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Approximately 2/3 of patients with hypertrophic cardiomyopathy (HCM) have significant left ventricular outflow tract obstruction (LVOTO), which is caused by the interaction mitral valve apparatus and the hypertrophied septum. The contribution of mitral valve remodeling to the development of obstruction over time has never been described. We analyzed retrospectively 40 patients with HCM and no baseline obstruction followed up for a median of 2179 days. At follow up, 13 patients developed significant LVOTO. Patients who developed LVOTO had longer posterior leaflets and longer anterior leaflet residual length.

Background: Previous research has shown the potential benefit of eosinophilia in respiratory viral infections, which could suggest a milder clinical course and outcome for those with COVID-19 infection. However, there is mixed evidence regarding peripheral eosinophilia with regards to acute respiratory distress syndrome and there is little data in critically ill patients. Methods: To evaluate the effect on clinical outcomes of developing peripheral eosinophilia during hospitalization for severe COVID-19 we performed a retrospective case control study comparing outcomes in patients who did and did not develop peripheral eosinophilia during hospitalization. Results: Patients who developed peripheral eosinophilia during hospitalization had a more prolonged intensive care unit course, course of mechanical ventilation and hospital course. This was also seen in a sub-analysis of only patients who survived to hospital discharge. The two most identifiable causes of eosinophilia were related to antibiotics and secondary fungal or parasitic infections. Patients with an identifiable cause of eosinophilia had a more prolonged course of mechanical ventilation. Most cases had no cause identified. Conclusion: Our findings support completing a work-up for newly developed peripheral eosinophilia since it may be an early sign of secondary infection, but it may be a result of medical treatments such as antibiotic therapy. Regardless of the cause, our data suggests secondary eosinophilia is associated with increased morbidity in critically ill patients.

De novo primary angiosarcoma of the bladder in the absence of radiation has only been reported in 20 cases worldwide. If patients with prior a history of radiation or cancer are included this number climbs to nearly 50 reported cases. Here, we report the 21st case of bladder angiosarcoma with primary origin in the absence of any known carcinogenic exposures. We describe a 62-year-old male with intermittent hematuria who had a 2.5 cm bladder mass on a CT scan. He was initially treated with a TURBT down to the muscularis layer without evidence of invasion, followed by discharge from the hospital. Ultimately, the patient underwent definitive management with a radical cystoprostatectomy and bilateral pelvic lymph node dissection. A comprehensive review of the literature was also conducted. Given the nature of these aggressive tumors, most patients expired within one year of diagnosis, but a multimodal approach suggested a survival benefit in four of seven patients. Overall, this is an aggressive tumor with a benign presentation and should be included in the differential as the number of cases reported have increased over the past 50 years.

Black Americans suffer lower life expectancy and show signs of accelerated aging compared to other Americans. While previous studies observe these differences in children and populations with chronic illness, whether these pathologic processes exist or how these pathologic processes progress has yet to be explored prior to the onset of significant chronic illness, within a young adult population. Therefore, we investigated race-related differences in epigenetic age in a cross-sectional sample of young putatively healthy adults and assessed whether lifetime stress and/or trauma mediate those differences. Biological and psychological data were collected from self-reported healthy adult volunteers within the local New Haven area (399 volunteers, 19.8% Black, mean age: 29.28). Stress and trauma data was collected using the Cumulative Adversity Inventory (CAI) interview, which assessed specific types of stressors, including major life events, traumatic events, work, financial, relationship and chronic stressors cumulatively over time. GrimAge Acceleration (GAA), determined from whole blood collected from participants, measured epigenetic age. In order to understand the impact of stress and trauma on GAA, exploratory mediation analyses were then used. We found cumulative stressors across all types of events (mean difference of 6.9 p = 2.14e-4) and GAA (β = 2.29 years [1.57–3.01, p = 9.70e-10] for race, partial η2 = 0.091, model adjusted R2 = 0.242) were significantly greater in Black compared to White participants. Critically, CAI total score (proportion mediated: 0.185 [0.073–0.34, p = 6e-4]) significantly mediated the relationship between race and GAA. Further analysis attributed this difference to more traumatic events, particularly assaultive traumas and death of loved ones. Our results suggest that, prior to development of significant chronic disease, Black individuals have increased epigenetic age compared to White participants and that increased cumulative stress and traumatic events may contribute significantly to this epigenetic aging difference.

Abstract Genealogical networks (i.e. family trees) are of growing interest, with the largest known data sets now including well over one billion individuals. Interest in family history also supports an 8.5 billion dollar industry whose size is projected to double within 7 years [FutureWise report HC-1137]. Yet little mathematical attention has been paid to the complex network properties of genealogical networks, especially at large scales. The structure of genealogical networks is of particular interest due to the practice of forming unions, e.g. marriages, that are typically well outside one’s immediate family. In most other networks, including other social networks, no equivalent restriction exists on the distance at which relationships form. To study the effect this has on genealogical networks we use persistent homology to identify and compare the structure of 101 genealogical and 31 other social networks. Specifically, we introduce the notion of a network’s persistence curve, which encodes the network’s set of persistence intervals. We find that the persistence curves of genealogical networks have a distinct structure when compared to other social networks. This difference in structure also extends to subnetworks of genealogical and social networks suggesting that, even with incomplete data, persistent homology can be used to meaningfully analyze genealogical networks. Here we also describe how concepts from genealogical networks, such as common ancestor cycles, are represented using persistent homology. We expect that persistent homology tools will become increasingly important in genealogical exploration as popular interest in ancestry research continues to expand.

Abstract Resilience has become an increasingly important concept in the cultural heritage field, particularly in the aftermath of the unprecedented challenges the COVID-19 global pandemic brought. However, on a conceptual and practical level, resilience remains closely linked to the technical conservation of built heritage, and there remains a need to develop broader approaches inclusive of cultural and socioeconomic components. This article investigates the potential applicability of theoretical concepts linked to identity and identities in heritage planning to help fill these gaps and develop approaches that consider resilience and are better able to address a range of unanticipated disasters. We first review the literature and policy documents to define and identify the potential for identities-based approaches. We then examine the case of Matera, an extremely fragile world heritage site in southern Italy that has been continuously inhabited for more than 8000 years and provides a relevant example of resilience. We explore the trends and effects of globalised tourism development before the pandemic and the post pandemic emergence of more local/regional and slow tourism patterns, largely based on cultural solutions to local development challenges and knowledge exchange. Through this comparison, we analyse the potential and limitations of introducing identities-based concepts into heritage planning as a more robust way to enhance resilience and prepare cities for unexpected future crises.

Augochloropsis and other shiny green Halictinae have had various taxonomic issues and are often misidentified. One prevailing taxonomic issue is that Augochloropsis metallica (Fabricius) has two subspecies, that have long been recognized as morphologically distinct (Augochloropsis metallica metallica and Augochloropsis metallica fulgida (Smith), but the subspecies are inconsistently applied in the literature. Here, we review the Augochloropsis of the Midwest and further address the Augochloropsis species in the broader United States to resolve the outstanding taxonomic issues with the midwestern species. We provide identification keys and diagnoses for the genera and species of the shiny green Halictinae of the midwestern United States, which includes the genera Agapostemon, Augochlora, Augochlorella, and Augochloropsis. This work results in taxonomic changes to Augochloropsis. Augochloropsis sumptuosa (Smith) is split into two species, with the name Augochloropsis sumptuosa retained for the eastern form, and Augochloropsis humeralis (Patton), stat. nov., reinstated for the western form. Augochloropsis metallica is split into five species, with two of those species occurring in the midwestern United States: Augochloropsis metallica and Augochloropsis viridula (Smith), stat. nov. Examination of the holotype of Augochloropsis fulgida (Smith) revealed that it does not agree with the prevailing concept of Augochloropsis metallica fulgida; it is reinstated as Augochloropsis fulgida, stat. nov., but is currently known only from the holotype female from Florida. Augochloropsis cuprea (Smith), long considered to be a synonym of Augochloropsis metallica, is also distinct, and we are reinstating Augochloropsis cuprea, stat. nov., though the range of this species is unclear. We further recognize Augochloropsis fulvofimbriata (Friese), stat. nov., from South and Central America, as distinct. These changes result in a total of three Augochloropsis species in the Midwest and seven named species in the United States. We are aware of additional species from the southern and southwestern United States that are undescribed, and we highlight additional taxonomic work that remains to be done.

Abstract Despite the proposed ‘certainty’ in a city or region hosting a mega-event, there has long been issues of uncertainty surrounding the planning and implementation of what have until now essentially been mega-projects. Large events have found a variety of ways to adapt and respond to unforeseen circumstances due to political conflicts, planning of oversize venues, limited time of implementation, and legacies that are difficult to manage. Considering the further increased uncertainty surrounding the planning of mega-events as a result of the COVID-19 pandemic, this paper examines how an accompanying cultural component—e.g., the Cultural Olympiad—may help cities that plan for events like the Olympics transition toward diversified drivers and long-term legacy. In particular, the case of cultural offering in Milan between the two mega-events of Expo 2015 and the upcoming 2026 Milano-Cortina Olympic Games shows how host cities can address growing uncertainty through the expanded role of a cultural programme combined with the rescaling of traditional mega-event formats. With this purpose, 2012 London Cultural Olympiad has been selected as an antecedent example—with positive and negative outcomes—to critically review the relationships between the Olympics and the Cultural Olympiad, as well as their widespread spatial strategy and public engagement. In addition, the paper offers more general conclusions regarding learning potentials of jointly studying mega-events and cultural policy.

Abstract Achieving food security in sub-Saharan Africa (SSA) is a multidimensional challenge. SSA reliance on food imports is expected to grow in the coming decades to meet the population's demand, projected to double to over 2 billion people by 2050. In addition, climate change is already affecting food production and supply chains across the region. Addressing these multiple food security challenges will necessitate rapid enhancements in agricultural productivity, which is influenced by a host of demographic, agronomic, and climatic factors. We use statistical approaches to examine rainfed maize in Kenya, where maize cultivation and consumption are widespread and central to livelihoods and national food security. We find that improving a suite of agronomic factors, such as applying fertilizer, planting certified seeds, and extension services, will have a greater effect on rainfed maize productivity than demographics and can offset the effects of climate change. These findings could also offer insights into similar challenges for other crops in Kenya and other SSA countries.

Abstract Caregivers for patients with cirrhosis face immense physical and psychological strain that negatively impact quality of life and ability to care for oneself. The aim is to explore the caregiver experience for patients with cirrhosis, identify prominent stressors, and understand the multidimensional contributors to caregiver burden, to help tailor effective interventions. The caregivers of 25 patients with decompensated cirrhosis underwent semistructured in‐person interviews and completed written exercises targeting emotional disclosure or resilience training that were analyzed for dominant emotions and themes. Burden was quantified using the Zarit Burden Interview‐12 (ZBI, range 0–48), Distress Thermometer (0–10), and Caregiver Captivity Index (0–4). Quality of life was assessed with a visual analog scale (0–100). Median ZBI was moderate (14 [10–19]), as was distress (5 [2–7]), and captivity (2 [1–4]). Quality of life was fair (80 [70–85]). Dominant emotions included anxiety, guilt, fear, frustration, captivity, and resentment. Prominent themes included lack of time for self‐care, hierarchy of caregiver role, support from versus frustration with medical professionals, social support, spirituality and religion, and disease‐related restrictions. Hepatic encephalopathy, and need to follow strict nutrition and diet recommendations, are frequent sources of disease‐related caregiver burden. The health care system confers some degree of burden, especially when doubts arise regarding physician competence. Conclusion: Caregiver burden is significant. The impact of interventions to alleviate caregiver burden should be explored, so that their appreciated efforts do not have such detrimental effects on their quality of life.

Abstract Background Smell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID‐19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID‐19 patients suggests that self‐reported measures are insufficient for capturing patients with chemosensory dysfunction. Objectives The purpose of this study was to quantify the impact of recent COVID‐19 infection on chemosensory function and demonstrate the use of at‐home objective smell and taste testing in an at‐risk population of healthcare workers. Methods Two hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self‐administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one‐month follow‐up surveys were completed. Results Among subjects with prior SARS‐CoV‐2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self‐reported smell and taste loss were both strong predictors of COVID‐19 positivity. Subjects with evidence of recent SARS‐CoV‐2 infection (

Summary: SORL1 is implicated in the pathogenesis of Alzheimer’s disease (AD) through genetic studies. To interrogate the roles of SORL1 in human brain cells, SORL1-null induced pluripotent stem cells (iPSCs) were differentiated to neuron, astrocyte, microglial, and endothelial cell fates. Loss of SORL1 leads to alterations in both overlapping and distinct pathways across cell types, with the greatest effects in neurons and astrocytes. SORL1 loss induces a neuron-specific reduction in apolipoprotein E (APOE) and clusterin (CLU) and altered lipid profiles. Analyses of iPSCs derived from a large cohort reveal a neuron-specific association between SORL1, APOE, and CLU levels, a finding validated in postmortem brain. Enhancement of retromer-mediated trafficking rescues tau phenotypes observed in SORL1-null neurons but does not rescue APOE levels. Pathway analyses implicate transforming growth factor β (TGF-β)/SMAD signaling in SORL1 function, and modulating SMAD signaling in neurons alters APOE RNA levels in a SORL1-dependent manner. Taken together, these data provide a mechanistic link between strong genetic risk factors for AD.

In this review, we provide a comprehensive overview of common sleep disorders during pregnancy, including their characterization, prevalence, risk factors, and possible contribution to maternal and fetal outcomes. We conducted a quasi-systematic literature search of the MEDLINE database and identified 744 studies from 1991 through 2021, inclusive, that met our inclusion criteria. We synthesized the existing literature on sleep disorders during pregnancy and highlighted controversies, research gaps, and needed clinical developments. Our review covers a range of sleep disorders, including insomnia, obstructive sleep apnea, restless legs syndrome, and circadian rhythm disorders. We discuss the prevalence of these disorders in pregnancy and their potential impact on maternal and fetal health outcomes. We also explore the relationship between sleep disorders, pre-pregnancy comorbidities such as obesity, and pregnancy-related conditions such as gestational diabetes mellitus and preeclampsia. In addition to summarizing the existing literature on sleep disorders during pregnancy, we also highlight opportunities for further research in this area. We suggest that future studies should strive to employ validated and objective measurement tools for sleep disorders and prioritize utilization of longitudinal methods with participant follow-up through postpartum, mid-life, menopause, and beyond. We also put forward investigation into the impact of circadian rhythm disruption on reproductive physiology and early pregnancy outcomes as an area of important work. Overall, our review provides valuable insights on sleep and reproduction and into common sleep disorders during pregnancy and their potential impact on maternal and fetal health outcomes.

BK polyomavirus nephropathy (BKVN) is a common cause of nephropathy in kidney transplant patients and is typically seen within the first year after transplantation. BK polyomavirus nephropathy can occur in the native kidneys of patients with nonrenal solid-organ transplants (NRSOT). However, this is rare, especially outside the early post-transplant period, and BKVN is not usually considered in the differential diagnosis for acute kidney injury in NRSOT patients. We present a case of a 75-year-old man who had undergone orthotopic heart transplant 13 years prior with stable allograft function who developed progressive renal dysfunction in the setting of recent unilateral obstructive nephrolithiasis requiring ureteral stenting. Kidney biopsy demonstrated evidence of polyomavirus nephritis. Serum BK viral load was elevated. Despite reducing immunosuppression and initiating leflunomide, viral clearance was never achieved. The patient experienced progressive failure to thrive before ultimately transitioning to hospice care and dying. The intensity of immunosuppression is a well-known risk factor for viral replication; ureteral stenting has also been associated with BKVN. However, since clinical manifestations of BK viral infections often include a genitourinary (GU) tract pathology, it is important for clinicians to consider BKVN in patients with NRSOT with progressive renal dysfunction, especially in the clinical context of known GU disease.

Study region: Chaco Culture National Historical Park (CCNHP) is in the San Juan Basin of northwestern New Mexico, U.S.A. Its only water supply is in Gallup Sandstone aquifer, stratigraphically surrounded by layers long targeted for oil and natural gas extraction. Study focus: To assess groundwater flow direction, age, mixing between aquifers, and whether hydrocarbons extraction may affect water quality, we completed a geochemical groundwater sampling campaign. Groundwater at 11 sites was analyzed for major ions, hydrocarbon associated volatile organic carbon (VOC) compounds, noble gases, and the isotope systems δ2H, δ18O, 87Sr/86Sr, δ13C, and 14C. New hydrological insights for the region: Results demonstrate that all sampled groundwaters are exceedingly old and geochemically evolved, with a median 14C age of ∼41,000 years before present and a north flowing path. Three lines of evidence suggest mixing between aquifers through relatively impermeable shale units and mixing with hydrocarbons: 1) noble gases are fractionated likely through mixing with connate water expelled during hydrocarbon genesis; 2) several wells—including the park’s main supply well—contained trace amounts of hydrocarbon related VOC compounds; and 3) major ion analysis shows mixing trends between aquifers. We hypothesize that cross-aquifer mixing may be facilitated through the region’s numerous hydrocarbon related boreholes. Whether our findings are the result of oil and gas extraction or represent the natural state of the aquifers will require more research.

Golf is increasing in popularity with 24.8 million golfers in the U.S. in 2020, a 2% increase from the previous year. This number increased to 37.5 million in 2021 which can be further broken down to 25.1 million on course and 12.4 million participating in off course activities. Playing golf does not come without risk of injury, with an annual incidence between 15.8% and 40.9% in amateurs and 31% in professional golfers. Most injuries in golf occur due to overuse (82.6%) and only a small percentage occur from a single traumatic event (17.4%). Injuries most commonly occur at the low back followed by the wrist. Injury prevention programs have shown to be successful in other sports however to date there are no studies assessing a golfer's specific program. The purpose of this clinical commentary is to describe three individualized and unsupervised golf exercise programs (The Golfer's Fore, Fore+, and Advanced Fore+), of varying difficultly, designed to reduce the risk of injury, improve strength/mobility, and optimize performance. # Level of Evidence 5

Objective: Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease, yet little is known about Lp(a) testing patterns in real-world practice. The objective of this analysis was to determine how Lp(a) testing is used in clinical practice in comparison with low density lipoprotein cholesterol (LDL-C) testing alone, and to determine whether elevated Lp(a) level is associated with subsequent initiation of lipid-lowering therapy (LLT) and incident cardiovascular (CV) events. Methods: This is an observational cohort study, based on lab tests administered between Jan 1, 2015 and Dec 31, 2019. We used electronic health record (EHR) data from 11 United States health systems participating in the National Patient-Centered Clinical Research Network (PCORnet). We created two cohorts for comparison: 1) the Lp(a) cohort, of adults with an Lp(a) test and 2) the LDL-C cohort, of 4:1 date- and site-matched adults with an LDL-C test, but no Lp(a) test. The primary exposure was the presence of an Lp(a) or LDL-C test result. In the Lp(a) cohort, we used logistic regression to assess the relationship between Lp(a) results in mass units (< 50, 50-100, and > 100mg/dL) and molar units ( 250nmol/L) and initiation of LLT within 3 months. We used multivariable adjusted Cox proportional hazards regression to evaluate these Lp(a) levels and time to composite CV hospitalization, including hospitalization for myocardial infarction, revascularization and ischemic stroke. Results: Overall, 20,551 patients had Lp(a) test results and 2,584,773 patients had LDL-C test results (82,204 included in the matched LDL-C cohort). Compared with the LDL-C cohort, the Lp(a) cohort more frequently had prevalent ASCVD (24.3% vs. 8.5%) and multiple prior CV events (8.6% vs. 2.6%). Elevated Lp(a) was associated with greater odds of subsequent LLT initiation. Elevated Lp(a) reported in mass units was also associated with subsequent composite CV hospitalization [aHR (95% CI): Lp(a) 50-100mg/dL 1.25 (1.02-1.53), p 100mg/dL 1.23 (1.08-1.40), p

The optical properties of light-absorbing materials in optical shutter devices are critical to the use of such platforms for optical applications. We demonstrate switchable optical properties of dyes and nanoparticles in liquid-based electrowetting-on-dielectric (EWOD) devices. Our work uses narrow-band-absorbing dyes and nanoparticles, which are appealing for spectral-filtering applications targeting specific wavelengths while maintaining device transparency at other wavelengths. Low-voltage actuation of boron dipyromethene (BODIPY) dyes and nanoparticles (Ag and CdSe) was demonstrated without degradation of the light-absorbing materials. Three BODIPY dyes were used, namely Abs 503 nm, 535 nm and 560 nm for dye 1 (BODIPY-core), 2 (I2BODIPY) and 3 (BODIPY-TMS), respectively. Reversible and low-voltage (≤20 V) switching of dye optical properties was observed as a function of device pixel dimensions (300 × 900, 200 × 600 and 150 × 450 µm). Low-voltage and reversible switching was also demonstrated for plasmonic and semiconductor nanoparticles, such as CdSe nanotetrapods (abs 508 nm), CdSe nanoplatelets (Abs 461 and 432 nm) and Ag nanoparticles (Abs 430 nm). Nanoparticle-based devices showed minimal hysteresis as well as faster relaxation times. The study presented can thus be extended to a variety of nanomaterials and dyes having the desired optical properties.

Background: The Reducing Air Pollution in Detroit Intervention Study (RAPIDS) was designed to evaluate cardiovascular health benefits and personal fine particulate matter (particulate matter < 2.5 μm in diameter, PM2.5) exposure reductions via portable air filtration units (PAFs) among older adults in Detroit, Michigan. This double-blind randomized crossover intervention study has shown that, compared to sham, air filtration for 3 days decreased 3-day average brachial systolic blood pressure by 3.2 mmHg. The results also showed that commercially available HEPA-type and true HEPA PAFs mitigated median indoor PM2.5 concentrations by 58% and 65%, respectively. However, to our knowledge, no health intervention study in which a significant positive health effect was observed has also evaluated how outdoor and indoor PM2.5 sources impacted the subjects. With that in mind, detailed characterization of outdoor and indoor PM2.5 samples collected during this study and a source apportionment analysis of those samples using a positive matrix factorization model were completed. The aims of this most recent work were to characterize the indoor and outdoor sources of the PM2.5 this community was exposed to and to assess how effectively commercially available HEPA-type and true HEPA PAFs were able to reduce indoor and outdoor PM2.5 source contributions. Methods: Approximately 24 h daily indoor and outdoor PM2.5 samples were collected on Teflon and Quartz filters from the apartments of 40 study subjects during each 3-day intervention period. These filters were analyzed for mass, carbon, and trace elements. Environmental Protection Agency Positive Matrix Factorization (PMF) 5.0 was utilized to determine major emission sources that contributed to the outdoor and indoor PM2.5 levels during this study. Results: The major sources of outdoor PM2.5 were secondary aerosols (28%), traffic/urban dust (24%), iron/steel industries (15%), sewage/municipal incineration (10%), and oil combustion/refinery (6%). The major sources of indoor PM2.5 were organic compounds (45%), traffic + sewage/municipal incineration (14%), secondary aerosols (13%), smoking (7%), and urban dust (2%). Infiltration of outdoor PM2.5 for sham, HEPA-type, and true HEPA air filtration was 79 ± 24%, 61 ± 32%, and 51 ± 34%, respectively. Conclusions: The results from our study showed that intervention with PAFs was able to significantly decrease indoor PM2.5 derived from outdoor and indoor PM2.5 sources. The PAFs were also able to significantly reduce the infiltration of outdoor PM2.5. The results of this study provide insights into what types of major PM2.5 sources this community is exposed to and what degree of air quality and systolic blood pressure improvements are possible through the use of commercially available PAFs in a real-world setting.

Molnupiravir was the first orally available SARS-CoV-2 antiviral approved for outpatient use against SARS-CoV-2, but its efficacy against variants of concern, especially delta, was questioned. Here the authors evaluate molnupiravir against variant of concern in numerous models, including human airway epithelium organoids, ferrets and Roborovski dwarf hamsters.

The objectives of the present study were to measure and describe the baseline participant needs of a hospital-based violence intervention 1-year pilot program, assess differences in expected hospital revenue based on changes in health insurance coverage resulting from program implementation and discuss the program’s limitations. Methods: Between September 2020 and September 2021 Encompass Omaha enrolled 36 participants. A content analysis of 1199 progress notes detailing points of contact with participants was performed to determine goal status. Goals were categorized and goal status was defined as met, in process, dropped, or participant refusal. Results: The most frequently identified needs were help obtaining short-term disability assistance or completing FMLA paperwork (86.11%), immediate financial aid (86.11%), legal aid (83.33%), access to food (83.3%), and navigating medical issues other than the primary reason for hospitalization (83.33%). Conclusions: Meeting the participants’ short-term needs is critical for maintaining their engagement in the long-term. Further, differences in expected hospital revenue for pilot participants compared with a control group were examined, and this analysis found a reduction in medical and facility costs for program participants. The pilot stage highlighted how complex the needs and treatment of victims of violence are. As the program grows and its staff become more knowledgeable about social work, treatment, and resource access processes, the program will continue to improve.

Objectives:. Many investigations have evaluated local and systemic consequences of intramedullary (IM) reaming and suggest that reaming may cause, or exacerbate, injury to the soft tissues adjacent to fractures. To date, no study has examined the effect on local muscular physiology as measured by intramuscular pH (IpH). Here, we observe in vivo IpH during IM reaming for tibia fractures. Methods:. Adults with acute tibia shaft fractures (level 1, academic, 2019–2021) were offered enrollment in an observational cohort. During IM nailing, a sterile, validated IpH probe was placed into the anterior tibialis (

Stochastic simulations are ubiquitous across scientific disciplines. The Multiphysics Object-Oriented Simulation Environment (MOOSE) includes an optional module – stochastic tools – for implementing stochastic simulations. It implements an efficient and scalable scheme for performing stochastic analysis in memory. It can be used for building meta models to reduce the computational expense of multiphysics problems as well as perform analyses requiring up to millions of stochastic simulations. To illustrate, we have provided an example that trains a proper orthogonal decomposition reduced-basis model. The impact of the module is detailed by explaining how it is being used for failure analysis in nuclear fuel and reducing the computational burden via dynamic meta model training. The module is unique in that it provides the ability to use a single framework for simulations and stochastic analysis, especially for memory intensive problems and intrusive meta modeling methods.

Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4'-Fluorouridine (4'-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus (RSV), we explored activity of the compound against seasonal and highly pathogenic influenza (HPAI) viruses in cell culture, human airway epithelium (HAE) models, and/or two animal models, ferrets and mice, that assess IAV transmission and lethal viral pneumonia, respectively. 4'-FlU inhibited a panel of relevant influenza A and B viruses with nanomolar to sub-micromolar potency in HAE cells. In vitro polymerase assays revealed immediate chain termination of IAV polymerase after 4'-FlU incorporation, in contrast to delayed chain termination of SARS-CoV-2 and RSV polymerase. Once-daily oral treatment of ferrets with 2 mg/kg 4'-FlU initiated 12 hours after infection rapidly stopped virus shedding and prevented transmission to untreated sentinels. Treatment of mice infected with a lethal inoculum of pandemic A/CA/07/2009 (H1N1)pdm09 (pdmCa09) with 4'-FlU alleviated pneumonia. Three doses mediated complete survival when treatment was initiated up to 60 hours after infection, indicating a broad time window for effective intervention. Therapeutic oral 4'-FlU ensured survival of animals infected with HPAI A/VN/12/2003 (H5N1) and of immunocompromised mice infected with pdmCa09. Recoverees were protected against homologous reinfection. This study defines the mechanistic foundation for high sensitivity of influenza viruses to 4'-FlU and supports 4'-FlU as developmental candidate for the treatment of seasonal and pandemic influenza.

Introduction Orthopaedic trauma and fracture care commonly cause perioperative anaemia and associated functional iron deficiency due to a systemic inflammatory state. Modern, strict transfusion thresholds leave many patients anaemic; managing this perioperative anaemia is an opportunity to impact outcomes in orthopaedic trauma surgery. The primary outcome of this pilot study is feasibility for a large randomised controlled trial (RCT) to evaluate intravenous iron therapy (IVIT) to improve patient well-being following orthopaedic injury. Measurements will include rate of participant enrolment, screening failure, follow-up, missing data, adverse events and protocol deviation.Methods and analysis This single-centre, pilot, double-blind RCT investigates the use of IVIT for acute blood loss anaemia in traumatically injured orthopaedic patients. Patients are randomised to receive either a single dose infusion of low-molecular weight iron dextran (1000 mg) or placebo (normal saline) postoperatively during their hospital stay for trauma management. Eligible subjects include adult patients admitted for lower extremity or pelvis operative fracture care with a haemoglobin of 7–11 g/dL within 7 days postoperatively during inpatient care. Exclusion criteria include history of intolerance to intravenous iron supplementation, active haemorrhage requiring ongoing blood product resuscitation, multiple planned procedures, pre-existing haematologic disorders or chronic inflammatory states, iron overload on screening or vulnerable populations. We follow patients for 3 months to measure the effect of iron supplementation on clinical outcomes (resolution of anaemia and functional iron deficiency), patient-reported outcomes (fatigue, physical function, depression and quality of life) and translational measures of immune cell function.Ethics and dissemination This study has ethics approval (Oregon Health & Science University Institutional Review Board, STUDY00022441). We will disseminate the findings through peer-reviewed publications and conference presentations.Trial registration number NCT05292001; ClinicalTrials.gov.

Abstract Background Metabolic flexibility is the ability of skeletal muscle to adapt fuel utilization to the demand for fuel sources [carbohydrates (CHO) and fats (FAT)]. The purpose of this study was to explore muscle energy metabolism and metabolic flexibility under various conditions in sarcopenic (S) versus nonsarcopenic (NS) older adults. Methods Twenty‐two older adults aged 65 years or older were categorized as NS [n = 11; mean ± standard deviation (SD); age = 73.5 ± 6.0 years (males, n = 5; females, n = 6)] or S [n = 11; 81.2 ± 10.5 years (males, n = 6; females, n = 5) based on handgrip strength, body composition and physical performance. Indirect calorimetry was recorded before and after consumption of a high‐CHO meal and during aerobic and anaerobic exercise. Respiratory quotient (RQ), CHO and FAT oxidation were assessed. Venous blood samples were collected for glucose and insulin concentrations. Results At rest, compared with NS, S exhibited a 5–8% higher RQ at 0 (0.72 vs. 0.76) and 120 (0.77 vs. 0.82), 150 (0.76 vs. 0.80), and 180 min (0.74 vs. 0.80) (P = 0.002–0.025); 59–195% higher CHO oxidation at 0, 120, and 180 min (0.0004–0.002 vs. 0.001–0.002 g·min−1·kg‐1) (P = 0.010–0.047); and 20–31% lower FAT oxidation at 0, 15, and 90–180 min (0.0009–0.0022 vs. 0.0011–0.002 g·min−1·kg−1) (P = 0.004–0.038). Glucose levels were significantly elevated in S versus NS at 0, 60 and 75 min (144.64–202.78 vs. 107.70–134.20 mg·dL−1) but not insulin. During aerobic exercise, RQ was 5% greater (0.90 vs. 0.86) (P = 0.039), and FAT oxidation was 35% lower at 6–8 min (0.003 vs. 0.005 g·min−1·kg−1) (P = 0.033) in S versus NS. During anaerobic exercise, CHO oxidation was 31% greater in NS versus S at 60–80% time to exhaustion (0.011 vs. 0.007 g·min−1·kg−1) (P = 0.015). Per cent contribution to energy expenditure was greater in S for CHO but lower for FAT at 0 (CHO: 22% vs. 10%; FAT: 78% vs. 91%) and 120–180 min (CHO: 35–42% vs. 17–25%; FAT: 58–65% vs. 75%–84%) (P = 0.003–0.046) at rest and 6–8 min during aerobic exercise (CHO: 70% vs. 57%; FAT: 30% vs. 45%) (P = 0.046). Conclusions The data show differences in skeletal muscle energy metabolism and substrate utilization between S and NS at rest, transitioning from fasted to fed state, and during exercise. Compared with NS, S displayed a diminished ability to adapt fuel utilization in response to feeding and exercise, reflecting metabolic inflexibility. Impaired metabolic flexibility could be a mechanism underlying the losses of strength and physical function accompanying sarcopenia.

Toxoplasma gondii is a common parasite that infects warm-blooded animals and influences host physiology. T. gondii is known to target the host's central nervous system, affecting circulating levels of steroid hormones, fear-related behaviors, and health, although these effects appear to vary among host taxa. Here, we investigated the relationship between T. gondii infection and levels of plasma testosterone and cortisol within a wild population of spotted hyenas (Crocuta crocuta, n = 109). In our analyses, we accounted for age and sex via stratified regression analyses. We detected a negative association between circulating plasma testosterone and T. gondii infection among female cubs and subadults as well as adult male hyenas. We found no associations between T. gondii infection and cortisol in any age class or sex group of hyenas. Our work adds to a growing body of literature by characterizing the relationship between T. gondii infection and physiology in a novel host in its natural habitat. In a broader context, our findings indicate that responses to infection vary with characteristics of the host and point to a clear need for additional studies and priorities for future work that include diverse taxa and ecological settings.

Antimicrobial resistance continues to be a major threat to world health, with the continued emergence of resistant bacterial strains. Antimicrobial peptides have emerged as an attractive option for the development of novel antimicrobial compounds in part due to their ubiquity in nature and the general lack of resistance development to this class of molecules. In this work, we analyzed the antimicrobial peptide C18G and several truncated forms for efficacy and the underlying mechanistic effects of the sequence truncation. The peptides were screened for antimicrobial efficacy against several standard laboratory strains, and further analyzed using fluorescence spectroscopy to evaluate binding to model lipid membranes and bilayer disruption. The results show a clear correlation between the length of the peptide and the antimicrobial efficacy. Furthermore, there is a correlation between peptide length and the hydrophobic thickness of the bilayer, indicating that hydrophobic mismatch is likely a contributing factor to the loss of efficacy in shorter peptides.

Hydrate risk management is critically important for an energy industry that continues to see increasing demand. Hydrate formation in production lines is a potential threat under low temperature and high-pressure conditions where water and light gas molecules are present. Here, we introduce a 1-inch OD single-pass flow loop and demonstrate the Joule-Thomson (JT) expansion of a methane-ethane mixture. Initially, dry gas flowed through the apparatus at a variable pressure-differential. Larger pressure differentials resulted in more cooling, as predicted by standard thermodynamic models. A systematic deviation noted at higher pressure differentials was partially rectified through corrections incorporating heat transfer, thermal mass and kinetic energy effects. A wet gas system was then investigated with varying degrees of water injection. At the lowest rate, hydrate plugging occurred close to the expansion point and faster than for higher injection rates. This immediate and severe hydrate plugging has important implications for the design of safety relief systems in particular. Furthermore, this rate of plugging could not be predicted by existing software tools, suggesting that the atomization of liquids over an expansion valve is a critical missing component that must be incorporated for accurate predictions of hydrate plug formation severity.

In the context of a growing body of evidence associating olfactory dysfunction (OD) with cognitive decline, this cross-sectional study used data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) sample in order to explore the role of dietary intake in this association. Leveraging a nationally representative sample of U.S. adults aged 60 years and older, this study analyzed dietary patterns using exploratory factor analysis. OD was categorized based on the NHANES Pocket Smell Test, and cognitive function was measured with a battery of tests. Survey-weighted multivariable regressions and causal mediation analysis were used to examine the relationship between dietary patterns, OD, and cognitive function. Results indicated that a poor adherence to a diet rich in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs) was independently associated with both cognitive and olfactory dysfunctions, after adjusting for sociodemographic and health factors. Moreover, the relationship between OD and cognitive decline was found to be partly mediated by adherence to such a diet. This study proposes a potential link between diet, olfactory function, and cognitive decline, highlighting the role of nutritional interventions in mitigating cognitive decline, particularly in individuals with olfactory impairment.

Abstract Background Rabacfosadine (RAB, Tanovea‐CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs. Hypothesis/Objectives To determine the efficacy and safety of RAB in dogs with lymphoma. Animals One hundred and fifty‐eight client‐owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019. Methods Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression‐free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected. Results The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P

The cystic fibrosis (CF) transmembrane conductance regulator corrector/potentiator combinations lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor improve sweat chloride, pulmonary function, and nutrition. Yet it is unclear whether they may also impact the progression of liver fibrosis, which is a substantial source of morbidity and mortality for patients with CF. We conducted a retrospective, single-center analysis of children and adolescents with CF treated with lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor therapy, focusing on alterations in liver function tests and fibrosis indices using previously-established thresholds that corresponded with increased liver elastography. In pairwise comparisons of before and during treatment timepoints, we found that those with CF-associated liver involvement experienced significant decreases in gamma-glutamyl transferase, aspartate aminotransferase-to-platelet index, and gamma-glutamyl transferase-to-platelet ratio while on lumacaftor/ivacaftor. These differences were not observed in patients treated with elexacaftor/tezacaftor/ivacaftor, nor were they observed in patients without underlying CF-associated liver disease. These results provide the first evidence that lumacaftor/ivacaftor may improve liver fibrosis in children and adolescents with CF and suggest it may be beneficial in the treatment of CF-associated liver disease.