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AlphaFold can accurately predict static protein structures but does not account for solvent conditions. Human leucine zipper EF-hand transmembrane protein-1 (LETM1) has one sequence-identifiable EF-hand but how calcium (Ca 2+ ) affects structure and function remains enigmatic. Here, we used highly confident AlphaFold Cα predictions to guide nuclear Overhauser effect (NOE) assignments and structure calculation of the LETM1 EF-hand in the presence of Ca 2+ . The resultant NMR structure exposes pairing between a partial loop-helix and full helix-loop-helix, forming an unprecedented F-EF-hand with non-canonical Ca 2+ coordination but enhanced hydrophobicity for protein interactions compared to calmodulin. The structure also reveals the basis for pH sensing at the link between canonical and partial EF-hands. Functionally, mutations that augmented or weakened Ca 2+ binding increased or decreased matrix Ca 2+ , respectively, establishing F-EF as a two-way mitochondrial Ca 2+ regulator. Thus, we show how to synergize AI prediction with NMR data, elucidating a solution-specific and extraordinary LETM1 F-EF-hand., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Opioid use disorder (OUD) is a chronic condition that requires regular visits and care continuity. Telehealth implementation has created multiple visit modalities for OUD care. There is limited knowledge of patients' and clinicians' perceptions and experiences related to multi-modality care and when different modalities might be best employed., Objective: To identify patients' and clinicians' experiences with multiple visit modalities for OUD treatment in primary care., Design: Comparative case study, using video- and telephone-based semi-structured interviews., Participants: Patients being treated for OUD (n = 19) and clinicians who provided OUD care (n = 15) from two primary care clinics within the same healthcare system., Approach: Using an inductive approach, interviews were analyzed to identify patients' and clinicians' experiences with receiving/delivering OUD care via different visit modalities. Clinicians' and patients' experiences were compared using a group analytical process., Key Results: Patients and clinicians valued having multiple modalities available for care, with flexibility identified as a key benefit. Patients highlighted the decreased burden of travel and less social anxiety with telehealth visits. Similarly, clinicians reported that telehealth decreased medical intrusion into the lives of patients stable in recovery. Patients and clinicians saw the value of in-person visits when establishing care and for patients needing additional support. In-person visits allowed the ability to conduct urine drug testing, and to foster relationships and trust building, which were more difficult, but not impossible via a telehealth visit. Patients preferred telephone over video visits, as these were more private and more convenient. Clinicians identified benefits of video, including being able to both hear and see the patient, but often deferred to patient preference., Conclusions: Considerations for utilization of visit modalities for OUD care were identified based on patients' needs and preferences, which often changed over the course of treatment. Continued research is needed determine how visit modalities impact patient outcomes., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Mitochondrial magnesium (Mg 2+ ) is a crucial modulator of protein stability, enzymatic activity, ATP synthesis, and cell death. Mitochondrial RNA splicing protein 2 (MRS2) is the main Mg 2+ channel in the inner mitochondrial membrane that mediates influx into the matrix. Recent cryo-electron microscopy (cryo-EM) human MRS2 structures exhibit minimal conformational changes at high and low Mg 2+ , yet the regulation of human MRS2 and orthologues by Mg 2+ binding to analogous matrix domains has been well established. Further, a missense variation at D216 has been identified associated with malignant melanoma and MRS2 expression and activity is implicated in gastric cancer. Thus, to gain more mechanistic and functional insight into Mg 2+ sensing by the human MRS2 matrix domain and the association with proliferative disease, we assessed the structural, biophysical, and functional effects of a D216Q mutant. We show that the D216Q mutation is sufficient to abrogate Mg 2+ -binding and associated conformational changes including increased α-helicity, stability, and monomerization. Further, we reveal that the MRS2 matrix domains interact with ~μM affinity, which is weakened by up to two orders of magnitude in the presence of Mg 2+ for wild-type but unaffected for D216Q. Finally, we demonstrate the importance of Mg 2+ sensing by MRS2 to prevent matrix Mg 2+ overload as HeLa cells overexpressing MRS2 show enhanced Mg 2+ uptake, cell migration, and resistance to apoptosis while MRS2 D216Q robustly potentiates these cancer phenotypes. Collectively, our findings further define the MRS2 matrix domain as a critical Mg 2+ sensor that undergoes conformational and assembly changes upon Mg 2+ interactions dependent on D216 to temper matrix Mg 2+ overload., (© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Health care institutions play an essential role in community resilience. As one of the largest health care systems in the United States, the Veterans Health Administration (VHA) plays a critical role in supporting medically vulnerable Veterans during disasters. Disasters require large-scale outreach to individuals in affected areas, including the capability to identify patients, establish contact, determine needs, and deliver required services. Here we describe the development and implementation of VHA's Vulnerable Patient Care, Access, and Response in Emergencies (VP CARE) program, a data-driven system of outreach to preidentified medically vulnerable patients, which seeks to streamline this process. VP CARE was inspired by the VHA's Home-Based Primary Care (HBPC) program and the US Department of Health and Human Services' emPOWER program. It seeks to enhance Veteran patients' well-being and continuity of care during disasters using 3 components: (1) improving the readiness and resilience of vulnerable patients and their caregivers; (2) establishing an organization, policies, procedures, and competency-based training exercises to guide outreach and assistance; and (3) creating and implementing standardized 1- and 2-way outreach technology and reporting. Using Geographic Information Systems embedded in VP CARE, VHA can generate a list of high-risk patients and deploy a 2-way texting capability to contact and receive responses from them. VP CARE automatically tracks patient contact and responses, reducing duplication of effort and freeing up VA staff to focus on patients with immediate needs. Patients and their caregivers benefit from the reassurance of knowing that VHA is focused on their well-being and available to support them. The technologies deployed in VP CARE improve the efficiency of outreach efforts and reduce the risk of life-threatening harm, while reducing the cost and demands on VA staff. This article concludes with lessons learned that may be instructive for other health care systems seeking to establish similar outreach capabilities., Competing Interests: Disclosure The authors declare no conflicts of interest., (Published by Elsevier Inc.)

Objectives: Right ventricular failure following implantation of a durable left ventricular assist device (LVAD) is a major driver of mortality. Reported survival following biventricular (BiVAD) or total artificial heart (TAH) implantation remains substantially inferior to LVAD alone. We report our outcomes with LVAD and BiVAD HeartMate 3 (HM3)., Methods: Consecutive patients undergoing implantation of an HM3 LVAD between November 2014 and December 2021, at The Alfred, Australia were included in the study. Comparison was made between the BiVAD and LVAD alone groups., Results: A total of 86 patients, 65 patients with LVAD alone and 21 in a BiVAD configuration underwent implantation. The median age of the LVAD and BiVAD groups was 56 years (Interquartile range 46-62) and 49 years (Interquartile range 37-55), respectively. By 4 years after implantation, 54% of LVAD patients and 43% of BiVAD patients had undergone cardiac transplantation. The incidence of stroke in the entire experience was 3.5% and pump thrombosis 5% (all in the RVAD). There were 14 deaths in the LVAD group and 1 in the BiVAD group. The actuarial survival for LVAD patients at 1 year was 85% and BiVAD patients at 1 year was 95%., Conclusions: The application of HM 3 BiVAD support in selected patients appears to offer a satisfactory solution to patients requiring biventricular support., (© 2024 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

As large-scale disasters continue to become increasingly common worldwide, nursing homes, whose residents are more vulnerable to disaster-related health and psychosocial shocks, and their staff, are carrying progressively more responsibility for health care readiness practices. Implementation science is a research discipline that seeks to improve uptake of evidence-based practices, such as health care readiness planning, and thus has potential to improve nursing home care delivery during and after disasters. We describe the limited field of existing evidence-based strategies in the peer-reviewed literature that seek to advance health care readiness in the nursing home setting and illustrate how implementation science can better support health care readiness planning for nursing homes. We rest on 3 main themes: (1) implementation science frameworks can strengthen nursing home staff engagement around health care readiness; (2) implementation science can support tailoring of emergency preparedness plans to individual nursing homes' unique needs; and (3) implementation science can advance the integration of nursing homes into local, state, and federal health care readiness planning initiatives. Finally, research is urgently needed to both generate and disseminate implementation strategies that increase uptake of evidence-based health care readiness practices in the nursing home setting., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.)

Background: The efficacy of household emergency preparedness interventions for community-dwelling, non-institutionalized people is largely unknown., Objective: To ascertain the state of the science on social support, educational, and behavioral modification interventions to improve all-hazard household disaster preparedness., Design: Systematic review and meta-analysis., Methods: Databases, trial registers, reports, and websites were searched, and citation trails followed utilizing replicable methods. Individual, cluster, and cross-over randomized controlled trials of non-institutionalized, community-dwelling populations and non-randomized controlled trials, controlled before-after, and program evaluation studies were included. At least two review authors independently screened each potentially relevant study for inclusion, extracted data, and assessed the risk of bias. Risk of bias was assessed using Cochrane's RoB2 tool for randomized studies and ROBINS-I tool for nonrandomized studies. Meta-analyses were applied using a random-effects model. Where meta-analysis was not indicated, results were synthesized using summary statistics of intervention effect estimates and vote counting based on effect direction. The evidence was rated using GRADE., Results: 17 studies were included with substantial methodological and clinical diversity. No intervention effect was observed for preparedness supplies (OR = 6.12, 95% 0.13 to 284.37) or knowledge (SMD = 0.96, 95% CI -0.15 to 2.08) outcomes. A small positive effect (SMD = 0.53, 95% CI 0.16 to 0.91) was observed for preparedness behaviors, with very low certainty of evidence. No studies reported adverse effects from the interventions., Conclusion: Research designs elucidating the efficacy of practical yet complex and multi- faceted social support, educational, and behavioral modification interventions present substantial methodological challenges where rigorous study design elements may not match the contextual public health priority needs and resources where interventions were delivered. While the overall strength of the evidence was evaluated as low to very low, we acknowledge the valuable and informative work of the included studies. The research represents the seminal work in this field and provides an important foundation for the state of the science of household emergency preparedness intervention effectiveness and efficacy. The findings are relevant to disaster preparedness practice and research, and we encourage researchers to continue this line of research, using these studies and this review to inform ongoing improvements in study designs., Competing Interests: TH reports conducting two household preparedness intervention studies. Neither study met inclusion criteria for this review. TH did not determine whether her studies should be included in this systematic review. JC reports being the principal owner of Castner Incorporated, a woman-owned enterprise small business where she is employed; Editor-in-Chief (Independent Contractor) for Journal of Emergency Nursing: paid to institution; reports NIH/NIA award subcontract to University at Louisville and Kansas University Medical Center: paid to institution; reports lecture payments from Notify, LLC: paid to institution; and Emergency Nurses Association Trauma Nursing Core Course: paid to institution and author. SB reports payments from HDR, Inc., a subcontractor for the US Army Corps of Engineers. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Amberson, Heagele, Wyte-Lake, Couig, Bell, Mammen, Wells and Castner.)

Objectives: Some state veterans homes (SVHs) received media attention in the wake of the COVID-19 pandemic because of allegations of poor infection control and excess mortality. However, little research has investigated how these facilities differ from community nursing homes (CNHs) and what the geographical trends of these infection and mortality differences are. We aimed to test (1) whether infection was overall lower in SVHs than CNHs, (2) whether mortality was overall lower in SVHs than CNHs, as well as the geographic distribution of nursing home infection and mortality across the United States., Design: Retrospective nationwide cohort study., Setting and Participants: Skilled nursing facilities in the United States from May 2020 to July 2022 during the COVID-19 pandemic., Methods: Using multilevel negative binomial regression, we modeled COVID-19 infection and mortality rates in skilled nursing homes, testing for overall SVH differences from May 2020 to July 2022, placing random effects on counties to calculate adjusted county-level infection and mortality rates., Results: SVHs experienced 18% fewer cases but 25% more deaths overall compared with CNHs. Counties with the highest levels of facility infection, including counties with SVHs, were situated mainly in Midwestern, Atlantic, and Southern states, with the majority of counties with low infection levels in Central and Western states. Counties with the highest levels of facility mortality emerged in Rust Belt and Midwestern states down to Southern states, with the lowest levels of county-level mortality, particularly among counties containing SVHs, occurring westward to Central and Western states., Conclusion and Implications: SVHs experienced lower infection levels but higher mortality levels than CNHs, and fewer extremely high infection and mortality rates in counties containing SVHs despite higher mortality risk in SVHs, calling attention to unobserved facility-level differences such as gender and age distributions and future research opportunities using more granular geographical aggregations to better understand facility-level SVH risk within the broader neighborhood context., Competing Interests: Disclosure The authors declare no conflicts of interest., (Published by Elsevier Inc.)

Objectives: To understand the role of health information technology (IT) vendors and health IT functionality in supporting advanced primary care., Study Design: We synthesized multiple rounds of surveys and interviews (2017-2022) from a mixed-methods evaluation of Comprehensive Primary Care Plus (CPC+), a multipayer model developed by CMS. CPC+ was the first federal advanced primary care reform effort that formalized health IT vendors' roles in supporting health IT implementation and specified detailed health IT requirements for practices., Methods: We conducted content analysis to identify cross-cutting themes related to health IT for both practices and vendors, comparing similarities and differences across participants and (when possible) over time., Results: Vendors and practices reported advances in registries and dashboards for improved information management within the practice as well as strengthened relationships between vendors and practices that supported health IT implementation. However, CPC+ practices noted several gaps or challenges using existing functionalities, and both vendors and practices reported broader challenges for more transformative health IT change, particularly the lack of interoperable health information exchange needed to support care management and care coordination. Key factors constraining vendors' investment in further advances included long product development schedules, making it difficult to respond to rapidly evolving model requirements. Vendors also shared that CPC+ practices represented a small fraction of their client base, so investing in developing new functionality was not strategic unless it was more broadly relevant outside CPC+., Conclusions: Continued collaboration among health IT vendors, practices, policy makers, and payers could support continued technological improvements, particularly related to information exchange and communication. Aligning requirements more closely with other federal and private models could also help mitigate the risk for vendors.