Miliary osteoma cutis in a climbing mantella frog (Mantella laevigata).

A climbing mantella frog (Mantella laevigata) was presented with nodular thickened skin. Histological examination revealed dermal nodules composed of differentiated bone consistent with miliary osteoma cutis, a non-neoplastic condition where bone is abnormally deposited within the skin. This is the first report of idiopathic osteoma cutis in an amphibian.

Prevalence of hepatitis C virus exposure and infection among Indigenous and tribal populations: a global systematic review and meta-analysis.

OBJECTIVES: The objective of this study was to estimate prevalence of hepatitis C virus (HCV) exposure and infection among Indigenous and tribal populations globally. STUDY DESIGN: Systematic review and meta-analysis. METHODS: We systematically searched bibliographic databases and grey literature (1/01/2000-16/06/2022). Prevalence estimates were synthesised overall, by World Health Organization region and HCV-risk group. For studies with comparator populations, prevalence ratios were estimated and pooled. RESULTS: Ninety-two studies were included. Globally, among general Indigenous and tribal populations, the median prevalence of HCV antibody (HCV Ab) was 1.3% (interquartile range [IQR]: 0.3-3.8%, I2 = 98.5%) and HCV RNA was 0.4% (IQR: 0-1.3%, I2 = 96.1%). The Western Pacific Region had the highest prevalence (HCV Ab: median: 3.0% [IQR: 0.4-11.9%], HCV RNA: median 5.6% [IQR: 2.0-8.8%]). Prevalence was highest in people who injected drugs (HCV Ab: median: 59.5%, IQR: 51.5-67.6%, I2 = 96.6%; and HCV RNA: median: 29.4%, IQR: 21.8-35.2%, I2 = 97.2%). There was no association between HCV Ab prevalence and Indigenous/tribal status for general populations (prevalence ratio = 0.91; 95% CI: 0.56, 1.49) or key risk groups. CONCLUSIONS: Indigenous and tribal peoples from the Western Pacific Region and recognised at-risk sub-populations had higher HCV prevalence. HCV prevalence showed no association with Indigenous/tribal status. However, this review was limited by heterogeneity and poor quality of constituent studies, varying definitions of Indigenous/tribal status, regional data gaps, and limited studies on chronic infection (HCV RNA). Comprehensive quality evidence on HCV epidemiology in Indigenous and tribal peoples is needed to tailor preventive and treatment interventions so these populations are not left behind in elimination efforts.

Primary Care Practice Characteristics Associated With Medical Assistant Staffing Ratios.

This study characterized adult primary care medical assistant (MA) staffing. National Survey of Healthcare Organizations and Systems (n = 1,252) data were analyzed to examine primary care practice characteristics associated with MA per primary care clinician (PCC) staffing ratios. In 2021, few practices (11.4%) had ratios of 2 or more MAs per PCCs. Compared with system-owned practices, independent (odds ratio [OR] = 1.76, P <0.05) and medical group-owned (OR = 2.09, P <0.05) practices were more likely to have ratios of 2 or more MAs per PCCs, as were practices with organizational cultures oriented to innovation (P <0.05). Most primary care practices do not have adequate MA staffing.

Chemical bonding in phase-change chalcogenides.

Almost all phase-change memory materials (PCM) contain chalcogen atoms, and their chemical bonds have been denoted both as 'electron-deficient' [sometimes referred to as 'metavalent'] and 'electron-rich' ['hypervalent', multicentre]. The latter involve lone-pair electrons. We have performed calculations that can discriminate unambiguously between these two classes of bond and have shown that PCM have electron-rich, 3c-4e ('hypervalent') bonds. Plots of charge transferred between (ET) and shared with (ES) neighbouring atoms cannot on their own distinguish between 'metavalent' and 'hypervalent' bonds, both of which involve single-electron bonds. PCM do not exhibit 'metavalent' bonding and are not electron-deficient; the bonding is electron-rich of the 'hypervalent' or multicentre type.

Exotic Dark Matter Search with the Majorana Demonstrator.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

Endogenous feline leukemia virus long terminal repeat integration site diversity is highly variable in related and unrelated domestic cats.

Endogenous retroviruses (ERV) are indicators of vertebrate evolutionary history and play important roles as homeostatic regulators. ERV long terminal repeat (LTR) elements may act as cis-activating promoters or trans-activating enhancer elements modifying gene transcription distant from LTR insertion sites. We previously documented that endogenous feline leukemia virus (FeLV)-LTR copy number variation in individual cats tracks inversely with susceptibility to virulent FeLV disease. To evaluate FeLV-LTR insertion characteristics, we assessed enFeLV-LTR integration site diversity in 20 cats from three genetically distinct populations using a baited linker-mediated PCR approach. We documented 765 individual integration sites unequally represented among individuals. Only three LTR integration sites were shared among all individuals, while 412 sites were unique to a single individual. When primary fibroblast cultures were challenged with exogenous FeLV, we found significantly increased expression of both exogenous and endogenous FeLV orthologs, supporting previous findings of potential exFeLV-enFeLV interactions; however, viral challenge did not elicit transcriptional changes in genes associated with the vast majority of integration sites. This study assesses FeLV-LTR integration sites in individual animals, providing unique transposome genotypes. Further, we document substantial individual variation in LTR integration site locations, even in a highly inbred population, and provide a framework for understanding potential endogenous retroviral element position influence on host gene transcription.

Transient anticonvulsant effects of time-restricted feeding in the 6-Hz mouse model.

INTRODUCTION: Intermittent fasting enhances neural bioenergetics, is neuroprotective, and elicits antioxidant effects in various animal models. There are conflicting findings on seizure protection, where intermittent fasting regimens often cause severe weight loss resembling starvation which is unsustainable long-term. Therefore, we tested whether a less intensive intermittent fasting regimen such as time-restricted feeding (TRF) may confer seizure protection. METHODS: Male CD1 mice were assigned to either ad libitum-fed control, continuous 8 h TRF, or 8 h TRF with weekend ad libitum food access (2:5 TRF) for one month. Body weight, food intake, and blood glucose levels were measured. Seizure thresholds were determined at various time points using 6-Hz and maximal electroshock seizure threshold (MEST) tests. Protein levels and mRNA expression of genes, enzyme activity related to glucose metabolism, as well as mitochondrial dynamics were assessed in the cortex and hippocampus. Markers of antioxidant defence were evaluated in the plasma, cortex, and liver. RESULTS: Body weight gain was similar in the ad libitum-fed and TRF mouse groups. In both TRF regimens, blood glucose levels did not change between the fed and fasted state and were higher during fasting than in the ad libitum-fed groups. Mice in the TRF group had increased seizure thresholds in the 6-Hz test on day 15 and on day 19 in a second cohort of 2:5 TRF mice, but similar seizure thresholds at other time points compared to ad libitum-fed mice. Continuous TRF did not alter MEST seizure thresholds on day 28. Mice in the TRF group showed increased maximal activity of pyruvate dehydrogenase in the cortex, which was accompanied by increased protein levels of mitochondrial pyruvate carrier 1 in the cortex and hippocampus. There were no other major changes in protein or mRNA levels associated with energy metabolism and mitochondrial dynamics in the brain, nor markers of antioxidant defence in the brain, liver, or plasma. CONCLUSIONS: Both continuous and 2:5 TRF regimens transiently increased seizure thresholds in the 6-Hz model at around 2 weeks, which coincided with stability of blood glucose levels during the fed and fasted periods. Our findings suggest that the lack of prolonged anticonvulsant effects in the acute electrical seizure models employed may be attributed to only modest metabolic and antioxidant adaptations found in the brain and liver. Our findings underscore the potential therapeutic value of TRF in managing seizure-related conditions.

Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

Antemortem cytologic diagnosis of pulmonary Langerhans cell histiocytosis in a cat.

Feline pulmonary Langerhans cell histiocytosis (FPLCH) is a rare histiocytic proliferative disease of middle-aged to older domestic cats. Langerhans cells in the terminal airways proliferate and infiltrate the interstitium and the airways to a lesser degree, widely effacing normal parenchyma. Historically, definitive diagnosis has required postmortem evaluation where pulmonary lesions have a classic gross and histologic morphology. Here, we present the first documented antemortem diagnosis of FPLCH using bronchoalveolar lavage (BAL) cytology and immunocytochemistry (ICC) in a 9-year-old British shorthair mix. The cat had a 3-month history of respiratory difficulty that was refractory to steroids and antimicrobials. Pulmonary radiographs had marked diffuse changes with a complex bronchointerstitial and micronodular pattern. BAL cytology revealed neutrophilic inflammation and markedly increased histiocytes with morphology distinct from typical pulmonary macrophages. ICC characterized histiocytes as CD1a+ /E-cadherin+ /CD11b- /PanCK- , consistent with a Langerhans cell phenotype. The cat was humanely euthanized due to poor prognosis and presented for necropsy. Gross, histopathologic, immunophenotypic, and ultrastructural findings confirmed a diagnosis of FPLCH. Proliferative cells were E-cadherin+ /Iba-1+ /CD18+ /CD1a+ /CD5+ /MHCII+ /CD204- /CD4- ; transmission electron microscopy identified the presence of Birbeck granules in the proliferating histiocytes, consistent with previous reports of FPLCH.

Constraints on the Decay of

^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known ß and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation. For this study, we repurposed the Majorana Demonstrator, an experimental search for the neutrinoless double-beta decay of ^{76}Ge using an array of high-purity germanium detectors, to search for the decay of ^{180m}Ta. More than 17 kg, the largest amount of tantalum metal ever used for such a search, was installed within the ultralow-background detector array. In this Letter, we present results from the first year of Ta data taking and provide an updated limit for the ^{180m}Ta half-life on the different decay channels. With new limits up to 1.5×10^{19} yr, we improved existing limits by 1-2 orders of magnitude which are the most sensitive searches for a single ß and electron capture decay ever achieved. Over all channels, the decay can be excluded for T_{1/2}<0.29×10^{18} yr.

Dark Matter Constraints from Isomeric

We describe a first measurement of the radiation from a ^{178m}Hf sample to search for dark matter. The γ flux from this sample, possessed by Los Alamos National Laboratory nuclear chemistry, was measured with a Ge detector at a distance of 1.2 m due to its high activity. We search for γ's that cannot arise from the radioactive decay of ^{178m}Hf but might arise from the production of a nuclear state due to the inelastic scattering with dark matter. The limits obtained on this γ flux are then translated into constraints on the parameter space of inelastic dark matter. Finally, we describe the potential reach of future studies with ^{178m}Hf.

Racial differences in low value care among older adult Medicare patients in US health systems: retrospective cohort study.

OBJECTIVE: To characterize racial differences in receipt of low value care (services that provide little to no benefit yet have potential for harm) among older Medicare beneficiaries overall and within health systems in the United States. DESIGN: Retrospective cohort study SETTING: 100% Medicare fee-for-service administrative data (2016-18). PARTICIPANTS: Black and White Medicare patients aged 65 or older as of 2016 and attributed to 595 health systems in the United States. MAIN OUTCOME MEASURES: Receipt of 40 low value services among Black and White patients, with and without adjustment for patient age, sex, and previous healthcare use. Additional models included health system fixed effects to assess racial differences within health systems and separately, racial composition of the health system's population to assess the relative contributions of individual patient race and health system racial composition to low value care receipt. RESULTS: The cohort included 9 833 304 patients (6.8% Black; 57.9% female). Of 40 low value services examined, Black patients had higher adjusted receipt of nine services and lower receipt of 20 services than White patients. Specifically, Black patients were more likely to receive low value acute diagnostic tests, including imaging for uncomplicated headache (6.9% v 3.2%) and head computed tomography scans for dizziness (3.1% v 1.9%). White patients had higher rates of low value screening tests and treatments, including preoperative laboratory tests (10.3% v 6.5%), prostate specific antigen tests (31.0% v 25.7%), and antibiotics for upper respiratory infections (36.6% v 32.7%; all P<0.001). Secondary analyses showed that these differences persisted within given health systems and were not explained by Black and White patients receiving care from different systems. CONCLUSIONS: Black patients were more likely to receive low value acute diagnostic tests and White patients were more likely to receive low value screening tests and treatments. Differences were generally small and were largely due to differential care within health systems. These patterns suggest potential individual, interpersonal, and structural factors that researchers, policy makers, and health system leaders might investigate and address to improve care quality and equity.

Sources of Low-Value Care Received by Medicare Beneficiaries and Associated Spending Within US Health Systems.

This cross-sectional study examines referrals for low-value health care services and associated spending by ordering clinician among Medicare beneficiaries.

Who's Accountable? Low-Value Care Received By Medicare Beneficiaries Outside Of Their Attributed Health Systems.

Policy makers and payers increasingly hold health systems accountable for spending and quality for their attributed beneficiaries. Low-value care-medical services that offer little or no benefit and have the potential for harm in specific clinical scenarios-received outside of these systems could threaten success on both fronts. Using national Medicare data for fee-for-service beneficiaries ages sixty-five and older and attributed to 595 US health systems, we describe where and from whom they received forty low-value services during 2017-18 and identify factors associated with out-of-system receipt. Forty-three percent of low-value services received by attributed beneficiaries originated from out-of-system clinicians: 38 percent from specialists, 4 percent from primary care physicians, and 1 percent from advanced practice clinicians. Recipients of low-value care were more likely to obtain that care out of system if age 75 or older (versus ages 65-74), male (versus female), non-Hispanic White (versus other races or ethnicities), rural dwelling (versus metropolitan dwelling), more medically complex, or experiencing lower continuity of care. However, out-of-system service receipt was not associated with recipients' health systems' accountable care organization status. Health systems might improve quality and reduce spending for their attributed beneficiaries by addressing out-of-system receipt of low-value care-for example, by improving continuity.

Extracorporeal Membrane Oxygenation for Acute Respiratory Failure Due to COVID-19: A Multicenter Matched Cohort Study.

Mechanical ventilation for respiratory failure due to COVID-19 is associated with significant morbidity and mortality. Veno-venous extracorporeal membrane oxygenation (ECMO) is an attractive management option. This study sought to determine the effect of ECMO on hospital mortality and discharge condition in this population. We conducted a retrospective multicenter study to emulate a pragmatic targeted trial comparing ECMO to mechanical ventilation without ECMO for severe COVID-19. Data were gathered from a large hospital network database in the US. Adults admitted with COVID-19 were included if they were managed with ECMO or mechanical ventilation for severe hypoxemia and excluded if they had significant comorbidities or lacked functional independence on admission. The groups underwent coarsened exact matching on multiple clinical variables. The primary outcome was adjusted in-hospital mortality; secondary outcomes included ventilator days, intensive care days, and discharge destination. A total of 278 ECMO patients were matched to 2,054 comparison patients. Adjusted in-hospital mortality was significantly less in the ECMO group (38.8% vs. 60.1%, p < 0.001). Extracorporeal membrane oxygenation was associated with higher rates of liberation from mechanical ventilation, intensive care discharge, and favorable discharge destination. These findings support the use of ECMO for well-selected patients with severe acute respiratory failure due to COVID-19.

Metabolic aspects of genetic ion channel epilepsies.

Nowadays, particularly in countries with high incomes, individual mutations in people affected by genetic epilepsies are identified, and genetic therapies are being developed. In addition, drugs are being screened to directly target specific mutations, and personalised medicine is possible. However, people with epilepsy do not yet benefit from these advances, and many types of epilepsies are medication-resistant, including Dravet syndrome. Thus, in the meantime, alternative and effective treatment options are needed. There is increasing evidence that metabolic deficits contribute to epileptic seizures and that such metabolic impairments may be amenable to treatment, with metabolic treatment options like the ketogenic diet being employed with some success. However, the brain metabolic alterations that occur in ion channel epilepsies are not well-understood, nor how these may differ from epilepsies that are of acquired and unknown origins. Here, we provide an overview of studies investigating metabolic alterations in epilepsies caused by mutations in the SCN1A and KCNA1 genes, which are currently the most studied ion channel epilepsies in animal models. The metabolic changes found in these models are likely to contribute to seizures. A metabolic basis of these ion channel epilepsies is supported by human and/or animal studies that show beneficial effects of the ketogenic diet, which may be mediated by the provision of auxiliary brain fuel in the form of ketone bodies. Other potentially more preferred dietary therapies including medium-chain triglycerides and triheptanoin have also been tested in a limited number of studies, but their efficacies remain to be clearly established. The extent to which brain metabolism is affected in people with Dravet syndrome, KCNA1 epilepsy and the models thereof still requires clarification. This requires more experiments that yield functional insight into metabolism.

Multiple quantum filtered nuclear magnetic resonance of 23Na+ in uniformly stretched and compressed hydrogels.

Stretching or compressing hydrogels creates anisotropic environments that lead to motionally averaged alignment of embedded guest quadrupolar nuclear spins such as 23Na+. These distorted hydrogels can elicit a residual quadrupolar coupling that gives an oscillation in the trajectories of single quantum coherences (SQCs) as a function of the evolution time during a spin-echo experiment. We present solutions to equations of motion derived with a Liouvillian superoperator approach, which encompass the coherent quadrupolar interaction in conjunction with relaxation, to give a full analytical description of the evolution trajectories of rank-1 (T^1±1), rank-2 (T^2±1), and rank-3 (T^3±1) SQCs. We performed simultaneous numerical fitting of the experimental 23Na nuclear magnetic resonance (NMR) spectra and rank-2 (T^2±1) and rank-3 (T^3±1) SQC evolution trajectories measured in double and triple quantum filtered experiments, respectively. We estimated values of the quadrupolar coupling constant CQ, rotational correlation time τC, and 3 × 3 Saupe order matrix. We performed simultaneous fitting of the analytical expressions to the experimental data to estimate values of the quadrupolar coupling frequency ωQ/2π, residual quadrupolar coupling ωQ/2π, and corresponding spherical order parameter S0*, which showed a linear dependence on the extent of uniform hydrogel stretching and compression. The analytical expressions were completely concordant with the numerical approach. The insights gained here can be extended to more complicated (biological) systems such as 23Na+ bound to proteins or located inside and outside living cells in high-field NMR experiments and, by extension, to the anisotropic environments found in vivo with 23Na magnetic resonance imaging.

Erratum: Search for Spontaneous Radiation from Wave Function Collapse in the Majorana Demonstrator [Phys. Rev. Lett. 129, 080401 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.129.080401.