Brief Report: Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion

Cornelia de Lange syndrome (CdLS) is a developmental multisystem disorder frequently associated with mutations in NIPBL. CdLS is thought to arise from developmental gene regulation defects, but how NIPBL mutations cause these is unknown. Here we show that several NIPBL mutations impair the DNA loop extrusion activity of cohesin. Because this activity is required for the formation of chromatin loops and topologically associating domains, which have important roles in gene regulation, our results suggest that defects in cohesin-mediated loop extrusion contribute to the etiology of CdLS by altering interactions between developmental genes and their enhancers.     

对接大健康产业发展的康复治疗学人才培养体系的构建

在大健康产业发展背景下,康复服务产业发展模式和服务理念逐步转变。康复人力资源是康复服务产业发展的基石,文章基于《国际功能、残疾和健康分类》(international classification of functioning,disability and health,ICF)康复科学理论体系,切合康复服务产业化和专业化需求,重构康复治疗学专业人才培养的课程体系,强化实践教学,探讨构建康复治疗学专业人才培养新模式。     

Assessment of functioning in Dutch primary care: Development study of a consultation tool for patients with chronic conditions and multimorbidity

BackgroundIn primary care, a shift from a disease‐oriented approach for patients with multimorbidity towards a more person‐centred approach is needed.AimTo transform a self‐report questionnaire for patients with chronic conditions in primary care, the Primary Care Functioning Scale (PCFS), into an understandable, visually attractive and feasible consultation tool for patients and health care providers. The consultation tool consists of a web‐based version of the PCFS, which is filled in by the patient and is processed to a feedback report that summarizes and visualizes the main findings. The feedback report can be discussed with the patient to facilitate a more person‐centred conversation for patients with chronic conditions and multimorbidity in general practice.Design and SettingIn this qualitative study, we developed the consultation tool by using design thinking in a participatory developmental process.MethodsIn the first phase, we constructed five different feedback report templates to summarize and display the results of a completed PCFS questionnaire in a series of two expert meetings with patients and general practitioners (GPs). In the second phase, we performed an exploratory qualitative interview study involving dyads of patients with chronic conditions and their practice nurses. In an iterative process, we explored their experiences with the consultation tool.ResultsPatients, as well as GPs, preferred a clear manner of presenting the results of the questionnaire in a feedback report. In 18 interviews with patients and practice nurses during three different interview rounds, we adjusted the feedback report and consultation tool based on the input from patients and practice nurses. After the final interview round, patients and practice nurses consented that the consultation tool was useful for having a more in‐depth consultation about functioning and patients'' preferences when integrated into the regularly scheduled consultations.ConclusionWe were able to develop an understandable and feasible consultation tool that is applicable in already existing chronic disease management programmes in general practice in the Netherlands.Patient or Public ContributionTo increase the understandability and feasibility of the consultation tool, we collaborated with end‐users and actively involved patients, GPs and practice nurses in a participatory development process.     

Clinical Situations in Which the Diagnosis of Autism is Debatable: An Analysis and Recommendations

The “autism spectrum disorder” (ASD) construct and its current diagnostic criteria have led to the inclusion of increasingly heterogeneous and decreasingly atypical individuals under its definition. This broad category, based on the polymorphic clinical expression of common genetic variants underpinning the risk of autism, is likely beneficial for certain individuals. However, determining the boundaries between ASD and typical individuals, as well as those with other neurodevelopmental conditions, remains an issue of which the importance is growing with the increase in ASD prevalence. We identified four clinical contexts associated with a questionable, poorly justified, or unhelpful ASD diagnosis: (1) those in which diagnostic instruments raise uncertainties, (2) in the context of a subclinical presentation, (3) when early autistic signs tend to fade away during development, and (4) when comorbidities are prominent. We argue that in certain cases, a diagnosis of ASD may not be the most suitable, timely, or helpful medical act and provide recommendations for clinical practice when facing such situations.     

脑卒中病人发生残疾的影响因素分析

  目的  分析辽宁农村地区脑卒中患者残障现状及其相关危险因素,为脑卒中后减少残障发生提供理论依据。  方法  2017年9月至2018年5月按照分层整群随机抽样方法在辽宁省农村地区随机选取四个县19个村庄,对年龄 ≥ 40岁的731例脑卒中患者进行残障现状及其相关危险因素调查,mRS评分3分及以上定义为残障。  结果  辽宁省农村40岁及以上脑卒中患者残障率为13.41 %,缺血性卒中和出血性卒中分别为11.96 % 和21.86 %。男性缺血性卒中残障率随着年龄增加而升高,男性缺血性卒中mRS平均分高于女性。老龄化和性别是卒中后残障的主要危险因素。多因素logistic回归分析显示,男性（OR = 1.90,95 % CI = 1.18～3.05）、家庭年均总收入高（OR = 0.39,95 % CI = 0.18～0.83）、超重或肥胖（OR = 0.47,95 % CI = 0.30～0.73）、吸烟（OR = 0.44,95 % CI = 0.24～0.80）是患脑卒中残障的影响因素。  结论  辽宁省农村地区40岁以上人群脑卒中后残障率高,亟待早期发现并控制相关不良影响因素,采取有效且针对性强的措施,以减少卒中后残障发生概率,综合提高卒中患者的生活质量。     

Mothers' questionnaire of preschoolers' language and motor skills: a validation study

Objective Parent questionnaires of child motor and language skills are useful in many contexts. This study validates one such measure, the Preschool Child Development Inventory (PCDI), a mother‐answered standardized measure of motor (fine and gross) and language (expression and comprehension) skills of 3–6‐year‐old children. Methods Eighty‐one mothers answered the inventory and their children were concurrently tested on six verbal subtests of WPPSI‐R^IS. Results The six language and motor subtests of the PCDI revealed the predicted convergent and divergent correlations with the verbal subtests of the WPPSI‐R^IS. As predicted, the motor subtests diverged and the language subtests converged with the expected WPPSI‐R^IS subtests. Principal components analysis of all the measures (the PCDI and the WPPSI‐R^IS subtests) revealed two components, verbal and motor in content. Conclusions The findings support the validity of a mother‐answered inventory to assess language and motor development. It is pointed out that such inventories are a viable brief and cost effective alternative to individual testing, both to supplement such measures in clinical practice and as main information in research, for example on determinants of development. Some suggestions are made for future research and applications.     

Self-Identity in an Adolescent a Decade after Spinal Cord Injury

ABSTRACT

The purpose of this mixed methods case study was to describe the current self-identity of an adolescent a decade after spinal cord injury and how he recalls his rehabilitative journey through recovery. The instruments included three in-depth interviews, administration of the Lin Interest Check List, the Stress Profile, and the Tennessee Self Concept Scale: 2. An association between participation in meaningful occupations and regaining self-identity was articulated. Results revealed above average self-concept and adequate coping skills with high use of positive appraisal. Higher scores in family and social self-concept validate his strong reliance on spirituality and his local church as a support system. In contrast, this client also scored above average on negative appraisal and on self-criticism. Implications for improved practice for occupational therapists and other rehabilitation science professionals are discussed.