Development of a self-assessment tool to address the functioning of community-dwelling older adults in general practice: a validation study of the EFA23 questionnaire.

BACKGROUND: Multimorbidity is increasingly prevalent among ageing patients, leading to reduced daily functioning. To address the challenges posed by multimorbidity in older adults, a person- and context-centred approach is needed. This study aimed to develop a questionnaire as a self-assessment tool for older adults focusing on functioning in general practice based on the International Classification of Functioning, Disability and Health (ICF). METHODS: A mixed-methods approach was employed in the development and validation of the German EFA23 (Erfassung Funktionaler Gesundheit im Alter - 23 Fragen; Assessing Functional Health in Old Age - 23 questions) questionnaire. Based on an ICF subset developed in a preparatory phase and consensus study, questionnaire items were formulated and tested in a qualitative pretest, followed by a validation study. A workshop with general practitioners (GPs) was held to develop a supplementary manual for GPs on how to interpret the questionnaire results and discuss them with the patients. RESULTS: A total of 69 items were developed and tested in the qualitative pretest with 15 respondents, resulting in 37 items for the validation study. The validation study, involving 237 older adults, showed the presence of one significant principal component. It demonstrated good internal consistency (Cronbach's alpha = 0.967) and construct validity, showing positive correlations with established assessment tools. Descriptive statistics showed differences between the means of self-assessment by patients and an external GP assessment. The final EFA23 questionnaire consists of 23 items assessing limitations in functioning. CONCLUSIONS: The EFA23 questionnaire can be used as a valid self-assessment instrument to measure functioning in older adults, supporting a person- and context-centred approach in general practice.

Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by reduced survival motor neuron (SMN) protein. Recently, SMN dysfunction has been linked to individual aspects of motor circuit pathology in a severe SMA mouse model. To determine whether these disease mechanisms are conserved, we directly compared the motor circuit pathology of three SMA mouse models. The severe SMNΔ7 model exhibits vast motor circuit defects, including degeneration of motor neurons, spinal excitatory synapses, and neuromuscular junctions (NMJs). In contrast, the Taiwanese model shows very mild motor neuron pathology, but early central synaptic loss. In the intermediate Smn 2B/- model, strong pathology of central excitatory synapses and NMJs precedes the late onset of p53-dependent motor neuron death. These pathological events correlate with SMN-dependent splicing dysregulation of specific mRNAs. Our study provides a knowledge base for properly tailoring future studies and identifies central excitatory synaptopathy as a key feature of motor circuit pathology in SMA.

Protein-loss of SWI/SNF-complex core subunits influences prognosis dependent on histological subtypes of intra- and extrahepatic cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive malignancy with a 5-year-survival rate of <10%, mainly due to diagnosis in advanced stages and limited therapeutic options in case of progressive disease. Recently, evidence has indicated that alterations in the SWI/SNF-complex (SWI/SNF) may have an important role in the tumorigenesis of CCA. SWI/SNF-related chromatin remodeling has been reported to be crucial for differentiation and tumor suppression, and loss-of-function mutations of SWI/SNF are present in 20% of human malignancies; however, at present, little is known about its relevance in CCA. In the present study, a cohort of 52 patients with the diagnosis of primary CCA was retrospectively collected. All patients underwent surgery with curative intent. Tissue microarray analysis was performed on each tumor for immunohistochemical loss-of-protein analysis of the SWI/SNF core subunits ARID1A, INI-1, BRG1, PBRM-1 and BRM, corresponding to the following CCA subtypes: Extrahepatic CCA (ECCA), small duct or large duct intrahepatic CCA (ICCA). Kaplan-Meier analysis was used to determine survival distribution and survival differences were evaluated by log-rank test. In total, 14 of 52 patients (~35%) exhibited protein-loss of any tested SWI/SNF core subunit. Notably, 17% of patients exhibited a loss of ARID1a; this was the protein loss with the highest frequency. Patients with small and large duct ICCA with protein-loss of any tested SWI/SNF subunit exhibited significantly worse survival compared with the wild-type cohort with proficient protein expression (P=0.013 and P=0.002), whereas no significant survival difference was detected for patients with ECCA. SWI/SNF and its core subunits may be considered promising predictive and therapeutic targets, and require further investigation in patients with CCA.

A visual analogue scale for food intake as a screening test for malnutrition in the primary care setting: Prospective non-interventional study.

INTRODUCTION AND AIMS: The Self-Evaluation of Food Intake (SEFI®) is a simple tool to assess food intake that correlates well with the diagnosis of malnutrition in the hospital setting. AIMS: to evaluate the validity of SEFI® for the diagnosis of malnutrition among adults in the primary care setting (primary aim); to assess the prevalence of malnutrition, the feasibility of the SEFI® and the variables associated with malnutrition (secondary aims). METHODS: A non-interventional prospective study on consecutive patients at three primary care practices. Primary endpoint: confrontation of a SEFI® visual analogue scale score <7/10 with the diagnosis of malnutrition as defined by the Global Leadership Initiative on Malnutrition criteria. Secondary endpoints: the proportion of patients for whom a SEFI® score was collected. Multivariate analysis: threshold α = 0.20 in univariate analyses, step-by-step logistic regression. RESULTS: Among 747 eligible patients, 505 were included: mean age (±SD) 56 ± 19 yrs, 61% female, 49% presenting with acute medical problems, 15.8% (n = 80) with SEFI® score <7/10, and 4.2% (n = 21) with malnutrition. The predictive performance of the SEFI® score <7 for the diagnosis of malnutrition was good (AUC = 0.82 [95% confidence interval (CI), 0.72-0.92]): sensitivity 76.2% (n = 16/21, [58.0-94.4]), specificity 86.8% (n = 420/484, [83.8-89.8]), positive predictive value 20.0% (n = 16/80, [11.2-28.8]), and negative predictive value 98.8% (n = 420/425, [97.8-99.8]). The feasibility of the SEFI® 10-point visual analogue scale was 100% (505/505). The variables independently associated with malnutrition were: female gender (odds ratio 4.9 [95% CI, 1.7-14.2], P = 0.003), cancer (4.8 [1.4-15.9], P = 0.011) and chronic alcohol consumption (7.4 [1.3-41.4], P = 0.023). CONCLUSIONS: The prevalence of malnutrition was 4.2% in this primary care setting. The SEFI® visual analogue scale for food intake is feasible and could be helpful for the diagnosis of malnutrition in this setting.

Home environment: respiratory and allergic phenotypes from birth to age six in the PELAGIE cohort.

Childhood asthma and allergies are particularly prevalent diseases. Our objective is to identify respiratory and allergic phenotypes from birth to 6 years of age, and to explore their environmental determinants, especially those related to the home environment. Data on respiratory and allergic health outcomes and domestic environmental exposure were collected for 935 mother-infant pairs from a longitudinal mother-child cohort based on mothers, included before 19 weeks of gestation in Brittany between 2002 and 2006. Information was obtained by self-administered questionnaires completed by parents at inclusion, delivery, and when the child was 2 and 6 years old. Kml3D clustering was used to describe profiles of children who shared similar trajectories of symptoms as phenotypes. Association with environmental determinants was estimated by polytomous logistic regression. Five phenotypes were identified: a reference group characterized by low symptom levels (31.1%), a transient cough phenotype (36.5%), an eczema/cough phenotype (12.3%), a wheeze/cough phenotype (11.8%), and finally a mixed phenotype (8.0%). The wheeze/cough profile was associated with postnatal exposure to glues used in renovation activities (aOR 2.3 [1.2-4.7]), and the mixed phenotype with postnatal exposure to paint (aOR 2.1 [1-4.5]). The phenotypes observed showed some consistencies with those seen in previous studies. Some exposures associated with respiratory/allergic phenotypes observed in this study are avoidable. If confirmed by further research including interventional trials, home-based environmental counseling could be a possible prevention target for primary care professionals.

Programing stimuli-responsiveness of gelatin with electron beams: basic effects and development of a hydration-controlled biocompatible demonstrator.

Biomimetic materials with programmable stimuli responsiveness constitute a highly attractive material class for building bioactuators, sensors and active control elements in future biomedical applications. With this background, we demonstrate how energetic electron beams can be utilized to construct tailored stimuli responsive actuators for biomedical applications. Composed of collagen-derived gelatin, they reveal a mechanical response to hydration and changes in pH-value and ion concentration, while maintaining their excellent biocompatibility and biodegradability. While this is explicitly demonstrated by systematic characterizing an electron-beam synthesized gelatin-based actuator of cantilever geometry, the underlying materials processes are also discussed, based on the fundamental physical and chemical principles. When applied within classical electron beam lithography systems, these findings pave the way for a novel class of highly versatile integrated bioactuators from micro- to macroscales.