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.

Hepatokine Profile in Adolescents with Polycystic Ovary Syndrome: A Case-Control Study.

The current guidelines suggest routine screening for non-alcoholic fatty liver disease (NAFLD) in patients with polycystic ovary syndrome (PCOS). Hepatokines seem to be promising surrogate endpoints for the diagnosis and severity of NAFLD. PCOS has its onset in adolescence and its metabolic sequalae begin during the same period. There are scarce data on the hepatokine profile of adolescent PCOS patients. This case-control study examined the serum profile of the hepatokines sex hormone-binding globulin (SHBG), selenoprotein P, fibroblast growth factor 21 (FGF21), and fetuin A in a sample of adolescent PCOS patients, and their association to metabolic and hormonal parameters. The selenoprotein P and SHBG serum concentrations were significantly decreased in PCOS patients vs. the controls (median (IQR), 2.47 (0.40) vs. 2.66 (0.36) µg/mL, p = 0.025; mean ± SD, 41.71 ± 19.41 vs. 54.94 ± 22.12 nmol/L, p = 0.011, respectively), whereas selenoprotein P was significantly and positively associated with testosterone (r = 0.325, p = 0.007) and the free androgen index (r = 0.361, p = 0.002). The SHBG demonstrated multiple significant negative correlations with adverse metabolic parameters. Among the PCOS patients, the FGF21 concentrations were significantly higher in those with NAFLD, whereas a 1 pg/mL increase in the FGF21 concentration increased the odds of NAFLD diagnosis by liver ultrasound by 1%, suggesting FGF21 as a potential biomarker for hepatic disease in females with PCOS in adolescence. Fetuin A was the least differentiated hepatokine between the PCOS patients and controls with the least associations with metabolic and hormonal parameters.

The Burden of Non-Alcoholic Fatty Liver Disease in Adolescents with Polycystic Ovary Syndrome: A Case-Control Study.

The aim of this case-control study was to assess the burden of non-alcoholic fatty liver disease (NAFLD) in adolescents with polycystic ovary syndrome (PCOS) and its associations with insulin resistance, hyperandrogenism, and other metabolic characteristics of the syndrome. A total of 87 Caucasian adolescent girls (47 with PCOS and 40 controls), aged 12.3-20.4 years, underwent blood sampling for glucose metabolism, hormonal and lipid profile, gynecological and liver ultrasound, and liver elastography. Indices of insulin resistance, liver steatosis, and liver fibrosis were calculated. NAFLD diagnosed by ultrasound was more prevalent in adolescents with PCOS than controls (22.7% vs. 6.1%, p = 0.046), and was also verified by liver steatosis indices. The latter was not apparent for hepatic fibrosis, as assessed by Fibroscan® and calculated indices. The homeostatic model assessment for insulin resistance (HOMA-IR) was found to predict NAFLD diagnosis by the liver fat score (LFS) index (ß = 0.709, p = 0.002). Adolescents with PCOS and high free androgen index (FAI) presented worse NAFLD than those adolescents with PCOS and lower FAI. In addition, adolescents with PCOS and concurrent NAFLD had worse insulin sensitivity indices (HOMA-IR, QUICKI, and glucose to insulin ratio) than adolescents with PCOS alone. Adolescent insulin resistance could be considered a confounder of the association between PCOS and NAFLD.

Comparison of Hospital Consultation and Summer Camp Lifestyle Intervention Programs for Sustained Body Weight Loss in Overweight/Obese Greek Children.

Two lifestyle intervention programs of a health initiative named "Evrostia" were conducted at (a) an outpatient obesity clinic of a children's hospital and (b) summer camp (SC), respectively. Thirty overweight/obese children were randomly selected to participate in each intervention arm to assess the efficacy of the SC intervention and its possible superiority over usual hospital consultation (HC) practice. There was a statistically significant decrease in body weight (BW), and body mass index (BMI) in both programs. A higher duration of reduced BW was observed in the SC compared to HC intervention. Regarding the nutritional behavior, there was a significant increase in the consumption of breakfast, fruit and vegetables, and a reduction in the consumption of beverages and sweets in the SC group. A significant increase in the hours of weekly physical activity was also observed in children of the SC program. The comparison between the two lifestyle intervention programs showed that the SC program improved nutritional behaviors and physical activity and promoted longer preservation of BW loss than that of the HC program. Thus, the holistic and experiential approach of the SC program was more successful in the treatment of overweight and obesity in children than a conventional HC program.

Vulvar Varicosities in an Adolescent Girl with Morbid Obesity: A Case Report.

Vulvar varicosities in nonpregnant females, either isolated or as a part of the pelvic congestion syndrome, are rare. We present a case of an adolescent girl with morbid obesity with bilateral bluish protrusions on the labia minora, as an incidental finding, that coincided with her excessive weight gain. The adolescent underwent thorough clinical examination, doppler ultrasound, contrast venography and varicography, and magnetic resonance angiography to rule out alternative diagnoses. Imaging results confirmed the presence of large venous lakes. Venous drainage to the internal iliac vein and connections with the long saphenous vein were delineated. Incompetence, dilatation, or reflux of ovarian or internal iliac veins, or their main tributaries, were not noted. Since the adolescent was asymptomatic and other pathologies, such as vascular malformations or hemangiomas were excluded, she was managed conservatively with counseling about lifestyle modification and weight reduction. This is only the third reported case of vulvar venous varicosities in adolescents. Female sex, along with obesity, are known risk factors for varicose vein formation; however, the pathogenesis is not fully understood. Additional research is needed to elucidate the role of excess adipose tissue in the pathophysiology of vulvar varicose veins and to optimize diagnostic workup and management in adolescence.

HPV infection: immunological aspects and their utility in future therapy.

High prevalence and mortality rates of cervical cancer create an imperative need to clarify the uniqueness of HPV (Human Papillomavirus) infection, which serves as the key causative factor in cervical malignancies. Understanding the immunological details and the microenvironment of the infection can be a useful tool for the development of novel therapeutic interventions. Chronic infection and progression to carcinogenesis are sustained by immortalization potential of HPV, evasion techniques, and alterations in the microenvironment of the lesion. Inside the lesion, Toll-like receptors expression becomes irregular; Langerhans cells fail to present the antigens efficiently, tumor-associated macrophages aggregate resulting in an unsuccessful immune response by the host. HPV products also downregulate the expression of microenvironment components which are necessary for natural-killer cells response and antigen presentation to cytotoxic cells. Additionally HPV promotes T-helper cell 2 (Th2) and T-regulatory cell phenotypes and reduces Th1 phenotype, leading to suppression of cellular immunity and lesion progression to cancer. Humoral response after natural infection is inefficient, and neutralizing antibodies are not adequate in many women. Utilizing this knowledge, new endeavors, such as therapeutic vaccination, aim to stimulate cellular immune response against the virus and alter the milieu of the lesion.