Search

Medical instruments that are not autoclavable but may become contaminated with high-risk human papillomaviruses (HPVs) during use must be thoroughly disinfected to avoid the possibility of iatrogenic transmission of infection. There is an expectation that prolonged soaking of instruments in the United States Food and Drug Administration-cleared chemical disinfectant solutions will result in high-level decontamination, but HPV16 and HPV18 are known to be resistant to commonly used formulations. However, they are susceptible to a variety of oxidative agents, including those based on chlorine. Here, we tested the efficacy of homogeneous hypochlorous acid (HOCl) solutions against mature infectious virions of HPV16 and HPV18 dried onto butadiene styrene coupons and ultrasonic probes. Both viruses were inactivated to4 log reduction value (LRV) after 15 s on coupons and 5 min on ultrasonic probes. Morphologic changes became evident within those contact times by transmission electron microscopy when HPV16 virus-like particles were exposed to HOCl under identical conditions. Mass spectrometry analysis of trypsin-digested products of L1 capsid proteins exposed to HOCl showed that mostly conserved residues were modified by oxidation and that these changes rapidly lead to instability of the protein demonstrable on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Modifications to these residues may contribute to rapid virus inactivation. The use of homogeneous HOCl solutions for HPV decontamination provides a highly effective means of assuring the safety of nonautoclavable medical instruments.

The loss of large animals due to overhunting and habitat loss potentially affects tropical tree populations and carbon cycling. Trees reliant on large-bodied seed dispersers are thought to be particularly negatively affected by defaunation. But besides seed dispersal, defaunation can also increase or decrease seed predation. It remains unclear how these different defaunation effects on early life stages ultimately affect tree population dynamics. We review the literature on how tropical animal loss affects different plant life stages, including conducting a meta-analysis of seed predation effects, and use this information to parameterize models assessing how defaunation-caused changes in seed dispersal and predation affect the population growth rates of a suite of tree species. We find that, on average, population-level effects of defaunation are negligible, suggesting that defaunation may not cause the massive reductions in forest carbon storage that have been predicted. In contrast to previous hypotheses, we did not detect an effect of seed size on changes in seed predation rates. We also found that the change in seed predation did not differ significantly between exclosure experiments and observational studies, though the results of observational studies were far more variable. While defaunation will surely affect certain tree taxa, we currently remain unable to predict 'winners', 'losers', or net changes in forest carbon storage based on best available data. Further research on how interactions such as seed predation vary across tree species and defaunation scenarios is necessary for understanding cascading changes in species composition and diversity. This article is protected by copyright. All rights reserved.

Heterocyclic N-halamine compounds such as 1-monochloro-5,5-dimethylhydantoin (MCDMH) and 1,3-dichlor-5,5-dimethylhydantoin (DCDMH) show antimicrobial activity and odour control. Both MCDMH and DCDMH stabilise and display oxidative chlorine (Cl+1) and, in aqueous environments, generate hypochlorous acid (HOCl). It is well known that HOCl, produced by neutrophils as part of the respiratory immune response, is used as a defence mechanism against foreign bodies. This study aimed to investigate the antibacterial efficacy of proprietary foaming formulations containing mixtures of MCDMH and DCDMH provided by MedeSol Inc., as a potential delivery mechanism for HOCl. The efficacy of the foams containing active chlorine concentrations of 350 ppm and 1050 ppm was tested against single and multi-species bacterial mixtures of S. aureus, P. aeruginosa, E. coli, E. faecalisand K. pneumoniae. Cellulose filters were contaminated with single/multispecies bacterial suspensions and left to air-dry; the two foam concentrations were applied for 15, 30 and 60 seconds at a time. Samples were taken and the total viable count method was employed to determine antibacterial efficacy of the foams. Following the use of both foam concentrations, no colonies were recovered at any time-points in both single and multi-species experiments. In contrast, the negative controls where the foam application was omitted, resulted in high numbers of bacterial colonies. MCDMH-containing foams have very strong antibacterial potential as a result of active chlorine release. Further studies are needed to determine concentration dependence and use in other applications including hand sanitation.

Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied.To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19.Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C).Aspirin use within the first day of hospitalization.The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.Among the 2 446 650 COVID-19-positive patients who were screened, 189 287 were hospitalized and 112 269 met study inclusion. For the full cohort, Median age was 63 years (IQR, 47-74 years); 16.1% of patients were African American, 3.8% were Asian, 52.7% were White, 5.0% were of other races and ethnicities, 22.4% were of unknown race and ethnicity. In-hospital mortality occurred in 10.9% of patients. After inverse probability treatment weighting, 28-day in-hospital mortality was significantly lower in those who received aspirin (10.2% vs 11.8%; odds ratio [OR], 0.85; 95% CI, 0.79-0.92; P .001). The rate of pulmonary embolism, but not deep vein thrombosis, was also significantly lower in patients who received aspirin (1.0% vs 1.4%; OR, 0.71; 95% CI, 0.56-0.90; P = .004). Patients who received early aspirin did not have higher rates of gastrointestinal hemorrhage (0.8% aspirin vs 0.7% no aspirin; OR, 1.04; 95% CI, 0.82-1.33; P = .72), cerebral hemorrhage (0.6% aspirin vs 0.4% no aspirin; OR, 1.32; 95% CI, 0.92-1.88; P = .13), or blood transfusion (2.7% aspirin vs 2.3% no aspirin; OR, 1.14; 95% CI, 0.99-1.32; P = .06). The composite of hemorrhagic complications did not occur more often in those receiving aspirin (3.7% aspirin vs 3.2% no aspirin; OR, 1.13; 95% CI, 1.00-1.28; P = .054). Subgroups who appeared to benefit the most included patients older than 60 years (61-80 years: OR, 0.79; 95% CI, 0.72-0.87; P .001;80 years: OR, 0.79; 95% CI, 0.69-0.91; P .001) and patients with comorbidities (1 comorbidity: 6.4% vs 9.2%; OR, 0.68; 95% CI, 0.55-0.83; P .001; 2 comorbidities: 10.5% vs 12.8%; OR, 0.80; 95% CI, 0.69-0.93; P = .003; 3 comorbidities: 13.8% vs 17.0%, OR, 0.78; 95% CI, 0.68-0.89; P .001;3 comorbidities: 17.0% vs 21.6%; OR, 0.74; 95% CI, 0.66-0.84; P .001).In this cohort study of US adults hospitalized with moderate COVID-19, early aspirin use was associated with lower odds of 28-day in-hospital mortality. A randomized clinical trial that includes diverse patients with moderate COVID-19 is warranted to adequately evaluate aspirin's efficacy in patients with high-risk conditions.

Patterns of co-occurrence among species can help reveal the structure and assembly of ecological communities. However, studies have been limited by measuring co-occurrence in either space or time but not both simultaneously. This is especially problematic in systems such as masting forests where resources are highly variable, meaning that spatial use and co-occurrence patterns can change on fine spatiotemporal scales. We develop an analytical framework for assessing species co-occurrence at fine spatial and temporal scales simultaneously and apply these models to a camera trapping dataset from Borneo. We sought to determine how substantial variation in food availability across space and time affects co-occurrence among terrestrial vertebrates. We detect many significant, mostly positive, co-occurrence patterns among species, but almost entirely in unlogged forest and during dipterocarp mast years. The most strongly co-occurring pair of species, bearded pig (Sus barbatus) and sambar (Rusa unicolor), only positively co-occur in areas and years when fruit is locally abundant. Species occurrences in logged forest and non-mast years are mostly random with respect to other species. This suggests that frugivore-granivore species positively co-occur when resources are plentiful (i.e., large trees are present and fruiting), likely because they use the same resources; these patterns disappear when food availability is lower. Our approach demonstrates the utility of measuring co-occurrence in space and time together and highlights the importance of resource abundance for driving the co-occurrence structure of communities. Furthermore, our method could be broadly applied to other systems to assess fine-scale spatiotemporal patterns across a range of taxa.

Evidence is emerging of the beneficial effects of inhaling microaerosolized hypochlorous acid (HOCl) as an intervention in the prevention and treatment of respiratory virus infections, including SARS CoV-2. However, little information is available about the effects of inhalation of homogenous HOCl solutions in normal human subjects or in experimental animals. In this report we establish through independent laboratories that the SARS-CoV-2 virus is rapidly inactivated by exposure to HOCl. Inhalation of an aerosolized form of the same HOCl solution by rodents, in accordance with a US-EPA acute 4-hour inhalation toxicity protocol, then provided observational, gross pathological, and histopathological evidence that their pulmonary exposure did not result in any difference when compared to control animals. During the pandemic lockdown, subjective impressions of exposure to aerosolized HOCl were submitted as self-reported responses by employees of a machine-tool shop located in Tacoma, Washington, about 35 miles from Seattle. At that location exposure to HOCl was adopted by a subset of employees as a routine for entry into the facilities. Under short-term, controlled conditions those individuals breathed HOCl misted from a reservoir containing 180 ppm free active chlorine (FAC). Their reports were used to arrive at inferences regarding the effects of exposure. Chemical and antimicrobial characterizations of the aerosols used for these exposures were also performed. Results are discussed in relation to (1) published accounts of HOCl preparations and their effects on respiratory viruses, including rhinoviruses and coronaviruses, and (2) the potential for rational intervention in infections arising from aerosolized pathogens, including the pandemic SARS-CoV-2, using inhalation as a method for administration of HOCl.

Functional box plots satisfy two needs; visualization of functional data, and the calculation of important box plot statistics. Data visualization illuminates key characteristics of functional sets missed by statistical tests and summary statistics. The calculation of box plot statistics for functional sets permits a novel comparison more suited to functional data. The functional box plot uses a depth method to visualize and rank smooth functional curves in terms of a mean, box, whiskers, and outliers. The functional box plot improves upon other classic functional data analysis tools such as functional principal components and discriminant analysis for outlier detection. This research adds wavelet analysis as a generating mechanism along with depth for functional box plots to visualize functional data and calculate relevant statistics. The wavelet analysis of variance box plot tool gives competitive error rates in Gaussian test cases with magnitude outliers, and outperforms the functional box plot, for Gaussian test cases with shape outliers. Further, we show wavelet analysis is well suited at approximating irregular and noisy functional data and show the enhanced capability of WANOVA box plots to classify shape outliers which follow a different pattern than other functional data for both simulated and real data instances.

Interleukin-6 (IL-6) has been implicated in the pathogenesis of acute inflammatory events in COVID-19 patients. We exposed IL-6 to hypochlorous acid (HOCl) in vitro at concentrations reported to develop in vivo. After HOCl treatment the cytokine failed to bind to IL-6 receptors in a bioassay using engineered human cells. Similar results followed exposure of IL-6 to N-chlorotaurine (NCT) and hypobromous acid (HOBr). SDS-PAGE analysis of HOCl-treated IL-6 showed neither fragmentation nor aggregation, suggesting that the modifications induced by these agents occurred on the intact protein. Mass spectrometry of intact and trypsin-digested fragments identified oxidative changes limited to two amino acid residues, methionine 161 and tryptophan 157, both of which have been implicated in receptor binding of the cytokine. Further studies on the effects of hypohalous acids and their halogenated amine derivatives on IL-6 and related cytokines is needed.

Objective To describe the sedation, narcotic and neuromuscular blockade usage in ventilated patients with COVID-19 pneumonia. Design Single-Center Retrospective Review. Setting George Washington University Hospital in Washington, D.C. Patients 62 patients with COVID-19 respiratory failure requiring mechanical ventilation admitted from March 2020 to June 2020. Intervention None. Measurements and main results Patients with COVID-19 respiratory failure required multiple sedative/narcotic infusions to achieve sedation requirements and at doses that were significantly more when compared to a general medical-surgical ICU population (represented by the MIND-USA cohort). The most common infusions were Dexmedetomadine and Propofol. Approximately 17% of our patients required a neuromuscular blockade infusion as well. Prior to intubation, narcotic utilization was stable and low. Conclusion Patients with COVID-19 respiratory failure requiring mechanical ventilation have higher sedation and narcotic requirements than general ICU patients.

Overhunting reduces important plant-animal interactions such as vertebrate seed dispersal and seed predation, thereby altering plant regeneration and even above-ground biomass. It remains unclear, however, if non-hunted species can compensate for lost vertebrates in defaunated ecosystems. We use a nested exclusion experiment to isolate the effects of different seed enemies in a Bornean rainforest. In four of five tree species, vertebrates kill many seeds (13–66%). Nonetheless, when large mammals are excluded, seed mortality from insects and fungi fully compensates for the lost vertebrate predation, such that defaunation has no effect on seedling establishment. The switch from seed predation by generalist vertebrates to specialist insects and fungi in defaunated systems may alter Janzen–Connell effects and density-dependence in plants. Previous work using simulation models to explore how lost seed dispersal will affect tree species composition and carbon storage may require reevaluation in the context of functional redundancy within complex species interactions networks., Ecologists predict that loss of large vertebrates will alter tropical plant communities. Here, the authors report a field experiment on seed mortality and seedling establishment in Borneo, in which experimental defaunation of large seed consumers was functionally compensated by insects and fungi.

Introduction Adolescents are particularly susceptible to social influence and previous studies have shown that this susceptibility decreases with age. The current study used a cross-sectional experimental paradigm to investigate the effect of age and puberty on susceptibility to both prosocial and antisocial influence. Methods Participants (N = 520) aged 11–18 from London and Cambridge (United Kingdom) rated how likely they would be to engage in a prosocial (e.g. “help a classmate with their work”) or antisocial (e.g. “make fun of a classmate”) act. They were then shown the average rating (in fact fictitious) that other adolescents had given to the same question, and were then asked to rate the same behaviour again. Results Both prosocial and antisocial influence decreased linearly with age, with younger adolescents being more socially influenced when other adolescents’ ratings were more prosocial and less antisocial than their own initial rating. Both antisocial and prosocial influence significantly decreased across puberty for boys but not girls (independent of age). Conclusions These findings suggest that social influence declines with increasing maturity across adolescence. However, the exact relationship between social influence and maturity is dependent on the nature of the social influence and gender. Understanding when adolescents are most susceptible to different types of social influence, and how this might influence their social behaviour, has important implications for understanding adolescent social development.

Rocky Mountain elk (Cervus canadensis) is a major reservoir for Brucella abortus in the Greater Yellowstone area, which has significant economic implications to the cattle industry. Vaccination attempts against intracellular bacterial diseases in elk populations have not been successful due to a negligible adaptive cellular immune response. A lack of genomic resources has impeded attempts to better understand why vaccination does not induce protective immunity. To overcome this limitation, PacBio, Illumina, and HiC sequencing with a total of 686-fold coverage was used to assemble the elk genome into 35 pseudomolecules. A robust gene annotation was generated resulting in 18,013 gene models and 33,422 mRNAs. The accuracy of the assembly was assessed using synteny to the red deer and cattle genomes identifying several chromosomal rearrangements, fusions and fissions. Because this genome assembly and annotation provide a foundation for genome-enabled exploration of Cervus species, we demonstrate its utility by exploring the conservation of immune system-related genes. We conclude by comparing cattle immune system-related genes to the elk genome, revealing nine putative gene losses in elk.Author SummaryBrucellosis, also known as contagious abortion, is a bacterial disease that commonly affects livestock and remains prevalent in Rocky Mountain elk (Cervus canadensis). Since the 1920’s the USDA has led a program to eradicate Brucellosis from cattle, yet wild Rocky Mountain elk continue to be a source of transmission. Attempts to vaccinate wild elk herds have been unsuccessful, due to a poor and short-lived immune response. To investigate the genetic basis for this inherent difference, we created the first genome and annotation for the Rocky Mountain elk. This genome assembly is of the highest quality and contains single linear sequences for all 35 chromosomes. In order to generate gene models, an array of RNA-Seq data and proteins from many different organ tissues and cells were used in gene prediction software. Specifically, we compare cattle immune system genes with the Rocky Mountain elk, revealing the putative loss of nine immune-system related genes in elk.

Hypokalemia can cause reactions from mild muscular cramping to life-threatening paralysis and cardiac dysrhythmias. This article describes a patient whose unusual, recurrent muscular symptoms and electrolyte abnormalities were eventually identified as Gitelman syndrome, a rare genetic disorder resulting in severe refractory hypokalemia.

There has been an explosion of interest in mindfulness-based programs (MBPs) such as Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy. This is demonstrated in increased research, implementation of MBPs in healthcare, educational, criminal justice and workplace settings, and in mainstream interest. For the sustainable development of the field there is a need to articulate a definition of what an MBP is and what it is not. This paper provides a framework to define the essential characteristics of the family of MBPs originating from the parent program MBSR, and the processes which inform adaptations of MBPs for different populations or contexts. The framework addresses the essential characteristics of the program and of teacher. MBPs: are informed by theories and practices that draw from a confluence of contemplative traditions, science, and the major disciplines of medicine, psychology and education; underpinned by a model of human experience which addresses the causes of human distress and the pathways to relieving it; develop a new relationship with experience characterized by present moment focus, decentering and an approach orientation; catalyze the development of qualities such as joy, compassion, wisdom, equanimity and greater attentional, emotional and behavioral self-regulation, and engage participants in a sustained intensive training in mindfulness meditation practice, in an experiential inquiry-based learning process and in exercises to develop understanding. The paper's aim is to support clarity, which will in turn support the systematic development of MBP research, and the integrity of the field during the process of implementation in the mainstream.

© 2019 Elsevier Ltd. All rights reserved., Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.

INTRODUCTION: Low tidal volume ventilation (LTVV), defined as 6 to 8cc of tidal volume per kilogram of ideal body weight (IBW), has been shown to reduce mortality and days requiring invasive ventilation when utilized in the acute respiratory distress syndrome (ARDS) The degree of hypoxemia in respiratory failure experienced in the SARSCOV2 infection (COVID-19) is similar to ARDS from other respiratory pathologies;however, there appears to be notable heterogeneity in lung compliance of COVID-19 patients as well as higher rate of mortality for ARDS supported with invasive mechanical ventilation in COVID-19 It remains unknown if lung protective tidal volume strategies confer a significant benefit for COVID-19 ARDS as they do for ARDS due to other etiologies We aim to determine if LTVV was associated with decreased mortality, ventilator days, ICU length of stay, or decreased length of hospital stay METHODS: A prospective observational study was performed with inclusion criteria of a positive COVID-19 test and intubation for non-operative indications Ideal body weight was calculated to determine whether or not each patient ever exceeded or achieved LTVV, here defined as less than 6cc/kg of ideal body weight The primary outcome was mortality The secondary outcomes were length of stay in the hospital, ICU days, and ventilator days RESULTS: A total of 75 COVID positive patients were intubated at our facility 60 (80%) of these patients died Exceeding 6cc/kg IBW LTVV trended towards more days in the ICU (p= 089) and number of days intubated (p= 148), but only increased hospital length of stay was statistically significant (p= 025) Patients who did maintain LTVV at least one day did have decreased crude odds of mortality at 0 281 (95% CI 0482-1 6395) LTVV was not correlated with fewer ICU days (p= 846), number of days intubated (p= 709), or length of hospital stay (p= 699) CONCLUSIONS: Failure to maintain LTVV was associated with increased mortality and hospital LOS It also trended toward an increase in ICU days days of mechanical ventilation Further prospective studies are required