Perceptions of Digital Health Education Among European Medical Students: Mixed Methods Survey

Background: Digital health technologies hold promise to enhance patient-related outcomes, to support health care staff by reducing their workload, and to improve the coordination of care. As key users of digital health technologies, health care workers are crucial to enable a meaningful digital transformation of health care. Digital health literacy and digital skills should become prerequisite competencies for health professionals to facilitate the implementation and leverage the potential of digital technologies to improve health. Objective: We aimed to assess European medical students' perceived knowledge and opinions toward digital health, the status of digital health implementation in medical education, and the students' most pressing needs. Methods: The explanatory design of our mixed methods study was based on an online, anonymous, self-administered survey targeted toward European medical students. A linear regression analysis was used to identify the influence of the year of medical studies on the responses. Additional analysis was performed by grouping the responses by the self-evaluated frequency of eHealth technology use. Written responses to four qualitative questions in the survey were analyzed using an inductive approach. Results: The survey received a total of 451 responses from 39 European countries, and there were respondents for every year of medical studies. The majority of respondents saw advantages in the use of digital health. While 40.6% (183/451) felt prepared to work in a digitized health care system, more than half (240/451, 53.2%) evaluated their eHealth skills as poor or very poor. Medical students considered lack of education to be the reason for this, with 84.9% (383/451) agreeing or strongly agreeing that more digital health education should be implemented in the medical curriculum. Students demanded introductory and specific eHealth courses covering data management, ethical aspects, legal frameworks, research and entrepreneurial opportunities, role in public health and health systems, communication skills, and practical training. The emphasis lay on tailoring learning to future job requirements and interprofessional education. Conclusions: This study shows a lack of digital health-related formats in medical education and a perceived lack of digital health literacy among European medical students. Our findings indicate a gap between the willingness of medical students to take an active role by becoming key players in the digital transformation of health care and the education that they receive through their faculties

Evaluation framework of community-based livestock breeding programs

The objective of this paper is to present an evaluation framework to provide guidance for an assessment of the performance, outputs and associated impacts of community-based livestock breeding programs (CBBPs), responding to the need of formalizing the evaluation procedures as it was stressed by FAO. The purpose of such evaluation is to monitor and evaluate on-going activities in CBBPs, to identify challenges and mistakes in the execution of the program, so that appropriate actions can be taken. This evaluation also serves as a guide for funding bodies to measure socio-economic impact on the livelihoods of livestock farmers in order to decide if the program’s goals have been met. The evaluation framework is divided into three domains: evaluation of CBBP implementation based on organizational and technical criteria; monitoring of implementation outputs to evaluate genetic improvement at herd/flock level and the consequential changes at the household level and the community at large; and evaluation of impacts to assess improvement in livelihoods of livestock farmers and eventual effects on the environment. For each evaluation criteria, several indicators are provided.EEA BarilocheFil: Lamuno, Doreen. National Animal Genetic Resources Centre and Databank; UgandaFil: Sölkner, Johann. National Animal Genetic Resources Centre and Databank; UgandaFil: Mészáros, Gabor. National Animal Genetic Resources Centre and Databank; UgandaFil: Nakimbugwe, Helen. National Animal Genetic Resources Centre and Databank; UgandaFil: Mulindwa, Henry. National Agricultural Research Organization, UgandaFil: Nandolo, Wilson. Lilongwe University of Agriculture and Natural Resources, MalawiFil: Gondwe, Timothy. United States Department of Agriculture; Estados UnidosFil: van Tassel, Curt. United States Department of Agriculture; Estados UnidosFil: Mueller, Joaquín Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: Wursinger, Maria. University of Natural Resources and Life Sciences; AustriaFil: Gutierrez, Gustavo. Universidad Nacional Agraria La Molina; Per

A Missense Change in the ATG4D Gene Links Aberrant Autophagy to a Neurodegenerative Vacuolar Storage Disease

Inherited neurodegenerative disorders are debilitating diseases that occur across different species. We have performed clinical, pathological and genetic studies to characterize a novel canine neurodegenerative disease present in the Lagotto Romagnolo dog breed. Affected dogs suffer from progressive cerebellar ataxia, sometimes accompanied by episodic nystagmus and behavioral changes. Histological examination revealed unique pathological changes, including profound neuronal cytoplasmic vacuolization in the nervous system, as well as spheroid formation and cytoplasmic aggregation of vacuoles in secretory epithelial tissues and mesenchymal cells. Genetic analyses uncovered a missense change, c.1288G>A; p.A430T, in the autophagy-related ATG4D gene on canine chromosome 20 with a highly significant disease association (p = 3.8 x 10(-136)) in a cohort of more than 2300 Lagotto Romagnolo dogs. ATG4D encodes a poorly characterized cysteine protease belonging to themacroautophagy pathway. Accordingly, our histological analyses indicated altered autophagic flux in affected tissues. The knockdown of the zebrafish homologue atg4da resulted in a widespread developmental disturbance and neurodegeneration in the central nervous system. Our study describes a previously unknown canine neurological disease with particular pathological features and implicates the ATG4D protein as an important autophagy mediator in neuronal homeostasis. The canine phenotype serves as a model to delineate the disease-causing pathological mechanism(s) and ATG4D function, and can also be used to explore treatment options. Furthermore, our results reveal a novel candidate gene for human neurodegeneration and enable the development of a genetic test for veterinary diagnostic and breeding purposes.Peer reviewe

Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinsons disease study.

Estimates of the spectrum and frequency of pathogenic variants in Parkinsons disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinsons disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD

Survival analysis of white Leghorn laying hens in the early and late production period

The aim of the study was to carry out survival analysis to evaluate fixed effects and to estimate genetic parameters on survival of laying hens. The data set contained 16,694 records of three purebred White Leghorn layer lines coded W1, WB and WF. At 17 weeks old after rearing, hens were transported to two laying stables and were randomly assigned to traditional 4–birds battery cages. Censoring status i.e. alive or dead was recorded. The traits studied were overall survival during the entire laying period (17 to 64 weeks of age), survival in the early production period (17 to 40 weeks of age) and survival in late production period (41 to 64 weeks of age). The results showed all fixed effects in the model i.e. stable by corridor interaction effect, mortality of back cage neighbors, level and layer lines were highly significant. Overall survival during the entire laying period was 60.4 % while survival during early laying period was 85.1 % and survival in the late laying period was 70.9%. Different risk ratio patterns were observed between the two laying stables. Hens in the top row had about 20% higher risk of death. Number of death cases in the back neighbor cage had a negative effect on the survival. Highest risk of death for line WB and lowest risk for line WF were found. Heritability for survival traits ranged from 0.04 to 0.15. This indicates genetic improvement is possible. Genetic correlation between overall survival and early laying period and between overall survival and late were high, indicating positive correlated response through selection

Ex Vivo Generation of CAR Macrophages from Hematopoietic Stem and Progenitor Cells for Use in Cancer Therapy

Chimeric antigen receptor (CAR) T-cell therapies have shown impressive results in patients with hematological malignancies; however, little success has been achieved in the treatment of solid tumors. Recently, macrophages (M phi s) were identified as an additional candidate for the CAR approach, and initial proof of concept studies using peripheral blood-derived monocytes showed antigen-redirected activation of CAR M phi s. However, some patients may not be suitable for monocyte-apheresis, and prior cancer treatment regimens may negatively affect immune cell number and functionality. To address this problem, we here introduce primary human hematopoietic stem and progenitor cells (HSPCs) as a cell source to generate functional CAR M phi s ex vivo. Our data showed successful CAR expression in cord blood (CB)-derived HSPCs, with considerable cell expansion during differentiation to CAR M phi s. HSPC-derived M phi s showed typical M phi morphology, phenotype, and basic anti-bacterial functionality. CAR M phi s targeting the carcinoembryonic antigen (CEA) and containing either a DAP12- or a CD3 zeta-derived signaling domain showed antigen redirected activation as they secreted pro-inflammatory cytokines specifically upon contact with CEA(+) target cells. In addition, CD3 zeta-expressing CAR M phi s exhibited significantly enhanced phagocytosis of CEA(+) HT1080 cells. Our data establish human HSPCs as a suitable cell source to generate functional CAR M phi s and further support the use of CAR M phi s in the context of solid tumor therapy

Plasma concentrations of afamin are associated with the prevalence and development of metabolic syndrome

BACKGROUND: -Afamin is a human plasma vitamin E-binding glycoprotein primarily expressed in the liver and secreted into the bloodstream. Since little is known about (patho)-physiological functions of afamin, we decided to identify phenotypes associated with afamin by investigating transgenic mice overexpressing the human afamin gene and performing large-scale human epidemiological studies. METHODS AND RESULTS: -Transgenic mice overexpressing afamin revealed increased body weight and serum concentrations of lipids and glucose. We applied a random-effects meta-analysis using age- and sex-adjusted baseline and follow-up investigations in the population-based Bruneck (n=826), SAPHIR (n=1499), and KORA F4 studies (n=3060). Mean afamin concentrations were 62.5±15.3, 66.2±14.3, and 70.6±17.2 mg/L in Bruneck, SAPHIR and KORA F4, respectively. Per 10 mg/L increment in afamin measured at baseline, the number of metabolic syndrome components increased by 19% (incidence rate ratio (IRR)=1.19 (95%CI 1.16-1.21), p=5.62×10(-64)). With the same afamin increment used at baseline we observed an 8% gain in metabolic syndrome components between baseline and follow-up (IRR=1.08 (95%CI 1.06-1.10), p=8.87×10(-16)). Afamin concentrations at baseline were highly significantly related to all individual metabolic syndrome components at baseline and follow-up. This observation was most pronounced for elevated waist circumference (OR=1.79 (95%CI 1.54-2.09), p=4.15×10(-14) at baseline and OR=1.46 (95%CI 1.31-1.63), p=2.84×10(-11) for change during follow-up) and for elevated fasting glucose concentrations (OR=1.46 (95%CI 1.40-1.52), p=1.87×10(-69), and OR=1.46 95%CI 1.24-1.71, p=5.13×10(-6), respectively). CONCLUSIONS: -This study in transgenic mice and more than 5,000 participants in epidemiological studies shows that afamin is strongly associated with the prevalence and development of metabolic syndrome and all its components

Predictive Factors for Survival in Children Receiving Liver Transplants for Wilson's Disease: A Cohort Study Using European Liver Transplant Registry Data.

Liver transplantation (LT) is a rescue therapy for life-threatening complications of Wilson's disease (WD). However, data on the outcome of WD patients after LT are scarce. The aim of our study was to analyze a large pediatric WD cohort with the aim of investigating the longterm outcome of pediatric WD patients after LT and to identify predictive factors for patient and transplant survival. This is a retrospective cohort study using data of all children (<18 years) transplanted for WD enrolled in the European Liver Transplant Registry from January 1968 until December 2013. In total, 338 patients (57.6% female) transplanted at 80 different European centers (1-26 patients per center) were included in this study. The median age at transplantation was 14.0 years (interquartile range [IQR], 11.2-16.1 years); patients were followed up for a median of 5.4 years (IQR, 1.0-10.9 years) after LT. Overall patient survival rates were high with 87% (1-year survival), 84% (5-year survival), and 81% (10-year survival); survival rates increased considerably with the calendar year (P < 0.001). Early age at LT, living donation, and histidine tryptophan ketoglutarate preservation liquid were identified as risk factors for poor patient survival in the multivariate analysis. LT is an excellent treatment option for pediatric patients with WD and associated end-stage liver disease. Longterm outcome in these patients is similar to other pediatric causes for LT. Overall patient and graft survival rates improved considerably over the last decades. To improve future research in the field, the vast variability of allocation strategies should be harmonized and a generally accepted definition or discrimination of acute versus chronic WD needs to be found