Association of Plasma Irisin Levels with Circulating Endothelial Microparticles (EMPs) and Endothelial Progenitor Cells (EPCs) in Children Born Prematurely

Prematurity has been linked with endothelial dysfunction in later life. The purpose of this study was to evaluate the association between plasma irisin, an adipomyokine reported to protect the functional integrity of vascular endothelium, and circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs), consisting early biomarkers of endothelial dysfunction, in preterm-born children. We studied 131 prepubertal children; 61 preterm and 70 born at term (controls). Plasma irisin was determined by ELISA. Circulating CD62E(+), CD144(+) and CD31(+)/CD42b(-) EMPs, and CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs, were determined by flow cytometry. Body mass index, waist-to-hip ratio, neck circumference, systolic and diastolic blood pressure, and biochemical parameters (glucose, lipids, insulin, HOMA-IR) were also evaluated. Plasma irisin was significantly lower (p = 0.001), whereas circulating EMPs and EPCs were higher, in children born prematurely compared to controls. Irisin was recognized as independent predictor for CD144(+) and CD31(+)/CD42b(-) EMPs, CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs in the total study population, and for CD31(+)/CD42b(-) EMPs in the preterm group. In conclusion, plasma irisin correlates independently with circulating EMP and EPC subpopulations in prepubertal children and in preterm-born ones. Further studies in children will potentially elucidate the link between irisin and the primary stages of prematurity-related endothelial dysfunction

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

BackgroundEndothelial progenitor cells (EPCs) ensure vascular integrity and neovascularization. No studies have investigated EPCs in preterm-born children beyond infancy.MethodsOne 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.ResultsCirculating 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.ConclusionsCirculating 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.ImpactMounting 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

Probiotics in Adolescent Prediabetes: A Pilot RCT on Glycemic Control and Intestinal Bacteriome

Dysbiosis of intestinal ecology could be implicated in prediabetes. The aim of this pilot randomized controlled trial (RCT) was to collect preliminary data on the effects of probiotic supplementation (Vivomixx©) on markers of glucose metabolism, intestinal microbiome composition, and intestinal health indices, of prediabetic adolescents. The intervention group was administered probiotic sachets twice daily for 4 months, while both intervention and control groups received weekly consultation sessions for a healthier lifestyle. Thirty-two participants were recruited (1.3 participants per month) and were randomized (16 in control and 16 in intervention group). Fifteen of them signed the inform consent and never entered the study (6 in control and 9 in intervention group). Thus, seventeen participants completed the study (10 in control and 7 in intervention group), with no serious adverse events. After the 4-month intervention, no difference was observed in the markers of glycemic control between the two groups, although a minor effect was observed for fasting glucose at 1-month, probably due to the initial higher adherence to the probiotic supplements. Modifications of the protocol procedures are warranted because of the high attrition rates and suboptimal compliance that were noted. Future studies and further RCTs with larger samples need to be conducted to fully elucidate the potential effects of probiotics in the glycemic control of prediabetic adolescents

Neuroendocrine System Adaptation during Consecutive Extrinsic Stimuli: A Pilot Dynamic Study

This pilot repeated measures study aims to evaluate the dynamics of the autonomic nervous system (ANS), the hypothalamic–pituitary–adrenal (HPA) axis, and/or their interplay with low-level inflammation in healthy schoolchildren during consecutive extrinsic stimuli. Twenty healthy schoolchildren and adolescents aged 11–14 years (12.5 ± 1.5) were consecutively exposed to an oral task (#2) and an arithmetic task (#3) (Trier Social Stress Test for Children (TSST-C)), lasting 5 min each, and a three-minute cellular phone call (#4). Salivary cortisol (SC) was sampled at baseline (#1) and immediately after each exposure (#2, 3, and 4). Baseline serum high-sensitivity C-reactive protein (hsCRP) and cortisol levels were also assessed. ANS dynamics and complexity were measured using Sample Entropy (SampEn) at each experimental time period (#1–4). Baseline serum hCRP and cortisol correlated negatively to each other, while the ANS and HPA axis acute reactions to the three consecutive stimuli differed over time. The ANS adaptation to these stimuli included complexity modulation, which was not dependent on baseline hsCRP or cortisol, and weakened during the third stimulation. However, baseline hsCRP and cortisol had a weakening and an increasing effect on the HPA axis over time, respectively. We conclude that low-level inflammation and baseline morning cortisol level have no effect on ANS dynamics but influence the HPA axis response to consecutive external stimuli

Neuroendocrine System Adaptation during Consecutive Extrinsic Stimuli: A Pilot Dynamic Study

This pilot repeated measures study aims to evaluate the dynamics of the autonomic nervous system (ANS), the hypothalamic–pituitary–adrenal (HPA) axis, and/or their interplay with low-level inflammation in healthy schoolchildren during consecutive extrinsic stimuli. Twenty healthy schoolchildren and adolescents aged 11–14 years (12.5 ± 1.5) were consecutively exposed to an oral task (#2) and an arithmetic task (#3) (Trier Social Stress Test for Children (TSST-C)), lasting 5 min each, and a three-minute cellular phone call (#4). Salivary cortisol (SC) was sampled at baseline (#1) and immediately after each exposure (#2, 3, and 4). Baseline serum high-sensitivity C-reactive protein (hsCRP) and cortisol levels were also assessed. ANS dynamics and complexity were measured using Sample Entropy (SampEn) at each experimental time period (#1–4). Baseline serum hCRP and cortisol correlated negatively to each other, while the ANS and HPA axis acute reactions to the three consecutive stimuli differed over time. The ANS adaptation to these stimuli included complexity modulation, which was not dependent on baseline hsCRP or cortisol, and weakened during the third stimulation. However, baseline hsCRP and cortisol had a weakening and an increasing effect on the HPA axis over time, respectively. We conclude that low-level inflammation and baseline morning cortisol level have no effect on ANS dynamics but influence the HPA axis response to consecutive external stimuli

Serum Spexin is Correlated with Lipoprotein(a) and Androgens in Female Adolescents

The Spexin gene is considered the most dysregulated in obese human fat. Limited data suggest that the novel peptide spexin may potentially impact food intake, weight regulation and body adiposity. The aim of this case-control study was to compare fasting serum spexin concentrations between normal weight (NW) and overweight/obese (OB/OW) adolescent females and explore the relationship between circulating spexin and anthropometric, bone and fat mass, metabolic and hormonal parameters. Eighty post-menarcheal females (mean age ± SD 16.23 ± 2.26 years); 55 NW (mean BMI ± SD 19.72 ± 2.52 kg/m2) and 25 OB/OW (mean BMI ± SD 29.35 ± 3.89 kg/m2) participated in the study. Circulating spexin levels did not differ significantly (p = 0.378) between NW (median (interquartile range), 0.26 (0.17) ng/mL) and OB/OW (median (interquartile range), 0.28 (0.06) ng/mL) adolescents and did not correlate with BMI (rs = −0.090, p = 0.438), % body fat (rs = −0.173, p = 0.409), glucose or insulin resistance indices derived from fasting and oral glucose tolerance states. In the total study sample, spexin concentrations correlated positively with lipoprotein(a) (rs = 0.402, p = 0.046). In the OB/OW adolescents spexin levels correlated positively with testosterone (rs = 0.727, p = 0.011) and free androgen index (rs = 0.755, p = 0.007). In the NW adolescents, spexin concentrations correlated negatively with dehydroepiandrosterone sulphate (rs = −0.445, p = 0.038). Results may suggest potential involvement of spexin in the regulation of lipoprotein(a) and of the reproductive/adrenal axis in post-menarcheal adolescent females

Circulating FGF21 vs. Stress Markers in Girls during Childhood and Adolescence, and in Their Caregivers: Intriguing Inter-Relations between Overweight/Obesity, Emotions, Behavior, and the Cared-Caregiver Relationship

Fibroblast growth factor-21 (FGF21) acts on several brain regions, including the hypothalamic paraventricular nucleus, which is involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study was to investigate the interrelations between FGF21 and stress indices in girls, as well as in their caregivers. 78 girls, aged between 5 and 15 years, were studied; 50 of them were overweight and obese (OB) and 28 in the control group (C). Serum FGF21 and hair and diurnal salivary cortisol were measured. Children participants filled in the Children’s Depression Inventory (CDI) and the State-Trait Anxiety Inventory for Children (STAIC), while their caregivers filled in the State-Trait Anxiety Inventory (STAI), the Perceived Stress Scale (PSS), and the Holmes-Rahe Stress Events Scale (HRSES). The OB group girls had significantly higher levels of FGF21 than the C group (p < 0.001). In contrast to the C group, in whom FGF21 levels were positively correlated with both hair and salivary AUCg cortisol concentrations (p = 0.045 and p = 0.007, respectively), no such correlations were observed in the OB group. In the caregivers of the OB group, STAI-state (r = 0.388, p = 0.008), STAI-trait (r = 0.4, p = 0.006), PSS (r = 0.388, p = 0.008), and HRSES (r = 0.358, p = 0.015) scores, all correlated positively with the FGF21 levels of the children under their care. FGF21 concentrations positively correlated with hair and salivary cortisol levels in the C group only. These findings may represent an interesting correlation dictated by bi-directional empathy links between the primary caregivers and the children under their care

Is there an association between thyroid function abnormalities and breast cancer?

ABSTRACT Objective The aim of this study was to evaluate the association between thyroid function abnormalities and breast cancer and, in particular, the prognostic markers of breast cancer.. Subjects and methods Baseline levels of thyrotropin, free triiodothyronine, free thyroxine and thyroid autoantibodies were measured in 97 women with primary breast cancer, 27 women with benign breast disease, and 4 women with atypical ductal hyperplasia. Their baseline levels were compared with those in 48 healthy women with a normal mammography in the last 2 years. Results There were no significant associations between history of thyroid disease and breast cancer (p = 0.33). The mean baseline levels of triiodothyronine and thyrotropin did not differ significantly between the compared groups. The mean baseline levels of free thyroxine were found to be significantly higher in the breast cancer group, even after adjusting for thyroid replacement therapy. The presence of thyroid antibodies did not differ significantly between the compared groups. In a subgroup analysis, breast cancer cases with thyroid disease and particularly hypothyroidism had a significantly lower incidence of lymph node metastases compared with breast cancer cases without thyroid disease. Conclusions Our data confirmed the proliferative effect of thyroid hormones on breast cells, which had previously been shown in vitro. Additionally, thyroid disease and particularly hypothyroid function appeared to be associated with a lower incidence of lymph node metastases. Further studies to determine the prognostic role of thyroid hormones in breast cancer are warranted

Stress, Inflammation and Metabolic Biomarkers Are Associated with Body Composition Measures in Lean, Overweight, and Obese Children and Adolescents

The aim of this study was to examine the associations between multiple indices of stress, inflammation and metabolism vs. body composition parameters in 121 (43 boys, 78 girls) children and adolescents, aged 5–15 y. Subjects were divided into two groups: normal weight (N) (N = 40, BMI z-score = −0.1923 ± 0.6), and overweight/obese (OB) (N = 81, BMI z-score = 2.1947 ± 1.4). All subjects completed the State-Trait Anxiety Inventory for Children (STAIC) and Children’s Depression Inventory, and underwent cortisol measurements in hair, diurnal series of saliva, and morning serum. Circulating concentrations of high sensitivity C-reactive protein (hsCRP) and other inflammation biomarkers were also obtained. Body composition analysis was performed with a clinically validated, advanced bioimpedance apparatus (BIA), while heart rate variability (HRV) was measured as a stress biomarker by photoplethysmography (PPG). The OB group had a higher STAIC-state score, waist-to-hip ratio, skeletal muscle mass, and total and abdominal fat mass, and a lower percent fat-free mass (FFM) and bone density than the N group. HRV did not differ between the groups. In the entire population, percent fat mass correlated strongly with circulating hsCRP (r = 0.397, p = 0.001), ferritin, and other inflammatory biomarkers, as well as with indices of insulin resistance. A strong correlation between serum hsCRP and hair cortisol was also observed (r = 0.777, p < 0.001), suggesting interrelation of chronic stress and inflammation. Thus, body fat accumulation in children and adolescents was associated with an elevation in clinical and laboratory biomarkers of stress, inflammation, and insulin resistance. BIA-ACC and PPG can be utilized as a direct screening tool for assessing overweight- and obesity -related health risks in children and adolescents