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Adults in rural counties in the United States (US) experience higher rates broadly of cardiovascular disease (CVD) compared with adults in urban counties. Mortality rates specifically due to heart failure (HF) have increased since 2011, but estimates of heterogeneity at the county-level in HF-related mortality have not been produced. The objectives of this study were 1) to quantify nationwide trends by rural-urban designation and 2) examine county-level factors associated with rural-urban differences in HF-related mortality rates. We queried CDC WONDER to identify HF deaths between 2011-2018 defined as CVD (I00-78) as the underlying cause of death and HF (I50) as a contributing cause of death. First, we calculated national age-adjusted mortality rates (AAMR) and examined trends stratified by rural-urban status (defined using 2013 NCHS Urban-Rural Classification Scheme), age (35-64 and 65-84 years), and race-sex subgroups per year. Second, we combined all deaths from 2011-2018 and estimated incidence rate ratios (IRR) in HF-related mortality for rural versus urban counties using multivariable negative binomial regression models with adjustment for demographic and socioeconomic characteristics, risk factor prevalence, and physician density. Between 2011-2018, 162,314 and 580,305 HF-related deaths occurred in rural and urban counties, respectively. AAMRs were consistently higher for residents in rural compared with urban counties (73.2 [95% CI: 72.2-74.2] vs. 57.2 [56.8-57.6] in 2018, respectively). The highest AAMR was observed in rural Black men (131.1 [123.3-138.9] in 2018) with greatest increases in HF-related mortality in those 35-64 years (+6.1%/year). The rural-urban IRR persisted among both younger (1.10 [1.04-1.16]) and older adults (1.04 [1.02-1.07]) after adjustment for county-level factors. Main limitations included lack of individual-level data and county dropout due to low event rates (<20). Differences in county-level factors may account for a significant amount of the observed variation in HF-related mortality between rural and urban counties. Efforts to reduce the rural-urban disparity in HF-related mortality rates will likely require diverse public health and clinical interventions targeting the underlying causes of this disparity.

Long non-coding RNAs (lncRNAs) are emerging regulators of pathophysiological processes including atherosclerosis. Using RNA-seq profiling of the intima of lesions, here we identify a macrophage-specific lncRNA MAARS (Macrophage-Associated Atherosclerosis lncRNA Sequence). Aortic intima expression of MAARS increases by 270-fold with atherosclerotic progression and decreases with regression by 60%. MAARS knockdown reduces atherosclerotic lesion formation by 52% in LDLR −/− mice, largely independent of effects on lipid profile and inflammation, but rather by decreasing macrophage apoptosis and increasing efferocytosis in the vessel wall. MAARS interacts with HuR/ELAVL1, an RNA-binding protein and important regulator of apoptosis. Overexpression and knockdown studies verified MAARS as a critical regulator of macrophage apoptosis and efferocytosis in vitro, in an HuR-dependent manner. Mechanistically, MAARS knockdown alters HuR cytosolic shuttling, regulating HuR targets such as p53, p27, Caspase-9, and BCL2. These findings establish a mechanism by which a macrophage-specific lncRNA interacting with HuR regulates apoptosis, with implications for a broad range of vascular disease states. Long non coding RNA molecules have been implicated in the immunopathology of a range of inflammatory pathologies. Here the authors show lncRNA MAARS regulates apoptosis via interaction with HuR in the context of atherosclerosis.

Laser wakefield accelerators (LWFAs) have electric fields that are orders of magnitude larger than those of conventional accelerators, promising an attractive, small-scale alternative for next-generation light sources and lepton colliders. The maximum energy gain in a single-stage LWFA is limited by dephasing, which occurs when the trapped particles outrun the accelerating phase of the wakefield. Here, we demonstrate that a single space–time structured laser pulse can be used for ionization injection and electron acceleration over many dephasing lengths in the bubble regime. Simulations of a dephasingless laser wakefield accelerator driven by a 6.2-J laser pulse show 25 pC of injected charge accelerated over 20 dephasing lengths (1.3 cm) to a maximum energy of 2.1 GeV. The space–time structured laser pulse features an ultrashort, programmable-trajectory focus. Accelerating the focus, reducing the focused spot-size variation, and mitigating unwanted self-focusing stabilize the electron acceleration, which improves beam quality and leads to projected energy gains of 125 GeV in a single, sub-meter stage driven by a 500-J pulse.

Emulation of the \"target trial\" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients. We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance. We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44). In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.

Background: Hand hygiene is the most important tool for preventing the spread of infections in the healthcare environment. Personal protective equipment (PPE) and nails policy are important additional measures for limiting infectious spread. Our facility typically performs both covert and overt hand hygiene, PPE and nail audits. Compliance rates with hand hygiene and PPE have declined since the COVID-19 pandemic. More information was needed on factors contributing to decreasing compliance rates. Methods An anonymous hybrid electronic and print survey was distributed at annual Infection Prevention fair across a 9-hospital system in Eastern North Carolina from April 2025-November 2025. The survey was conducted via Qualtrics. Results There were 432 total responses, 41% were registered nurses, 7% radiation technologists, 6% nursing assistants and 3% or less of a wide variety of other specialties/departments. Community hospitals represented 83% of responses and 17% were from a large academic medical center. Overall self-reported hand hygiene and PPE compliance was 96.10% and 94.3% whereas perceived compliance of peers was 89.29% and 88.7% respectively. Individual unit audits reported a rate of 89.9% hand hygiene compliance during this time period. When asked about specific scenarios, 84.6% of healthcare workers stated they would wear PPE for isolation precautions when entering the room, but patient contact was not anticipated. Conclusions Healthcare workers report high levels of compliance with hand hygiene and PPE but report lower numbers for perceived compliance of peers. In our health system opportunities to improve isolation precaution compliance include increasing availability of PPE and education on need for PPE even when patient contact is not anticipated. There is strong support for a natural nails policy among healthcare workers in our system, but among the minority that were opposed many left comments expressing strong opposition.

Background: Hospital acquired infections are known to increase hospital stays and increase morbidity and mortality. Historically, Methicillin-resistance Staphylococcus aureus (MRSA) screening and contact precautions have been the primary strategy to prevent the spread of MRSA in healthcare systems. Increasing evidence supports the role for MRSA decolonization to decrease the spread of this important pathogen. The COVID-19 pandemic and related personal protective equipment conservation has led to many programs re-examining contact precautions for MRSA. Methods: In February of 2024 MRSA screening was discontinued for new admissions and an MRSA decolonization protocol was implemented for patients at high risk for MRSA infection as defined in the SHEA compendium for reducing MRSA infections. Decolonization included nasal Mupirocin 2% ointment and 2% Chlorhexidine Gluconate (CHG) bathing for five days in the adult inpatient population. High risk patients targeted for this intervention included patients transferred from another healthcare facility, admitted from home health, on dialysis, prior history of MRSA infection or those with central venous catheters. Contact isolation precautions for MRSA colonization were discontinued but maintained for active infection with MRSA. Results: After implementation, MRSA nares screening tests declined by 24.4% while utilization of mupirocin increased 5.85 times the pre-implementation average. In the twelve months prior to the intervention there were 221.1 new MRSA infections per 1000 inpatient admissions and in the 12 months following intervention there were 155.4 new MRSA infections per 1000 inpatient admissions. The rate of MRSA infections had been increasing prior to intervention and the rate of increase decreased by 54.8% after implementation. We estimated a cost savings of$194,745 if all patients that were previously screened were instead decolonized. We additionally noted an approximate 18% reduction in isolation gown use resulting an additional estimated annual cost savings of $ 115,369 per year if sustained. Conclusions: The implementation of a MRSA decolonization program resulted in significant cost savings without any associated increase in clinical MRSA cultures. The program appeared to have far greater buy-in than the previous screen and isolate program despite having similar patient selection criteria. This may reflect a greater perceived importance of screening relative to a treatment strategy. A decolonization strategy was found to be effective at decreasing the rate of new MRSA infections even with the removal of isolation precautions for colonization. Low compliance with isolation precautions for colonization are thought to be a contributing factor in the limited efficacy of a screen and isolate strategy.

For the last forty years in the United States, there has been a progressively widening disparity in cardiovascular disease (CVD) morbidity and mortality between rural and urban areas known as the “rural mortality penalty.” Drivers of rural-urban disparities in CVD are multifactorial, including differences in demographics, education, economic opportunity, access to care, and healthcare quality. Because of the complex and heterogenous nature of rural areas in the United States, definitions of rural vary significantly, leading to challenges in quantifying disparities and targeting interventions. Potential solutions to increase access to cardiovascular care in rural areas include initiatives to expand the primary care and cardiology workforces, build partnerships between rural healthcare providers and academic medical centers (AMC), establish more outreach clinics in underserved or poorly resourced rural communities, develop rural provider training programs, expand and improve telemedicine offerings, develop community wide CVD prevention programs, expand health insurance coverage in rural areas, continue government support of rural hospitals and address social determinants of health as rural populations often face higher rates of poverty, food insecurity, unemployment, housing instability, and limited access to education, all of which exacerbate health disparities.

A 65-year-old man with HIV sought treatment for fever, weight loss, and productive cough after returning to the United States from Liberia. Fungal cultures grew Emergomyces pasteurianus, and the patient's health improved after beginning voriconazole. We describe the clinical case and review the literature, treatment, and susceptibilities for E. pasteurianus.

Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has led to a global pandemic, failures of local health care systems, and global economic recession. MicroRNAs (miRNAs) have recently emerged as important regulators of viral pathogenesis, particularly among RNA viruses, but the impact of host miRNAs on SARS-CoV-2 infectivity remains unknown. In this study, we utilize the combination of powerful bioinformatic prediction algorithms and miRNA profiling to predict endogenous host miRNAs that may play important roles in regulating SARS-CoV-2 infectivity. We provide a collection of high-probability miRNA binding sites within the SARS-CoV-2 genome as well as within mRNA transcripts of critical viral entry proteins ACE2 and TMPRSS2 and their upstream modulators, the interferons (IFN). By utilizing miRNA profiling datasets of SARS-CoV-2-resistant and -susceptible cell lines, we verify the biological plausibility of the predicted miRNA–target RNA interactions. Finally, we utilize miRNA profiling of SARS-CoV-2-infected cells to identify predicted miRNAs that are differentially regulated in infected cells. In particular, we identify predicted miRNA binders to SARS-CoV-2 ORFs (miR-23a (1ab), miR-29a, -29c (1ab, N), miR-151a, -151b (S), miR-4707-3p (S), miR-298 (5′-UTR), miR-7851-3p (5′-UTR), miR-8075 (5′-UTR)), ACE2 3′-UTR (miR-9-5p, miR-218-5p), TMPRSS2 3′-UTR (let-7d-5p, -7e-5p, miR-494-3p, miR-382-3p, miR-181c-5p), and IFN-α 3′-UTR (miR-361-5p, miR-410-3p). Overall, this study provides insight into potential novel regulatory mechanisms of SARS-CoV-2 by host miRNAs and lays the foundation for future investigation of these miRNAs as potential therapeutic targets or biomarkers.