Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections.

Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC, CC) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (C)/EC, were used to predict the potential in vivo efficacy.

Precision or Pitfall? Evaluating the Accuracy of ICD-10 Coding for Cemented Total Hip Arthroplasty: A Multicenter Study.

Background: The International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Procedure Coding System (ICD-10-PCS) was adopted in the U.S. in 2015.

Orthopedic Manifestations of Hereditary Sensory and Autonomic Neuropathy IV in a 10-Year-Old Patient.

Hereditary sensory and autonomic neuropathy type IV (HSAN) is a rare and debilitating disorder highlighted by congenital absence of pain and anhidrosis. Orthopedic sequelae include physeal fractures, Charcot joint development, excessive joint laxity, soft tissue infections and recurrent painless dislocations, all of which often present in a delayed fashion. While there is no accepted guideline on management of these patients, several case studies have highlighted the importance of early diagnosis and cautioned against surgical intervention in these patients due to their inability to perceive pain and comply with post-operative restriction.

Retrieval of a Lane Plate 82 Years After Implantation: Case Report, Metallurgical Analysis, and Historical Review.

Background: The Lane plate was one of the first widely used bone plates, utilized in the first decades of the twentieth century. Here we present the results of a retrieval analysis on a Lane plate, and a review of the history of these plates. Our patient underwent plating of her femur with a Lane plate in 1938.

Retinal Displacement after Scleral Buckle versus Combined Buckle and Vitrectomy for Rhegmatogenous Retinal Detachment: ALIGN Scleral Buckle versus Pars Plana Vitrectomy with Scleral Buckle.

Purpose: To assess the risk of retinal displacement after scleral buckle (SB) versus pars plana vitrectomy with SB (PPV-SB).

Design: Multicenter prospective nonrandomized clinical trial.

Methods: The study took place at VitreoRetinal Surgery in Minneapolis, Minnesota, Sankara Nethralaya in Chennai, India, and St.

Primary ocular toxoplasmosis secondary to venison consumption.

Purpose: To describe primary ocular toxoplasmosis infection related to ingestion of undercooked venison.

Observations: This single site, retrospective case series reviewed 4 patients with primary ocular toxoplasmosis that was acquired by ingesting undercooked venison. De-identified data was collected regarding baseline patient characteristics including age, sex, past medical and ocular history, onset of symptoms, visual acuity (VA), response to treatment, and workup.

Discovery of a 2'-Fluoro,2'-Bromouridine Phosphoramidate Prodrug Exhibiting Anti-Yellow Fever Virus Activity in Culture and in Mice.

Yellow fever virus (YFV) is a potentially lethal, zoonotic, blood-borne flavivirus transmitted to humans and non-human primates by mosquitoes. Owing to multiple deadly epidemics, the WHO classifies YFV as a "high impact, high threat disease" with resurgent epidemic potential. At present, there are no approved antiviral therapies to combat YFV infection.

Comparison of anti-SARS-CoV-2 activity and intracellular metabolism of remdesivir and its parent nucleoside.

Remdesivir, a monophosphate prodrug of nucleoside analog GS-441524, is widely used for the treatment of moderate to severe COVID-19. It has been suggested to use GS-441524 instead of remdesivir in the clinic and in new inhalation formulations. Thus, we compared the anti-SARS-CoV-2 activity of remdesivir and GS-441524 in Vero E6, Vero CCL-81, Calu-3, Caco-2 ​cells, and anti-HCoV-OC43 activity in Huh-7 ​cells.

Recent Increases in Outpatient Total Hip Arthroplasty Have Not Increased Early Complications.

Background: Outpatient total hip arthroplasty (THA) has increased in recent years. Recent regulatory changes may allow and incentivize outpatient THA in more patients; however, there are concerns regarding safety. The purpose of this study is to assess early complications in outpatient THA compared to longer hospitalization.

Pharmacokinetics of Ruxolitinib in HIV Suppressed Individuals on Antiretroviral Agent Therapy from the ACTG A5336 Study.

Ruxolitinib is a US Food and Drug Administration-approved orally administered Janus kinase (1/2) inhibitor that reduces cytokine-induced inflammation. As part of a randomized, phase 2, open-label trial, ruxolitinib (10 mg twice daily) was administered to HIV-positive, virologically suppressed individuals (33 men, 7 women) on antiretroviral therapy (ART) for 5 weeks. Herein, we report the population PK subsequently determined from this study.

Teaching Smartphone Funduscopy with 20 Diopter Lens in Undergraduate Medical Education.

Purpose: To assess attitudes of pre-clinical undergraduate medical students toward learning smartphone funduscopy (SF) and its appropriateness as a teaching tool.

Patients And Methods: Second year medical students received instruction on direct ophthalmoscopy (DO) and SF; they were then paired with a peer and randomly assigned to perform DO or SF first. The SF technique involved freehand alignment of the axes of the smartphone camera with a condenser lens.

Dental Screening in Elective Total Joint Arthroplasty: Risk Factors for Failure.

Background: Active dental infection at the time of total joint arthroplasty (TJA) or in the acute postoperative period following TJA is thought to increase the risk of periprosthetic joint infection (PJI). Many surgeons recommend preoperative dental screening. This study aimed to identify how many elective TJA patients failed preoperative dental screening and what patient risk factors were associated with failure.

Studies on the Efficacy, Potential Cardiotoxicity and Monkey Pharmacokinetics of GLP-26 as a Potent Hepatitis B Virus Capsid Assembly Modulator.

While treatment options are available for hepatitis B virus (HBV), there is currently no cure. Anti-HBV nucleoside analogs and interferon-alpha 2b rarely clear HBV covalently closed circular DNA (cccDNA), requiring lifelong treatment. Recently, we identified GLP-26, a glyoxamide derivative which modulates HBV capsid assembly.

Novel method to quantify phenotypic markers of HIV-associated neurocognitive disorder in a murine SCID model.

Despite combined antiretroviral therapy (cART), HIV infection in the CNS persists with reported increases in activation of macrophages (MΦ), microglia, and surrounding astrocytes/neurons, conferring HIV-induced inflammation. Chronic inflammation results in HIV-associated neurocognitive disorders (HAND) with reported occurrence of up to half of individuals with HIV infection. The existing HAND mouse model used by laboratories including ours, and the effect of novel agents on its pathology present with labor-intensive and time-consuming limitations since brain sections and immunohistochemistry assays have to be performed and analyzed.

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses.

Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia.

Might Doctors Really "Know Best"?: Utilizing Surgeon Intuition to Strengthen Preoperative Surgical Risk Assessment.

Background: Many clinical factors are known to increase an individual patient's risk of perioperative complications and hospital readmission. Several novel risk calculators have been created to predict the risk of postoperative complications for specific procedures that rely entirely on objective measurements. Our goal was to determine if surgeon intuition (an estimate of the percent likelihood of minor and major medical and surgical complications and 30-day readmission) could provide an additional source of data in the preoperative setting that may enhance the prediction of complications after surgery.

Mobile Health Intervention to Reduce HIV Transmission: A Randomized Trial of Behaviorally Enhanced HIV Treatment as Prevention (B-TasP).

Objectives: We conducted a randomized clinical trial to test a mobile health behavioral intervention designed to enhance HIV treatment as prevention (B-TasP) by simultaneously increasing combination antiretroviral therapies (cART) adherence and improving the sexual health of people living with HIV.

Methods: A cohort of sexually active men (n = 383) and women (n = 117) living with HIV were enrolled. Participants were baseline assessed and randomized to either (1) B-TasP adherence and sexual health intervention or (2) general health control intervention.

Artery/vein classification of retinal blood vessels using feature selection.

Automated classification of retinal vessels in fundus images is the first step towards measurement of retinal characteristics that can be used to screen and diagnose vessel abnormalities for cardiovascular and retinal disorders. This paper presents a novel approach to vessel classification to compute the artery/vein ratio (AVR) for all blood vessel segments in the fundus image. The features extracted are then subjected to a selection procedure using Random Forests (RF) where the features that contribute most to classification accuracy are chosen as input to a polynomial kernel Support Vector Machine (SVM) classifier.

Chronic liver inflammation modifies DNA methylation at the precancerous stage of murine hepatocarcinogenesis.

Chronic liver inflammation precedes the majority of hepatocellular carcinomas (HCC). Here, we explore the connection between chronic inflammation and DNA methylation in the liver at the late precancerous stages of HCC development in Mdr2(-/-) (Mdr2/Abcb4-knockout) mice, a model of inflammation-mediated HCC. Using methylated DNA immunoprecipitation followed by hybridization with "CpG islands" (CGIs) microarrays, we found specific CGIs in 76 genes which were hypermethylated in the Mdr2(-/-) liver compared to age-matched healthy controls.

Asymmetric binding to NS5A by daclatasvir (BMS-790052) and analogs suggests two novel modes of HCV inhibition.

Symmetric, dimeric daclatasvir (BMS-790052) is the clinical lead for a class of picomolar inhibitors of HCV replication. While specific, resistance-bearing mutations at positions 31 and 93 of domain I strongly suggest the viral NS5A as target, structural mechanism(s) for the drugs' activities and resistance remains unclear. Several previous models suggested symmetric binding modes relative to the homodimeric target; however, none can fully explain SAR details for this class.

Enhanced antiretroviral therapy in rhesus macaques improves RT-SHIV viral decay kinetics.

Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(-)-FTC], tenofovir (TFV), and efavirenz (EFV).

Approaches to hepatitis C treatment and cure using NS5A inhibitors.

Recent progress in the understanding of hepatitis C virus (HCV) biology and the availability of in vitro models to study its replication have facilitated the development of direct-acting antiviral agents (DAAs) that target specific steps in the viral replication cycle. Currently, there are three major classes of DAA in clinical development: NS3/4A protease inhibitors, NS5B polymerase inhibitors, and NS5A directed inhibitors. Several compounds thought to bind directly with NS5A are now in various clinical trial phases, including the most advanced, daclatasvir (BMS-790052), ledipasvir (GS-5885), and ABT-267.