Splicing accuracy varies across human introns, tissues and age.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigated mis-splicing using RNA-sequencing data from ~14K control samples and 42 human body sites, focusing on split reads partially mapping to known transcripts in annotation. We show that mis-splicing occurs at different rates across introns and tissues and that these splicing inaccuracies are primarily affected by the abundance of core components of the spliceosome assembly and its regulators. Using publicly available data on short-hairpin RNA-knockdowns of numerous spliceosomal components and related regulators, we found support for the importance of RNA-binding proteins in mis-splicing. We also demonstrated that age is positively correlated with mis-splicing, and it affects genes implicated in neurodegenerative diseases. This in-depth characterisation of mis-splicing can have important implications for our understanding of the role of splicing inaccuracies in human disease and the interpretation of long-read RNA-sequencing data.

Fifteen years of follow-up of a liver transplant recipient with glycogen storage disease type Ia (Von Gierke disease).

Von Gierke's disease or glycogen storage disease type Ia (GSD-Ia) is an infrequent metabolic disease caused by an atypical accumulation of glycogen. The principal cause of this pathology is deficiency of the glucose-6-phosphatase enzyme. Herein we have reported a case of a young man with a history of Von Gierke's disease (GSD-Ia) since childhood who developed hepatocellular adenomatosis brought to light by ultrasounds and TACs. The patient began to develop early chronic renal failure, necessitating simultaneous liver and kidney transplantation. Years later continuous reviews at the nephrology and hepatobiliopancreatic surgery services show he has a good quality of life and a normal hepatorenal profile.

[Do paediatricians perform lumbar puncture correctly? Review of recommendations and analysis the technique in Spain]. / ¿Se realiza correctamente la punción lumbar en pediatría? Revisión de las recomendaciones actuales y análisis de la realidad.

INTRODUCTION: Lumbar puncture (LP) is a commonly performed procedure in paediatrics. Performing this technique properly can avoid the most common associated complications. OBJECTIVE: To assess whether paediatricians and paediatric residents in Spain follow current recommendations for the LP technique. MATERIAL AND METHODS: A cross-sectional study was conducted by sending a questionnaire by mail through the Spanish Society of Paediatric Emergencies, collecting demographic information and responses to multiple choice questions about LP technique. RESULTS: A total of 206 questionnaires were analysed, of which 143 (69.5%) were answered by paediatricians, and 63 (30.5%) by paediatric residents. The majority (128; 62.1%) of physicians did not allow parents to be present during LP, 198 (96.1%) routinely use analgesia and sedation; 84 (42%) only used local anaesthesia. The majority of respondents used standard Quincke needles (126; 62.7%). The bevel was correctly positioned when puncturing the dura mater by 22 residents (36.1%) and 21 paediatricians (15.1%), a variation that was statistically significant (P=.001). For neonatal lumbar punctures, 63 paediatricians (46%) and 19 paediatric residents used a butterfly needle which did not contain a stylet, and this difference was also statistically significant (P=.035). Of those surveyed, 190 (92.2%) re-inserted the stylet when re-orientating the needle, and 186 (93%) re-oriented this when removing it. The recommendation of bed rest was made by 195 (94.7%) physicians. CONCLUSIONS: The majority of paediatricians orient the bevel wrongly when inserting the needle during LP, and still use "butterfly" needles in newborns, despite warnings to the contrary. Paediatric residents and less experienced paediatricians follow the recommendations more frequently.

[Staphylococcus aureus infections in the intensive care unit: clinical and epidemiological characteristics]. / Infecciones por Staphylococcus aureus en cuidados intensivos: características clínicas y epidemiológicas.

INTRODUCTION: There has been an increase in invasive Staphylococcus Aureus infections over the last few years, which have required admission to the pediatric intensive care unit (PICU). PATIENTS AND METHODS: All patients with S. aureus infection who were admitted to PICU were enrolled in a retrospective study (January 2006-June 2010). The patients were classified into 2 groups: community-acquired infection (Group 1) and nosocomial infection (Group 2). We recorded epidemiological data, type of S. aureus (methicillin-susceptible S. aureus [MSSA], methicillin-resistant S. aureus [MRSA]), risk factors, site of infection, presence of hemodynamic instability, respiratory support, and mortality. RESULTS: A total of 51 patients were enrolled, 21 belonging to Group 1 and 30 to Group 2. The median age was lower in Group 1 (1.6 years vs 3.2 years; P=.009). MSSA was isolated in 88% of cases. MRSA was detected in 6/51 (12%) of cases, which were isolated in the later study period (January 2009-June 2010). The risk factors for infection were: immunosuppression, venous catheter, institutionalization, mechanical ventilation, previous surgery, previous trauma and chronic osteomyelitis. A large majority (83%) of the patients with MRSA infection had risk factors. The type of infection was varied, with respiratory tract infection being the most common (75%). Hemodynamic instability was observed in 43% of patients. Most patients (86%) required respiratory support. One patient in Group 1 died of necrotizing pneumonia caused by MSSA. CONCLUSIONS: Infections by S. aureus in children are severe and have a high morbidity. Respiratory infection was the most common in our series. Isolation of MSSA is common in these infections, although, an increase in the number of infections by MRSA was observed during the latter part of the study.