Proteomic Discovery of VEEV E2-Host Partner Interactions Identifies GRP78 Inhibitor HA15 as a Potential Therapeutic for Alphavirus Infections.

Alphaviruses are a genus of the family and are widely distributed across the globe. Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), cause encephalitis and neurological sequelae while chikungunya virus (CHIKV) and Sindbis virus (SINV) cause arthralgia. There are currently no approved therapeutics or vaccines available for alphaviruses.

The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection.

We identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone , a compound in clinical trials for anti-fibrotic and anti-inflammatory applications , as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry . We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection.

The transcriptional landscape of Venezuelan equine encephalitis virus (TC-83) infection.

Venezuelan Equine Encephalitis Virus (VEEV) is a major biothreat agent that naturally causes outbreaks in humans and horses particularly in tropical areas of the western hemisphere, for which no antiviral therapy is currently available. The host response to VEEV and the cellular factors this alphavirus hijacks to support its effective replication or evade cellular immune responses are largely uncharacterized. We have previously demonstrated tremendous cell-to-cell heterogeneity in viral RNA (vRNA) and cellular transcript levels during flaviviral infection using a novel virus-inclusive single-cell RNA-Seq approach.

Striatal Direct Pathway Targets Npas1 Pallidal Neurons.

The classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known.

Pemphigoid gestationis: a rare pregnancy dermatosis treated with a combination of IVIg and rituximab.

Pemphigoid gestationis is a rare autoimmune subepidermal bullous dermatosis occurring during pregnancy and post partum. A 32-year-old woman developed itchy urticarial wheals over the trunk and extremities at 6 months of gestation. This was not controlled with antihistamines, and 2 months later, the patient developed multiple vesiculobullous lesions.

Durability of Viral Neutralization in Asymptomatic Coronavirus Disease 2019 for at Least 60 Days.

A cohort consisting of asymptomatic healthcare workers donated temporal serum samples after infection with severe acute respiratory syndrome coronavirus 2. Analysis shows that all asymptomatic healthcare workers had neutralizing antibodies, that these antibodies persist for ≥60 days, and that anti-spike receptor-binding domain immunoglobulin G levels were correspondingly durable over the same time period.

Computed Tomographic Study of Remarkable Anatomic Variations in Paranasal Sinus Region and their Clinical Importance - A Retrospective Study.

Introduction: With the advent of functional endoscopic sinus surgery and coronal computed tomography (CT) imaging, more attention has been paid toward paranasal region anatomy. Detailed knowledge of anatomic variations in paranasal sinus region is critical for surgeons performing endoscopic sinus surgery as well as for the radiologist involved in the pre- and post-operative assessment. The anatomical variants with some accompanying pathologies would directly influence the success of diagnostic and therapeutic management of paranasal sinus diseases.

Status of eye health among tribal school children in South India.

Purpose: Global trends show a high prevalence of refractive errors among children. The prevalence of vision impairment due to uncorrected refractive errors among school children is increasing and the need for management of other ocular conditions is also reported. This study presents the status of eye health and pattern of daily activities among the school children of a tribal location in Tamil Nadu, South India.

Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also referred to as Host Defense Proteins/Peptides (HDPs), can inhibit SARS-CoV-2, paving the way for the potential clinical use of these molecules as therapeutic options.

Management of Spontaneous Liver Hematoma in Ehlers-Danlos Syndrome Type IV: A Case Report.

Introduction: Liver hematoma is an uncommon feature of Ehlers-Danlos syndrome (EDS) type IV. The limited literature that exists to guide management does not establish a standard of care.

Case Presentation: A 26-year-old man presented with acute abdominal pain caused by a large, spontaneous liver hematoma.

PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease.

Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu → Val) on the β-chain of adult hemoglobin (HbA) that results in sickled hemoglobin (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke.

Altered Gut Microbiome under Antiretroviral Therapy: Impact of Efavirenz and Zidovudine.

Millions of individuals currently living with HIV globally are receiving antiretroviral therapy (ART) that suppresses viral replication and improves host immune responses. The involvement of gut microbiome during HIV infection has been studied, exposing correlation with immune status and inflammation. However, the direct effect of ART on gut commensals of HIV-infected individuals has been mostly overlooked in microbiome studies.

Synthetic Host Defense Peptides Inhibit Venezuelan Equine Encephalitis Virus Replication and the Associated Inflammatory Response.

Venezuelan equine encephalitis virus (VEEV), a New World alphavirus of the Togaviridae family of viruses causes periodic outbreaks of disease in humans and equines. Disease following VEEV infection manifests as a febrile illness with flu-like symptoms, which can progress to encephalitis and cause permanent neurological sequelae in a small number of cases. VEEV is classified as a category B select agent due to ease of aerosolization and high retention of infectivity in the aerosol form.

Role of Mitochondria in Cancer Immune Evasion and Potential Therapeutic Approaches.

The role of mitochondria in cancer formation and progression has been studied extensively, but much remains to be understood about this complex relationship. Mitochondria regulate many processes that are known to be altered in cancer cells, from metabolism to oxidative stress to apoptosis. Here, we review the evolving understanding of the role of mitochondria in cancer cells, and highlight key evidence supporting the role of mitochondria in cancer immune evasion and the effects of mitochondria-targeted antitumor therapy.

Optimal Versus Approximate Channel Selection Methods for EEG Decoding With Application to Topology-Constrained Neuro-Sensor Networks.

Channel selection or electrode placement for neural decoding is a commonly encountered problem in electroencephalography (EEG). Since evaluating all possible channel combinations is usually infeasible, one usually has to settle for heuristic methods or convex approximations without optimality guarantees. To date, it remains unclear how large the gap is between the selection made by these approximate methods and the truly optimal selection.

Systems analysis of avascular necrosis of femoral head using integrative data analysis and literature mining delineates pathways associated with disease.

Avascular necrosis of femoral head (AVNFH) is a debilitating disease, which affects the middle aged population. Though the disease is managed using bisphosphonate, it eventually leads to total hip replacement due to collapse of femoral head. Studies regarding the association of single nucleotide polymorphisms with AVNFH, transcriptomics, proteomics, metabolomics, biophysical, ultrastructural and histopathology have been carried out.

Convergent and Stereoselective Method for the Synthesis of Acyclic α-Chloroenamides.

A direct, stereocontrolled synthesis of acyclic α-chloroenamides is presented. Our methodology showed good yields and substrate scope. Mechanistic insights are provided that account for the high levels of stereoselectivity reported.

Identification of a pocket factor that is critical to Zika virus assembly.

Zika virus (ZIKV) is an emerging mosquito borne flavivirus and a major public health concern causing severe disease. Due to the presence of a lipid membrane and structural heterogeneity, attaining an atomic resolution structure is challenging, but important to understand virus assembly and life cycle mechanisms that offer distinct targets for therapeutic intervention. We here use subvolume refinement to achieve a 3.

Surgical Strategies: Necrotizing Fasciitis of the Foot and Ankle Treated With Dermal Regeneration Matrix for Limb Salvage.

Although necrotizing fasciitis is a life-threatening entity that needs expeditious treatment, cases involving the lower extremity are less commonly encountered than in the upper extremity. Surgical intervention is often required and likely lead to amputation (below-knee or above-knee) vs debridement in the lower extremity.Coverage options in the foot and ankle after serial debridements can present many challenges for limb salvage.

SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2.

We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD). Docking studies suggest a heparin/heparan sulfate-binding site adjacent to the ACE2-binding site. Both ACE2 and heparin can bind independently to spike protein in vitro, and a ternary complex can be generated using heparin as a scaffold.

Venezuelan Equine Encephalitis Virus nsP3 Phosphorylation Can Be Mediated by IKKβ Kinase Activity and Abrogation of Phosphorylation Inhibits Negative-Strand Synthesis.

Venezuelan equine encephalitis virus (VEEV), a mosquito transmitted alphavirus of the family, can cause a highly inflammatory and encephalitic disease upon infection. Although a category B select agent, no FDA-approved vaccines or therapeutics against VEEV currently exist. We previously demonstrated NF-κB activation and macromolecular reorganization of the IKK complex upon VEEV infection in vitro, with IKKβ inhibition reducing viral replication.

Nuclei Isolation from Fresh Frozen Brain Tumors for Single-Nucleus RNA-seq and ATAC-seq.

Adult diffuse gliomas exhibit inter- and intra-tumor heterogeneity. Until recently, the majority of large-scale molecular profiling efforts have focused on bulk approaches that led to the molecular classification of brain tumors. Over the last five years, single cell sequencing approaches have highlighted several important features of gliomas.

Forecasting in humanitarian operations: Literature review and research needs.

Forecasting research in the humanitarian context is scarce. In this literature review, our goal is not only to show why forecasting research is important for the humanitarian sector, but also to identify what has been done so far, and where are the needs for further research. We conducted a structured literature search in Scopus, Web of Science, ABI Inform, and Google Scholar resulted in only 38 papers published between 1990 and 2018.

A novel way to quantify schizophrenia symptoms in clinical trials.

Background: A major problem in quantifying symptoms of schizophrenia is establishing a reliable distinction between enduring and dynamic aspects of psychopathology. This is critical for accurate diagnosis, monitoring and evaluating treatment effects in both clinical practice and trials.

Materials And Methods: We applied Generalizability Theory, a robust novel method to distinguish between dynamic and stable aspects of schizophrenia symptoms in the widely used Positive and Negative Symptom Scale (PANSS) using a longitudinal measurement design.