A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data

Colonização por micro-organismo resistente e infecção relacionada ao cuidar em saúde Colonización por microorganismo resistente e infección relacionada al cuidar en salud Colonization by resistant micro-organism and infection related to health care

OBJETIVO: Identificar os fatores de risco para o desenvolvimento de colonização por microrganismo resistente (MR) e para infecção relacionada ao cuidar em saúde (IRCS) em pacientes da sala de emergência (SE) de uma unidade de Pronto Atendimento (PA) em um hospital universitário. MÉTODOS: estudo de abordagem quantitativa, epidemiológico realizado entre agosto de 2009 e março de 2010, entre pacientes adultos da SE de uma unidade de Pronto Atendimento de um Hospital Universitário da cidade de Belo Horizonte, Minas Gerais. Foram acompanhados 254 pacientes. RESULTADOS: Do total de 254 pacientes, 6,3% foram colonizados por MR e 11,4% desenvolveram IRCS. Identificou-se o tempo de permanência na SE > 9 dias (OR=28,7) e a presença de infecção comunitária (OR=5) para a colonização por MR e, para as IRCS apenas o tempo de permanência na SE > 5 dias (OR:19,8), como fatores de risco, sendo este comum tanto à colonização do paciente por MR como para IRCS. CONCLUSÃO: Confirmou-se a inadequação da SE, cuja prioridade deve ser a primeira atenção qualificada, resolutiva e/ou o encaminhamento do paciente a uma unidade especializada.<br>OBJETIVO: Identificar los factores de riesgo para el desarrollo de colonización por microorganismo resistente (MR) y para la infección relacionada al cuidar en salud (IRCS) en pacientes de la sala de emergencia (SE) de una unidad de Pronta Atención (PA) en un hospital universitario. MÉTODOS: estudio de abordaje cuantitativo, epidemiológico realizado entre agosto del 2009 y marzo del 2010, entre pacientes adultos de la SE de una unidad de Pronta Atención de un Hospital Universitario de la ciudad de Belo Horizonte, Minas Gerais. Fueron acompañados 254 pacientes. RESULTADOS: Del total de 254 pacientes, el 6,3% fueron colonizados por MR y el 11,4% desarrollaron IRCS. Se identificó el tiempo de permanencia en la SE > 9 días (OR=28,7) y la presencia de infección comunitaria (OR=5) para la colonización por MR y, para las IRCS apenas el tiempo de permanencia en la SE > 5 días (OR:19,8), como factores de riesgo, siendo éste común tanto a la colonización del paciente por MR como para IRCS. CONCLUSIÓN: Se confirmó la inadecuación de la SE, cuya prioridad debe ser la primera atención calificada, resolutiva y/o el encaminamiento del paciente a una unidad especializada.<br>OBJECTIVE: To identify risk factors for the development of colonization by resistant microorganisms (MR) and for infections related to health care (IRCS) in patients from the emergency room (SE) of a unit of Urgent Care (PA) in a hospital university. METHODS: An epidemiological study of quantitative approach, conducted between August 2009 and March 2010, among adult patients of a SE in a PA unit of a university hospital in the city of Belo Horizonte, Minas Gerais. 254 patients were followed. RESULTS: Of 254 total patients, 6.3% were colonized with MR and 11.4% developed IRCS. We identified the time spent in the SE > 9 days (OR = 28.7) and the presence of community infection (OR = 5) for colonization by MR and, for IRCS only the time spent in the SE > 5 days (OR: 19.8), as risk factors, which is common to both the colonization of the patient for MR and to IRCS. CONCLUSION: This study confirmed the inadequacy of the SE, whose priority should be the qualified primary attention, resolving and / or referring patients to a specialty unit

Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study

Aim: Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery. Method: This was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were divided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30 days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis. Results: A total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7%; routine NGT 5.2%; reactive NGT 10.6%; prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56–1.87, P = 0.932). Conclusion: In patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30 days of surgery compared with reactive insertion