Management of Portal Hypertension in Children

Management of portal hypertension in children has evolved over the past several decades. Portal hypertension can result from intrahepatic or extrahepatic causes. Management should be tailored to the child based on the etiology of the portal hypertension and on the functionality of the liver. The most serious complication of portal hypertension is gastroesophageal variceal bleeding, which has a mortality of up to 30%. Initial treatment of bleeding focuses on stabilizing the patient. Further treatment measures may include endoscopic, medical, or surgical interventions as appropriate for the child, depending on the cause of the portal hypertension. β-Blockers have not been proven to effectively prevent primary or secondary variceal bleeding in children. Sclerotherapy and variceal band ligation can be used to stop active bleeding and can prevent bleeding from occurring. Transjugular intrahepatic portosystemic shunts and surgical shunts may be reserved for those who are not candidates for transplant or have refractory bleeding despite medical or endoscopic treatment

The 24-h Energy Intake of Obese Adolescents Is Spontaneously Reduced after Intensive Exercise: A Randomized Controlled Trial in Calorimetric Chambers

Background: Physical exercise can modify subsequent energy intake and appetite and may thus be of particular interest in terms of obesity treatment. However, it is still unclear whether an intensive bout of exercise can affect the energy consumption of obese children and adolescents. [br/] Objective: To compare the impact of high vs. moderate intensity exercises on subsequent 24-h energy intake, macronutrient preferences, appetite sensations, energy expenditure and balance in obese adolescent. [br/] Design: This randomized cross-over trial involves 15 obese adolescent boys who were asked to randomly complete three 24-h sessions in a metabolic chamber, each separated by at least 7 days: (1) sedentary (SED); (2) Low-Intensity Exercise (LIE) (40% maximal oxygen uptake, VO(2)max); (3) High-Intensity Exercise (HIE) (75% VO(2)max). Results: Despite unchanged appetite sensations, 24-h total energy intake following HIE was 6-11% lower compared to LIE and SED (p<0.05), whereas no differences appeared between SED and LIE. Energy intake at lunch was 9.4% and 8.4% lower after HIE compared to SED and LIE, respectively (p<0.05). At dinner time, it was 20.5% and 19.7% lower after HIE compared to SED and LIE, respectively (p<0.01). 24-h energy expenditure was not significantly altered. Thus, the 24-h energy balance was significantly reduced during HIE compared to SED and LIE (p<0.01), whereas those of SED and LIE did not differ. [br/] Conclusions: In obese adolescent boys, HIE has a beneficial impact on 24-h energy balance, mainly due to the spontaneous decrease in energy intake during lunch and dinner following the exercise bout. Prescribing high-intensity exercises to promote weight loss may therefore provide effective results without affecting appetite sensations and, as a result, food frustrations

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Hystérie de l'enfant

Gueriot C., Duché D. J. Hystérie de l'enfant. In: Bulletin de psychologie, tome 25 n°297, 1972. pp. 402-404

Molecular Mechanism of Action of Pore-Forming Colicins and of their Immunity Proteins

International audiencePore-forming colicins constitute a large family of homologous bacteriocins that are of interest for a variety of problems related to membranes. Topics such as toxin action, polypeptide translocation across and into membranes, voltage-gated channels, receptor function, protein-protein interactions in membranes will benefit from the simple model system provided by the colicins. Mostly colicins A and El have been studied, however, only the three-dimensional structure of the pore-forming C-terminal domain of colicin A has been solved at 2.4 Å resolution. This domain can exist both in a water soluble as well as in a membrane form. Colicins bind to a receptor in the outer membrane and are then translocated across the cell envelope to the inner membrane. Import of colicins involves a cascade of steps which use specific proteins in the outer and inner membranes that are probably required for the acquisition and stabilization of a translocation-competent intermediate state. A membrane potential-dependent movement of a large region of the channel peptide into the membrane bilayer is required for channel opening. Pore-forming colicins span the whole cell envelope even after channel opening. Thus, they probably remain at putative translocation contact sites between the outer and inner membranes. Site-directed mutagenesis studies are now used to probe models concerning the dynamics of conformational changes of the C-terminal domain upon pore-formation. The protective action of immunity proteins against pore-forming colicins is a challenging problem. This action is specifically directed against the C-terminal domain of colicins. Studies using homologous recombination between the genes for colicins A and B provided hybrid colicins which allowed us to demonstrate that the specificity determinant in the pore-forming domain is constituted by the two hydrophobic helices of the structure. Despite extensive studies on the topography and identification of critical regions in the immunity polypeptide which spans the inner membrane four times, it is not yet known whether the formation of the channel or its opening is prevented by the immunity protein

Association between Low Energy Availability (LEA) and Impaired Sleep Quality in Young Rugby Players

Low energy availability (LEA) has been associated with several physiological consequences, but its impact on sleep has not been sufficiently investigated, especially in the context of young athletes. This study examined the potential association between energy availability (EA) status and objective sleep quality in 42 male rugby players (mean age: 16.2 ± 0.8 years) during a 7-day follow-up with fixed sleep schedules in the midst of an intensive training phase. Participants’ energy intake was weighed and recorded. Exercise expenditure was estimated using accelerometry. Portable polysomnography devices captured sleep on the last night of the follow-up. Mean EA was 29.3 ± 9.14 kcal·kg FFM−1·day−1, with 47.6% of athletes presenting LEA, 35.7% Reduced Energy Availability (REA), and 16.7% Optimal Energy Availability (OEA). Lower sleep efficiency (SE) and N3 stage proportion, along with higher wake after sleep onset (WASO), were found in participants with LEA compared to those with OEA (p = 0.04, p = 0.03 and p = 0.005, respectively, with large effect sizes). Segmented regression models of the EA-sleep outcomes (SE, sleep onset latency [SOL]), WASO and N3) relationships displayed two separate linear regions and produced a best fit with a breakpoint between 21–33 kcal·kg FFM−1·day−1. Below these thresholds, sleep quality declines considerably. It is imperative for athletic administrators, nutritionists, and coaches to conscientiously consider the potential impact of LEA on young athletes’ sleep, especially during periods of heavy training