Abstract
Recent evidence has shown that patterns of cortico-cortical functional synchronization are consistently traceable by the end of the third trimester of pregnancy. The involvement of ...subcortical structures in early functional and cognitive development has never been explicitly investigated, notwithstanding their pivotal role in different cognitive processes. We address this issue by exploring subcortico-cortical functional connectivity at rest in a group of normally developing fetuses between the 25th and 32nd weeks of gestation. Results show significant functional coupling between subcortical nuclei and cortical networks related to: (i) sensorimotor processing, (ii) decision making, and (iii) learning capabilities. This functional maturation framework unearths a Cognitive Development Blueprint, according to which grounding cognitive skills are planned to develop with higher ontogenetic priority. Specifically, our evidence suggests that a newborn already possesses the ability to: (i) perceive the world and interact with it, (ii) create salient representations for the selection of adaptive behaviors, and (iii) store, retrieve, and evaluate the outcomes of interactions, in order to gradually improve adaptation to the extrauterine environment.
The ability to detect the spatial characteristics of objects and to rotate them mentally is frequently impaired in early treated congenital hypothyroidism (CH) children.
To explore the neural ...substrate of the visuospatial difficulty in children with CH, we studied 15 children with CH (8-10 years) and 13 age-matched control children with functional magnetic resonance imaging (fMRI) using a mental rotation task (VST).
Performance at VST was significantly different between the two groups. Moreover, fMRI data showed greater activation in the superior parietal cortex in control children while children with CH had greater activation in the bilateral SMA and the opercular region of the precentral gyrus, the adjacent insula and the left somatosensory parietal cortex. Furthermore, children with CH deactivated the inferior parietal cortex (Brodmann area 40) more than controls.
We suggest that the poorer performance of children with CH on VST task is related to the decreased activation in brain areas important for the mental representation of the objects' spatial characteristics, with increased recruitment of regions involved in the representation of somatosensory whole-body information. More studies will be necessary to understand if this different effectiveness in VST reflects immaturity of the neural system or its actual impairment.
Allogeneic hematopoietic stem-cell transplantation is the standard of care for Hurler syndrome (mucopolysaccharidosis type I, Hurler variant MPSIH). However, this treatment is only partially curative ...and is associated with complications.
We are conducting an ongoing study involving eight children with MPSIH. At enrollment, the children lacked a suitable allogeneic donor and had a Developmental Quotient or Intelligence Quotient score above 70 (i.e., none had moderate or severe cognitive impairment). The children received autologous hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with an α-L-iduronidase (IDUA)-encoding lentiviral vector after myeloablative conditioning. Safety and correction of blood IDUA activity up to supraphysiologic levels were the primary end points. Clearance of lysosomal storage material as well as skeletal and neurophysiological development were assessed as secondary and exploratory end points. The planned duration of the study is 5 years.
We now report interim results. The children's mean (±SD) age at the time of HSPC gene therapy was 1.9±0.5 years. At a median follow-up of 2.10 years, the procedure had a safety profile similar to that known for autologous hematopoietic stem-cell transplantation. All the patients showed prompt and sustained engraftment of gene-corrected cells and had supraphysiologic blood IDUA activity within a month, which was maintained up to the latest follow-up. Urinary glycosaminoglycan (GAG) excretion decreased steeply, reaching normal levels at 12 months in four of five patients who could be evaluated. Previously undetectable levels of IDUA activity in the cerebrospinal fluid became detectable after gene therapy and were associated with local clearance of GAGs. Patients showed stable cognitive performance, stable motor skills corresponding to continued motor development, improved or stable findings on magnetic resonance imaging of the brain and spine, reduced joint stiffness, and normal growth in line with World Health Organization growth charts.
The delivery of HSPC gene therapy in patients with MPSIH resulted in extensive metabolic correction in peripheral tissues and the central nervous system. (Funded by Fondazione Telethon and others; ClinicalTrials.gov number, NCT03488394; EudraCT number, 2017-002430-23.).
Chrono-nutrition studies dietary habits and their role in the onset of metabolic diseases. The aim of this study is to describe chrono-nutritional patterns based on the analysis of the eating habits ...of patients with severe obesity during the 24-h cycle and investigate a possible relationship between these profiles, the comorbidities, and the psychological status. From the overall evaluation of the chrono-nutritional profiles of 173 patients with severe obesity, four predominant eating patterns were obtained with a refined statistical model. A regression analysis was performed to determine the relationship between chrono-nutritional patterns, medical comorbidities, and psychological status. Profile 1 was the most frequent (46.2%) and characterised by the regular presence of the three main meals. The distribution of the chrono-nutritional profiles did not vary with BMI. Chrono-nutritional profiles affected predominantly psychological variables, with lower performances among chrono-nutritional profiles 3 (to eat during all the 24-h, with nibbling and snacking also during the night) and 4 (like the fourth but without night-eating). This finding could be useful in the assessment and treatment of patients with obesity, allowing the identification of patients with a higher probability of suffering from a psychopathological condition simply by knowing the patients' dietary profiles.
Sommario
La chirurgia bariatrica risulta essere a tutt’oggi la modalità di trattamento più efficace nell’indurre e mantenere un significativo calo ponderale e un miglioramento delle comorbidità nei ...pazienti con obesità grave o complicata. La chirurgia bariatrica presenta tuttavia anche rischi, effetti collaterali e complicazioni nel breve e nel lungo termine, e non è inoltre esente dal rischio di recupero ponderale. Il recupero ponderale è possibile dopo qualsiasi di procedura di chirurgia bariatrica ed è probabilmente causato, almeno in parte, dagli stessi meccanismi biologici che lo determinano dopo terapia medica dell’obesità. Una intensificazione degli interventi comportamentali sullo stile di vita (nutrizione e attività fisica) può avere un ruolo nella prevenzione del recupero ponderale dopo chirurgia bariatrica. L’utilizzo dei farmaci anti-obesità nel paziente bariatrico con insufficiente calo di peso o recupero ponderale appare una opzione promettente nel cercare di ridurre il ricorso alla chirurgia di revisione, anche se non sono al momento disponibili trial randomizzati controllati ad hoc.
ABSTRACT
Introduction
Human respiratory syncytial virus (RSV) is one of the most frequent causes of respiratory infections in children under 5 years of age, but its socioeconomic impact and burden in ...primary care settings is still little studied.
Methods
During the 2022/2023 winter season, 55 pediatricians from five Italian regions participated in our community‐based study. They collected a nasal swab for RSV molecular test from 650 patients under the age of 5 with acute respiratory infections (ARIs) and performed a baseline questionnaire. The clinical and socioeconomic burden of RSV disease in primary care was evaluated by two follow‐up questionnaires completed by the parents of positive children on Days 14 and 30.
Results
RSV laboratory‐confirmed cases were 37.8% of the total recruited ARI cases, with RSV subtype B accounting for the majority (65.4%) of RSV‐positive swabs. RSV‐positive children were younger than RSV‐negative ones (median 12.5 vs. 16.5 months). The mean duration of symptoms for all children infected by RSV was 11.47 ± 6.27 days. We did not observe substantial differences in clinical severity between the two RSV subtypes, but RSV‐A positive patients required more additional pediatric examinations than RSV‐B cases. The socioeconomic impact of RSV infection was considerable, causing 53% of children to be absent from school, 46% of parents to lose working days, and 25% of families to incur extra costs.
Conclusions
Our findings describe a baseline of the RSV disease burden in primary care in Italy before the introduction of upcoming immunization strategies.
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