Heart rate variability,exercise capacity and levels of daily physical activity in children and adolescents with mild-to-moderate cystic fibrosis

Background:Autonomic nervous system balance is altered in cystic fibrosis (CF), although its influence on physical fitness has been poorly explored.Objective:This study aimed to evaluate the association of heart rate variability (HRV) with exercise capacity and levels of daily physical activity in children and adolescents with mild-to-moderate CF.Methods:A cross-sectional study including individuals with CF aged 6–18 years, not under CFTR modulator therapy, was performed. Sociodemographic (age, sex) and clinical information (airway colonization, pancreatic insufficiency, and genotyping) were collected. In addition, exercise capacity (modified shuttle test — MST), lung function (spirometry), body composition (bioimpedance), levels of daily physical activity (5-day accelerometer), and HRV (both at rest and during the MST) were evaluated.Results:30 individuals (20 females) aged 11.2±3.7 years, mean FEV162.8±27.6%, were included. A sympathovagal balance (LF/HF) increase (p<0.001) during the MST was shown, indicating a predominance of sympathetic modulation. The standard deviation of all RR intervals (SDNN) and the high frequency (HF) index during exercise correlated significantly with FEV₁ (r=0.45, p=0.01 and r=0.46, p=0.01; respectively). MST distance also correlated positively and significantly with SDNN (r=0.43, p=0.01), square root of the mean of the sums of squares of frequencies between RR intervals greater than 50 ms — RMSSD (r=0.53, p<0.01), low frequency — LF (r=0.48, p<0.01), HF (r=0.64, p<0.01), dispersion of points perpendicular to the short-term identity line — SD1 (r=0.40, p=0.02) and negatively with LF/HF (r=−0.57, p<0.01). Regarding daily physical activity, SDNN at rest (r=0.37, p=0.04) and exercise (r=0.41, p=0.02) showed positive correlations with time in moderate-to-vigorous activities. When normalizing the SDNN and classifying individuals as normal or altered, those presenting altered SDNN showed poorest FEV₁ (p=0.001) and lower exercise capacity (p=0.027).Conclusion:HRV correlates with lung function, exercise capacity and levels of daily physical activity in children and adolescents with CF. The study highlights the influence of CF on autonomic function and suggests HRV measurement as an easy tool to be used in clinical settings as an alternative marker to monitor CF individuals.     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

Predicting financial deficits from a standard neuropsychological assessment: preliminary evidence in mild cognitive impairment

Neurological Sciences - Patients with mild cognitive impairment (MCI) might experience difficulties in numerical and financial abilities of daily living that compromise their autonomy. The aim of...     

Longitudinal Nutritional Intakes in Italian Pregnant Women in Comparison with National Nutritional Guidelines

Background: Nutritional quality during pregnancy is crucial for mother and child health and their short/long-term outcomes. The aim of this study is to evaluate the adherence to nutritional recommendations in Italy during the three pregnancy trimesters in Normal Weight (NW) and Over Weight (OW) women. Methods: Data from a multicenter randomized controlled trial included 176 women (NW = 133; OW = 43) with healthy singleton pregnancies enrolled within 13 + 6 weeks of gestation. Dietary intake was assessed every trimester by a Food Frequency Questionnaire. Results: OW and NW had similar gestational weight gain. However, as Institute of Medicine (IOM) recommend lower gestational weight gain (GWG) for OW, they exceeded the suggested range. In both groups, caloric intake during the three trimesters never met recommendations. Protein intake in first and second trimester was higher than recommendations, as was sugars percentage. Dietary fiber intake was lower in OW. Polyunsaturated fatty acids, calcium, iron and folic acid requirements were never satisfied, while sodium intake exceeded recommendations. Conclusions: NW and OW women in Italy do not adhere to nutritional recommendations during pregnancy, with lower caloric intake, protein and sugars excess and inadequacies in micronutrients intake. Pregnant women in Italy should be provided with an adequate counseling and educational intervention as well as supplementation when indicated.     

Recent Developments in Health Care Law: Culture and Controversy

This article reviews recent developments in health care law, focusing on controversy at the intersection of health care law and culture. The article addresses: emerging issues in federal regulatory oversight of the rapidly developing market in direct-to-consumer genetic testing, including questions about the role of government oversight and professional mediation of consumer choice; continuing controversies surrounding stem cell research and therapies and the implications of these controversies for healthcare institutions; a controversy in India arising at the intersection of abortion law and the rights of the disabled but implicating a broader set of cross-cultural issues; and the education of U.S. health care providers and lawyers in the theory and practice of cultural competency.     

Transepidermal Water Loss in Newborns Within the First 24 Hours of Life: Baseline Values and Comparison with Adults

The measurement of transepidermal water loss (TEWL) is important for evaluating the integrity of the barrier function of the stratum corneum. Normal TEWL values in healthy adults and in children ages 2 and older are well known, but few studies have been performed in infants and neonates. TEWL in healthy neonates younger than 24 hours old was assessed and compared with that of an adult study population. We also studied possible correlations between this parameter, gestational age, and mode of delivery. A prospective study was conducted in healthy newborns. The areas tested were the volar forearm and the popliteal fossa. Ninety‐nine healthy newborns were enrolled and 33 healthy adults were analyzed as controls. Statistically significant differences were noted between newborns and adults in TEWL (p < 0.01). Newborns had a much higher mean TEWL than adults. Differences in the morphology and physiology between newborn and mature skin can explain the higher TEWL in newborns. Higher TEWL could also be due to the sudden functional adaptation of the skin immediately after delivery, when the newborn transits from a liquid to the dry, gaseous extrauterine environment. Functional evaluation of the neonatal skin barrier is important mainly because maintaining skin integrity facilitates cutaneous adaptation.