Quadriceps Strength and Knee-Related Symptom State 6 Months After Anterior Cruciate Ligament Reconstruction.

Context: Isometric quadriceps strength metrics and patient-reported outcomes are commonly used in return-to-sport assessments in those with anterior cruciate ligament reconstruction (ACLR). Patients may experience clinical knee-related symptoms aggravating enough to seek additional medical care after ACLR. In addition to seeking additional medical care, these patient-reported clinical knee-related symptoms may also influence function after ACLR.

A high throughput screening assay for inhibitors of SARS-CoV-2 pseudotyped particle entry.

Effective small molecule therapies to combat the SARS-CoV-2 infection are still lacking as the COVID-19 pandemic continues globally. High throughput screening assays are needed for lead discovery and optimization of small molecule SARS-CoV-2 inhibitors. In this work, we have applied viral pseudotyping to establish a cell-based SARS-CoV-2 entry assay.

A high throughput screening assay for inhibitors of SARS-CoV-2 pseudotyped particle entry.

Effective small molecule therapies to combat the SARS-CoV-2 infection are still lacking as the COVID-19 pandemic continues globally. High throughput screening assays are needed for lead discovery and optimization of small molecule SARS-CoV-2 inhibitors. In this work, we have applied viral pseudotyping to establish a cell-based SARS-CoV-2 entry assay.

Inhibitors of L-Type Calcium Channels Show Therapeutic Potential for Treating SARS-CoV-2 Infections by Preventing Virus Entry and Spread.

COVID-19 is caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2). The virus is responsible for an ongoing pandemic and concomitant public health crisis around the world. While vaccine development is proving to be highly successful, parallel drug development approaches are also critical in the response to SARS-CoV-2 and other emerging viruses.

Optical Mass Spectrometry of Cold RaOH^{+} and RaOCH_{3}^{+}.

We present an all-optical mass spectrometry technique to identify trapped ions. The new method uses laser-cooled ions to determine the mass of a cotrapped dark ion with a sub-dalton resolution within a few seconds. We apply the method to identify the first controlled synthesis of cold, trapped RaOH^{+} and RaOCH_{3}^{+}.

Proteolytic Activation of SARS-CoV-2 Spike at the S1/S2 Boundary: Potential Role of Proteases beyond Furin.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses its spike (S) protein to mediate viral entry into host cells. Cleavage of the S protein at the S1/S2 and/or S2' site(s) is associated with viral entry, which can occur at either the cell plasma membrane (early pathway) or the endosomal membrane (late pathway), depending on the cell type. Previous studies show that SARS-CoV-2 has a unique insert at the S1/S2 site that can be cleaved by furin, which appears to expand viral tropism to cells with suitable protease and receptor expression.

Identifying SARS-CoV-2 Entry Inhibitors through Drug Repurposing Screens of SARS-S and MERS-S Pseudotyped Particles.

While vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection are urgently needed. Here, inhibitors of spike (S) mediated cell entry were identified in a high throughput screen of an approved drugs library with SARS-S and MERS-S pseudotyped particle entry assays. We discovered six compounds (cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol) to be broad spectrum inhibitors for spike-mediated entry.

β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway.

β-Coronaviruses are a family of positive-strand enveloped RNA viruses that includes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much is known regarding their cellular entry and replication pathways, but their mode of egress remains uncertain. Using imaging methodologies and virus-specific reporters, we demonstrate that β-coronaviruses utilize lysosomal trafficking for egress rather than the biosynthetic secretory pathway more commonly used by other enveloped viruses.

Identifying SARS-CoV-2 entry inhibitors through drug repurposing screens of SARS-S and MERS-S pseudotyped particles.

While vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection are urgently needed. Here, inhibitors of spike (S) mediated cell entry were identified in a high throughput screen of an approved drugs library with SARS-S and MERS-S pseudotyped particle entry assays. We discovered six compounds (cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol) to be broad spectrum inhibitors for spike-mediated entry.

Ca Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity.

Fusion with, and subsequent entry into, the host cell is one of the critical steps in the life cycle of enveloped viruses. For Middle East respiratory syndrome coronavirus (MERS-CoV), the spike (S) protein is the main determinant of viral entry. Proteolytic cleavage of the S protein exposes its fusion peptide (FP), which initiates the process of membrane fusion.

SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.

Viruses possessing class I fusion proteins require proteolytic activation by host cell proteases to mediate fusion with the host cell membrane. The mammalian SPINT2 gene encodes a protease inhibitor that targets trypsin-like serine proteases. Here we show the protease inhibitor, SPINT2, restricts cleavage-activation efficiently for a range of influenza viruses and for human metapneumovirus (HMPV).

Human matriptase/ST 14 proteolytically cleaves H7N9 hemagglutinin and facilitates the activation of influenza A/Shanghai/2/2013 virus in cell culture.

Background: Influenza is a zoonotic disease that infects millions of people each year resulting in hundreds of thousands of deaths, and in turn devastating pandemics. Influenza is caused by influenza viruses, including influenza A virus (IAV). There are many subtypes of IAV but only a few seem to be able to adapt to humans and to cause disease.

Calcium Ions Directly Interact with the Ebola Virus Fusion Peptide To Promote Structure-Function Changes That Enhance Infection.

Ebola virus disease is a serious global health concern given its periodic occurrence, high lethality, and the lack of approved therapeutics. Certain drugs that alter intracellular calcium, particularly in endolysosomes, have been shown to inhibit Ebola virus infection; however, the underlying mechanism is unknown. Here, we provide evidence that (EBOV) infection is promoted in the presence of calcium as a result of the direct interaction of calcium with the EBOV fusion peptide (FP).

Intimate Partner Violence: A Multinational Test of Cultural Spillover Theory.

Cultural spillover theory asserts that the prevalence of socially legitimate violence to attain ends for which there is widespread social approval is part of the explanation for the prevalence of illegitimate violence. This study was a test of the cultural spillover theory as it applies to intimate partner violence (IPV). Based on data from the International Dating Violence Study (IDVS) in 32 countries, we tested the proposition that agreement with socially approved forms of violence "spills over" into violence against an intimate partner.

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation.

Enveloped viruses such as coronaviruses or influenza virus require proteolytic cleavage of their fusion protein to be able to infect the host cell. Often viruses exhibit cell and tissue tropism and are adapted to specific cell or tissue proteases. Moreover, these viruses can introduce mutations or insertions into their genome during replication that may affect the cleavage, and thus can contribute to adaptations to a new host.

Concordance Between Parents in Perpetration of Child Mistreatment: How Often Is It by Father-Only, Mother-Only, or by Both and What Difference Does It Make?

Research on child mistreatment tends to focus on the mother or the father as the abusing parent, even though there is wide agreement that both theory and practice should deal with child maltreatment as a family system problem. Most children have the benefit or the risk of more than one caretaker for substantial periods of their lives, most often two parents or stepparents. This article is intended to illustrate the value of research which uses concordance analysis (CA) to identify children who experienced three (DCTs) of mistreatment: , or parents, including single-parent combinations of caretakers.

A peptide-based approach to evaluate the adaptability of influenza A virus to humans based on its hemagglutinin proteolytic cleavage site.

Cleavage activation of the hemagglutinin (HA) protein by host proteases is a crucial step in the infection process of influenza A viruses (IAV). However, IAV exists in eighteen different HA subtypes in nature and their cleavage sites vary considerably. There is uncertainty regarding which specific proteases activate a given HA in the human respiratory tract.

Early Psychosis and Trauma-Related Disorders: Clinical Practice Guidelines and Future Directions.

Despite high rates of trauma-related disorders among individuals with early psychosis, no clinical practice guidelines for the treatment of comorbid early psychosis and trauma-related disorders exist to date. Indeed, the routine exclusion of individuals with past and current psychosis from participation in trauma research and practice has limited the accumulation of research that could support such clinical practice guidelines. While preliminary research evidence suggests that traditional, evidence-based treatments for trauma-related disorders can be safely and effectively employed to reduce symptoms of posttraumatic stress and chronic psychosis, it remains unclear whether such treatments are appropriate for individuals in the early stages of psychotic illness.

Randomized Controlled Trial Comparing Exercise to Health Education for Stimulant Use Disorder: Results From the CTN-0037 STimulant Reduction Intervention Using Dosed Exercise (STRIDE) Study.

Objective: To evaluate exercise as a treatment for stimulant use disorders.

Methods: The STimulant Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized clinical trial conducted in 9 residential addiction treatment programs across the United States from July 2010 to February 2013. Of 497 adults referred to the study, 302 met all eligibility criteria, including DSM-IV criteria for stimulant abuse and/or dependence, and were randomized to either a dosed exercise intervention (Exercise) or a health education intervention (Health Education) control, both augmenting treatment as usual and conducted thrice weekly for 12 weeks.

Risk Factors for Concordance Between Partners in Assault Among University Student Couples.

Based on information 11,408 university students provided on perpetration of physical assault in a romantic relationship, they were classified into three Dyadic Concordance Types (DCTs). We then examined six risk factors drawn from previous literature of partner violence: physical abuse as a child, antisocial personality characteristics, alcohol abuse, coercive control, chronic denigration in a relationship, and patriarchy at the societal level. We hypothesized that some risk factors for assault are different dependent on the DCT.

Conformational toggling controls target site choice for the heteromeric transposase element Tn7.

The bacterial transposon Tn7 facilitates horizontal transfer by directing transposition into actively replicating DNA with the element-encoded protein TnsE. Structural analysis of the C-terminal domain of wild-type TnsE identified a novel protein fold including a central V-shaped loop that toggles between two distinct conformations. The structure of a robust TnsE gain-of-activity variant has this loop locked in a single conformation, suggesting that conformational flexibility regulates TnsE activity.

Addressing violence by female partners is vital to prevent or stop violence against women: evidence from the multisite batterer intervention evaluation.

This article presents a reanalysis of data from Gondolf's (2012) article in this journal on reoffending by men in the 15-month period subsequent to participation in batterer intervention programs. Gondolf concludes that violence by the female partners "was relatively low and does not appear to influence the program outcome in terms of men's reassault" (p. 10).

Preventing deaths from rising opioid overdose in the US - the promise of naloxone antidote in community-based naloxone take-home programs.

The opioid overdose epidemic is an alarming and serious public health problem in the United States (US) that has been escalating for 11 years. The 2011 National Survey on Drug Use and Health (NSDUH) demonstrated that 1 in 20 persons in the US aged 12 or older reported nonmedical use of prescription painkillers in the past year. Prescription drug overdose is now the leading cause of accidental death in the United States - surpassing motor vehicle accidents.

Mutuality, severity, and chronicity of violence by Father-Only, Mother-Only, and mutually violent parents as reported by university students in 15 nations.

This article aims to provide a more complete description of the violence between parents experienced by children than is usual in research and to suggest the practicality and importance of doing so. It presents results on the percent of parents in each of three Dyadic Types: Father-Only (the father assaulted the mother and the mother did not assault), Mother-Only (mother assaulted and the father did not assault), and Both-Assault; and on differences between these three types in the chronicity and severity of assaults. Questionnaires were completed by convenience samples of university students in 15 nations (N=11,408).