2, TGF-β2 and MCP-1) in the blood serum of women of reproductive age with uterine fibroids, depending on the size and nature of tumor growth. A comparative analysis of the results of examination of 123 women with uterine fibroids, who made up 2 groups: 1st group of 65 women with simple uterine fibroids and 2nd group of 58 women with rapidly growing uterine fibroids, is presented. The examination included a comprehensive clinical and laboratory study. The level of cytokines (IL-1β, IL- 2, TGF-β2, MCP-1) in the blood serum was assessed by ELISA. It was found that in patients of reproductive age with uterine fibroids, there is an increase in the levels of IL-1β, TGF-β2 and MCP-1. In women with rapidly growing uterine fibroids, these changes are more pronounced. The concentration of IL-2 is reduced in all women with uterine fibroids, regardless of the size and nature of tumor growth. It has been established that an increase in the size of myomatous nodes is accompanied by an increase in immune imbalance: there is an increase in the levels of pro-inflammatory cytokines (IL-1β, TGF-β2, MCP-1) against the background of a reduced content of the lymphokine IL-2, which we regard as possible links in the pathogenesis of uterine fibroids. A pronounced deficiency of IL-2 in the blood serum against the background of a sharp increase in the concentration of TGF-β2 and MCP-1 in the blood of women with uterine fibroids can be considered as a negative criterion for predicting disease progression and used as an additional prognostic marker of tumor growth

Features of liver structural organization in posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a severe psychological condition resulting from traumatic experiences, leading to long-term physiological changes in the body. It affects mental health and induces hormonal imbalances that disrupt the hypothalamus-pituitary-adrenal axis, influencing multiple organ systems. While PTSD is often linked with comorbid conditions like depression and anxiety, its effects on the hepatobiliary system are less understood. Aim. This study aimed to assess PTSD's impact on liver morphology in rats of different sexes and compare the severity of changes between males and females, contributing to the understanding of stress-related physiological effects. Materials and Methods. The experiment involved 40 Wistar rats, divided into control and PTSD-induced groups for both sexes. A validated stress induction protocol was used, followed by a thorough morphological analysis of liver specimens fixed in 10% formalin and stained with hematoxylin-eosin. Histopathological evaluation focused on liver architecture, hepatocyte condition, vascular integrity, and cellular organization. Results. Control animals displayed standard liver structure, while PTSD-induced groups exhibited significant morphological changes, such as dystrophic alterations in hepatocytes, congestion in hepatic veins, and the formation of blood clots. Female rats showed more pronounced changes than males, including hepatocyte swelling and vacuolization, indicating heightened cellular stress and reduced regenerative capacity. Conclusions. The findings highlight that PTSD-related liver changes were more significant in female rats, emphasizing the importance of considering gender differences in stress-related disorders. These alterations suggest a complex interaction between chronic psychological stress and liver physiology, warranting further research on mechanisms by which PTSD affects the hepatobiliary system and potential therapeutic interventions. for at-risk populations.

Individual and combined effects of commercial glyphosate, atrazine and 2,4-D herbicides on the gerbil ventral prostate

Exposure to pesticides, individually or in a mixture, in drinking water is one of the main sources of human contamination, which causes adverse effects on the reproductive system. Our study aimed to investigate, the effects of a 90-day exposure to low concentrations of glyphosate (GLY), atrazine (ATZ), and 2,4-dichlorophenoxyacetic acid (2,4-D), in commercial formulations, on morphological, molecular, and hormonal parameters of the ventral prostate of gerbils (Meriones unguiculatus). The animals were exposed via drinking water to individual concentrations of GLY: 700 μg/L, ATZ: 3 μg/L, and 2,4-D: 70 μg/L, as well as to their mixture (MIX). Our findings showed an increase in prostatic complex relative weight in ATZ-exposed animals. Stereological and morphometric techniques indicated an increase in the percentage and thickness of muscular stroma, following an increase in the amount of collagen and reticular fibers in the MIX group. Histopathological analysis showed a decrease in the incidence of epithelial atrophy, subepithelial inflammation, and microacini in the MIX. On the other hand, ATZ-exposed animals showed an increase in hyperplasia and total prostatic intraepithelial neoplasia (PIN). The expression of caspase-3 decreased and estrogen receptor alpha (ERα) increased in the 2,4-D and MIX. Western blotting showed an increase in estrogen receptor beta (ERβ) expression in MIX-exposed animals. Testosterone levels decreased in animals from the GLY, ATZ and 2,4-D groups. Our findings provide evidence that individual or combined exposure to herbicides causes hormonal imbalance and morphological alterations, besides favoring the incidence of proliferative lesions in the prostate, predisposing the gland to more severe injuries.

Mendelian randomization and multi-omics approach analyses reveal impaired glucose metabolism and oxidative phosphorylation in visceral adipose tissue of women with polycystic ovary syndrome.

What is the significance of visceral adipose tissue (VAT) in the pathogenesis of polycystic ovary syndrome (PCOS) and its impact on the regulation of metabolic disorders in women with PCOS? We revealed a potentially causal relationship between increased genetically predicted VAT and PCOS-related traits, and found that VAT exhibited impaired glucose metabolism and mitochondrial oxidative phosphorylation (OXPHOS) in women with PCOS. PCOS is a common reproductive endocrine disorder accompanied by many metabolic abnormalities. Adipose tissue is a metabolically active endocrine organ that regulates multiple physiological processes, and VAT has a much stronger association with metabolism than subcutaneous adipose tissue does. Mendelian randomization (MR) analysis was used to investigate the potential causal association between genetically predicted VAT and the risk of PCOS. Data for MR analysis were extracted from European population cohorts. VAT samples from sixteen PCOS patients and eight control women who underwent laparoscopic surgery were collected for proteomics and targeted metabolomics analyses. PCOS was diagnosed according to the 2003 Rotterdam Criteria. The control subjects were women who underwent laparoscopic investigation for infertility or benign indications. Proteomics was performed by TMT labeling and liquid chromatography-tandem mass spectrometry analysis, and targeted metabolomics was performed by ultra-performance liquid chromatography-tandem mass spectrometry analysis. The key differentially expressed proteins (DEPs) were validated by immunoblotting. MR analysis revealed a potentially causal relationship between increased genetically predicted VAT and PCOS, as well as related traits, such as polycystic ovaries, total testosterone, bioavailable testosterone, and anti-Müllerian hormone, while a negative relationship was found with sex hormone-binding globulin. Enrichment pathway analysis of DEPs indicated the inhibition of glycolysis and activation of mitochondrial OXPHOS in the VAT of PCOS patients. MR analysis revealed that key DEPs involved in glycolysis and OXPHOS were significantly linked to PCOS and its related traits. Dot blot assay confirmed a significant decrease in glycolysis enzymes PKM2 and HK1, and an increase in mitochondrial Complex I and III subunits, NDUFS3 and UQCR10. Moreover, metabolomics analysis confirmed down-regulated metabolites of energy metabolic pathways, in particular glycolysis. Further analysis of PCOS and control subjects of normal weight revealed that dysregulation of glucose metabolism and OXPHOS in VAT of women with PCOS was independent of obesity. The mass spectrometry proteomics data have been deposited to the iProX database (http://www.iprox.org) with the iProX accession: IPX0005774001. There may be an overlap in some exposure and outcome data, which might affect the results in the MR analysis. The changes in protein expression of key enzymes affect their activities and disrupt the energy metabolic homeostasis in VAT, providing valuable insight for identifying potential intervention targets of PCOS. This work was supported by the National Key Research and Development Project of China (2021YFC2700402), the National Natural Science Foundation of China (82071608, 82271665), the Key Clinical Projects of Peking University Third Hospital (BYSY2022043), and the CAMS Innovation Fund for Medical Sciences (2019-I2M-5-001). All authors report no conflict of interest. N/A.

Comparative Study of Prolactin Levels in Acne and Non-Acne Individuals among Adolescent

Background: One of the most prevalent dermatological conditions affecting adolescents is acne vulgaris. The production of acne vulgaris lesions is a result of hormonal imbalances that impact skin conditions. Prolactin (PRL) is widely known for its involvement in the formation and operation of the mammary glands in addition to its more than three hundred non-lactational activities. Objective: This study aimed to evaluate and compare prolactin levels in serum hormone between persons with acne vulgaris and those without acne. Materials and Methods: In this cross-sectional case control study, serum levels of prolactin were collected and estimated in 80 subjects consisting of 40 males and 40 females each; of which 20 were the control group and 20, the test group in each category respectively. Also, certain criteria’s were looked into such as subject’s age, state of health, menstrual patterns (for females) and much more. Data collected was analyzed using the Software Package for Social Sciences (SPSS). At the end of the experiment, the result showed no significant change (p&lt;0.05). Result: In both male and female adolescents, the mean serum prolactin level of those with acne was higher than that of those without the condition. In adolescents with acne, the mean serum prolactin level was higher (19.48 ± 11.04) than in those without acne (13.48 ± 5.22). P less than 0.05 indicated statistical significance. Conclusion: An increase in the mean serum prolactin levels of acne subjects in both categories when compared to non-acne subjects indicates the contribution of prolactin in the pathogenesis of acne.

Longitudinal assessment of the impact of prevalent diabetes on hospital admissions and mortality in the general population: a prospective population-based study with 19 years of follow-up

BackgroundHospitalization indicates the presence of severe disease and constitutes a leading cost in health care. We aimed to prospectively assess if prevalent diabetes mellitus contributes to excess all-cause and cause-specific hospital admissions and mortality at the population level.MethodsWe used a Swedish prospective population-based cohort, including 25,642 individuals of whom 4.2% had prevalent diabetes at baseline (mean age 61.2 ± 6.8 years, age range 44.8–73.4 years). We compared the number of hospitalizations and mortality classified according to the main chapters of the 10th revision of the International Classification of Diseases (ICD-10) during follow-up using nationwide inpatient registries, comparing individuals with and without prevalent diabetes, using multivariate adjusted negative binomial regression (incidence rate ratio, IRR) and Cox regression, respectively.ResultsDuring a median follow-up of 19 years, 18,904 subjects were hospitalized at least once [median 3 (IQR 2–6)] and 6767 (26.4%) individuals died. Overall, subjects with diabetes were hospitalized (IRR 1.83, p < 0.001) more often, and had a higher incidence rate of hospital admissions due to endocrine diseases (IRR 14.6, p < 0.001), dermatological diseases (IRR 3.7, p < 0.001), injuries and poisoning (IRR 2.7, p < 0.001), infectious diseases (IRR 2.5, p < 0.001), psychiatric diseases (IRR 2.0, p < 0.001), but also cardiovascular, hematological, genitourinary, neurologic and respiratory diseases compared with non-diabetic individuals. No difference was observed for hospital admissions due to cancer or musculoskeletal disorders. All-cause mortality was higher (HR 1.77, p < 0.001) in individuals with diabetes, with disease-specific mortality being significant only for cardiovascular and endocrine disease-related death.ConclusionsAt the population level, prevalent diabetes increased the hospitalization burden longitudinally due to diseases of most of the ICD-10 main chapters, except for cancer and musculoskeletal disorders. These novel findings challenge the current view on the spectrum of prevalent diabetes-related conditions and may have implications for screening and treatment strategies in diabetes.Permission of graphical illustrationsSource: Pixabay.com. No permission or acknowledgement is required.

The Enigma That Is ROHHAD Syndrome: Challenges and Future Strategies

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare syndrome presenting in early childhood associated with a high risk of mortality between 50 and 60%. It is characterised by rapid, early onset of obesity between 1.5–7 years, along with central hypoventilation and hypothalamic dysfunction, such as central hypothyroidism, hyperprolactinemia, disorders of sodium and water balance, growth hormone deficiency, adrenocortical insufficiency, or disorders of puberty and features of autonomic dysregulation. Up to half of cases have neural crest tumours, most commonly ganglioneuromas or ganglioneuroblastomas. The incidence of ROHHAD syndrome in any population is unknown. Currently, there is no specific diagnostic or genetic biomarker for ROHHAD, and diagnosis is based on clinical signs and symptoms, which is often challenging, and consequently may be delayed or unrecognised. Early diagnosis is important, as without intervention, ROHHAD is associated with high morbidity and mortality. Aetiology remains unclear; an autoimmune origin has been postulated, with immunosuppressive agents being used with variable benefit. With no cure, multidisciplinary management is largely supportive. Therefore, there are many unanswered questions in ROHHAD syndrome. In this review article, we outline the challenges posed by ROHHAD syndrome, including aetiology, genetics, diagnosis, screening, management, and prognosis. We present research priorities to tackle these issues to improve outcomes.

Retinol intake and PCOS management: a plasma metabolite and protein analysis via Mendelian randomization and NHANES 2011-2016.

Polycystic Ovary Syndrome (PCOS) represents a complex endocrine disorder characterized by a significant interplay with metabolic dysfunction and obesity. This research endeavors to elucidate the causal dynamics among plasma metabolites, proteins, and PCOS, alongside Body Mass Index (BMI), to pinpoint prospective therapeutic interventions. This investigation employed Mendelian randomization (MR) analyses combined with data derived from the National Health and Nutrition Examination Survey (NHANES) to explore the relationships between 1,400 plasma metabolites and PCOS, factoring in BMI adjustments. Additionally, the study examined the influence of plasma proteins and performed a retrospective cross-sectional analysis focusing on retinol consumption and testosterone levels. MR analyses showed metabolite Glycosyl-N-(2-hydroxynervonoyl)-sphingosine (GNS) and protein Keratin 19 (KRT19) were identified as significant markers in the context of PCOS and BMI adjustments. A Phenome-Wide Association Study (PheWAS) underscored the linkage between KRT19 and BMI, while gene-drug interaction findings demonstrated a connection between KRT19 and retinol. Analysis for NHANES data disclosed a negative correlation between retinol intake and testosterone levels, particularly within normal weight and obese cohorts, suggesting the feasibility of dietary interventions for PCOS management. The study sheds light on the intricate interactions between plasma metabolites, proteins, and PCOS, considering BMI variations, and highlights KRT19 protein as a promising therapeutic target. The outcomes support the integration of retinol consumption into dietary strategies to regulate testosterone levels and potentially alleviate PCOS symptoms, underscoring the necessity for personalized nutritional and therapeutic approaches in the effective management of PCOS.

CystNet: An AI driven model for PCOS detection using multilevel thresholding of ultrasound images

Polycystic Ovary Syndrome (PCOS) is a widespread endocrinological dysfunction impacting women of reproductive age, categorized by excess androgens and a variety of associated syndromes, consisting of acne, alopecia, and hirsutism. It involves the presence of multiple immature follicles in the ovaries, which can disrupt normal ovulation and lead to hormonal imbalances and associated health complications. Routine diagnostic methods rely on manual interpretation of ultrasound (US) images and clinical assessments, which are time-consuming and prone to errors. Therefore, implementing an automated system is essential for streamlining the diagnostic process and enhancing accuracy. By automatically analyzing follicle characteristics and other relevant features, this research aims to facilitate timely intervention and reduce the burden on healthcare professionals. The present study proposes an advanced automated system for detecting and classifying PCOS from ultrasound images. Leveraging Artificial Intelligence (AI) based techniques, the system examines affected and unaffected cases to enhance diagnostic accuracy. The pre-processing of input images incorporates techniques such as image resizing, normalization, augmentation, Watershed technique, multilevel thresholding, etc. approaches for precise image segmentation. Feature extraction is facilitated by the proposed CystNet technique, followed by PCOS classification utilizing both fully connected layers with 5-fold cross-validation and traditional machine learning classifiers. The performance of the model is rigorously evaluated using a comprehensive range of metrics, incorporating AUC score, accuracy, specificity, precision, F1-score, recall, and loss, along with a detailed confusion matrix analysis. The model demonstrated a commendable accuracy of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$96.54\\%$$\\end{document} when utilizing a fully connected classification layer, as determined by a thorough 5-fold cross-validation process. Additionally, it has achieved an accuracy of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$97.75\\%$$\\end{document} when employing an ensemble ML classifier. This proposed approach could be suggested for predicting PCOS or similar diseases using datasets that exhibit multimodal characteristics.