APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia.

Several genetic risk factors for Alzheimer's disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells1. However, the relationship between lipid metabolism in glia and Alzheimer's disease pathology remains poorly understood. Through single-nucleus RNA sequencing of brain tissue in Alzheimer's disease, we have identified a microglial state defined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most abundant in patients with Alzheimer's disease having the APOE4/4 genotype. In human induced pluripotent stem cell-derived microglia, fibrillar Aß induces ACSL1 expression, triglyceride synthesis and lipid droplet accumulation in an APOE-dependent manner. Additionally, conditioned media from lipid droplet-containing microglia lead to Tau phosphorylation and neurotoxicity in an APOE-dependent manner. Our findings suggest a link between genetic risk factors for Alzheimer's disease with microglial lipid droplet accumulation and neurotoxic microglia-derived factors, potentially providing therapeutic strategies for Alzheimer's disease.

Perioperative patient safety indicators-A Delphi study.

AIM: To identify, define and achieve consensus on perioperative patient safety indicators within a Swedish context. DESIGN: A modified Delphi method. METHODS: A purposeful sample of 22 experts, all experienced operating room nurse specialists, was recruited for this study. A questionnaire was constructed incorporating statements derived from a preceding study. The experts were asked to rate the importance of each statement concerning patient safety during the perioperative phase. The data collection occurred through an online survey platform between November 2022 and April 2023. The CREDES checklist guided the reporting of this study. RESULTS: The three-round Delphi study resulted in consensus on 73 statements out of 103, encompassing 74% process indicators and 26% structure indicators. Key areas of consensus included the use of the Surgical Safety Checklist and optimizing the operating room environment. CONCLUSION: Consensus was reached on perioperative safety indicators, underscoring the intricate challenges involved in ensuring patient safety in the operating room. It emphasizes the important integration of both structure and process indicators for comprehensive safety assessment during surgical procedures. Recognizing the difficulty in measuring factors like teamwork and communication, essential for patient safety, the study offers practical guidance. It underlines a balanced approach and specific consensus areas applicable in clinical practice to enhance perioperative patient safety. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: This study provides concrete practice guidance and establishes a structured framework for evaluating perioperative care processes. It emphasizes the critical role of professionals having the necessary skills and being present during surgical procedures. Additionally, the study underscores the paramount importance of effective communication and teamwork within the operating room team, substantively contributing to overall patient safety enhancement. IMPACT: The study focused on addressing the challenge of ensuring patient safety in operating rooms, acknowledging the persistent complications related to surgery despite global efforts to eliminate avoidable harm in healthcare. Consensus was reached on 73 crucial indicators for perioperative patient safety, emphasizing a balanced approach integrating both process and structure indicators for a comprehensive assessment of safety during surgical procedures. The study has a broad impact on professionals and healthcare systems, providing concrete guidance for practice and offering a structured process for evaluating perioperative care. REPORTING METHOD: The study is reported informed by 'Guidance on Conducting and REporting DElphi Studies (CREDES) in palliative care: Recommendations derived from a methodological systematic review'. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Effects of an advanced first aid course or real-time video communication with ambulance personnel on layperson first response for building-site severe injury events: a simulation study.

BACKGROUND: The risk of high-energy trauma injuries on construction sites is relatively high. A delayed response time could affect outcomes after severe injury. This study assessed if an advanced first aid course for first aid response for laypersons (employees or apprentices) in the construction industry or real-time video communication and support with ambulance personnel, or neither, together with access to an advanced medical kit, would have an effect on immediate layperson vital responses in a severe injury scenario. METHOD: This was a controlled simulation study. Employees or apprentices at a construction site were recruited and randomly allocated into a group with video support or not, and advanced first aid course or not, and where one group had both. The primary outcomes were correct behavior to recognize and manage an occluded airway and correct behavior to stop life-threatening bleeding from a lower extremity injury. Secondary outcomes included head-to-toe assessment performed, placement of a pelvic sling, and application of remote vital signs monitors. RESULTS: Ninety participants were included in 10 groups of 3 for each of 4 exposures. One group was tested first as a baseline group, and then later after having done the training course. Live video support was effective in controlling bleeding. A first aid course given beforehand did not seem to be as effective on controlling bleeding. Video support and the first aid course previously given improved the ability of bystanders to manage the airway, the combination of the two being no better than each of the interventions taken in isolation. Course exposure and video support together were not superior to the course by itself or video by itself, except regarding placing the biosensors on the injured after video support. Secondary results showed an association between video support and completing a head-to-toe assessment. Both interventions were associated with applying a pelvic sling. CONCLUSION: These findings show that laypersons, here construction industry employees, can be supported to achieve good performance as first responders in a major injury scenario. Prior training, but especially live video support without prior training, improves layperson performance in this setting.

Longer work experience and age associated with safety attitudes in operating room nurses: an online cross-sectional study.

BACKGROUND: Patient safety is fundamental when providing care in the operating room. Still, adverse events and errors are a challenge for patient safety worldwide. To avoid preventable patient harm, organisations need a positive safety culture, the measurable component of which is known as the safety climate. To best improve the safety climate the current attitudes to safety must first be understood. AIM: To explore operating room nurses' safety attitudes and their views on how to improve patient safety in operating rooms. METHOD: A cross-sectional study using the Swedish-translated version of the Safety Attitudes Questionnaire, Operating Room version. Data were collected using an online survey platform. RESULTS: 358 operating room nurses completed the questionnaire. The results show that the older age group rated their working conditions and management support as better than the younger age groups. The older age group also rated their stress recognition as lower compared with the younger age groups. The same pattern was seen in terms of work experience, with more-experienced respondents showing a higher mean score for the factor working conditions and a lower mean score for the factor stress recognition as compared with their less-experienced colleagues. When comparing hospital types, county hospital employees had higher factor scores for safety climate, job satisfaction and working conditions than university hospital employees. The respondents' most recurring recommendations for improving patient safety were 'Having better and clearer communication' followed by 'Having enough time to do things the way they should be done'. CONCLUSION: More focus on safety with increasing age and experience was observed in this cohort. Need for improvements is reported for patient safety in operating rooms, mainly when it comes to communication and workload. To improve and develop patient safety in the operating room, the organisational safety climate needs to be actively managed and developed. One step in actively managing the safety climate may be efforts to retain experienced operating room nurses.

Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.