Orthopoxvirus Purification for High Containment Laboratories.

Purification of large viruses in a high containment laboratory can create unique challenges. Traditional purification methods for large viruses rely on equipment and techniques that are not ideal for high containment work. Poxvirus purification has long relied on the use of Genetron, a reagent that is no longer available.

Successful Collaborations that Resulted in Increased U.S. Diagnostic Testing During the 2022 Mpox Outbreak.

Context: The first case of mpox was detected in the United States in a Laboratory Response Network (LRN) laboratory at the Massachusetts Department of Public Health on May 17, 2022. Through previous years of smallpox preparedness efforts by the United States government, testing capacity in LRN laboratories across the United States utilizing the FDA-cleared Centers for Disease Control and Prevention (CDC) Non-variola orthopoxvirus (NVO) test was approximately 6000 tests weekly across the nation prior to the mpox outbreak. By early June 2022, the LRN laboratories had capacity to perform up to 8000 tests per week.

Cigarette Smoking and Observed Growth of Unruptured Intracranial Aneurysms: A Systematic Literature Review and Meta-Analysis.

Background: Smoking and observed growth of intracranial aneurysms are known risk factors for rupture. The mechanism by which smoking increases this risk is not completely elucidated. Furthermore, an association between smoking and aneurysm growth has not been clearly defined in the literature.

Variola Virus and Clade I Mpox Virus Differentially Modulate Cellular Responses Longitudinally in Monocytes During Infection.

Variola virus (VARV), the etiological agent of smallpox, had enormous impacts on global health prior to its eradication. In the absence of global vaccination programs, mpox virus (MPXV) has become a growing public health threat that includes endemic and nonendemic regions across the globe. While human mpox resembles smallpox in clinical presentation, there are considerable knowledge gaps regarding conserved molecular pathogenesis between these 2 orthopoxviruses.

Associations between menopause and body image: A systematic review.

Background: The menopausal transition involves multiple biological and psychosocial challenges that may render middle-aged women vulnerable to body image concerns.

Objective: The aim of this study was to summarize evidence on the associations between menopause and body image perception in healthy middle-aged women.

Design: This study is a systematic review of observational studies.

Increased Endocrine Activity of Xenobiotic Chemicals as Mediated by Metabolic Activation.

The US Environmental Protection Agency (USEPA) is faced with long lists of chemicals that require hazard assessment. The present study is part of a larger effort to develop in vitro assays and quantitative structure-activity relationships applicable to untested chemicals on USEPA inventories through study of estrogen receptor (ER) binding and estrogen-mediated gene expression in fish. The present effort investigates metabolic activation of chemicals resulting in increased estrogenicity.

Identification of Small Molecules with Improved Potency against Orthopoxviruses from Vaccinia to Smallpox.

The genus Orthopoxvirus contains several human pathogens, including vaccinia, monkeypox, cowpox, and variola virus, the causative agent of smallpox. Although there are a few effective vaccines, widespread prophylactic vaccination has ceased and is unlikely to resume, making therapeutics increasingly important to treat poxvirus disease. Here, we described efforts to improve the potency of the anti-poxvirus small molecule CMLDBU6128.

Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.

Smallpox, caused by the solely human pathogen Variola virus (VARV), was declared eradicated in 1980. While known VARV stocks are secure, smallpox remains a bioterrorist threat agent. Recent U.

New methylene blue derivatives suggest novel anti-orthopoxviral strategies.

Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes over time. As such, there is a concomitant increase in the incidence of human OPXV infections worldwide.

Rabies surveillance in the United States during 2019.

Objective: To provide epidemiological information on animal and human cases of rabies occurring in the United States during 2019 and summaries of 2019 rabies surveillance for Canada and Mexico.

Animals: All animals submitted for laboratory diagnosis of rabies in the United States during 2019.

Procedures: State and territorial public health departments and USDA Wildlife Services provided data on animals submitted for rabies testing in the United States during 2019.

Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model.

Smallpox, caused by (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the importance of oral antivirals and recommend therapeutics with different mechanisms of action. (MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing.

Laboratory Infection of Novel Akhmeta Virus in CAST/EiJ Mice.

Akhmeta virus is a zoonotic first identified in 2013 in the country of Georgia. Subsequent ecological investigations in Georgia have found evidence that this virus is widespread in its geographic distribution within the country and in its host-range, with rodents likely involved in its circulation in the wild. Yet, little is known about the pathogenicity of this virus in rodents.

Laser-assisted skin delivery of immunocontraceptive rabies nanoparticulate vaccine in poloxamer gel.

A painless skin delivery of vaccine for disease prevention is of great advantage in improving compliance in patients. To test this idea as a proof of concept, we utilized a pDNA vaccine construct, pDNAg333-2GnRH that has a dual function of controlling rabies and inducing immunocontraception in animals. The pDNA was administered to mice in a nanoparticulate form delivered through the skin using the P.

Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread.

Although orthopoxviruses (OPXV) are known to encode a majority of the genes required for replication in host cells, genome-wide genetic screens have revealed that several host pathways are indispensable for OPXV infection. Through a haploid genetic screen, we previously identified several host genes required for monkeypox virus (MPXV) infection, including the individual genes that form the conserved oligomeric Golgi (COG) complex. The COG complex is an eight-protein (COG1-COG8) vesicle tethering complex important for regulating membrane trafficking, glycosylation enzymes, and maintaining Golgi structure.

Discovery of Retro-1 Analogs Exhibiting Enhanced Anti-vaccinia Virus Activity.

Orthopoxviruses (OPXVs) are an increasing threat to human health due to the growing population of OPXV-naive individuals after the discontinuation of routine smallpox vaccination. Antiviral drugs that are effective as postexposure treatments against variola virus (the causative agent of smallpox) or other OPXVs are critical in the event of an OPXV outbreak or exposure. The only US Food and Drug Administration-approved drug to treat smallpox, Tecovirimat (ST-246), exerts its antiviral effect by inhibiting extracellular virus (EV) formation, thereby preventing cell-cell and long-distance spread.

Residency Training: A practical guide for medical students who are planning a future in neurology.

Medical students choose neurology for many reasons, including interest in neuroscience, the intellectual challenge of diagnosing and treating disorders of the nervous system, and the opportunity for continuity of care. Neurologists have great flexibility in choice of practice environment, ranging from an exclusively inpatient setting to a strictly clinic-based practice. The purpose of this article is to provide practical, actionable, systematic advice for medical students at every level of training on how to prepare for a neurology residency application and a career in neurology.

Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro.

Currently, no rabies virus-specific antiviral drugs are available. Ranpirnase has strong antitumor and antiviral properties associated with its ribonuclease activity. TMR-001, a proprietary bulk drug substance solution of ranpirnase, was evaluated against rabies virus in three cell types: mouse neuroblastoma, BSR (baby hamster kidney cells), and bat primary fibroblast cells.

Using the LN34 Pan-Lyssavirus Real-Time RT-PCR Assay for Rabies Diagnosis and Rapid Genetic Typing from Formalin-Fixed Human Brain Tissue.

Human rabies post mortem diagnostic samples are often preserved in formalin. While immunohistochemistry (IHC) has been routinely used for rabies antigen detection in formalin-fixed tissue, the formalin fixation process causes nucleic acid fragmentation that may affect PCR amplification. This study reports the diagnosis of rabies in an individual from the Dominican Republic using both IHC and the LN34 pan-lyssavirus real-time RT-PCR assay on formalin-fixed brain tissue.