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Objectives To investigate whether outcomes of patients who were admitted to hospital differ between those treated by younger and older physicians.Design Observational study.Setting US acute care hospitals.Participants 20% random sample of Medicare fee-for-service beneficiaries aged ≥65 admitted to hospital with a medical condition in 2011-14 and treated by hospitalist physicians to whom they were assigned based on scheduled work shifts. To assess the generalizability of findings, analyses also included patients treated by general internists including both hospitalists and non-hospitalists.Main outcome measures 30 day mortality and readmissions and costs of care. Results 736 537 admissions managed by 18 854 hospitalist physicians (median age 41) were included. Patients' characteristics were similar across physician ages. After adjustment for characteristics of patients and physicians and hospital fixed effects (effectively comparing physicians within the same hospital), patients' adjusted 30 day mortality rates were 10.8% for physicians aged <40 (95% confidence interval 10.7% to 10.9%), 11.1% for physicians aged 40-49 (11.0% to 11.3%), 11.3% for physicians aged 50-59 (11.1% to 11.5%), and 12.1% for physicians aged ≥60 (11.6% to 12.5%). Among physicians with a high volume of patients, however, there was no association between physician age and patient mortality. Readmissions did not vary with physician age, while costs of care were slightly higher among older physicians. Similar patterns were observed among general internists and in several sensitivity analyses.Conclusions Within the same hospital, patients treated by older physicians had higher mortality than patients cared for by younger physicians, except those physicians treating high volumes of patients.

Concepts: Medicine, Death, Patient, Hospital, Physician, Doctor-patient relationship, Internal medicine, Residency

141

Elevated level of serum triglyceride (TG) is a characteristic of type 2 diabetes. We evaluated the clinical significance of intervention for the serum TG levels in the fasting and postprandial states in patients with type 2 diabetes.

Concepts: Diabetes mellitus type 2, Statin, Triglyceride, Fibrate

141

Cuticle collagens form a major part of the nematode cuticle and are responsible for maintaining the overall shape of the animal and its protection from the external environment. Although substantial research on cuticle collagen genes has been carried out in Caenorhabditis elegans, their isolation and characterization in plant parasitic nematodes have been limited to a few genes only. In this study, a cuticle collagen gene, Mi-col-5, was isolated from root-knot nematode, Meloidogyne incognita. A partial segment of 402 bp was first cloned and analyzed on Gbrowse followed by subsequent cloning of the 1047 bp long full cDNA specifying the open reading frame. The deduced amino acid sequence showed 92% sequence identity with that of Mj-col-5. However, a transmembrane helix was predicted in Mi-col-5 which was not present in Mj-col-5. The conserved pattern of cysteine residues in Mi-col-5 suggested that it belonged to group 2 of nematode cuticle collagens but with a longer carboxy terminal region as was the case with Mj-col-5. Domain prediction revealed the presence of a nematode cuticle collagen N terminal domain and a pfam collagen domain along with collagen triple helix repeats. A phylogenetic tree based on the amino acid sequences showed evolutionary relationship of Mi-col-5 with cuticle collagens genes of other nematodes. 3D models for Mi-col-5 were predicted with the best confidence score of -2.78. Expression of Mi-col-5 transcript was found to be maximum in egg masses followed by adult females and J2s suggesting its role in the early stages of the development of the nematode during its life cycle.

Concepts: DNA, Protein, Amino acid, Collagen, Caenorhabditis elegans, Nematode, Nematodes, Root-knot nematode

23

Objective: To investigate the association between APOB gene R532W polymorphism and the risk of coronary heart disease (CHD) in patients without lipid-lowering treatment and to analyze the interactions between the variation of R532W and different risk factors of CHD. Methods: CHD and non-CHD were diagnosed according to coronary artery angiography (CAG) and/or coronary computed tomography angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD patients and 772 age- and sex-matched non-CHD controls, who never accepted any lipid-lowering treatments, were collected. R532W was genotyped by HumanExome BeadChip at BGI and strict quality control was made. Firstly, the association between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG, AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was explored. Then, the interactions between the variation of this loci and risk factors related to CHD were investigated. Results: (1) Total cholesterol (TC) levels were significantly lower in AA genotype than in GA genotype in the total cohort and non-CHD controls, but was similar among the 3 genotypes in CHD patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532 polymorphism was related to the incidence of CHD in the dominant model, and A-allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI 0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W polymorphism had positive interactions with hypertension (1.452) and smoke (1.077), while negative interaction with diabetes (0.553) in the occurrence of CHD. Conclusions: APOB gene R532W polymorphism is related to TC levels in Chinese north Han population. A-allele carries of R532W loci is linked with reduced risk of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a positive additive interaction with hypertension and smoke, while a negative additive interaction with diabetes mellitus in the occurrence of CHD.

Concepts: Genetics, Genotype, Allele, Atherosclerosis, Diabetes mellitus, Heart, Atheroma, Artery

23

Obesity is repeatedly emphasized as a risk factor for atrial fibrillation or flutter (AF). However, the underlying evidence may be questioned, as the obvious correlations between various anthropometric measures hamper identification of the characteristics that are biologically driving AF risk, and recent studies suggest that fat carries limited or no independent risk of AF.

Concepts: Heart, Atrial fibrillation, Anthropometry, Atrial flutter, Body shape

23

Astrocytes are the most populous glial subtype and are critical for brain function. Despite this, historically there have been few studies into the role that they may have in neurodegenerative diseases, such as Parkinson’s disease (PD). Recently, however, several studies have determined that genes known to have a causative role in the development of PD are expressed in astrocytes and have important roles in astrocyte function. Here, we review these recent developments and discuss their impact on our understanding of the pathophysiology of PD, and the implications that this might have for its treatment.

Concepts: Medicine, Sociology, Neurology, Neurodegenerative disorders, Parkinson's disease, Gap junction, Social sciences, Blood-brain barrier

23

Duchenne muscular dystrophy is caused by mutations in DMD which disrupt the reading frame. Therapeutic strategies that restore DMD’s reading frame, such as exon skipping and CRISPR/Cas9, need to be tested in the context of the human DMD sequence in vivo. We have developed a novel dystrophic mouse model by using CRISPR/Cas9 to delete exon 45 in the human DMD gene in hDMD mice, which places DMD out-of-frame. We have utilized this model to demonstrate that our clinically-relevant CRISPR/Cas9 platform, which targets deletion of human DMD exons 45-55, can be directly applied in vivo to restore dystrophin.

Concepts: DNA, Gene, Genetics, Spliceosome, Muscular dystrophy, Duchenne muscular dystrophy, Dystrophin, Morpholino

23

HER2 testing of invasive breast cancer by in-situ hybridisation guides therapy decisions. Probing HER2 and cen17 simultaneously is supposed to reveal both a potential HER2 gene amplification and polysomy 17. However, a considerable number of breast cancer patients with quasi polysomy 17 are considered “equivocal” which is diagnostically meaningless. Moreover, patients with equivocal / false polysomic tumours are prevented from a potentially beneficial anti-HER2 treatment. Here we evaluated the RAI1, D17S122, and TP53 hybridisation markers to reliably indicate true polysomy and to accurately reclassify equivocal samples as HER2-positive.

Concepts: Cancer, Breast cancer, Metastasis, Oncology

23

The purpose of this study was to determine differences in lifestyle and dietary habits between pregnant women with small for gestational age (SGA) fetuses and those appropriate for gestational age (AGA).

Concepts: Pregnancy, Embryo, Prenatal development, Fetus, Uterus, Obstetrics, Abortion, Gestational age

23

We present a laparoscopic and single intercostal space thoracoscopic approach (SICS group) for Ivor Lewis minimally invasive esophagectomy (MIE) and provide postoperative analgesia with a continuous multiple intercostal nerve blocking technique. The characters of this technique are evaluated.

Concepts: Minimally invasive