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MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors) are synaptic cell surface molecules that regulate the formation of trans-synaptic bridges between neurexins (NRXNs) and neuroligins (NLGNs), which promote synaptic development. Mutations in MDGAs are implicated in various neuropsychiatric diseases. MDGAs bind NLGNs in cis on the postsynaptic membrane and physically block NLGNs from binding to NRXNs. In crystal structures, the six immunoglobulin (Ig) and single fibronectin III domains of MDGA1 reveal a striking compact, triangular shape, both alone and in complex with NLGNs. Whether this unusual domain arrangement is required for biological function or other arrangements occur with different functional outcomes is unknown. Here, we show that WT MDGA1 can adopt both compact and extended 3D conformations that bind NLGN2. Designer mutants targeting strategic molecular elbows in MDGA1 alter the distribution of 3D conformations while leaving the binding affinity between soluble ectodomains of MDGA1 and NLGN2 intact. In contrast, in a cellular context, these mutants result in unique combinations of functional consequences, including altered binding to NLGN2, decreased capacity to conceal NLGN2 from NRXN1β, and/or suppressed NLGN2-mediated inhibitory presynaptic differentiation, despite the mutations being located far from the MDGA1-NLGN2 interaction site. Thus, the 3D conformation of the entire MDGA1 ectodomain appears critical for its function, and its NLGN-binding site on Ig1-Ig2 is not independent of the rest of the molecule. As a result, global 3D conformational changes to the MDGA1 ectodomain via strategic elbows may form a molecular mechanism to regulate MDGA1 action within the synaptic cleft.

Background: The increasing prevalence of dementia with the constant availability of general practitioners is a significant challenge for healthcare systems worldwide. Advanced nursing practice (ANP) was implemented in several countries as one possible solution to overcome this challenge. However, this concept of care is not yet implemented in Germany. The InDePendent study ("Advanced nursing practice and interprofessional dementia care") is the first study in Germany, aiming to implement and evaluate a model of ANP for persons with dementia (PwDs) living at home and their caregivers where tasks were reorganized between dementia‐specific qualified nurses and physicians. Methods: The Independent study is a multi‐center, cluster‐randomized, controlled, crossover interventional trial. Whereas the waiting‐control group receive care as usual, the InDePendent intervention of the intervention group aims to provide optimum care for PwD and their caregivers by integrating multimodal strategies of an individualized care within the framework of the German healthcare system by a reorganization of tasks between general practitioners and nurses. Dementia‐specific qualified nurses, who passed a specific state exam, conduct the interventions. Based on evidence‐based guidelines a comprehensive set of 115 intervention modules were defined. Each module consists of predefined trigger conditions and recommendations of actions. The intervention starts with a set of assessment instruments for PwD to identify the unmet needs, individual situation and resources of PwD and caregiver. Subsequently, an intervention tasks list was generated to address each of the identified unmet needs. The tasks lists were carried out by the dementia‐specific nurse in close cooperation with general practitioners. For the first time in Germany, nurses were able to carry out tasks that are usually carried out by general practitioners, like prescription of care aids and outpatient care. Expected results: We expect statistically significant differences between waiting‐control‐group and intervention‐group across the primary (unmet needs) and secondary outcomes (quality of life, caregiver burden, acceptance, cost‐effectiveness). This study can provide evidence concerning the safety, efficacy, and cost‐effectiveness of ANP in Germany, supporting the implementation of the ANP concept into German routine care. [ABSTRACT FROM AUTHOR]

The International Union of Biochemistry and Molecular Biology (IUBMB) Trainee Initiative aims to identify challenges experienced by biochemistry and molecular biology trainees and create programming to foster their growth and development as the next generation of scientists. Here, we highlight resources and events developed by the Trainee Initiative in their endeavor to support trainees around the world., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Medical research studies which involve electronic data capture of sensitive data about human subjects need to manage medical and identifying participant data in a secure manner. To protect the identity of data subjects, an independent trusted third party should be responsible for pseudonymization and management of the identifying data., Methods: We have developed a web-based integrated solution that combines REDCap as an electronic data capture system with the trusted third party software tools of the University Medicine Greifswald, which provides study personnel with a single user interface for both clinical data entry and management of identities, pseudonyms and informed consents., Results: Integration of the two platforms enables a seamless workflow of registering new participants, entering identifying and consent information, and generating pseudonyms in the trusted third party system, with subsequent capturing of medical data in the electronic data capture system, while maintaining strict separation of medical and identifying data in the two independently managed systems., Conclusion: Our solution enables a time-efficient data entry workflow, provides a high level of data protection by minimizing visibility of identifying information and pseudonym lists, and avoids errors introduced by manual transfer of pseudonyms between separate systems.

Background: Determining unmet need patterns and associated factors in primary care can potentially specify assessment batteries and tailor interventions in dementia more efficiently., Objective: To identify latent unmet healthcare need patterns and associated sociodemographic and clinical factors., Methods: This Latent Class Analysis (LCA) includes n = 417 community-dwelling people living with dementia. Subjects completed a comprehensive, computer-assisted face-to-face interview to identify unmet needs. One-hundred-fifteen predefined unmet medical, medication, nursing, psychosocial, and social care needs were available. LCA and multivariate logistic regressions were performed to identify unmet needs patterns and patient characteristics belonging to a specific pattern, respectively., Results: Four profiles were identified: [1] "few needs without any psychosocial need" (n = 44 (11%); mean: 7.4 needs), [2] "some medical and nursing care needs only" (n = 135 (32%); 9.7 needs), [3] "some needs in all areas" (n = 139 (33%); 14.3 needs), and [4] "many medical and nursing needs" (n = 99 (24%); 19.1 needs). Whereas the first class with the lowest number of needs comprised younger, less cognitively impaired patients without depressive symptoms, the fourth class had the highest number of unmet needs, containing patients with lower health status, less social support and higher comorbidity and depressive symptoms. Better access to social care services and higher social support reduced unmet needs, distinguishing the second from the third class (9.7 versus 14.3 needs)., Conclusions: Access to the social care system, social support and depressive symptoms should be assessed, and the patient's health status and comorbidities monitored to more comprehensively identify unmet needs patterns and more efficiently guide tailored interventions.

Background: Patients of geriatrics are often treated by several health care providers at the same time. The spatial, informational, and organizational separation of these health care providers can hinder the effective treatment of these patients., Objective: This study aimed to develop a regional health information exchange (HIE) system to improve HIE in geriatric treatment. This study also evaluated the usability of the regional HIE system and sought to identify barriers to and facilitators of its implementation., Methods: The development of the regional HIE system followed the community-based participatory research approach. The primary outcomes were the usability of the regional HIE system, expected implementation barriers and facilitators, and the quality of the developmental process. Data were collected and analyzed using a mixed methods approach., Results: A total of 3 focus regions were identified, 22 geriatric health care providers participated in the development of the regional HIE system, and 11 workshops were conducted between October 2019 and September 2020. In total, 12 participants responded to a questionnaire. The main results were that the regional HIE system should support the exchange of assessments, diagnoses, medication, assistive device supply, and social information. The regional HIE system was expected to be able to improve the quality and continuity of care. In total, 5 adoption facilitators were identified. The main points were adaptability of the regional HIE system to local needs, availability to different patient groups and treatment documents, web-based design, trust among the users, and computer literacy. A total of 13 barriers to adoption were identified. The main expected barriers to implementation were lack of resources, interoperability issues, computer illiteracy, lack of trust, privacy concerns, and ease-of-use issues., Conclusions: Participating health care professionals shared similar motivations for developing the regional HIE system, including improved quality of care, reduction of unnecessary examinations, and more effective health care provision. An overly complicated registration process for health care professionals and the patients' free choice of their health care providers hinder the effectiveness of the regional HIE system, resulting in incomplete patient health information. However, the web-based design of the system bridges interoperability problems that exist owing to the different technical and organizational structures of the health care facilities involved. The regional HIE system is better accepted by health care professionals who are already engaged in an interdisciplinary, geriatric-focused network. This might indicate that pre-existing cross-organizational structures and processes are prerequisites for using HIE systems. The participatory design supports the development of technologies that are adaptable to regional needs. Health care providers are interested in participating in the development of an HIE system, but they often lack the required time, knowledge, and resources., (©Nils Pfeuffer, Angelika Beyer, Peter Penndorf, Maren Leiz, Franziska Radicke, Wolfgang Hoffmann, Neeltje van den Berg. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 15.09.2022.)

Background: In the German health care system, parents with an acutely ill child can visit an emergency room (ER) 24 hours a day, seven days a week. At the ER, the patient receives a medical consultation. Many parents use these facilities as they do not know how urgently their child requires medical attention. In recent years, paediatric departments in smaller hospitals have been closed, particularly in rural regions. As a result of this, the distances that patients must travel to paediatric care facilities in these regions are increasing, causing more children to visit an ER for adults. However, paediatric expertise is often required in order to assess how quickly the patient requires treatment and select an adequate treatment. This decision is made by a doctor in German ERs. We have examined whether remote paediatricians can perform a standardised urgency assessment (triage) using a video conferencing system., Methods: Only acutely ill patients who were brought to a paediatric emergency room (paedER) by their parents or carers, without prior medical consultation, have been included in this study. First, an on-site paediatrician assessed the urgency of each case using a standardised triage. In order to do this, the Paediatric Canadian Triage and Acuity Scale (PaedCTAS) was translated into German and adapted for use in a standardised IT-based data collection tool. After the initial on-site triage, a telemedicine paediatrician, based in a different hospital, repeated the triage using a video conferencing system. Both paediatricians used the same triage procedure. The primary outcome was the degree of concordance and interobserver agreement, measured using Cohen's kappa, between the two paediatricians. We have also included patient and assessor demographics., Results: A total of 266 patients were included in the study. Of these, 227 cases were eligible for the concordance analysis. In n = 154 cases (68%), there was concordance between the on-site paediatrician's and telemedicine paediatrician's urgency assessments. In n = 50 cases (22%), the telemedicine paediatrician rated the urgency of the patient's condition higher (overtriage); in 23 cases (10%), the assessment indicated a lower urgency (undertriage). Nineteen medical doctors were included in the study, mostly trained paediatric specialists. Some of them acted as an on-site doctor and telemedicine doctor. Cohen's weighted kappa was 0.64 (95% CI: 0.49-0.79), indicating a substantial agreement between the specialists., Conclusions: Telemedical triage can assist in providing acute paediatric care in regions with a low density of paediatric care facilities. The next steps are further developing the triage tool and implementing telemedicine urgency assessment in a larger network of hospitals in order to improve the integration of telemedicine into hospitals' organisational processes. The processes should include intensive training for the doctors involved in telemedical triage., Trial Registration: DRKS00013207., Competing Interests: The authors have declared that no competing interests exist.