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Infertility affects millions of couples worldwide and can result from various factors, including sexually transmitted infections. Although syphilis is known to contribute to a small number of infertility cases through chronic pelvic inflammatory disease, which ultimately impairs fertility, detailed descriptions of such cases are limited. In this report, we present a case of primary infertility caused by extensive peritoneal granulomatous inflammation, adhesions, and tubal obstruction resulting from syphilis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tsakos et al.)

Purpose: The need to investigate the pathogenesis and treatment of nonalcoholic fatty liver disease (NAFLD) has led to the development of multiple mouse models. The aim of this study was to validate a fast food diet (FFD) mouse model that is introduced as being close to the human disease., Methods: Eight to nine weeks old male and female C57BL/6 J mice were randomly allocated to a FFD group or to a chow diet (CD) group. Every four weeks, mice were weighed, and blood samples were collected for the measurement of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TGs) and total cholesterol. After 25 weeks, mice were sacrificed, and liver tissue was histologically evaluated., Results: FFD mice gained more weight (p = 0.049) and presented a higher liver-to-body weight ratio (p < 0.001) compared to CD mice. FFD group presented with greater steatosis, hepatocellular ballooning and NAFLD activity score (NAS), whereas lobular inflammation and fibrosis were not significantly different compared to CD. When stratified by sex, NAS was different between FFD and CD groups in both male and female mice. Group by time interaction was significant for weight, ALT and cholesterol, but not for glucose, AST and TGs., Conclusion: FFD mice presented with morphologic and biochemical features of NAFLD and with greater hepatic steatosis, hepatocellular ballooning and NAS, but not lobular inflammation and fibrosis, compared to CD mice. These results only partly validate the FFD mouse model for NAFLD, at least for a 6-month feeding period., (© 2024. The Author(s).)

Background: Single-nucleotide polymorphisms in LIN28B , critical regulators of female growth and puberty, have been linked to age at menarche., Methods: We assessed the association of rs7759938 , rs314280 , and rs314276 with menarcheal age in girls of Greek descent. We reviewed the records of 248 girls who had their first menstruation before 18 years and who attended the Greek Departments of Pediatric Endocrinology from January 2021 to July 2023. Genotyping was performed by standard DNA-based methods. Association analyses involved both parametric and non-parametric tests., Results: The average age of breast and pubic hair development was 9.95 years, and the age at menarche was 11.55 years. Menarche occurred ≤11 years (mean 10.24 years) in 108 girls (43.5%) and >11 years (mean 12.55 years) in 140 (56.5%). The girls' menarcheal age correlated significantly with that of their mothers (average 12.1 years, p -value < 0.0001, Spearman's r 0.350). The dominant rs7759938(TT) genotype was the most common (55.2%), followed by the dominant rs314276(CC) (53.2%) and dominant rs314280(TT) (14.5%) genotypes., Conclusions: There was no association between age at menarche and any of the polymorphism genotypes/alleles or between genotypes/alleles and birth weight, gestational week, mode of delivery, and maternal age at menarche. Future large sample studies are warranted to confirm these results.

Circulating cell-free DNA (ccfDNA) of mitochondrial origin (ccf-mtDNA) consists of a minor fraction of total ccfDNA in blood or in other biological fluids. Aberrant levels of ccf-mtDNA have been observed in many pathologies. Here, we introduce a simple and effective standardized Taqman probe-based dual-qPCR assay for the simultaneous detection and relative quantification of nuclear and mitochondrial fragments of ccfDNA. Three pathologies of major burden, one malignancy (Breast Cancer, BrCa), one inflammatory (Osteoarthritis, OA) and one metabolic (Type 2 Diabetes, T2D), were studied. Higher levels of ccf-mtDNA were detected both in BrCa and T2D in relation to health, but not in OA. In BrCa, hormonal receptor status was associated with ccf-mtDNA levels. Machine learning analysis of ccf-mtDNA datasets was used to build biosignatures of clinical relevance. (A) a three-feature biosignature discriminating between health and BrCa (AUC: 0.887) and a five-feature biosignature for predicting the overall survival of BrCa patients (Concordance Index: 0.756). (B) a five-feature biosignature stratifying among T2D, prediabetes and health (AUC: 0.772); a five-feature biosignature discriminating between T2D and health (AUC: 0.797); and a four-feature biosignature identifying prediabetes from health (AUC: 0.795). (C) a biosignature including total plasma ccfDNA with very high performance in discriminating OA from health (AUC: 0.934). Aberrant ccf-mtDNA levels could have diagnostic/prognostic potential in BrCa and Diabetes, while the developed multiparameter biosignatures can add value to their clinical management.

Background: Inherited retinopathies can initially present with high refractive error in the first decade of life, before accompanying signs or symptoms are evident., Case Presentation: A 4-year-old girl with high myopia (S-12.00 C-4.00 × 20 in the right and S-14.50 C-2.75 × 160 in the left eye), moderate visual acuity (0.3 logMAR in the right and 0.4 logMAR in the left eye), and left esotropia, presented with unremarkable past medical history and no family history of high refractive error or low vision. In optical coherence tomography imaging, macular thinning was evident, while morphology was normal. Full-field electroretinogram revealed normal implicit time recordings with reduced amplitudes in scotopic and photopic conditions. Fundus autofluorescence showed a radial pattern in both eyes. During a 5-year follow-up, significant myopia progression ensued (S-17.25 C-3.00 × 20 in the right and S-17.25 C-2.00 × 160 in the left eye), with a corresponding increase in axial length and an unchanged visual acuity. Whole-exome sequencing revealed a heterozygous termination codon variant c.212C>G (p.Ser71Ter) in RPGR , considered to be pathogenic. Segregation analysis precluded the variation in the mother and sister. A random pattern of X-chromosome inactivation was detected in the proband, without X-chromosome inactivation deviation., Conclusion: This is the second report associating this specific RPGR mutation with high myopia and the first report to identify it in a female proband. This case provides additional evidence on the genotypic-phenotypic correlation between RPGR c.212C>G mutation and high myopia.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease that affects motor neurons, leading to paralysis and death usually 3-5 years after the onset of symptoms. The investigation of both sporadic and familial ALS highlighted four main genes that contribute to the pathogenesis of the disease: SOD1 , FUS , TARDBP and C9orf72 . This study aims to provide a comprehensive investigation of genetic variants found in SOD1 , FUS and TARDBP genes in Greek sporadic ALS (sALS) cases. Our sequencing analysis of the coding regions of the abovementioned genes that include the majority of the variants that lead to ALS in 32 sALS patients and 3 healthy relatives revealed 6 variants in SOD1 , 19 variants in FUS and 37 variants in TARDBP , of which the SOD1 p.D90A and the FUS c.*356G>A (rs886051940) variants have been previously associated with ALS, while two novel nonsense pathogenic variants were also identified, namely FUS p.R241* and TDP-43 p.Y214*. Our study contributes to the worldwide effort toward clarifying the genetic basis of sALS to better understand the disease's molecular pathology.

The lipid profile is affected following menstrual cessation (MC). We aimed to evaluate the effects of goserelin-induced MC and subsequent menstrual restoration (MR) on lipid metabolism. Premenopausal women with histologically verified endometriosis (n = 15) received goserelin monthly for 6 months (6mο), resulting in MC, and were followed-up for another 6 months after MR (12mο). Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a ([Lp(a)] and lipidomics were measured at baseline, 6mo and 12mo. Shotgun quantitative deep lipidomics were determined at the level of lipid class category, subclass, species, and fatty acyl chain lengths and degree of saturation. TC ( p = 0.006), LDL-C ( p = 0.028), HDL-C ( p = 0.002), and apoA1 ( p = 0.013) increased during goserelin-induced MC and remained practically unchanged during MR. TG, apoB, and Lp(a) did not change. From the deep lipidomics analysis, multivariate statistical analysis demonstrated profound alterations in lipid species with MC, whereas no statistically valid models could be fitted for the restoration period. In conclusion, GnRH-analog-induced MC alters lipid profiles at various levels, from standard blood lipid and lipoprotein profiles to several lipid species as detected by lipidomics analysis. Changes largely persist for at least 6 m after MR.

Background: In syncopal patients without underlying structural disease, we sought to investigate the association of Adenosine Plasma Levels (ADP) with the clinical presentation of neurally mediated syncope (NMS) and the outcomes of Head-Up Tilt Table Test (HUTT) and Adenosine test (ADT)., Methods: We studied 124 patients with different clinical types of NMS, i.e., Vasovagal (VVS, n=58), non-prodromes (NPS, n=18), or situational syncope (SS, n=48), using a standard protocol including HUTT and ADT. During HUTT, ADP was measured in the supine position, at table tilting and in syncope., Results: Baseline ADP did not differ among groups. ADP at syncope were higher in NPS (n=5) compared to VVS (n=20): 0.23 vs. 0.12 μΜ, p=0.03, and SS (n=22): 0.04 μΜ, p=0.02. In NPS, ADP increased from supine to syncope (n=5): 0.15 vs. 0.23 μΜ, p=0.04. In VVS, ADP increased only from supine to tilt position: 0.11 vs. 0.14 μΜ, p=0.02. In SS, ADP did not change during HUTT. In positive vasodepressor HUTT, ADP increased from supine to tilt position (p=0.002) and at syncope (p=0.01). In SS, 20.0% exhibited cardioinhibitory HUTT vs. 6.8% in other forms of syncope (p=0.04). In SS, 22.9% manifested positive ADT vs 6.6% in other types of syncope (p=0.012)., Conclusion: The subset of NPS patients with positive HUTT, show excessive ADP release at the time of syncope. This may explain the lack of prodromes in this form of syncope. Such observations contribute to the understanding of distinct profiles of clinical forms of syncope and may differentiate the management approach accordingly., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: GnRH-analogs induce bone loss. We aimed to investigate the effects of goserelin-induced menstrual cessation (MC) and subsequent menstrual restoration (MR) on bone metabolism (BM)., Methods: In this prospective cohort study, premenopausal women (PMW) with histologically verified endometriosis (n = 21) received goserelin monthly for 6 months (6 m) resulting in MC and were followed up for another 6 m after MR (12 m). Age- and BMI-matched healthy PMW (n = 20) served as controls for bone mineral density (BMD) measurements. The primary endpoint was changes in lumbar spine (LS)-BMD at 6 m and 12 m; Secondary endpoints were changes in femoral neck (FN)-BMD, bone turnover markers (P1NP and CΤx), sclerostin, and expression of bone-related circulating microRNAs (miRNAs) at 6 m and 12 m., Results: Goserelin-induced MC reduced LS- and FN-BMD at 6 m (both p < 0.001). From 6 m to 12 m, LS-BMD increased (p < 0.001) but remained below baseline values (p = 0.012), whereas FN-BMD remained stable (p = 1.000). CTx and P1NP levels increased at 6 m (both p < 0.001) and decreased at 12 m (p < 0.001 and p = 0.013, respectively), while CTx (p = 1.000) alone and not P1NP (p = 0.020) returned to baseline. Sclerostin levels did not change. Relative expression of miRNAs targeting RUNX 2 and beta-catenin was significantly downregulated at 6 m compared to baseline (p < 0.001), while the expression of miRNAs targeting osteoblast and osteoclast function at both directions demonstrated a robust increase (up to 400fold) at 12 m (p < 0.001)., Conclusions: Six months of goserelin-induced MC lead to significant bone loss associated with increased bone turnover and changes in the expression of bone-related miRNAs, changes that are only partially reversed at 6 m after MR., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Backgrounds and Objectives : Fibroblast growth factor 21 (FGF-21) is a complex hormone, sharing common sites of action with thyroid hormones. We investigated the association among FGF-21 levels, resting metabolic rate (RMR), and l-thyroxin (LT4) treatment in children and adolescents with Hashimoto's thyroiditis. Materials and Methods : A total of 60 youngsters with chronic autoimmune thyroiditis (AIT) (30 with subclinical hypothyroidism, 30 with euthyroidism) and 30 age and sex-matched healthy participants (5-18 years old) were enrolled in the study. Anthropometric, biochemical parameters, and RMR levels were assessed in all participants; serum FGF-21 levels were measured in the control group and the group with subclinical hypothyroidism before and six months after medication with LT4. Results : FGF-21 levels were lower in the treatment group compared with the healthy ones, but this difference was not statistically significant ( p > 0.05); despite the increase in FGF-21 levels after six months of LT4 treatment, this difference was not statistically significant ( p > 0.05). Free thyroxin (FT4) levels correlated well with FGF-21 levels (r = 0.399, p < 0.01), but further analysis revealed no interaction between these two variables. Both patient groups presented elevated triglyceride (TG) levels compared to controls ( p < 0.05). LT4 treatment had no impact on RMR and lipid or liver or glycaemic parameters. An increase in fat mass and fat-free mass were reported, independently of FGF-21 levels. Conclusions : In youngsters with subclinical hypothyroidism due to Hashimoto's thyroiditis, the serum FGF-21 levels are not significantly lower than in healthy individuals and increase after treatment with LT4 without a statistical significance. Further studies with a large number of young patients and severe hypothyroidism are recommended to confirm our results.

Bullous pemphigoid (BP) patients are predominantly above 70 years of age, with limited tolerance to the side effects of the immunosuppressive drugs. Advancements in our understanding of the pathophysiology of BP have led to the development of molecules which target specific pathways involved in induction and perpetuation of disease. Patients with BP Disease Area Index above 60 and less than 100 were split into two groups-one with high and the other with normal levels of IgE. The tested parameters included eosinophils' count, total IgE serum level, and interleukins (IL) 16, 17A, and 23 counts in the peripheral blood and skin bulla serum, before any therapeutic intervention. Thirty individuals fulfilled the criteria for enrollment. Patients with high IgE blood serum levels had significantly higher levels of IL17A and normal IL23 levels in blood and bulla serum. Patients with normal serum IgE levels had slightly higher IL23 levels in blood and bulla serum. The eosinophil count was positively related to IL17 blood serum level and negatively related to IL23. IL16 did not differ in the two groups. BP patients may represent a group of patients benefiting most substantially from the introduction of nonimmunosuppressive therapeutics into the treatment regimens for their disease. Clinical criteria and immune biomarkers are needed for making the best therapeutic choice., (© 2020 Wiley Periodicals LLC.)

Aims and Objectives: We aimed to explore whether fasting insulin levels correlate with the risk of hypoglycemia in people with Type 2 diabetes (T2D) receiving sulfonylureas (SUs)., Materials and Methods: Our study included 58 individuals with T2D who had been on treatment with SUs, but not insulin, for more than 2 years. Confirmed hypoglycemic episodes during the past year were self-reported by the patients, and a potential relationship of hypoglycemic event frequency with fasting insulin levels was investigated., Results: Fasting insulin concentrations were found to have a low positive and statistically significant correlation with the number of cases of mild hypoglycemia per year ( ρ = 0.279/P = 0.034) and a moderately positive and statistically significant correlation with the number of severe hypoglycemic events per month ( ρ = 0.349/P = 0.007) and per year ( ρ = 0.39/P = 0.002)., Conclusion: Our results suggest that fasting insulin levels might be a predictor of the risk of hypoglycemia in people with T2D on treatment with SUs., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Pharmacology.)

Background: Although primary hyperparathyroidism has been associated with insulin resistance, potential optimal effects of parathyroidectomy (PTX) on glucose homeostasis remain controversial. Accordingly, the impact of PTX on glucose-stimulated incretin (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide) secretion has not been evaluated. The aim of this pilot study was to compare glucose-stimulated incretin secretion (GSIS) in patients with asymptomatic primary hyperparathyroidism with normal glucose homeostasis, before and after PTX., Methods: Fourteen patients were included in the study. Fasting calcium, parathyroid hormone, glucose, insulin, GLP-1, and gastric inhibitory peptide were measured pre- and post-operatively. Homeostasis Model Assessment 2, QUICKI, and Matsuda indexes were used as markers of insulin sensitivity and resistance before and after PTX. Preoperatively, a 75 g oral glucose tolerance test (OGTT) was performed to evaluate the response of glucose, insulin, and GSIS. OGTT measurements were repeated 6 ± 2 wk post-PTX., Results: Patients had a mean age of 52.93 ± 9.96 y, and female-to-male ratio was 12:2. Pre- and post-operatively, a positive correlation between parathyroid hormone and Homeostasis Model Assessment 2 for β-cell function was evident (r = 0.74, P = 0.002 and r = 0.55, P = 0.04, respectively). After PTX, a significant increase in GSIS for GLP-1 during OGTT was observed (in 60 min: 63.06 ± 44.78 versus 102.64 ± 40.19 pg/mL, P = 0.02; and in 120 min: 71.20 ± 35.90 versus 102.49 ± 40.02 pg/mL, P = 0.03)., Conclusions: The increase of GLP-1 response following oral glucose load after PTX may reflect an initial recovery phase of glucose homeostasis. Long-term studies are required to elucidate the physiological interplay between the normalization of calciotropic axis and the rising GLP-1 concentrations post-PTX., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: β-Type hemoglobinopathies are characterized by vast phenotypic diversity as far as disease severity is concerned, while differences have also been observed in hydroxyurea (HU) treatment efficacy. These differences are partly attributed to the residual expression of fetal hemoglobin (HbF) in adulthood. The Krüppel-like family of transcription factors (KLFs) are a set of zinc finger DNA-binding proteins which play a major role in HbF regulation. Here, we explored the possible association of variants in KLF gene family members with response to HU treatment efficacy and disease severity in β-hemoglobinopathies patients. Materials & methods: Six tag single nucleotide polymorphisms, located in four  KLF genes, namely KLF3, KLF4, KLF9 and KLF10 , were analyzed in 110 β-thalassemia major patients (TDT), 18 nontransfusion dependent β-thalassemia patients (NTDT), 82 sickle cell disease/β-thalassemia compound heterozygous patients and 85 healthy individuals as controls. Results: Our findings show that a KLF4 genomic variant (rs2236599) is associated with HU treatment efficacy in sickle cell disease/β-thalassemia compound heterozygous patients and two KLF10 genomic variants (rs980112, rs3191333) are associated with persistent HbF levels in NTDT patients. Conclusion: Our findings provide evidence that genomic variants located in KLF10 gene may be considered as potential prognostic biomarkers of β-thalassemia clinical severity and an additional variant in KLF4 gene as a pharmacogenomic biomarker, predicting response to HU treatment.

Aims: To assess the effect of liraglutide on 24-hour ambulatory blood pressure and heart rate in patients with hypertension (pre- and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%-10% [53-86 mmol/mol])., Materials and Methods: Eligible patients for this investigator-initiated, parallel-group, randomized, double-blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon-like peptide-1 receptor agonists and dipeptidyl-peptidase-4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24-hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling., Results: Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24-hour SBP by -5.73 mm Hg (95% confidence interval [CI] -9.81 to -1.65) and had a neutral effect on 24-hour DBP (mean difference - 1.42 mm Hg; 95% CI -4.25 to 1.40), whilst increasing 24-hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night-time measurements. Liraglutide did not increase urine sodium excretion., Conclusion: Based on 24-hour ambulatory measurements, short-term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate., (© 2018 John Wiley & Sons Ltd.)