Nerve Growth Factor and Brain-Derived Neurotrophic Factor as Potential Biomarkers of Mirabegron Efficacy in Patients with Overactive Bladder Syndrome.

INTRODUCTION: Overactive Bladder Syndrome (OAB) significantly impacts quality of life, necessitating improved diagnostic tools and treatment monitoring. This study explores the potential of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) as urinary biomarkers in patients with OAB undergoing mirabegron therapy, a ß3-adrenergic agonist. This investigation is aimed at providing insights into the potential of neurotrophins to enhance OAB diagnosis and assess treatment efficacy. MATERIALS AND METHODS: Urinary NGF and BDNF levels were measured in 15 healthy controls and 30 patients with OAB. Patients were treated with mirabegron 50 mg once daily. Urinary NGF and BDNF levels were measured by enzyme-linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cre and BDNF/Cre). The urinary NGF/Cre and BDNF/Cre levels were compared between controls and patients with OAB and subsequently at baseline and 3 months after mirabegron treatment. Treatment efficacy was assessed with the Indevus Urgency Severity Scale (IUSS) questionnaire. RESULTS: Urinary NGF/Cre and BDNF/Cre levels were significantly higher in patients with OAB than in the controls (p < 0.001 and p = 0.03 respectively). Moreover, NGF/Cre and BDNF/Cre levels significantly decreased post-mirabegron treatment (p < 0.001 and p = 0.005 respectively). Patients with improvement of OAB symptoms after treatment showed lower levels of NGF/Cre at the 3-month evaluation than those with no improvement (p = 0.05). CONCLUSION: Although both NGF/Cre and BDNF/Cre levels were significantly decreased after mirabegron treatment, only NGF/Cre levels were associated with treatment response.

Coagulation Profile in Neonates with Congenital Heart Disease: A Pilot Study.

Background and Objectives: congenital heart disease (CHD), cyanotic and, to a lesser degree, acyanotic, often are accompanied by coagulation abnormalities, impacting substantially morbidity and mortality. Until now, no consistent hemostatic patterns have been demonstrated in neonates and children with CHD because they represent a variable and heterogenous population. The aim of the present study is to investigate the hemostatic profile, as well as the role of ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type-1 motives), the cleaving protein of von Willebrand factor (VWF) in neonates with CHD and compare them to healthy age-matched controls. Materials and Methods: twenty neonates with a mean gestational age of 37.1 ± 2.5 weeks were included in the CHD group, and 18 healthy neonates with a mean gestational age of 38.2 ± 1.5 weeks were in the control group. Results: prothrombin time was significantly prolonged, and accordingly, factor VII (FVII) levels were significantly decreased in the CHD group in comparison to controls. Factor VIII (FVIII), VWF, and ristocetin cofactor activity (Rcof) levels were significantly higher in the study vs. control group. Concentrations of ADAMTS-13 were decreased in the CHD vs. control group, but the difference was not statistically significant. Our results, in combination, indicate a balanced hemostatic mechanism, although with greater variability in neonates with CHD, while developmental aspects of coagulation are evident in the specific patient population. Conclusions: the coagulation profile is moderately impaired early in the course of CHD, though increased thrombogenicity is already present and should not be ignored.

Evidence that platelets from transfusion-dependent ß-thalassemia patients induce T cell activation.

A hypercoagulable state leading to increased risk for thrombotic events represents one of the most common complications observed in transfusion-dependent ß-thalassemia (TDT) patients. TDT patients have increased frequencies of circulating activated platelets. However, there is no information so far if platelets from TDT patients can activate T cells. In the present study we showed that T cells treated with platelets from TDT patients showed significant increased surface expression of CD69 compared to the T cells treated with platelets from healthy individuals. Patients with splenectomy showed increased T cell activation compared to patients with intact spleen. No T cell activation was observed following incubation with plasma alone, nor with platelets from healthy subjects. The percentages of regulatory T cells (Tregs) were also examined. TDT patients showed statistically significant increased percentages of Tregs compared to healthy controls. Additionally, we observed a positive statistically significant correlation between the percentages of Tregs and the platelet-induced activated T cells in patients who were not treated with aspirin. TDT patients showed increased levels of sP-selectin, suPAR and GDF-15, molecules implicated in platelet activation. We show that platelets from TDT patients can activate T cells in vitro. This activation correlates with markers of platelet activation and increased numbers of Tregs, perhaps in an effort to eliminate immune dysregulation, conceivably secondary to platelet activation.

Serum concentrations of BDNF in adolescents with metabolic syndrome: a case-control study between normal - BMI adolescents and adolescents with obesity.

Brain-Derived Neurotrophic Factor (BDNF) has been linked to various conditions of the cardiovascular and nervous systems. Scarce data exist about the concentrations of BDNF in children and adolescents in relation with obesity and metabolic syndrome (MetS). The aim of this study was to examine the serum BDNF concentrations in adolescents with metabolic syndrome and according to their body mass index (BMI) status. This was a case-control study, assessing BDNF concentrations between adolescents with MetS (with obesity vs. normal-BMI), in relation to sex, anthropometric, metabolic and endocrine parameters. Participants included male and female adolescents, whose anthropometric and metabolic panel, as well as serum BDNF concentrations were measured. A total of 59 adolescents (obesity: 29; normal-BMI: 30) were included in the study. Increased serum BDNF concentrations were observed in MetS adolescents with obesity when compared with normal-BMI adolescents (p < 0.001). Males exhibited higher concentrations of BDNF than females (p = 0.045). The sample was further divided into four categories by sex and BMI status, with normal-BMI females exhibiting significantly lower BDNF concentrations than females and males with obesity(p = 0.005). In the entire study sample, serum BDNF concentrations correlated positively with BMI z-scores, however, this statistical significance was preserved only in the females of the sample. No statistical difference was observed between males of different BMI z-scores categories.  Conclusion: Obesity appeared as a major factor for increased serum BDNF concentrations in adolescents with MetS (vs. normal-BMI), with a higher impact on BDNF concentrations in females than males. What is Known: • The brain-derived neurotrophic factor (BDNF) is involved in metabolic syndrome in adults but data in adolescents are scarce. What is New: • Obesity (vs. normal BMI) was a major factor for increased serum BDNF in adolescents with metabolic syndrome. • Obesity had a higher impact on BDNF concentrations in females than males with metabolic syndrome.

Pythagorean Self-Awareness Intervention Promoted Healthy Dietary Patterns, Controlled Body Mass Index, and Reduced Self-Reported Stress Levels of Primary School Children: Α One-Arm Pilot Study.

Stress is common in childhood and an important factor that affects behavior later in adulthood. The aim of this study was to assess the effects of the Pythagorean Self-Awareness Intervention (PSAI), a holistic "cognitive reconstruction" technique to assess primary school children's stress levels, adherence to the Mediterranean diet, and body mass index. Secondary outcome measures included relations with peers, sleep, and hair cortisol concentrations. This one-arm pilot study took place in a primary school, from February to June 2019. Participants were 32 pupils attending the second grade of primary school who received the 8-week PSAI to adopt healthy behaviors and lifestyle. Self-report measures were applied for the evaluation of various variables at the beginning and the end of the eight-week intervention. There were statistically significant reductions in stress levels (p = 0.00), nightmares' frequency (p = 0.00), body mass index (p = 0.03), and bully scale (p = 0.00), and improvement in Mediterranean diet quality (p = 0.00). Hair cortisol concentrations increased (p = 0.02). The social scale significantly increased. Bedtime remained the same after the intervention. This pilot trial showed that the PSAI promoted healthy dietary patterns, controlled children's body mass index, and reduced their self-reported stress levels. Further research on the implementation of this holistic program on children is suggested, in well-powered randomized controlled trials.

Adrenocortical dysfunction in rheumatoid arthritis: Α narrative review and future directions.

BACKGROUND: Iatrogenic adrenal insufficiency (AI) secondary to long-term treatment with exogenous glucocorticoids (GC) is common in patients with systematic rheumatic diseases, including rheumatoid arthritis (RA). Moreover, a proportion of these patients is always in need of even small doses of glucocorticoids to maintain clinical remission, despite concomitant treatment with conventional and biologic disease-modifying drugs. METHODS: We conducted a literature review up to December 2020 on (a) the incidence of AI in both long-term GC-treated and GC-treatment naïve RA patients; (b) the potential effects of increased levels of circulating proinflammatory cytokines, as well as of chronic stress, in adrenocortical function in RA; (c) the circadian cortisol rhythm in RA; and (d) established and evolving methods of assessment of adrenocortical function. RESULTS: Up to 48% of RA patients develop glucocorticoid-induced AI; however, predictors are not established, while adrenocortical dysfunction may also occur in GC-treatment naïve RA patients. Experimental and clinical data have suggested that inadequate production of endogenous cortisol relative to enhanced clinical needs associated with the systemic inflammatory response, coined as the 'disproportion principle', may operate in RA. Although the underlying mechanisms are unknown, both proinflammatory cytokines and chronic stress may contribute the most in the adrenals hyporesponsiveness and the target tissue glucocorticoid resistance that have been described, but not systematically studied. A precise longitudinal assessment of endogenous cortisol production may be needed for optimal RA management. CONCLUSION: Apart from iatrogenic AI, an intrinsically compromised adrenal reserve in RA may have a pathogenetic role and interfere with effective management, thus deserving further research.

Bout duration in high-intensity interval exercise modifies hematologic, metabolic and antioxidant responses.

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.

Clinical value of amyloid-beta1-40 as a marker of thrombo-inflammation in antiphospholipid syndrome.

OBJECTIVE: Amyloid-beta1-40 (Aß40) is a pro-inflammatory peptide under investigation as a novel biomarker of vascular inflammation, endothelial dysfunction and atherothrombosis in the general population. Herein we tested the hypothesis that Aß40 is deregulated in APS, a systemic autoimmune disease characterized by a thrombo-inflammatory state. METHODS: Between January 2016 and July 2017, we consecutively recruited 80 regularly followed thrombotic APS patients (44 primary, 36 SLE/APS) and 80 age- and sex-matched controls. Plasma Aß40 levels were measured using ELISA and APS-related clinical and laboratory characteristics were recorded. The adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS), a validated risk score in APS, was calculated as a comparator to Aß40 performance to detect arterial thrombotic APS-related events. RESULTS: Higher Aß40 levels were significantly associated with the presence of APS [odds ratio (OR) 1.024 per 1 pg/ml (95% CI 1.007, 1.041)] after adjustment for cardiovascular risk factors (CVRFs), including smoking, arterial hypertension, dyslipidaemia and BMI, and for estimated glomerular filtration rate (eGFR). Among APS patients, increased high-sensitivity CRP (hs-CRP) serum levels was the only independent determinant of Aß40 levels. Importantly, Aß40 levels above the optimal receiver operating characteristics (ROC)-derived cut-off value were independently associated with recurrent arterial events [OR 4.93 (95% CI 1.31, 18.51)] after adjustment for age, sex, CVRFs, hs-CRP and high anti-ß2 glycoprotein I IgG titres. Finally, by ROC curve analysis, Aß40 provided incremental additive value over the aGAPSS by significantly improving its discrimination ability for recurrent arterial thromboses. CONCLUSION: In APS, Aß40 plasma levels are elevated and associated with an adverse thrombo-inflammatory profile. The pathophysiological and prognostic role of Aß40 in APS merits further investigation.

Increased circulating endothelial progenitor cells (EPCs) in prepubertal children born prematurely: a possible link between prematurity and cardiovascular risk.

BACKGROUND: Endothelial progenitor cells (EPCs) ensure vascular integrity and neovascularization. No studies have investigated EPCs in preterm-born children beyond infancy. METHODS: One hundred and thirty-six prepubertal children were enrolled: 63 preterm and 73 born at term (controls). Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were measured in preterm-born children compared to controls. Body mass index (BMI), waist-to-hip ratio (WHR), neck circumference, systolic and diastolic blood pressure (SBP and DBP, respectively), fasting glucose, insulin, lipid profile, common carotid and abdominal aortic intima-media thickness (cIMT and aIMT, respectively), endothelium-dependent brachial artery flow-mediated dilation (FMD), and echocardiographic parameters were also assessed. RESULTS: Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were significantly higher in preterm-born children compared to controls (p < 0.001 and p < 0.001, respectively). In total study population and in the preterm-born group, EPCs were significantly lower in children born to mothers with gestational diabetes compared to non-diabetic mothers. Prematurity was associated with higher WHR, neck circumference, SBP, DBP, cIMT, aIMT, mean pressure, and velocity of pulmonary artery; the peak velocity of the brachial artery was significantly lower in children born prematurely. In multiple regression analysis, preterm birth and maternal gestational diabetes were recognized as independent predictors of EPCs. CONCLUSIONS: Circulating EPCs were increased in prepubertal preterm-born children in comparison with peers born full-term. Maternal gestational diabetes was associated with a decrease in EPCs. IMPACT: Mounting evidence supports the adverse effect of prematurity on cardiovascular health. However, the underlying mechanisms that could lead to endothelial dysfunction in preterm-born individuals are not fully understood. Endothelial progenitor cells (EPCs) ensure vascular integrity, normal endothelial function and neovascularization. No studies have investigated the EPCs counts in peripheral blood beyond infancy in children born prematurely. Circulating EPCs were significantly higher in preterm-born prepubertal children compared to controls, thus indicating that prematurity is possibly associated with endothelial damage. In total study population and in the preterm-born group, maternal gestational diabetes was associated with decreased EPCs concentrations.

Cortisol to Dehydroepiandrosterone Sulphate Ratio and Executive Function in Bipolar Disorder.

INTRODUCTION: Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. Very few studies have assessed dehydroepiandrosterone sulphate (DHEA-S) in BD and its relation to cognitive functioning despite evidence showing its regulatory effects on glucocorticoid action. The aim of our study was to explore the association of cortisol, DHEA-S, and cortisol to DHEA-S ratio with visuospatial memory and executive functioning in BD. METHODS: Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using Cambridge Neuropsychological Test Automated Battery tasks targeting visuospatial memory (spatial recognition memory) and executive functions (planning [Stockings of Cambridge; SOC] and attentional set shifting [ID/ED]). Morning serum cortisol and DHEA-S levels were measured in patients. Main effects of cortisol, DHEA-S, and cortisol/DHEA-S ratio for each neurocognitive task were explored in multiple regression analyses correcting for demographic and clinical parameters as well as treatment-related factors (current use of antipsychotic and mood stabilizer medication). RESULTS: Bipolar patients showed poorer performance than healthy subjects in planning and attentional set shifting but not in visuospatial memory. Cortisol to DHEA-S ratio predicted worse performance in planning (SOC). CONCLUSIONS: This is the first study to assess memory and executive function in BD in relation to DHEA-S and cortisol to DHEA-S ratio. We report an association of cortisol to DHEA-S ratio with worse performance in planning in bipolar I patients, which warrants further investigation.

Effect of honey on glucose and insulin concentrations in obese girls.

BACKGROUND: Childhood obesity represents a major health problem of our century. The benefits of natural products, such as honey, in the management of obesity have gained renewed interest. In this study, we investigated the effect of honey on glucose and insulin concentrations in obese prepubertal girls. MATERIALS AND METHODS: Thirty healthy obese girls aged 10.55 (±SEM:0.34) years with a mean body mass index (BMI) above the 97th centile for age (28.58 ± 1.40 kg/m2 , BMI z-score 2.96) underwent a standard oral glucose tolerance test (OGTT) followed by an oral honey tolerance test (OHTT) 2 weeks later. Both solutions contained 75 g of glucose. Subsequently, subjects were randomized to receive either 15 g of honey or 15 g of marmalade daily, while both groups complied with dietetic instructions. Six months later all subjects were re-evaluated with an OGTT and an OHTT. RESULTS: At the end of the study, all subjects demonstrated a significant reduction in BMI (27.57 ± 1.40, z-score: 2.54 vs 28.58 ± 1.40 kg/m2 , z-score: 2.96, P < 0.001), however, there were no significant differences in BMI and all parameters tested between the group that received honey and the control group. The areas under the concentration-time curve for glucose and insulin for the entire population were significantly lower following ingestion of honey than glucose solution (P < 0.001) both at the beginning and at the end of study. CONCLUSIONS: These findings indicate that honey does not have an effect on stimulated plasma glucose and serum insulin concentrations compared with the standard glucose solution in obese prepubertal girls.

Serum irisin concentrations in lean adolescents with polycystic ovary syndrome.

OBJECTIVE: To explore differences in irisin concentrations between lean adolescents with PCOS and age- and body mass index (BMI)-matched controls and examine the associations of irisin with core features of the syndrome. DESIGN: Cross-sectional study. PATIENTS: Lean females with PCOS, aged 13-21 years. MEASUREMENTS: Physical, hormonal and sonographic assessment. Irisin concentrations were measured with ELISA. RESULTS: Participants included in total 39 sedentary females (mean ± SD; age 17.3 ± 2.1 years, BMI 20.7 ± 1.3 Kg/m2 ), 23 adolescents with PCOS and 16 controls. Adolescents with PCOS compared to controls had significantly elevated concentrations of fasting serum irisin (mean ± SD; PCOS, 1.7 ± 1.0 µg/mL vs controls, 1.0 ± 0.4 µg/mL; P = .007), luteinizing hormone (LH), oestradiol, testosterone, Δ4-androstenedione, 17-hydroxyprogesterone, glucose, as well as free androgen index, Ferriman-Gallwey score and mean ovarian volume (MOV). For the total sample, circulating irisin was positively correlated with MOV (r = .332, P = .041), glucose (r = .428, P = .007), insulin (rs  = .369, P = .021) and HOMA-IR (rs  = .422, P = .007) and negatively correlated with QUICKI (r = -.329, P = .041). Follicle-stimulating hormone (B = 0.295, Beta = .342, P = .042) and MOV (B = 0.182, Beta = 0.821, P = .001) were positive predictors, and LH (B = -0.108, Beta = -0.523, P = .010) and testosterone (B = -0.431, Beta = -0.457, P = .032) were negative predictors of irisin concentrations, whereas irisin positively predicted fasting glucose (B = 0.262, Beta = 0.428, P = .007). In the PCOS group, irisin concentrations were positively correlated with HOMA-IR (rs  = .416, P = .048) but negatively correlated with LH (rs  = -.499, P = .015), testosterone (r = -.585, P = .003), free androgen index (r = -.426, P = .048) and Ferriman-Gallwey score (r = -.533, P = .015). CONCLUSIONS: Irisin was associated with the adolescents' metabolic and reproductive characteristics and the hyperandrogenic phenotype of the syndrome. Much research is needed to ascertain mechanisms of elevated serum irisin in adolescent PCOS.

Associations of maternal oestradiol, cortisol, and TGF-ß1 plasma concentrations with thyroid autoantibodies during pregnancy and postpartum.

BACKGROUND: Thyroid physiology and autoimmunity are altered in pregnancy. While oestradiol, cortisol, and TGF-ß1 are implicated in these phenomena outside pregnancy, their associations with thyroid autoantibodies during pregnancy and postpartum are not thoroughly examined. This study aimed to unravel their eventual associations during pregnancy and postpartum in the same cohort of 93 pregnant women studied prospectively from 2015 to 2017. METHODS: Blood samples were drawn at the 24th and the 36th gestational week and at the 1st postpartum week for measurements of thyroid hormones, TSH, anti-TPO, anti-Tg, oestradiol, cortisol, and TGF-ß1. RESULTS: Serum anti-TPO was greater (P < 0.05) at the 1st postpartum than at the 24th and 36th gestational weeks. At the 36th gestational week, cortisol was greater (P < 0.05) and TGF-ß1 lower (P < 0.05) than at the 24th gestational and the 1st postpartum weeks. At the 1st postpartum week, cortisol correlated negatively with anti-Tg (r = -0.419) (P < 0.05). ΔTGF-ß1 was the best negative and Δoestradiol the best positive predictor of the 1st postpartum week anti-TPO (P < 0.05, b = -0.509; P < 0.05, b = 0.459 respectively). CONCLUSIONS: At postpartum, increased TGF-ß1 is related to a less pronounced anti-TPO increase as compared to the 3rd trimester, suggesting an immunosuppressive role for TGF-ß1. During pregnancy and postpartum, oestradiol, cortisol, and TGF-ß1 are associated with suppression of thyroid autoantibodies.

Body height in paediatric inflammatory bowel diseases: A structural equation model analysis.

BACKGROUND: Linear growth restriction is a unique feature of paediatric inflammatory bowel diseases (IBD), and reduced insulin-like growth factor (IGF-1) is a major determinant of short stature. We aimed to assess factors influencing somatic height in children suffering from IBD. MATERIALS AND METHODS: This was a retrospective, cross-sectional study conducted after approval by Institutional authorities. Anthropometric data, disease-related factors, biochemical and clinical indices of inflammation and endocrine parameters were recorded and considered as explanatory covariates. A structural equation model analysis was utilized. Somatic height was the outcome of interest, and possible associations of explanatory covariates directly or through the mediation effect of IGF-1 were assessed. RESULTS: Systemic inflammation, as expressed by high-sensitivity intereukin-6 (IL-6), and nutritional status described by body mass index (BMI) were the pathways that significantly affected stature through the mediation effect of IGF-1. Cortisol showed a direct, positive and independent of IGF-1 association with height. CONCLUSIONS: Insulin-like growth factor-1 is a key player in the process that results in impaired linear growth. Malnutrition and systemic inflammation have a restrictive action on growth by reducing circulating IGF-1. The positive relation of serum cortisol to height could correspond to suppressed pituitary-adrenal axis due to long-term use of glucocorticoids.

Increased hair cortisol and antecedent somatic complaints in children with a first epileptic seizure.

OBJECTIVE: Stress is the most frequent seizure-precipitating factor reported by patients with epilepsy, while stressful life events may increase seizure susceptibility in humans. In this study, we investigated the relations between both biological and behavioral measures of stress in children with a first epileptic seizure (hereafter called seizure). We hypothesized that hair cortisol, a biomarker of chronic stress reflecting approximately 3months of preceding exposure, might be increased in children with a first seizure. We also employed standardized questionnaires to examine presence of stress-related behavioral markers. METHODS: This was a cross-sectional clinical study investigating stress-related parameters in children with a first seizure (First Epileptic Seizure Group (FESG), n=22) in comparison to healthy children without seizures (Control Group, n=29). Within 24h after a first seizure, hair samples were collected from children for the determination of cortisol. In parallel, perceived stress and anxiety and depressive symptoms were examined with appropriate self- and parent-completed questionnaires, and history of stressful life events during the past year was recorded. Emotional and behavioral problems were also assessed by parent-reported validated and widely-used questionnaires. RESULTS: Higher hair cortisol measurements were observed in the FESG than control children (7.5 versus 5.0pg/mg respectively, p=0.001). The former were more likely to complain of somatic problems than the latter (59.8 vs. 55.4 according to DSM-oriented Scale, p=0.021); however, there were no differences in perceived stress and anxiety or depressive symptoms between the two groups. Using ROC analysis of hair cortisol measurements for predicting disease status, the maximum sensitivity and specificity were observed for a cut-off point of 5.25pg/mg. SIGNIFICANCE: Increased hair cortisol indicates chronic hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis prior to the first seizure. This might have contributed to the epileptogenesis process and may help explain the higher incidence of antecedent somatic complaints in the first seizure group.

Circulating levels of TNF-like cytokine 1A correlate with reflected waves and atherosclerosis extent and may predict cardiac death in patients with stable coronary artery disease.

BACKGROUND: TNF-like cytokine 1A (TL1A)-mediated interactions are involved in atheromatic plaque formation. In stable coronary artery disease (CAD) we examined whether circulating TL1A levels correlate with coronary and/or peripheral atherosclerosis extent and predict future cardiovascular events. METHODS: In this cross-sectional study, peripheral vascular studies and TL1A serum measurements were performed in 122 consecutive patients with angiographically confirmed CAD who were followed for a median of 41.9 months. TL1A levels were compared against controls (n = 63) and 20 patients with acute coronary syndrome (ACS). RESULTS: TL1A was higher in ACS than the 2 other groups (p < 0.001). In stable CAD, after adjustment for traditional risk factors independent positive correlations between TL1A serum levels and reflected waves (p = 0.049), and carotid atheromatic plaque score (p = 0.049) were evident. In stable patients with a history of ACS, TL1A levels correlated with worse endothelial function (p = 0.006), extent of CAD assessed by Gensini score (p = 0.042), and cardiac mortality (p = 0.051). CONCLUSIONS: This pilot study suggests that serum TL1A measurements are of clinical value in CAD. Studies on the pathogenetic role of TL1A in atherosclerosis and its sequelae are warranted.

Antioxidation improves in puberty in normal weight and obese boys, in positive association with exercise-stimulated growth hormone secretion.

BACKGROUND: Oxidative stress is associated with obesity while the evidence for the role of GH in pro- and antioxidation is inconclusive. This study investigates the relationships between growth hormone (GH), pro- and antioxidation in relation to obesity and puberty before and after an acute bout of exercise. METHODS: In this case-control study, 76 healthy normal-weight and obese, prepubertal and pubertal boys underwent a blood sampling before and immediately after an aerobic exercise bout until exhaustion at 70% maximal oxygen consumption. Markers of prooxidation (thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCs)) and antioxidation (glutathione (GSH), oxidized glutathione disulfide (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPX), catalase, and total antioxidant capacity (TAC)) and hormones (GH, insulin-like growth factor (IGF)-1, IGF-BP-3, luteinizing hormone, follicle-stimulating hormone, and testosterone) were measured. RESULTS: Baseline and postexercise TBARS and PCs were greater, while baseline GSH, GSH/GSSG ratio, GPX, and TAC were lower in obese than that in normal-weight participants. In all participants, waist was the best negative and positive predictor for postexercise GPX and TBARS, respectively. Baseline TAC was greater in pubertal than that in pre-pubertal participants. In all participants, baseline GH was the best negative predictor for postexercise PCs. Significant positive linear correlation exists between the exercise-associated GH, and GSSG increases in pubertal normal-weight boys. CONCLUSIONS: Higher prooxidation and lower antioxidation were observed in obese boys, while antioxidation improves with puberty and postexercise, paralleling GH accentuated secretion.

Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study.

OBJECTIVES: A reduced adrenal reserve-associated cortisol production relative to the enhanced needs of chronic inflammation (disproportion principle) has been observed in rheumatoid arthritis (RA). We examined the possible clinical value of diurnal cortisol measurements in active RA on treatment response prediction. METHODS: Diurnal cortisol production (measured at: 08-12:00/18:00-22:00) was assessed by electrochemiluminescence immunoassay in 28 consecutive patients with moderately/highly active RA, as well as 3 and 6 months after treatment initiation or/escalation. Twenty-eight COVID-19 patients and 28 age-matched healthy individuals (HC) served as controls. RESULTS: Saliva diurnal cortisol production in patients with RA was similar to that of HC, despite 12-fold higher serum C reactive protein (CRP) levels, and lower than COVID-19 patients (area under the curve: RA: 87.0±37.6 vs COVID-19: 146.7±14.3, p<0.001), having similarly high CRP. Moreover, a disturbed circadian cortisol rhythm at baseline was evident in 15 of 28 of patients with RA vs 4 of 28 and 20 of 28 of HC and COVID-19 patients, respectively. Treatment-induced minimal disease activity (MDA) at 6 months was achieved by 16 of 28 patients. Despite comparable demographics and clinical characteristics at baseline, non-MDA patients had lower baseline morning cortisol and higher adrenocorticotropic hormone (ACTH) levels compared with patients on MDA (cortisol: 10.9±4.0 vs 18.4±8.2 nmol/L, respectively, p=0.005 and ACTH: 4.8±3.3 vs 2.4±0.4 pmol/L, respectively, p=0.047). Baseline morning cortisol <13.9 nmol/L predicted non-MDA at 6 months (75% sensitivity, 92% specificity, p=0.006). Prospective measurements revealed that individualised diurnal cortisol production remained largely unchanged from baseline to 3 and 6 months. CONCLUSIONS: An impaired adrenal reserve is present in patients with RA. Further studies to confirm that assessment of diurnal cortisol production may be useful in guiding treatment decisions and/or predicting treatment response in RA are warranted. TRIAL REGISTRATION NUMBER: NCT05671627.

Serum Neuron-Specific Enolase as a Biomarker of Neonatal Brain Injury-New Perspectives for the Identification of Preterm Neonates at High Risk for Severe Intraventricular Hemorrhage.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Measurement of Calprotectin and PTH in the Amniotic Fluid of Early Second Trimester Pregnancies and Their Impact on Fetuses with Growth Disorders: Are Their Levels Related to Oxidative Stress?

Background: During the early stages of human fetal development, the fetal skeleton system is chiefly made up of cartilage, which is gradually replaced by bone. Fetal bone development is mainly regulated by the parathyroid hormone parathormone (PTH) and PTH-related protein, with specific calprotectin playing a substantial role in cell adhesion and chemotaxis while exhibiting antimicrobial activity during the inflammatory osteogenesis process. The aim of our study was to measure the levels of PTH and calprotectin in early second trimester amniotic fluid and to carry out a comparison between the levels observed among normal full-term pregnancies (control group) and those of the groups of embryos exhibiting impaired or enhanced growth. Methods: For the present prospective study, we collected amniotic fluid samples from pregnancies that underwent amniocentesis at 15 to 22 weeks of gestational age during the period 2021-2023. Subsequently, we followed up on all pregnancies closely until delivery. Having recorded fetal birthweights, we then divided the neonates into three groups: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: In total, 64 pregnancies, including 14 SGA, 10 LGA, and 40 AGA fetuses, were included in our study. Both substances were detected in early second trimester amniotic fluid in both groups. Concentrations of calprotectin differed significantly among the three groups (p = 0.033). AGA fetuses had a lower mean value of 4.195 (2.415-6.425) IU/mL, whereas LGA fetuses had a higher mean value of 6.055 (4.887-13.950) IU/mL, while SGA fetuses had a mean value of 5.475 (3.400-9.177) IU/mL. Further analysis revealed that only LGA fetuses had significantly higher calprotectin concentrations compared to AGA fetuses (p = 0.018). PTH concentration was similar between the groups, with LGA fetuses having a mean value of 13.18 (9.51-15.52) IU/mL, while SGA fetuses had a mean value of 14.18 (9.02-16.00) IU/mL, and AGA fetuses had similar concentrations of 13.35 (9.05-15.81) IU/mL. The differences in PTH concentration among the three groups were not statistically significant (p = 0.513). Conclusions: Calprotectin values in the amniotic fluid in the early second trimester were higher in LGA fetuses compared to those in the SGA and AGA categories. LGA fetuses can possibly be in a state of low-grade chronic inflammation due to excessive fat deposition, causing oxidative stress in LGA fetuses and, eventually, the release of calprotectin. Moreover, PTH concentrations in the amniotic fluid of early second trimester pregnancies were not found to be statistically correlated with fetal growth abnormalities in either LGA or SGA fetuses. However, the early time of collection and the small number of patients in our study should be taken into account.