Enteric anendocrinosis attributable to a novel Neurogenin-3 variant

Congenital diarrhea and enteropathies (CODEs) are a group of monogenic disorders that often present with severe diarrhea in the first weeks of life. Enteric anendocrinosis (EA), an extremely rare cause of CODE, is characterized by a marked reduction of intestinal enteroendocrine cells (EC). EA is associated with recessively inherited variants in Neurogenin-3 (NEUROG3) gene. Here we investigate a case of a male infant who presented with mysterious severe malabsorptive diarrhea since birth. Thorough clinical assessments and laboratory tests were successful to exclude the majority of differential diagnosis categories. However, the patient's diagnosis was not established until the genetic test using whole-exome sequencing (WES) was performed. We identified a novel homozygous missense disease-causing variant (DCV) in NEUROG3 (c.413C>G, p.Thr138Arg). Moreover, molecular dynamic simulation analysis showed that (p.Thr138Arg) led to a global change of the NEUROG3 orientation affecting its DNA binding capacity. To the best of our knowledge, this is the first time to apply WES to reach a differential diagnosis of patients with CODEs. Our study not only expands our knowledge about NEUROG3 variants and their clinical consequences but also proves that WES is a very effective tool for the diagnosis of CODEs. This might be of value in early diagnosis of diseases and prenatal CODEs detection.     

Gender,intoxication and the developing brain: Problematisations of drinking among young adults in Australian alcohol policy

In this article, we draw on recent scholarly work in the poststructuralist analysis of policy to consider how policy itself functions as a key site in the constitution of alcohol ‘problems’, and the political implications of these problematisations. We do this by examining Australian alcohol policy as it relates to young adults (18–24 years old). Our critical analysis focuses on three national alcohol policies (1990, 2001 and 2006) and two Victorian state alcohol policies (2008 and 2013), which together span a 25-year period. We argue that Australian alcohol policies have conspicuously ignored young adult men, despite their ongoing over-representation in the statistical ‘evidence base’ on alcohol-related harm, while increasingly problematising alcohol consumption amongst other population subgroups. We also identify the development of a new problem representation in Australian alcohol policy, that of ‘intoxication’ as the leading cause of alcohol-related harm and rising hospital admissions, and argue that changes in the classification and diagnosis of intoxication may have contributed to its prioritisation and problematisation in alcohol policy at the expense of other forms of harm. Finally, we draw attention to how preliminary and inconclusive research on the purported association between binge drinking and brain development in those under 25 years old has been mobilised prematurely to support calls to increase the legal purchasing age from 18 to 21 years. Our critical analysis of the treatment of these three issues – gender, intoxication, and brain development – is intended to highlight the ways in which policy functions as a key site in the constitution of alcohol ‘problems’.     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.     

中日友好医院分型股骨头坏死腓骨植入治疗的三维有限元分析

文题释义：股骨头坏死中日友好医院分型的有限元分析：根据李子荣等提出的中日友好医院分型，建立股骨头坏死三维模型，分为 M型(内侧型)、C型(中央型)和 L型(外侧型)，其中 L型包括L1型(次外侧型)、L2型(极外侧型)和 L3型(全头型)。通过对建立的模型进行有限元分析，为该分型的保髋治疗提供了一定力学依据，显示外侧柱的存留是精准预防塌陷的重要因素，为进一步实现个体化治疗提供力学基础。 腓骨支撑坏死股骨头保髋手术：是对于早中期股骨头坏死需要保留股骨头患者进行的一种手术方式。首先需对股骨头进行髓芯减压，清除一定坏死骨，空腔填塞松质骨(髂骨为主)，打压结实后植入腓骨(异体或自体)支撑，给坏死区的提供力学支撑及生物学修复，预防股骨头进一步坏死及塌陷。 背景：研究报道股骨头坏死的保髋疗效与外侧柱存留密切相关，中日友好医院分型是根据三柱结构确立的，对股骨头塌陷的预测准确性高。 目的：建立股骨头坏死中日友好医院分型各分型仿真的三维有限元模型，通过有限元分析各分型腓骨植入的力学变化，探讨外侧柱存留对保髋疗效的意义，为该分型的塌陷精准预测提供基础。 方法：建立正常股骨头、中日友好医院分型(M型、C型、L1型、L2型、L3型)股骨头坏死及其腓骨植入3组11种三维有限元模型，运用ANSYS软件进行有限元分析计算，观察各组模型的最大应力值、最大位移值及股骨头内部载荷传递模式。 结果与结论：①坏死组位移最大，应变最大，且因坏死分型不同而位移不同，位移变化如下：M型相似文献   

Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation

BackgroundIn the field of transplantation, inducing immune tolerance in recipients is of great importance. Blocking co-stimulatory molecule using anti-CD28 antibody could induce tolerance in a rat kidney transplantation model. Myeloid-derived suppressor cells (MDSCs) reveals strong immune suppressive abilities in kidney transplantation. Here we analyzed key genes of MDSCs leading to transplant tolerance in this model.MethodsMicroarray data of rat gene expression profiles under accession number {"type":"entrez-geo","attrs":{"text":"GSE28545","term_id":"28545"}}GSE28545 in the Gene Expression Omnibus (GEO) database were analyzed. Running the LIMMA package in R language, the differentially expressed genes (DEGs) were found. Enrichment analysis of the DEGs was conducted in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database to explore gene ontology (GO) annotation and their Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their protein-protein interactions (PPIs) were provided by STRING database and was visualized in Cytoscape. Hub genes were carried out by CytoHubba.ResultsThree hundred and thirty-eight DEGs were exported, including 27 upregulated and 311 downregulated genes. The functions and KEGG pathways of the DEGs were assessed and the PPI network was constructed based on the string interactions of the DEGs. The network was visualized in Cytoscape; the entire PPI network consisted of 192 nodes and 469 edges. Zap70, Cdc42, Stat1, Stat4, Ccl5 and Cxcr3 were among the hub genes.ConclusionsThese key genes, corresponding proteins and their functions may provide valuable background for both basic and clinical research and could be the direction of future studies in immune tolerance, especially those examining immunocyte-induced tolerance.     

北京市养老机构老年人营养状况调查及其影响因素研究

背景　在人口老龄化日益加剧的社会背景之下，家庭养老功能不断减弱，机构养老成为今后发展的必然趋势。据报道，很多养老机构的老年人营养不合理，严重影响老年人的健康状况与生活质量。目的　通过调查北京市养老机构老年人营养现状及其影响因素，为全科医师营养教育及老年人生活质量提升提供理论依据。方法　2014年10月-2015年12月，采用方便整群抽样的方法，抽取了北京市7家养老机构，对符合纳入标准的老年人进行面对面问卷调查，问卷内容包括：一般情况、微型营养评定量表（MNA）、日常生活活动能力指数（BI）、老年人抑郁量表（GDS）。采用二元Logistic回归分析养老机构老年人营养状况的影响因素。结果　本研究共发放问卷258份，回收有效问卷258份，有效回收率为100%。被调查的258例老年人中，存在营养不良及存在营养不良发生风险的老年人共计75例（29.1%）。不同年龄、性别、婚姻状况、体质指数（BMI）、医疗费用支付方式、生活自理能力及精神状态的老年人营养状况比较，差异有统计学意义（P<0.05）。二元Logistic回归分析结果显示：年龄〔OR（95%CI）=2.349（1.070，5.156）〕、BMI〔OR（95%CI）=0.092（0.036，0.239）〕、医疗费用支付方式〔OR（95%CI）=0.208（0.083，0.522）〕、日常活动能力〔OR（95%CI）=10.214（3.099，33.669）〕、患病种数〔OR（95%CI）=2.682（1.248，5.763）〕及精神状态〔OR（95%CI）=4.822（2.005，11.600）〕是老年人营养状况的影响因素（P<0.05）。结论　北京地区养老机构的老年人面临着营养不良及营养不良发生风险的健康威胁，高龄、低BMI、抑郁、合并多种疾病、日常活动能力低下及无医保是其独立危险因素，需要对老年人加强个性化营养教育和营养治疗。     

Lower body mass index and higher height are correlated with increased varicocele risk

To evaluate the anthropometric indexes in subjects with varicocele compared to controls and the incidence of varicocele in different body mass index (BMI) groups for the purpose of exploring the association between varicocele and anthropometric indexes. A comprehensive literature search was conducted by using PubMed, MEDLINE, EMBASE databases and Cochrane Library up to February 2019. A systematic review and meta‐analysis was conducted by STATA, and Newcastle–Ottawa Scale was utilised for assessing risk of bias. Ultimately, 13 articles containing seven case–control studies and six cross‐sectional studies with 1,385,630 subjects were involved in our study. Pooled results demonstrated that varicocele patients had a lower BMI (WMD = ?0.77, 95% CI = ?1.03 to ?0.51) and a higher height than nonvaricocele participants, especially in grade 3 varicocele patients. Subgroup analyses showed that normal BMI individuals had a higher risk of varicocele than obese or overweight individuals and a lower risk than underweight individuals. In conclusion, this study indicates that varicocele patients have a lower BMI and a higher height than nonvaricocele participants. Moreover, men with excess bodyweight have a lower incidence of varicocele compared to normal weight or underweight people. That is to say, high BMI and adiposity protect against varicocele and high BMI is associated with a decreased risk of varicocele.