Search

Background: The need for minimally invasive biomarkers for the early diagnosis of type 2 diabetes (T2DM) prior to the clinical onset and monitoring of β-pancreatic cell loss is emerging. Here, we focused on studying circulating cell-free DNA (ccfDNA) as a liquid biopsy biomaterial for accurate diagnosis/monitoring of T2DM. Methods: ccfDNA levels were directly quantified in sera from 96 T2DM patients and 71 healthy individuals via fluorometry, and then fragment DNA size profiling was performed by capillary electrophoresis. Following this, ccfDNA methylation levels of five βcell-related genes were measured via qPCR. Data were analyzed by automated machine learning to build classifying predictive models. Results: ccfDNA levels were found to be similar between groups but indicative of apoptosis in T2DM. INS (Insulin), IAPP (Islet Amyloid Polypeptide-Amylin), GCK (Glucokinase), and KCNJ11 (Potassium Inwardly Rectifying Channel Subfamily J member 11) levels differed significantly between groups. AutoML analysis delivered biosignatures including GCK, IAPP and KCNJ11 methylation, with the highest ever reported discriminating performance of T2DM from healthy individuals (AUC 0.927). Conclusions: Our data unravel the value of ccfDNA as a minimally invasive biomaterial carrying important clinical information for T2DM. Upon prospective clinical evaluation, the built biosignature can be disruptive for T2DM clinical management. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Adequate vitamin D levels are particularly important in pregnant women for both maternal and neonatal health. Prior studies have shown a significantly high prevalence of vitamin D deficiency (VDD) among refugees. However, no study has addressed the prevalence of VDD in pregnant refugees and its effects on neonatal health. In this study, we examined the prevalence of VDD in refugee pregnant women living in Greece and compared our results with Greek pregnant inhabitants. VDD was frequent in both groups but was significantly more common in refugees (92.2 vs 67.3% of Greek women, P = 0.003) with 70.6% of refugees having severe hypovitaminosis D (

Purpose: Serum and urinary bisphenol A (BPA) concentrations have been associated negatively with the number of retrieved oocytes after in vitro fertilization (IVF). The impact of BPA upon women with polycystic ovary syndrome (PCOS) and women with tubal factor infertility (TFI), following IVF, was investigated. To this purpose, associations among serum and urinary and follicular fluid (FF) BPA concentrations and the number of retrieved and fertilized oocytes and comparisons between pregnancy rates were evaluated. Methods: This was a cross-sectional study conducted at a university-affiliated assisted conception unit between January and November 2019, including 93 women of reproductive age (PCOS: 45; TFI: 48) following IVF. Unconjugated FF and serum BPA concentrations and total urinary BPA concentration were measured using a novel gas chromatography–mass spectrometry method. The number of retrieved and fertilized oocytes and pregnancy rate were documented and evaluated. Results: The number of oocytes retrieved from PCOS women was greater than that of 21 TFI women, independently of BMI. Lower FF BPA concentrations were found in all PCOS women and in overweight/obese PCOS compared to TFI women (0.50, 0.38, and 1.13 ng/mL, respectively). In TFI women, FF BPA concentrations correlated negatively with the number of retrieved oocytes. Serum and FF and urinary BPA concentrations did not significantly affect the number of fertilized oocytes and pregnancy rate in both groups. Conclusion: FF BPA concentrations were lower in all PCOS women and in overweight/obese PCOS than in TFI women. In TFI women, FF BPA concentrations correlated negatively with retrieved oocytes. Confirmation of these findings might lead to moderation of use of BPA-containing products by women undergoing IVF. © 2022, Hellenic Endocrine Society.

Objective: This study compared hematologic, metabolic and antioxidant responses between three high-intensity interval exercise (HIIE) trials of different bout duration and a continuous exercise trial (CON), all with equal average intensity, total work, and duration. Methods: Eleven healthy young males performed four trials involving 20 min of cycling, either continuously (49% of power at VO2max, PPO), or intermittently with 48 10-s bouts (HIIE10), 16 30-s bouts (HIIE30) or 8 60-s bouts (HIIE60) at 100% PPO, with a 1:1.5 work-to-recovery ratio at 15% PPO. Venous blood was obtained before, immediately after, and 1 h post-exercise to evaluate hematologic, metabolic and antioxidant responses. Blood lactate concentration was measured in capillary blood during exercise, while urine lactate was measured before and 1 h post-exercise. Results: Post-exercise leukocyte count (mean ± SD; 9.7 ± 2.8 k μL−1), uric acid concentration (0.35 ± 0.10 mmol L−1), glucose concentration (6.56 ± 1.44 mmol L−1), and plasma volume change (−13.5 ± 4.4%) were greater in HIIE60 compared to all other trials (p < 0.05). One-hour post-exercise, lymphocytes decreased below pre-exercise values in all HIIE trials, and uric acid increased in the HIIE60 trial (p < 0.05). Urine lactate concentration 1 h post-exercise increased compared to pre-exercise only in HIIE60 (19-fold, p < 0.001), and this was related with the higher blood lactate concentration during exercise in that trial. Conclusions: These findings highlight the importance of bout duration, given that shorter bouts of HIIE (30 s or 10 s) induce lower blood cell perturbations, metabolic stress, and antioxidant responses compared to the commonly used 1-min bouts, despite equal total work, duration, and work-to-recovery ratio. © 2022 The Society of Chinese Scholars on Exercise Physiology and Fitness

Objectives: This study compared physiological, perceptual, and affective responses to high-intensity interval training (HIIT) between two work-matched programs with different bout durations in obese males. Methods: Sixteen low-to-moderately active obese men completed an eight-week cycling program of supervised HIIT (3 days/week) using either short bouts [48 × 10 s at 100% of peak power output (PPO) with 15 s of recovery (HIIT10)] or long bouts [8 × 60 s at 100% PPO with 90 s of recovery (HIIT60)]. Workload was progressively adjusted, to maintain high intensity (100% PPO), throughout training. Blood lactate (BLa), heart rate (HR), ratings of perceived exertion (RPE), and feeling scale ratings (pleasure/displeasure) were measured in each HIIT session. Results: Average HR decreased in the last 2 weeks of training in both groups by 2.2 ± 1.8% of peak HR (p < 0.001). Training resulted in a reduction in BLa during exercise by 28 ± 19% (p < 0.001) from the 10th min onward only in HIIT10. Similarly, during the last weeks of training, RPE decreased (by 1.0 ± 1.1 units, p < 0.05) and feeling scale ratings were improved only in HIIT10, while RPE remained unchanged and feeling scale ratings deteriorated in HIIT60 (from 3.0 ± 1.1 to 2.1 ± 0.9 units, p < 0.001). No differences in post-exercise enjoyment were found. Conclusion: Both HIIT formats induced similar HR adaptations, but improvement of BLa, perceptual and affective responses occurred only when bout duration was shorter. Our findings suggest that, in low-to-moderately active obese men, HIIT may be more effective in improving metabolic, perceptual, and affective responses when shorter, rather than longer, bouts of exercise are used. © 2022 The Society of Chinese Scholars on Exercise Physiology and Fitness

Orphanet journal of rare diseases: OJRD 15(1), 144 (2020). doi:10.1186/s13023-020-01420-w, Published by BioMed Central, London

Initiation of desmopressin acetate (DDAVP) for untreated diabetes insipidus (DI) in Wolfram syndrome (WS) causes abrupt volume expansion resulting in particularly high secretion of Atrial Natriuretic Peptide (ANP) and/or Brain Natriuretic Peptide (BNP), which in turn blocks all stimulators of zona glomerulosa steroidogenesis, resulting in secondary mineralocorticoid deficiency and acute hyponatremia, causing renal salt wasting (RSW). Two sisters, a 19-y-old girl (A) and a 7-y-old girl (B) with WS, presented with severe polyuria-polydipsia due to never treated DI. Both had neurogenic bladder and “B” had severe hydronephrosis secondary to untreated grade III bilateral vesicoureteral reflux. They initiated therapy with oral melt DDAVP which resulted in RSW. ANP was found ×50 and BNP ×2–4 fold elevated. Fludrocortisone 100–200 × 2 μg/d controlled natriuresis and restored electrolytes to normal within 48 h. Fludrocortisone treatment rescues otherwise potentially life-threatening hyponatremia due to RSW and the secondary mineralocorticoid deficiency driven by elevated ANP and/or BNP, caused by sudden volume expansion following DDAVP initiation. © 2020, Dr. K C Chaudhuri Foundation.

Background: Both deviations from normal weight, namely, underweight and overweight/obese status, have been inversely associated with psychosocial health in adolescents. This study aimed to examine the relationship between psychosocial health and body mass index (BMI) among adolescents in five European countries, while assessing the effect of sociodemographic variables. Methods: A cross-sectional school-based study of adolescents aged 14-17.9 years was conducted in the framework of the European Network for Adolescent Addictive Behavior survey. Self-reported questionnaires from Greece, Iceland, the Netherlands, Romania and Spain were used for the current analysis. Associations between Youth Self-Report (YSR) scales and BMI status were investigated by multiple logistic regression analysis. The effect of sociodemographic variables was also measured. Results: Τhe sample consisted of 7005 adolescents aged 14-17.9 years. Borderline/clinical scores on some YSR scales were independently associated with overweight/obesity, specifically total problems (OR = 1.52, 95% CI: 1.18-1.96), internalizing (OR = 1.48, 95% CI: 1.16-1.91), externalizing (OR = 1.36, 95% CI: 1.10-1.68), social (OR = 1.67, 95% CI: 1.19-2.35) and thought problems (OR = 1.62, 95% CI: 1.20-2.20). Among subscales, overweight/obesity specifically correlated with anxiety/depression (OR = 1.83, 95% CI: 1.33-2.51), withdrawal/depression (OR = 1.58, 95% CI: 1.02-2.48) and rule-breaking behavior (OR = 1.55, 95% CI: 1.15-2.08). Underweight was associated with problems on activities (OR = 1.31, 95% CI: 1.01-1.68) and withdrawal/depression (OR = 1.95, 95% CI: 1.27-3.01). Conclusions: Lower levels of psychosocial health are associated with both deviations from normal weight. These findings suggest the need for health policies that target health habits and lifestyle, as well as positive attitudes towards the body image, with respect to the different psychosocial characteristics of each body weight status category. © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

The worldwide upward trend in obesity in adults and the increased incidence of overweight children suggests that the future risk of obesity-related illnesses will be increased. The existing anti-obesity drugs act either in the central nervous system (CNS) or in the peripheral tissues, controlling the appetite and metabolism. However, weight regain is a common homeostatic response; current anti-obesity medications show limited effectiveness in achieving long-term weight loss maintenance; in addition to being linked to various side effects. Combined anti-obesity medications (per os or injectable) target more than one of the molecular pathways involved in weight regulation, as well as structures in the CNS. In this systematic review, we conducted a search of PubMed and The ClinicalTrials.gov up to February 2021. We summarized the Food and Drug Administration (FDA)-approved medications, and we focused on the combined pharmacological treatments, related to the incretin hormones, currently in a clinical trial phase. We also assessed the mechanism of action and therapeutic utility of these novel hybrid peptides and potential interactions with other regulatory hormones that may have beneficial effects on obesity. As we improve our understanding of the pathophysiology of obesity, we hope to identify more novel treatment strategies. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during the first three days of life in human premature neonates which later developed NBI. It was conducted in a single tertiary hospital and eligible participants were live-born premature (

Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Context. Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? Objective. To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). Design. Open label, parallel randomized, single center study. Subjects and Methods. Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. Results. Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (r=0.008). During MET treatment a significant decrease in BMI (10.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FM) (p=0.006) was observed. Conclusions. Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism.

This study investigates follicular fluid (FF) from patients with poor and normal ovarian response undergoing natural assisted reproductive technology cycles. We report about (1) cell-free DNA (cfDNA), which reflects apoptosis; (2) corticotropin-releasing hormone (CRH); (3) interleukin (IL)-15, which reflects inflammation; (4) granulocyte colony–stimulating factor (G-CSF); (5) vascular endothelial growth factor (VEGF); and (6) insulin-like growth factor I (IGF-I), which reflects follicular growth. Forty-four poor responders and 44 normal responders—according to the Bologna criteria—were recruited. FF samples were prepared for cfDNA quantification employing Q-PCR and for CRH, IL-15, G-CSF, VEGF, and IGF-I quantification employing ELISA. Statistically nonsignificant different levels of FF cfDNA, CRH, IL-15, VEGF, and IGF-I were observed. Interestingly, statistically significant higher G-CSF levels were observed in normal responders (302.48 ± 474.36 versus 200.10 ± 426.79 pg/mL, P = 0.003). Lower cfDNA integrity was observed in cycles resulting in clinical pregnancy for both groups (normal: 0.07 ± 0.04 versus 0.25 ± 0.17 ng/μL, P < 0.001; poor: 0.10 ± 0.06 versus 0.26 ± 0.12 ng/μL, P < 0.001). The results predominantly showcase similarities between normal and poor responders pertaining to inflammatory, apoptotic, and growth factors. This may be attributed to the employment of natural cycles in order to exclude controlled ovarian stimulation as a factor—indicating its detrimental effect. As G-CSF levels presented significantly higher in normal responders, its vital role in understanding a compromised ovarian response is highlighted. © 2020 New York Academy of Sciences.

Aging is associated with the development of chronic low-grade systemic inflammation (LGSI) characterized by increased circulating levels of proinflammatory cytokines and acute phase proteins such as C-reactive protein (CRP). Collective evidence suggests that elevated levels of inflammatory mediators such as CRP, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) are correlated with deteriorated skeletal muscle mass and function, though the molecular footprint of this observation in the aged human skeletal muscle remains obscure. Based on animal models showing impaired protein synthesis and enhanced degradation in response to LGSI, we compared here the response of proteolysis- A nd protein synthesis-related signaling proteins as well as the satellite cell and amino acid transporter protein content between healthy older adults with increased versus physiological blood hs-CRP levels in the fasted (basal) state and after an anabolic stimulus comprised of acute resistance exercise (RE) and protein feeding. Our main findings indicate that older adults with increased hs-CRP levels demonstrate (i) increased proteasome activity, accompanied by increased protein carbonylation and IKKα/β phosphorylation; (ii) reduced Pax7+ satellite cells; (iii) increased insulin resistance, at the basal state; and (iv) impaired S6 ribosomal protein phosphorylation accompanied by hyperinsulinemia following an acute RE bout combined with protein ingestion. Collectively, these data provide support to the concept that age-related chronic LGSI may upregulate proteasome activity via induction of the NF-κB signaling and protein oxidation and impair the insulin-dependent anabolic potential of human skeletal muscle. © 2021 Dimitrios Draganidis et al.

Purpose: To examine the association of maternal bone markers [sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteocalcin, 25-hydroxyvitamin D3] with fetal intra-abdominal and subcutaneous adipose tissue deposition and birthweight during normal pregnancy. Methods: One hundred pregnant women (aged 30.4±5.6 years, mean±SD) with prepregnancy body mass index=24.1±4.6 kg/m2 were seen prospectively during each trimester. At each visit they were submitted to anthropometric measurements, a fasting blood sampling, a 75-g oral glucose tolerance test, and a fetal ultrasonogram. At birth, neonates had birth weight measurement. Results: In the second trimester, maternal sclerostin concentrations correlated positively with fetal abdominal circumference and birth weight; maternal sRANKL concentrations correlated positively with fetal abdominal subcutaneous fat thickness, sagittal abdominal diameter, and abdominal circumference. Fetuses born to mothers with greater (>254 ng/mL), compared to fetuses born to mothers with lower (≤254ng/mL), sRANKL concentrations had greater abdominal circumference, sagittal diameter, and abdominal subcutaneous fat thickness. Maternal serum sclerostin concentrations were the best positive predictors of birth weight. In the third trimester maternal sclerostin concentrations correlated positively with fetal sagittal abdominal diameter; maternal sRANKL concentrations positively correlated with fetal abdominal circumference and fetal abdominal sagittal diameter. Conclusions: Maternal bone markers sclerostin and sRANKL may relate to fetal intra-abdominal adipose tissue deposition through as yet unknown direct or indirect mechanisms, thus contributing to birthweight. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pesticide residues are largely found in daily consumed food because of their extensive use in farming and their long half-life, which prolongs their presence in the environment. Many of these pesticides act as endocrine-disrupting chemicals after pre-or postnatal exposure, significantly affecting, among other things, the time of puberty onset, progression, and completion. In humans, precocious or delayed puberty, and early or delayed sexual maturation, may entail several negative long-term health implications. In this review, we summarize the current evidence on the impact of endocrine-disrupting pesticides upon the timing of the landmarks of female and male puberty in both animals (vaginal opening, first estrus, and balanopreputial separation) and humans (thelarche, menarche, gonadarche). Moreover, we explore the possible mechanisms of action of the reviewed endocrine-disrupting pesticides on the human reproductive system. Access to safe, healthy, and nutritious food is fundamental for the maintenance of health and wellbeing. Eliminating the presence of hazardous chemicals in largely consumed food products may increase their nutritional value and be proven beneficial for overall health. Consequently, understanding the effects of human exposure to hazardous endocrine-disrupting pesticides, and legislating against their circulation, are of major importance for the protection of health in vulnerable populations, such as children and adolescents. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Objectives. The present paper aims to investigate the effects of both progesterone and progestin treatment mainly related to the occurrence of breast cancer in women. Materials and methods. Extensive systematic bibliographic review of Greek and International articles was conducted through the electronic databases Pubmed, Cinahl, Uptodate, and Google Scholar for the identification of articles related to progesterone, progestins and breast cancer treatment. Results. Hormone therapy with the use of estrogen alone presents a small increased risk or does not present at all an increased risk of breast cancer. With ORs in some studies below 1.0 in current users for 3 plus years and safe option until 7 years, while in other studies the risk was increased with the ORs 1.29. However, the use of estrogen in combination with progestogens, depending on the type of progestogens, shows an increased risk of breast cancer, with the ORs to vary between 1.14-2.38 from 3 to 5 years and is inversely proportional to the time of its use. This risk varies depending on the combination of the preparations. Other factors that are associated with breast cancer risk when receiving hormone therapy are the years that hormone therapy is taken, directly proportional to the risk. At higher risk are older women, women with low body mass index in menopause (BMI

Transforming growth factor beta (TGF-β), as a master regulator of immune response, is deeply implicated in the complex pathophysiology and development of autoimmune thyroid diseases. Based on the close interplay between thyroid autoimmunity and TGF-β, scientific inter-est was shifted to the understanding of the possible role of this molecule regarding the diagnosis, prognosis, and therapy of these diseases. The main aim of this review is to present research data about possible treatment options based on the role of TGF-β in thyroid autoimmunity. Suggested TGF-β-mediated therapeutic strategies regarding autoimmune thyroid diseases include either the enhancement of its immunosuppressive role or inhibition of its facilitatory role in thyroid autoimmu-nity. For example, the application of hr-TGF-β can be used to bolster the inhibitory role of TGF-β regarding the development of thyroid diseases, whereas anti-TGF-β antibodies and similar molecules could impede its immune-promoting effects by blocking different levels of TGF-β biosynthesis and activation pathways. In conclusion, TGF-β could evolve to a promising, novel therapeutic tool for thyroid autoimmunity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is increasingly hypothesized to be a factor contributing to changes in fetal growth velocity. BPA exposure may be environmental, occupational, and/or dietary, with canned foods and plastic bottles contributing significantly. Our systematic review aims to evaluate the current literature and to investigate the role of BPA in abnormal fetal growth patterns. A search was conducted in the PubMed and Cochrane databases. A total of 25 articles met the eligibility criteria and were included in this systematic review. Eleven of them failed to show a clear relationship between BPA and abnormal fetal growth. The majority of the remaining studies (9/14) found an inverse association of BPA with indicators of fetal growth, whereas three studies suggested increased fetal growth, and two studies produced contradictory findings. Of note, both of the studies that collected a sample (amniotic fluid) directly reflecting BPA concentration in the fetus during the first half of pregnancy revealed an inverse association with birth weight. In conclusion, there is mounting evidence that combined exposure to BPA from dietary and non-dietary sources during pregnancy may contribute to abnormal fetal growth; a tendency towards fetal growth restriction was shown, especially when exposure occurs during the first half. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Anorexia nervosa (AN) is a serious, multifactorial mental disorder affecting predominantly young females. This systematic review examines neuroimaging findings in adolescents and young adults up to 24 years old, in order to explore alterations associated with disease pathophysiology. Methods: Eligible studies on structural and functional brain neuroimaging were sought systematically in PubMed, CENTRAL and EMBASE databases up to 5 October 2020. Results: Thirty-three studies were included, investigating a total of 587 patients with a current diagnosis of AN and 663 healthy controls (HC). Global and regional grey matter (GM) volume reduction as well as white matter (WM) microstructure alterations were detected. The mainly affected regions were the prefrontal, parietal and temporal cortex, hippocampus, amygdala, insula, thalamus and cerebellum as well as various WM tracts such as corona radiata and superior longitudinal fasciculus (SLF). Regarding functional imaging, alterations were pointed out in large-scale brain networks, such as default mode network (DMN), executive control network (ECN) and salience network (SN). Most findings appear to reverse after weight restoration. Specific limitations of neuroimaging studies in still developing individuals are also discussed. Conclusions: Structural and functional alterations are present in the early course of the disease, most of them being partially or totally reversible. Nonetheless, neuroimaging findings have been open to many biological interpretations. Thus, more studies are needed to clarify their clinical significance. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

BACKGROUND Alopecia areata (AA) is an inflammatory disease with autoimmune, environmental, and inherited components directed at the hair follicle, either limited to patchy hair loss over the scalp (Focalis, AF), total loss of scalp hair (Totalis, AT), or total loss of both scalp and body hair (Universalis, AU). Despite multiple treatment modalities, no therapy exists. Vitamin D deficiency in patients with AA/AT/AF influences disease severity and duration, inversely correlating with inflammation histologically. CASE SUMMARY Three girls presented with AT (P1), AU (P2), and AF (P3) at the ages of 1, 5, and 5 years, respectively. For P1-P2, all available treatments implemented for 2 years had failed. We started an initial 6-mo repletion with oral cholecalciferol 2000/4000 IU/d, with no apparent effect. Then we attempted immunomodulation using oral calcitriol and its analog paricalcitol. On calcitriol, 0.5 mcg/d P1 regrew hair within 6 mo. After 4 years, a relapse with loss of eyebrow hair was resolved after doubling the calcitriol dose to 0.5 mcg × 2/d; the results have been maintained for 6 years to date. On calcitriol, 0.25 mcg × 3/d P2 led to the development of asymptomatic hypercalcemia-hypercalciuria, which was immediately resolved by switching to paricalcitol 2 mcg × 3/d; mild tolerable hypercalciuria was maintained. Hair regrowth was observed at 6 mo, stabilizing only as fur at 12 mo. AF in P3 was resolved completely within 3 mo on a daily high dose (8000 IU) of cholecalciferol. CONCLUSION Vitamin D may have immunomodulating therapeutic impact on AT/AU/AF, which needs to be explored with further pilot clinical trials. © 2021 The Authors.

Purpose: Low energy availability (LEA) may lead to menstrual disorders and low bone mineral density, predisposing to the female athlete triad. The primary aim of the present review was to systematically investigate the impact of chronic strenuous exercise on the energy status of professional female athletes compared to sedentary, recreationally active controls as concerns their menstrual status and bone mineral density (BMD). A secondary aim was evaluation of the combined prevalence of the components of the female athlete triad in athletes as compared to non-athletes. Methods: A systematic review was conducted from 2007 to February 2018. The inclusion and exclusion criteria of the studies were established in advance of the literature search according to the clinical inquiry and the study design. Results: Four studies were included in this systematic review. The female athlete triad was more prevalent in professional athletes compared to non-athletes. The same results were obtained for both LEA and menstrual disorders. However, BMD and Z-scores showed high heterogeneity among the studies. Conclusion: Both female athletes and non-athletes are prone to LEA and subsequent menstrual disorders and low BMD or osteoporosis. Future studies are needed to examine energy availability in elite female athletes as well as in non-athletes. © 2021, Hellenic Endocrine Society.

Physical exercise has been proposed as an adjunct in addiction treatment, including tobacco cigarette smoking. The physiological and biochemical mechanisms that could be affected by physical exercise in smokers and that could help quit smoking have not been investigated yet. Objective: To investigate whether the effects of acute exercise on smoking behavior and HPA axis activation in smokers are intensity-dependent. Methods: Healthy, non-systematically exercising individuals [25 smokers (age: 33±1.4 years) and 10 non-smokers (age: 34±2.1 years)] underwent three trials [moderate intensity (MI), high intensity (HI) exercise, control (C)] in a counterbalanced order, after an overnight fast and smoking abstinence, separated by at least six days. MI involved cycling at 50–60% of Heart Rate Reserve (HRR) for 30 min, HI involved cycling at 65–75% HRR for 30 min, while in C participants rested for 30 min. Time till the first cigarette following each trial was recorded. Smoking urge was evaluated and blood samples, [analyzed for β-endorphin (β-E), adrenocorticotropic hormone (ACTH), cortisol and catecholamines], were obtained prior to and immediately after each trial. Results: β-E, ACTH, catecholamines and cortisol responses to exercise were intensity-dependent and differed in smokers and non-smokers. Resting β-E levels were 2–2.5 times lower in smokers compared to non-smokers. HI resulted in increased β-E levels in both groups, with smokers exhibiting similar levels to that observed in non-smokers. Although smoking urge did not change post-exercise in smokers, time till first cigarette increased following both MI (64.6%) and HI (77.9%) compared to C. Conclusions: HPA axis activation in response to exercise may differ between smokers and non-smokers. Smokers have lower resting levels of β-E compared to non-smokers and, since HI exercise increases β-E to similar levels to those of non-smokers and delays smoking, this may be used as an adjunct in smoking cessation. © 2020 Elsevier Inc.

The effects of two high-intensity interval training (HIIT) protocols on regional body composition and fat oxidation in men with obesity were compared using a parallel randomized design. Sixteen inactive males (age, 38.9 ± 7.3 years; body fat, 31.8 ± 3.9%; peak oxygen uptake, VO2peak, 30.9 ± 4.1 mL/kg/min; all mean ± SD) were randomly assigned to either HIIT10 (48 × 10 s bouts at 100% of peak power [Wpeak ] with 15 s of recovery) or HIIT60 group (8 × 60 s bouts at 100% Wpeak with 90 s of recovery), and subsequently completed eight weeks of training, while maintaining the same diet. Analyses of variance (ANOVA) showed only a main effect of time (p < 0.01) and no group or interaction effects (p > 0.05) in the examined parameters. Total and trunk fat mass decreased by 1.81 kg (90%CI: −2.63 to −0.99 kg; p = 0.002) and 1.45 kg (90%CI: −1.95 to −0.94 kg; p < 0.001), respectively, while leg lean mass increased by 0.86 kg (90%CI: 0.63 to 1.08 kg; p < 0.001), following both HIIT protocols. HIIT increased peak fat oxidation (PFO) (from 0.20 ± 0.05 to 0.33 ± 0.08 g/min, p = 0.001), as well as fat oxidation over a wide range of submaximal exercise intensities, and shifted PFO to higher intensity (from 33.6 ± 4.6 to 37.6 ± 6.7% VO2peak, p = 0.039). HIIT, irrespective of protocol, improved VO2peak by 20.0 ± 7.2% (p < 0.001), while blood lactate at various submaximal intensities decreased by 20.6% (p = 0.001). In conclusion, both HIIT protocols were equally effective in improving regional body composition and fat oxidation during exercise in obese men. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Despite the production of clinical practice guidelines (CPGs) in many medical areas, their use is not sufficiently adopted in clinical practice. Incorporation of CPGs in knowledge tools (KnowT) or decision support systems (DSS) for routine use can improve healthcare providers' compliance to CPGs. Materials and methods: Clinical practice guidelines for gestational diabetes mellitus (GDM) were searched for, collected and compared. The CPG that met pre-specified criteria ([a] published by a European or American organization between 2010 and 2018, [b] being developed a systematic way and [c] having statements of “level of evidence” and “strength of recommendation”) was chosen for implementation (Endocrine Society, 2013). Its recommendations were deconstructed, re-organized and reconstructed as an algorithm (in the form of a flowchart), which was integrated into a KnowT. Content completeness and evaluation of CPG by the Guideline Implementability Appraisal tool (GLIA) were performed as well. The primary objective was the development of a clinical algorithm in the field of GDM and its integration into a KnowT. The secondary objective was to demonstrate the completeness of the CPG content and evaluate its implementability in the KnowT. Results: Endocrine Society 2013 CPG was restructured as a flowchart, and a KnowT was constructed with the use of the “Openlabyrinth” software. The completeness of the content was confirmed, and GLIA appraisal demonstrated its implementability. Conclusion: Endocrine Society 2013 CPG for GDM is a complete set of recommendations. Its structure makes possible the design of a clinical algorithm and its implementation into a KnowT. © 2020 Stichting European Society for Clinical Investigation Journal Foundation

Differences of Sex Development (DSD) comprise a variety of congenital conditions characterized by atypical chromosomal, gonadal, or anatomical sex. Diagnosis and monitoring of treatment of patients suspected of DSD conditions include clinical examination, measurement of peptide and steroid hormones, and genetic analysis. This position paper on peptide hormone analyses in the diagnosis and control of patients with DSD was jointly prepared by specialists in the field of DSD and/or peptide hormone analys is from the European Cooperation in Science and Technology (COST) Action DSDnet (BM1303) and the European Reference Network on rare Endocrine Conditions (Endo-ERN). The goal of this position paper on peptide hormone analysis was to establish laboratory guidelines that may contribute to improve optimal diagnosis and treatment control of DSD. The essential peptide hormones used in the management of patients with DSD conditions are follicle-stimulating hormone, luteinising hormone, anti-Müllerian hormone, and Inhibin B. In this context, the following position statements have been proposed: serum and plasma are the preferred matrices; the peptide hormones can all be measured by immunoassay, while use of LC-MS/MS technology has yet to be implemented in a diagnostic setting; sex- and age-related reference values are mandatory in the evaluation of these hormones; and except for Inhibin B, external quality assurance programs are widely available. © 2020 European Society of Endocrinology Printed in Great Britain.

Background: With the development of molecular high-throughput assays (i.e. next generation sequencing), the knowledge on the contribution of genetic and epigenetic alterations to the etiology of inherited endocrine disorders has massively expanded. However, the rapid implementation of these new molecular tools in the diagnostic settings makes the interpretation of diagnostic data increasingly complex. Main body: This joint paper of the ENDO-ERN members aims to overview chances, challenges, limitations and relevance of comprehensive genetic diagnostic testing in rare endocrine conditions in order to achieve an early molecular diagnosis. This early diagnosis of a genetically based endocrine disorder contributes to a precise management and helps the patients and their families in their self-determined planning of life. Furthermore, the identification of a causative (epi)genetic alteration allows an accurate prognosis of recurrence risks for family planning as the basis of genetic counselling. Asymptomatic carriers of pathogenic variants can be identified, and prenatal testing might be offered, where appropriate. Conclusions: The decision on genetic testing in the diagnostic workup of endocrine disorders should be based on their appropriateness to reliably detect the disease-causing and -modifying mutation, their informational value, and cost-effectiveness. The future assessment of data from different omic approaches should be embedded in interdisciplinary discussions using all available clinical and molecular data. © 2020 The Author(s).

Keratinocyte carcinoma (KC) is the most common malignancy in white skinned populations. Metformin one of the most commonly prescribed drugs and has been reported to protect against solid cancers. The association between metformin and KC has not been studied in patients at high risk for a subsequent KC. The purpose of this study is to evaluate the association between metformin and KC development in high-risk patients. We performed a secondary analysis of patients enrolled in the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial to compare risk for KC development between metformin users and non-users. Metformin-users compared to non-users had a significantly lower risk for squamous cell carcinoma with an adjusted Hazard ratio (HR): 0.45, (CI: 0.24-0.84, P

Ovarian insufficiency is described as a multifaceted issue typically encountered in the field of assisted reproduction. The three main identified diagnoses of ovarian insufficiency include premature ovarian failure (POF), poor ovarian response (POR), and advanced maternal age (AMA). Patient heterogeneity in the era of individualized medicine drives research forward leading to the emergence of novel approaches. This plethora of innovative treatments in the service of adequately managing ovarian insufficiency is called to undertake the challenge of addressing infertile patients exploring their reproductive options. This review provides an all-inclusive presentation and critical analysis on novel treatments that have not achieved routine clinical practice status yet, but have recently emerged as promising. In light of the lack of randomized controlled trials conveying safety and efficiency, clinicians are left puzzled in addressing the “how” and “for whom” these approaches may be beneficial. From ovarian injection employing platelet-rich plasma (PRP) or stem cells to artificial gametes and ovaries, ovarian transplantation, and mitochondrial replacement therapy, this descriptive review provides insight toward assisting the practitioner in decision making regarding these cutting-edge treatments. Biological mechanisms, invasiveness levels, efficiency, as well as possible complications, the current status along with bioethical concerns are discussed in the context of identifying future optimal treatment. © The Author(s) 2020.

Background: Despite many epidemiological studies having been conducted, the impact of postnatal exposure of endocrine disruptors (EDs) on testicular function remains a controversial issue. Aim: To systematically review the literature and perform a quantitative synthesis to evaluate the effect of EDs on testicular function. Materials and methods: A comprehensive search was conducted in the MEDLINE, Scopus, and CENTRAL databases. Eligible for the systematic review were observational (cross-sectional and cohort) studies with (i) adult men who had a high probability of postnatal exposure to EDs (“exposed”), (ii) adult men who had a low probability of postnatal exposure to EDs (“non-exposed”), and (iii) an outcome of interest [seminal parameters and reproductive hormone concentrations]. The continuous outcomes in each of the studies were synthesized by the random effects model and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Results: Thirteen studies, including 959 exposed and 907 non-exposed men, fulfilled the inclusion criteria. Exposure to EDs was associated with decreased LH [SMD − 0.17, 95% CI − 0.33 to − 0.02, 10 studies (616 exposed, 563 non-exposed), I2 40%, p = 0.09], progressive motility [SMD − 0.45, 95% CI − 0.77 to − 0.13, three studies (133 cases, 153 controls), I2 38%, p = 0.20], and normal morphology [SMD − 0.50, 95% CI − 0.85 to − 0.14, eight studies (562 cases, 540 controls), I2 87%, p < 0.01] compared with non-exposure. No difference was observed between the other study groups. Conclusions: Postnatal exposure to EDs is associated with decreased semen quality. Nevertheless, there is no evidence that a disruption of testicular function mediates the deterioration in semen quality. © 2020, Hellenic Endocrine Society.

Derangements in phosphate and calcium homeostasis are common in patients with beta-thalassemia. Fibroblast growth factor 23 (FGF23) is among the main hormones regulating phosphate levels, while several studies underline an interplay between iron (Fe) and FGF23. Herein, we investigated, for the first time, the serum intact molecule (iFGF23) and the carboxyl-terminal fragment (C-FGF23) and Klotho levels simultaneously in patients with beta-thalassemia major receiving iron chelation regimens in comparison to healthy control subjects. We also correlated them with the body iron burden. The observational case-control study included 81 subjects (40 thalassemic patients and 41 healthy controls). Serum iFGF23, C-FGF23 and Κlotho were measured by ELISA. Parathormone, 25-hydroxycholecalciferol, calcium, and phosphorus were measured in blood and/or urine. The degree of hemosiderosis was evaluated by assessing the serum ferritin levels and performing T2∗ MRI measurements. Serum C-FGF23 levels were significantly lower in patients compared to control subjects (p=0.04), while iFGF23 and Klotho levels did not differ. Serum C-FGF23 levels were negatively correlated with ferritin (r=-0,421, p=0.018), whereas there were no significant correlations of each of the three factors with the iron chelation therapy. Decreased serum C-FGF23 levels were found in βTh patients which may be attributed to inhibition of proteolytic cleavage of iFGF23. Further studies in a greater number of patients will shed more light on the disturbances of the iFGF23, Klotho and C-FGF23 in thalassemia and their possible role in bone disease of such patients. © 2020 BMJ Publishing Group. All rights reserved.

The aim of the study was to compare demographic, hormonal and clinical parameters in patients with premature ovarian insufficiency (POI) and women with early menopause in Greece. One hundred thirty-nine women of Greek origin, aged 14–45 years, referring for oligomenorrhea and having elevated FSH concentrations were divided into three groups regarding the age of menstrual disturbances onset [POI1

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

Background: How do stress related phenomena during labor differ between vaginal delivery (VD) and elective cesarean section (CS), remains of heightened interest. The purpose of this study is to investigate discrepancies regarding the stress response during VD and CS. Methods: Cortisol, interleukin 6 (IL-6), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels from parturients’ peripheral blood were evaluated on three time-points, namely during the first stage of labor (TP1), two hours post labor (TP2) and 48 h post labor (TP3). Levels were also evaluated from the umbilical cord blood. A total of 50 women were enrolled in this prospective cohort study, with 24 and 26 subjected to CS and VD, respectively. Results: No statistically significant differences were observed between the two groups at TP1. Only GH levels presented the same pattern during the three time-points among both groups. In the umbilical cord blood, the CS group presented statistically significant higher IGF-1 and GH levels. In the umbilical cord blood, IGF-1 and GH levels were positively correlated, while GH and cortisol levels were negatively correlated. Conclusion: CS is a less stressful procedure than VD and is further associated with less intense inflammation, albeit with a longer inflammatory response period. Labor physiology during CS differs considerably regarding respective observations during VD. This merits extensive investigation in order to decipher these data for optimal clinical practice and guidelines. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.