Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can cause neurological disease in humans, but little is known about the pathogenesis of SARS-CoV-2 infection in the central nervous system (CNS). Herein, using K18-hACE2 mice, we demonstrate that SARS-CoV-2 neuroinvasion and encephalitis is associated with mortality in these mice. Intranasal infection of K18-hACE2 mice with 10⁵ plaque-forming units of SARS-CoV-2 resulted in 100% mortality by day 6 after infection. The highest virus titers in the lungs were observed on day 3 and declined on days 5 and 6 after infection. By contrast, very high levels of infectious virus were uniformly detected in the brains of all the animals on days 5 and 6. Onset of severe disease in infected mice correlated with peak viral levels in the brain. SARS-CoV-2-infected mice exhibited encephalitis hallmarks characterized by production of cytokines and chemokines, leukocyte infiltration, hemorrhage and neuronal cell death. SARS-CoV-2 was also found to productively infect cells within the nasal turbinate, eye and olfactory bulb, suggesting SARS-CoV-2 entry into the brain by this route after intranasal infection. Our data indicate that direct infection of CNS cells together with the induced inflammatory response in the brain resulted in the severe disease observed in SARS-CoV-2-infected K18-hACE2 mice.     

Relationship status and quality moderate daily pain-related changes in physical disability,affect, and cognitions in women with chronic pain

The objectives of this study were to examine whether (1) daily pain-related changes in physical functioning differed between happily partnered, unhappily partnered, and unpartnered female chronic pain patients, and (2) affect and pain cognitions mediated the partner status effect on pain-related changes in physical functioning. Two hundred fifty-one women with chronic pain due to osteoarthritis and/or fibromyalgia completed 30 daily electronic diaries assessing pain, affect, pain-related cognitions, and physical functioning. Patients living with a romantic partner also completed a modified version of the Locke-Wallace Marital Adjustment Scale to assess relationship satisfaction. Multilevel modeling revealed that patients in satisfying unions showed more adaptive daily pain-related changes in physical functioning, pain coping difficulty, and catastrophizing compared to those in unsatisfying unions and those who were unpartnered. Both partnered groups also showed more adaptive pain-related changes in positive affect compared to the unpartnered group. The impact of relationship status on pain-related changes in physical functioning was partly mediated by the pain cognitions catastrophizing and coping difficulty. These results indicate that happily partnered pain patients show less pain-related physical disability and more adaptive affective and cognitive responses to daily pain changes than do unhappily partnered and unpartnered patients. Living in a happy union may bolster the capacity of patients to sustain a sense of pain coping efficacy during pain episodes, which in turn, minimizes pain-related physical activity limitations.     

Adverse event assessment,analysis, and reporting in recent published analgesic clinical trials: ACTTION systematic review and recommendations

The development of valid and informative treatment risk–benefit profiles requires consistent and thorough information about adverse event (AE) assessment and participants’ AEs during randomized controlled trials (RCTs). Despite a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement recommending the specific AE information that investigators should report, there is little evidence that analgesic RCTs adequately adhere to these recommendations. This systematic review builds on prior recommendations by describing a comprehensive checklist for AE reporting developed to capture clinically important AE information. Using this checklist, we coded AE assessment methods and reporting in all 80 double-blind RCTs of noninvasive pharmacologic treatments published in the European Journal of Pain, Journal of Pain, and PAIN® from 2006 to 2011. Across all trials, reports of AEs were frequently incomplete, inconsistent across trials, and, in some cases, missing. For example, >40% of trials failed to report any information on serious adverse events. Trials of participants with acute or chronic pain conditions and industry-sponsored trials typically provided more and better-quality AE data than trials involving pain-free volunteers or trials that were not industry sponsored. The results of this review suggest that improved AE reporting is needed in analgesic RCTs. We developed an ACTTION (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks) AE reporting checklist that is intended to assist investigators in thoroughly and consistently capturing and reporting these critically important data in publications.     

Embracing the population health framework in nursing research

MACDONALD SE, NEWBURN‐COOK CV, ALLEN M and REUTTER L. Nursing Inquiry 2013; 20 : 30–41
Embracing the population health framework in nursing research Individuals’ health outcomes are influenced not only by their knowledge and behavior, but also by complex social, political and economic forces. Attention to these multi‐level factors is necessary to accurately and comprehensively understand and intervene to improve human health. The population health framework is a valuable conceptual framework to guide nurse researchers in identifying and targeting the broad range of determinants of health. However, attention to the intermediate processes linking multi‐level factors and use of appropriate multi‐level theory and research methodology is critical to utilizing the framework effectively. Nurse researchers are well equipped to undertake such investigations but need to consider a number of political, societal, professional and organizational barriers to do so. By fully embracing the population health framework, nurse researchers have the opportunity to explore the multi‐level influences on health and to develop, implement and evaluate interventions that target immediate needs, more distal factors and the intermediate processes that connect them.     

Sustained MEK inhibition abrogates myeloproliferative disease in Nf1 mutant mice

Children with neurofibromatosis type 1 (NF1) are predisposed to juvenile myelomonocytic leukemia (JMML), an aggressive myeloproliferative neoplasm (MPN) that is refractory to conventional chemotherapy. Conditional inactivation of the Nf1 tumor suppressor in hematopoietic cells of mice causes a progressive MPN that accurately models JMML and chronic myelomonocytic leukemia (CMML). We characterized the effects of Nf1 loss on immature hematopoietic populations and investigated treatment with the MEK inhibitor PD0325901 (hereafter called 901). Somatic Nf1 inactivation resulted in a marked expansion of immature and lineage-committed myelo-erythroid progenitors and ineffective erythropoiesis. Treatment with 901 induced a durable drop in leukocyte counts, enhanced erythropoietic function, and markedly reduced spleen sizes in mice with MPN. MEK inhibition also restored a normal pattern of erythroid differentiation and greatly reduced extramedullary hematopoiesis. Remarkably, genetic analysis revealed the persistence of Nf1-deficient hematopoietic cells, indicating that MEK inhibition modulates the proliferation and differentiation of Nf1 mutant cells in vivo rather than eliminating them. These data provide a rationale for performing clinical trials of MEK inhibitors in patients with JMML and CMML.     

Traumatized muscle‐derived multipotent progenitor cells recruit endothelial cells through vascular endothelial growth factor‐A action

Traumatized muscle, such as that debrided from blast injury sites, is considered a promising and convenient tissue source for multipotent progenitor cells (MPCs), a population of adult mesenchymal stem cell (MSC)‐like cells. The present study aimed to assess the regenerative therapeutic potential of human traumatized muscle‐derived MPCs, e.g., for injury repair in the blast‐traumatized extremity, by comparing their pro‐angiogenic potential in vitro and capillary recruitment activity in vivo to those of MSCs isolated from human bone marrow, a widely‐used tissue source. MPCs were tested for their direct and indirect effects on human microvascular endothelial cells (ECs) in vitro. The findings reported here showed that MPC‐conditioned culture medium (MPC‐CM), like MSC‐CM, promoted EC‐cord network branching. Silent (si)RNA‐mediated silencing of vascular endothelial growth factor‐A (VEGF‐A) expression in MPCs attenuated this effect. In a chick embryonic chorioallantoic membrane in vivo angiogenesis assay, MPCs encapsulated in photocrosslinked gelatin scaffold recruited blood vessels more efficiently than either MSCs or human foreskin fibroblasts. Together, these findings support the potential application of traumatized muscle‐derived MPCs in cell‐based regenerative medicine therapies as a result of their influence on EC organization. Copyright © 2017 John Wiley & Sons, Ltd.     

Pain Anxiety and Its Association With Pain Congruence Trajectories During the Cold Pressor Task

Incongruence of pain severity ratings among people experiencing pain and their observers has been linked to psychological distress. Previous studies have measured pain rating congruence through static self-report, involving a single rating of pain; however, this method does not capture changes in ratings over time. The present study examined the extent to which partners were congruent on multiple ratings of a participants' pain severity during the cold pressor task. Furthermore, 2 components of pain anxiety—pain catastrophizing and perceived threat—were examined as predictors of pain congruence. Undergraduate couples in a romantic relationship (N = 127 dyads) participated in this study. Both partners completed measures of pain catastrophizing and perceived threat before randomization to their cold pressor participant or observer roles. Participants and observers rated the participant's pain in writing several times over the course of the task. On average, observers rated participants' pain as less severe than participants' rated their own pain. In addition, congruence between partners increased over time because of observers' ratings becoming more similar to participant's ratings. Finally, pain catastrophizing and perceived threat independently and jointly influenced the degree to which partners similarly rated the participant's pain.

Urban Farming: A Non-Traditional Intervention for HIV-Related Distress

As individuals with HIV are living longer with less morbidity, developing interventions that address co-morbidities are essential. Psychological distress symptoms fluctuate throughout HIV infection and interrupt self-care practices. This pilot study was conducted to test the implementation of a clinic-recruited sample to participate in a community-based urban farming intervention, and assess the efficacy of reducing psychological distress symptoms. While the changes were not statistically significant, participants reported less distress symptoms, improved overall general health, and reduced frequency of illicit drug use. These findings support the development of a larger scale study to examine the impact of this nontraditional intervention.