SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents.

Controversial reports have suggested that SARS-CoV E and 3a proteins are plasma membrane viroporins. Here, we aimed at better characterizing the cellular responses induced by these proteins. First, we show that expression of SARS-CoV-2 E or 3a protein in CHO cells gives rise to cells with newly acquired round shapes that detach from the Petri dish. This suggests that cell death is induced upon expression of E or 3a protein. We confirmed this by using flow cytometry. In adhering cells expressing E or 3a protein, the whole-cell currents were not different from those of the control, suggesting that E and 3a proteins are not plasma membrane viroporins. In contrast, recording the currents on detached cells uncovered outwardly rectifying currents much larger than those observed in the control. We illustrate for the first time that carbenoxolone and probenecid block these outwardly rectifying currents; thus, these currents are most probably conducted by pannexin channels that are activated by cell morphology changes and also potentially by cell death. The truncation of C-terminal PDZ binding motifs reduces the proportion of dying cells but does not prevent these outwardly rectifying currents. This suggests distinct pathways for the induction of these cellular events by the two proteins. We conclude that SARS-CoV-2 E and 3a proteins are not viroporins expressed at the plasma membrane.

Polyphenylene carboxymethylene (PPCM), the active component of the topical contraceptive Yaso-GEL, exhibits potent antimicrobial activity against Neisseria gonorrhoeae in preclinical studies.

INTRODUCTION: Polyphenylene carboxymethylene (PPCM) is a condensation polymer that has both contraceptive and antimicrobial activity against several sexually transmitted viruses including HIV, herpes simplex virus, Ebola virus and SARS-CoV-2 in preclinical studies. PPCM, both as an active pharmaceutical ingredient (API) and in a vaginal gel formulation (Yaso-GEL), has an excellent safety profile. Here, we evaluated the efficacy of PPCM against Neisseria gonorrhoeae in vitro and in a gonorrhoea mouse model. METHODS: The minimal inhibitory concentration (MIC) of PPCM was determined against 11 N. gonorrhoeae strains by agar dilution and a microtitre plate-based method. In vivo efficacy was tested in a murine model of N. gonorrhoeae genital tract infection by applying Yaso-GEL, PPCM incorporated in 2.7% hydroxyethylcellulose (HEC), or the HEC vehicle vaginally prior to challenge with N. gonorrhoeae. Vaginal swabs were quantitatively cultured over 5 days to assess efficacy. RESULTS: PPCM MIC against N. gonorrhoeae ranged between 5-100 µg/mL (agar dilution) and 50-200 µg/mL (microtitre plate method). PPCM/HEC gel applied vaginally prior to bacterial challenge resulted in a concentration-dependent inhibition of infection. Yaso-GEL containing 4% PPCM prevented infection in 100% of mice. Incubation of N. gonorrhoeae with PPCM increased membrane permeability, suggesting PPCM directly compromises N. gonorrhoeae viability, which may be a mechanism by which PPCM inhibits N. gonorrhoeae infection. CONCLUSIONS: Yaso-GEL containing the API PPCM showed significant activity against N. gonorrhoeae in vitro and in vivo in a female mouse model. These data support further development of Yaso-GEL as an inexpensive, non-hormonal and non-systemic product with both contraceptive and antimicrobial activity against gonorrhea and other common sexually transmitted infections (STIs). Such multipurpose prevention technology products are needed by women in all economic, social and cultural circumstances to prevent unintended pregnancy and STIs.

Behavioral and Brain Correlates of Emotional Distress in Older Adults During COVID-19 Quarantine.

COVID-19 led to unprecedented lockdowns and changes in older adults' lives, especially those with type 2 diabetes who have high risk of complications and mortality. We investigated the associations of cognitive and motor function and gray matter volumes (GMVs) with COVID-19 lockdown-related emotional distress of type 2 diabetes older adults, participating in the Israel Diabetes and Cognitive Decline Study. We administered a questionnaire to obtain information about anxiety, depression, general well-being, and optimism during a mandated lockdown. Lower grip strength before lockdown was associated with increased sadness, anxiety, and less optimism. Slower gait speed was associated with greater sadness. Lower GMV was related to greater anxiety during the lockdown when compared with anxiety levels before the COVID-19 outbreak. Yet, global cognition was not associated with any emotional distress measure. These results support the role of good motor function on emotional well-being during acute stress and GMV as a potential underlying mechanism.

Hydrogels for RNA delivery.

RNA-based therapeutics have shown tremendous promise in disease intervention at the genetic level, and some have been approved for clinical use, including the recent COVID-19 messenger RNA vaccines. The clinical success of RNA therapy is largely dependent on the use of chemical modification, ligand conjugation or non-viral nanoparticles to improve RNA stability and facilitate intracellular delivery. Unlike molecular-level or nanoscale approaches, macroscopic hydrogels are soft, water-swollen three-dimensional structures that possess remarkable features such as biodegradability, tunable physiochemical properties and injectability, and recently they have attracted enormous attention for use in RNA therapy. Specifically, hydrogels can be engineered to exert precise spatiotemporal control over the release of RNA therapeutics, potentially minimizing systemic toxicity and enhancing in vivo efficacy. This Review provides a comprehensive overview of hydrogel loading of RNAs and hydrogel design for controlled release, highlights their biomedical applications and offers our perspectives on the opportunities and challenges in this exciting field of RNA delivery.

Scorpion envenomation in Brazil: Current scenario and perspectives for containing an increasing health problem.

Opportunistic scorpion species can colonize urban environments, establishing high-density communities that enhance the chances of human accidents. This scenario has been taking place in Brazil, in which some Tityus species have taken city centers, causing an explosion in the number of scorpion envenoming cases. The characteristics of this scorpionism epidemic in Brazil is discussed in the present work. The number of Brazilian scorpion stings has surpassed 120,000 cases in 2017, and has been maintained above this number ever since, representing a more than 3-fold increase in 10 years, which was higher than the number of cases for most of the neglected tropical diseases in the country. The escalation in scorpionism cases is even higher in some regions of Brazil. Fortunately, the proportion of mild cases has also increased in the analyzed period, as well as the number of victims seeking for medical attention within the first hour after the accident. The species Tityus serrulatus, Tityus stigmurus, Tityus bahiensis, and Tityus obscurus are traditionally accountable for most of the scorpion accidents in different regions of Brazil, but other species deserve to be closely watched. Despite scorpionism being a notable health problem in Brazil, accident prevention and pest control regarding this venomous animal have not been properly addressed by the scientific community nor by policy makers. Therefore, this review also aims to point possible fields of research that could help to contain the aggravation of the current scorpionism landscape in Brazil.

Association of loneliness and social network size in adulthood with childhood maltreatment: Analyses of a population-based and a clinical sample.

BACKGROUND: Perceived loneliness and objective social network size are related but distinct factors, which negatively affect mental health and are prevalent in patients who have experienced childhood maltreatment (CM), for example, patients with persistent depressive disorder (PDD) and borderline personality disorder (BPD). This cross-diagnostic study investigated whether loneliness, social network size, or both are associated with self-reported CM. METHODS: Loneliness and social network size were assessed in a population-based sample at two time points (Study 1, N = 509), and a clinical group of patients with PDD or BPD (Study 2, N = 190) using the UCLA Loneliness Scale and the Social Network Index. Further measures were the Childhood Trauma Questionnaire, and standard depression rating scales. Linear regression analyses were applied to compare associations of loneliness or social network size with CM. Multiple mediation analyses were used to test the relative importance of loneliness and social network size in the relationship between CM and depressive symptoms. RESULTS: In both studies, loneliness showed a stronger association than social network size with CM. This was particularly marked for emotional neglect and emotional abuse. Loneliness but not social network size mediated the relationship between CM and depressive symptoms. CONCLUSIONS: Loneliness is particularly associated with self-reported CM, and in this respect distinct from the social network size. Our results underline the importance of differentiating both psychosocial constructs and suggest focusing on perceived loneliness and its etiological underpinnings by mechanism-based psychosocial interventions.

Familiarity in Rural Life: Protocol for a Scoping Review and Concept Analysis.

BACKGROUND: Familiarity is a concept often used in literature but is not well defined or understood. As a key concept in rural nursing theory, the conceptual understanding of familiarity is currently incomplete. The findings from this scoping review will inform a concept analysis using Walker and Avant's method and to identify and define the missing key components of familiarity. OBJECTIVE: The objective of this scoping review is to examine and analyze what is known in the existing literature about the concept of familiarity. METHODS: The Joanna Briggs Institute scoping review framework guided the identification of literature published from 2016 to 2022 on familiarity. Following the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) reporting standard, the familiarity scoping review is registered on Open Science Framework (registration digital object identifier: 10.17605/OSF.IO/ZB8VF). A total of 8 databases, including PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus with full text, APA PsychInfo, Communication Source, EBSCO MegaFILE, Medline, Nursing & Allied Health Database, and ScienceDirect, will be searched for 22 search terms. Covidence software will be used to manage the scoping review with each citation independently reviewed by 2 research team members for eligibility. Eligibility will be determined using a 2-level process. Each title and abstract will be screened for eligibility; for citations deemed eligible, a full-text article review will be conducted. The scoping review is expected to locate a large body of literature, and eligibility criteria will be refined during the title and abstract screening process. In addition, reference list scanning will be performed to locate relevant literature. RESULTS: Familiarity data will be collected beginning October 2021 with anticipated completion in March 2022. Dissemination of findings will occur through scholarly presentations and in rural-focused and nursing publications in 2022 or 2023. The findings from this review will further the understanding of familiarity and how it affects rural life and nursing practice. CONCLUSIONS: This review will support a full understanding and add clarity to the concept of familiarity as a component of rural life. These new insights will advance the understanding of how familiarity influences rural health care practice. The concept analysis will provide theoretical support for rural nursing theory and promote an understanding of the interrelationships of rural concepts. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/36930.

Reactogenic sleepiness after COVID-19 vaccination. A hypothesis involving orexinergic system linked to inflammatory signals.

Coronavirus disease 2019 (COVID-19) represents a global healthcare crisis that has led to morbidity and mortality on an unprecedented scale. While studies on COVID-19 vaccines are ongoing, the knowledge about the reactogenic symptoms that can occur after vaccination and its generator mechanisms can be critical for healthcare professionals to improve compliance with the future vaccination campaign. Because sleep and immunity are bidirectionally linked, sleepiness or sleep disturbance side effects reported after some of the COVID-19 vaccines advise an academic research line in the context of physiological or pathological neuroimmune interactions. On the recognized basis of inflammatory regulation of hypothalamic neurons in sickness behavior, we hypothesized that IL-1ß, INF-γ and TNF-α pro-inflammatory cytokines inhibit orexinergic neurons promoting sleepiness after peripheral activation of the innate immune system induced by the novel COVID-19 vaccines. In addition, based on knowledge of previous vaccines and disease manifestations of SARS-CoV-2 infection, it also suggests that narcolepsy must be included as potential adverse events of particular interest to consider in pharmacovigilance studies.

Aging-Related Impairments to M Cells in Peyer's Patches Coincide With Disturbances to Paneth Cells.

The decline in mucosal immunity during aging increases susceptibility, morbidity and mortality to infections acquired via the gastrointestinal and respiratory tracts in the elderly. We previously showed that this immunosenescence includes a reduction in the functional maturation of M cells in the follicle-associated epithelia (FAE) covering the Peyer's patches, diminishing the ability to sample of antigens and pathogens from the gut lumen. Here, co-expression analysis of mRNA-seq data sets revealed a general down-regulation of most FAE- and M cell-related genes in Peyer's patches from aged mice, including key transcription factors known to be essential for M cell differentiation. Conversely, expression of ACE2, the cellular receptor for SARS-Cov-2 virus, was increased in the aged FAE. This raises the possibility that the susceptibility of aged Peyer's patches to infection with the SARS-Cov-2 virus is increased. Expression of key Paneth cell-related genes was also reduced in the ileum of aged mice, consistent with the adverse effects of aging on their function. However, the increased expression of these genes in the villous epithelium of aged mice suggested a disturbed distribution of Paneth cells in the aged intestine. Aging effects on Paneth cells negatively impact on the regenerative ability of the gut epithelium and could indirectly impede M cell differentiation. Thus, restoring Paneth cell function may represent a novel means to improve M cell differentiation in the aging intestine and increase mucosal vaccination efficacy in the elderly.

Selecting a theoretical framework to guide research on the COVID-19 pandemic impacts on nursing care delivery and the critical care work system (using Reed's Intermodern approach to theory critique).

Understanding the impact of COVID-19 on nursing care delivery in critical care work systems is urgently needed. Theoretical frameworks guide understanding of phenomena in research. In this paper, we critique four theoretical frameworks (Donabedian's Quality Model, the Quality Health Outcomes Model, the Systems Research Organizing Model, and the Systems Engineering (SEIPS) 2.0 Model) using (blinded) (2018) Intermodern philosophical perspective of nursing science. (blinded) (2018) Intermodern approach to theory critique was selected for its pragmatic perspective and focus on personal and professional health and wellbeing. The SEIPS 2.0 Model was ultimately selected to guide the study of the impact of the COVID-19 Pandemic on nursing care delivery in the critical care work systems.

Policy and Environmental Predictors of Park Visits During the First Months of the COVID-19 Pandemic: Getting Out While Staying in

The COVID-19 pandemic may have altered visitation patterns to parks, with potential effects on human health. Little is known about park use early in the pandemic, how park availability influenced use, and whether park visits accelerated COVID-19 spread. Using weekly cell phone location data for 620 U.S. counties, we show park visits decreased by an average 26% between March 15 and May 9, 2020. Net of weekly trends, park visits were 2.2% lower when stay-at-home orders were in effect, yet increased by 8.4% with school closures and 4.4% with business closures. Park visits decreased less during the pandemic in counties where park availability was high. Levels of park visits were not associated with COVID-19 growth rate or incidence in the following weeks. Thus, parks served as recreation and leisure outlets when schools and businesses closed, especially where parks were more available, with no evidence of park use increasing COVID-19 spread.

Promoting Patient and Nurse Safety in Acute Dialysis Units Through Advocacy and Collaboration

Hospitals face the increasing challenge of balancing the need to provide quality care with that of being cost-effective. While guidelines and benchmarks for quality care exist in many areas within the hospital, those guidelines can be lacking for the acute (inpatient) dialysis setting. Nephrology nurses working in this setting may provide hemodialysis, peritoneal dialysis, continuous kidney replacement therapy, and apheresis treatments at the patient's bedside and in an acute dialysis unit. This article discusses the need to promote patient and nurse safety in acute dialysis settings through advocacy and collaboration.

Computational Analysis of SARS-CoV-2 and SARS-Like Coronavirus Diversity in Human, Bat and Pangolin Populations.

In 2019, a novel coronavirus, SARS-CoV-2/nCoV-19, emerged in Wuhan, China, and has been responsible for the current COVID-19 pandemic. The evolutionary origins of the virus remain elusive and understanding its complex mutational signatures could guide vaccine design and development. As part of the international "CoronaHack" in April 2020, we employed a collection of contemporary methodologies to compare the genomic sequences of coronaviruses isolated from human (SARS-CoV-2; n = 163), bat (bat-CoV; n = 215) and pangolin (pangolin-CoV; n = 7) available in public repositories. We have also noted the pangolin-CoV isolate MP789 to bare stronger resemblance to SARS-CoV-2 than other pangolin-CoV. Following de novo gene annotation prediction, analyses of gene-gene similarity network, codon usage bias and variant discovery were undertaken. Strong host-associated divergences were noted in ORF3a, ORF6, ORF7a, ORF8 and S, and in codon usage bias profiles. Last, we have characterised several high impact variants (in-frame insertion/deletion or stop gain) in bat-CoV and pangolin-CoV populations, some of which are found in the same amino acid position and may be highlighting loci of potential functional relevance.

Shifting digital, shifting context: (re)considering teacher professional development for online and blended learning in the COVID-19 era.

This paper is in response to the manuscript entitled, "Improving teacher professional development for online and blended learning: A systematic meta-aggregative review" (Philipsen et al. in Educ Technol Res Dev 67:1145-1174, 2019) from a research perspective. The impact of this study is that it resulted in a guiding framework for teacher professional development (TPD) for online and blended learning (OBL). The basis of this study may be applied to explore the quick shift to digital teaching and learning amidst the COVID-19 pandemic. A potential limitation of the resulting framework in this study is that TPD for OBL needs may currently differ, as teachers are experiencing appreciably different learning and performance contexts related to the mandated shift in professional practice to address continuity of instruction. The application of the methodology in this study combined with quick response research approaches (Quarantelli, in: Stallings (ed) Methods of disaster research, Philadelphia, Xlibris, 2002) could potentially extend the Philipsen et al. (Educ Technol Res Dev 67:1145-1174, 2019) TPD framework to address educator preparation for successful professional practice in online and blended environments in times of crisis.