The ongoing pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has placed a substantial strain on the supply of personal protective equipment, particularly the availability of N95 respirators for frontline healthcare personnel. These shortages have led to the creation of protocols to disinfect and reuse potentially contaminated personal protective equipment. A simple and inexpensive decontamination procedure that does not rely on the use of consumable supplies is dry heat incubation.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
December 2020
The urgent need for a cure for early phase COVID-19 infected patients critically underlines drug repositioning strategies able to efficiently identify new and reliable treatments by merging computational, experimental, and pharmacokinetic expertise. Here we report new potential therapeutics for COVID-19 identified with a combined virtual and experimental screening strategy and selected among already approved drugs. We used hydroxychloroquine (HCQ), one of the most studied drugs in current clinical trials, as a reference template to screen for structural similarity against a library of almost 4000 approved drugs.
View Article and Find Full Text PDFShortages of N95 respirators for use by medical personnel have driven consideration of novel conservation strategies, including decontamination for reuse and extended use. Decontamination methods listed as promising by the Centers for Disease Control and Prevention (CDC) (vaporous hydrogen peroxide (VHP), wet heat, ultraviolet irradiation (UVI)) and several methods considered for low resource environments (bleach, isopropyl alcohol and detergent/soap) were studied for two commonly used surgical N95 respirators (3M™ 1860 and 1870+ Aura™). Although N95 filtration performance depends on the electrostatically charged electret filtration layer, the impact of decontamination on this layer is largely unexplored.
View Article and Find Full Text PDFIn this study we analyzed gene co-expression networks of three immune-related skin diseases: cutaneous sarcoidosis (CS), discoid lupus erythematosus (DLE), and psoriasis. We propose that investigation of gene co-expression networks may provide insights into underlying disease mechanisms. Microarray expression data from two cohorts of patients with CS, DLE, or psoriasis skin lesions were analyzed.
View Article and Find Full Text PDFObjective: Care offerings vary across medical settings and between families for babies with trisomy 13 or 18. The purpose of this qualitative descriptive study was to explore nurse, advanced practice practitioner, and neonatologist perspectives on care for babies with trisomy 13 or 18 in the intensive care unit.
Study Design: Voice-recorded qualitative interviews occurred with 64 participants (41 bedside nurses, 14 advance practice practitioners, and 9 neonatologists) from two neonatal intensive care units (NICU) in the midwestern United States.
Front Med (Lausanne)
November 2020
Data on the clinical presentation and outcomes of sarcoidosis patients with coronavirus disease 19 (COVID-19) are scarce. In this case series, we identified 5 out of 238 sarcoidosis patients who are enrolled in an ongoing longitudinal observational study who developed COVID-19 during the study period and follow their clinical course. Four patients recovered completely, whereas one patient expired during hospital admission.
View Article and Find Full Text PDFThe capacity for macrophages to polarize into distinct functional activation states (e.g., M1, M2) is critical to tune an inflammatory response to the relevant infection or injury.
View Article and Find Full Text PDFBackground: Although research has shown that exposure to potentially traumatic and morally injurious events is associated with psychological symptoms among veterans, knowledge regarding functioning impacts remains limited.
Methods: A population-based sample of post-9/11 veterans completed measures of intimate relationship, health, and work functioning at approximately 9, 15, 21, and 27 months after leaving service. Moral injury, posttraumatic stress, and depression were assessed at ~9 months post-separation.
Two cosegregating single-nucleotide polymorphisms (SNPs) in human TLR4, an A896G transition at SNP rs4986790 (D299G) and a C1196T transition at SNP rs4986791 (T399I), have been associated with LPS hyporesponsiveness and differential susceptibility to many infectious or inflammatory diseases. However, many studies failed to confirm these associations, and transfection experiments resulted in conflicting conclusions about the impact of these SNPs on TLR4 signaling. Using advanced protein modeling from crystallographic data of human and murine TLR4, we identified homologous substitutions of these SNPs in murine Tlr4, engineered a knock-in strain expressing the D298G and N397I TLR4 SNPs homozygously, and characterized in vivo and in vitro responses to TLR4 ligands and infections in which TLR4 is implicated.
View Article and Find Full Text PDFObjective: To determine the optimal methods for measuring mismatch negativity (MMN), an auditory event-related potential (ERP), and quantify sources of MMN variance in a multisite setting.
Methods: Reliability of frequency, duration, and double (frequency + duration) MMN was determined from eight traveling subjects, tested on two occasions at eight laboratory sites. Deviant-specific variance components were estimated for MMN peak amplitude and latency measures using different ERP processing methods.
Background: While an established clinical outcome of high importance, social functioning has been emerging as possibly having a broader significance to the evolution of psychosis and long term disability. In the current study we explored the association between social decline, conversion to psychosis, and functional outcome in individuals at clinical high risk (CHR) for psychosis.
Methods: 585 subjects collected in the North American Prodrome Longitudinal Study (NAPLS2) were divided into 236 Healthy Controls (HCs), and CHR subjects that developed psychosis (CHR + C, N = 79), or those that did not (Non-Converters, CHR-NC, N = 270).
Comorbid diagnoses are common in youth who are at clinical high-risk (CHR) for developing psychosis, with depression being the most common. The aim of this paper is to examine depression over two years in a large sample of CHR youth who do not make the transition to psychosis, considering both categorical and dimensional ratings of depression severity. The sample consisted of 267 CHR youth who were followed for two years.
View Article and Find Full Text PDFSarcoidosis Vasc Diffuse Lung Dis
November 2020
Sarcoidosis is a systemic inflammatory disease characterized by granuloma formation in affected organs and caused by dysregulated immune response to an unknown antigen. Sarcoidosis patients receiving immunosuppressive medications are at increased risk of infection. Lymphopenia is also commonly seen among patient with sarcoidosis.
View Article and Find Full Text PDFBackground: Sulfadoxine-pyrimethamine (SP) is the only anti-malarial drug formulation approved for intermittent preventive treatment in pregnancy (IPTp). However, mutations in the Plasmodium falciparum dhfr (Pfdhfr) and dhps (Pfdhps) genes confer resistance to pyrimethamine and sulfadoxine, respectively. Here, the frequencies of SP resistance-associated mutations from 2005 to 2018 were compared in samples from Kenyan children with malaria residing in a holoendemic transmission region.
View Article and Find Full Text PDFBackground: Risk calculators are useful tools that can help clinicians and researchers better understand an individual's risk of conversion to psychosis. The North American Prodrome Longitudinal Study (NAPLS2) Individualized Risk Calculator has good predictive accuracy but could be potentially improved by the inclusion of a biomarker. Baseline cortisol, a measure of hypothalamic-pituitary-adrenal (HPA) axis functioning that is impacted by biological vulnerability to stress and exposure to environmental stressors, has been shown to be higher among individuals at clinical high-risk for psychosis (CHRP) who eventually convert to psychosis than those who do not.
View Article and Find Full Text PDFInt J Environ Res Public Health
October 2020
Drought is a threat to public health. Individual and community adaptive capacity is crucial when responding to the impacts of drought. Gaps remain in the understandings of the relationship between wellbeing and adaptive capacity, and whether increased wellbeing can lead to improved adaptive capacity (or vice versa).
View Article and Find Full Text PDFInt J Environ Res Public Health
October 2020
A growing body of literature recognises the profound impact of adversity on mental health outcomes for people living in rural and remote areas. With the cumulative effects of persistent drought, record-breaking bushfires, limited access to quality health services, the COVID-19 pandemic and ongoing economic and social challenges, there is much to understand about the impact of adversity on mental health and wellbeing in rural populations. In this conceptual paper, we aim to review and adapt our existing understanding of rural adversity.
View Article and Find Full Text PDFAbstract: Biomarkers are important in the study of the prodromal period of psychosis because they can help to identify individuals at greatest risk for future psychotic illness and provide insights into disease mechanism underlying neurodevelopmental abnormalities. The biomarker abnormalities can then be targeted with treatment, with an aim toward prevention or mitigation of disease. The human startle paradigm has been used in translational studies of psychopathology including psychotic illness to assess preattentive information processing for over 50 years.
View Article and Find Full Text PDFPrevailing models of psychosis risk incorporate positive subthreshold symptoms as defining features of risk or transition to psychotic disorders. Despite this, relatively few studies have focused on characterizing longitudinal symptom features, such as prevalence, concordance and structure, which may aid in refining methods and enhancing classification and prediction efforts. The present study aimed to fill these gaps using longitudinal 24-month follow-up data from the well-characterized NAPLS-2 multi-site investigation of youth at clinical high risk (CHR) who had (n = 86) and had not (n = 268) transitioned to a threshold psychotic disorder since baseline.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFOur goal was to identify gender differences in the prevalence and outcomes of exposure to potentially morally injurious events (PMIEs) in a sample of U.S. military veterans.
View Article and Find Full Text PDFAim: Childhood Adversity (CA) is strongly linked to psychotic-like symptoms across the clinical spectrum, though the mechanisms underlying these associations remain poorly understood. Negative cognitive schemas are associated with both CA exposure and psychotic symptoms, highlighting the possibility that cognitive schemas may be a key risk pathway. The purpose of this study was to determine whether negative cognitive schemas mediate the association between CA and specific attenuated psychotic symptoms in a large sample of clinical-high risk youth.
View Article and Find Full Text PDFThe mismatch negativity (MMN) event-related potential (ERP) component is increasingly viewed as a prediction error signal elicited when a deviant sound violates the prediction that a frequent "standard" sound will repeat. Support for this predictive coding framework emerged with the identification of the repetition positivity (RP), a standard stimulus ERP component that increases with standard repetition and is thought to reflect strengthening of the standard's memory trace and associated predictive code. Using electroencephalographic recordings, we examined the RP elicited by repeating standard tones presented during a traditional "constant standard" MMN paradigm in individuals with the psychosis risk syndrome (PRS; n = 579) and healthy controls (HC; n = 241).
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