Overnutrition in Infants Is Associated With High Level of Leptin, Viral Coinfection and Increased Severity of Respiratory Infections: A Cross-Sectional Study

Objective: To investigate the relationship of overnutrition (obese and overweight) with severity of illness in children hospitalized with acute lower respiratory infections (ALRIs), frequency of viral coinfections and leptin levels. Methods: We studied 124 children <2 years old that were hospitalized for ALRI. Nutritional status was calculated by z-scores according to weight-for-age z-scores, length or height-for-age z-scores, and weight-for-height z-scores. Nasopharyngeal aspirates (NPAs) were obtained and viral respiratory pathogens were identified using reverse transcription polymerase chain reactions (RT-PCR). Respiratory syncytial virus (RSV) load was assessed using quantitative RT-PCR. NPA and plasma leptin level were measured. Clinical data and nutritional status were recorded, and patients were followed up until hospital discharge. Viral coinfection was defined as the presence of two or more viruses detected in the same respiratory sample. Severity of illness was determined by length of hospitalization and duration of oxygen therapy. Results: Children with overnutrition showed a greater frequency of viral coinfection than those with normal weight (71% obese vs. 37% normal weight p = 0.013; 68% overweight vs. 37% normal weight p = 0.004). A lower RSV load was found in obese (5.91 log(10) copies/mL) and overweight children (6.49 log(10) copies/mL) compared to normal weight children (8.06 log(10) copies/mL; p = 0.021 in both cases). In multivariate analysis, obese, and overweight infants <6 months old were associated with longer hospital stays (RR = 1.68; CI: 1.30-2.15 and obese: RR = 1.68; CI: 1.01-2.71, respectively) as well as a greater duration of oxygen therapy (RR = 1.80; IC: 1.41-2.29 and obese: RR = 1.91; CI: 1.15-3.15, respectively). Obese children <6 months showed higher plasma leptin level than normal weight children (7.58 vs. 5.12 ng/mu l; p <0.046). Conclusions: In infants younger than 6 months, overnutrition condition was related to increased severity of infections and high plasma leptin level. Also, children with overnutrition showed a greater frequency of viral coinfection and low RSV viral load compared to normal weights children. These findings further contribute to the already existent evidence supporting the importance of overnutrition prevention in pediatric populations.Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1115059

Myofibers deficient in connexins 43 and 45 expression protect mice from skeletal muscle and systemic dysfunction promoted by a dysferlin mutation

Dysferlinopathy is a genetic human disease caused by mutations in the gene that encodes the dysferlin protein (DYSF). Dysferlin is believed to play a relevant role in cell membrane repair. However, in dysferlin-deficient (blAJ) mice (a model of dysferlinopathies) the recovery of the membrane resealing function by means of the expression of a mini-dysferlin does not arrest progressive muscular damage, suggesting the participation of other unknown pathogenic mechanisms. Here, we show that proteins called connexins 39, 43 and 45 (Cx39, Cx43 and Cx45, respectively) are expressed by blAJ myofibers and form functional hemichannels (Cx HCs) in the sarcolemma. At rest, Cx HCs increased the sarcolemma permeability to small molecules and the intracellular Ca2+ signal. In addition, skeletal muscles of blAJ mice showed lipid accumulation and lack of dysferlin immunoreactivity. As sign of extensive damage and atrophy, muscles of blAJ mice presented elevated numbers of myofibers with internal nuclei, increased number of myofibers with reduced cross-sectional area and elevated creatine kinase activity in serum. In agreement with the extense muscle damage, mice also showed significantly low motor performance. We generated blAJ mice with myofibers deficient in Cx43 and Cx45 expression and found that all above muscle and systemic alterations were absent, indicating that these two Cxs play a critical role in a novel pathogenic mechanism of dysfernolophaties, which is discussed herein. Therefore, Cx HCs could constitute an attractive target for pharmacologic treatment of dyferlinopathies.Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) CONICYT FONDECYT 11160739 1150291 1192329 Rings grant ACT 1121 Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) CONICYT PIA/BASAL CeBiB FB0001 ICM-ECONOMIA, Chile P09-022-