Evaluation of Four Humanized NOD-Derived Mouse Models for Dengue Virus-2 Infection.

Dengue is a significant public health problem with no specific viral treatment. One of the main challenges in studying dengue is the lack of adequate animal models recapitulating human immune responses. Most studies on humanized mice use NOD-scid IL2R gamma null (NSG) mice, which exhibit poor hematopoiesis for some cell populations.

Efficacy and immunogenicity following dengue virus-1 human challenge after a tetravalent prime-boost dengue vaccine regimen: an open-label, phase 1 trial.

Background: Dengue human infection models (DHIMs) are important tools to down-select dengue vaccine candidates and establish tetravalent efficacy before advanced clinical field trials. We aimed to provide data for the safety and immunogenicity of DHIM and evaluate dengue vaccine efficacy.

Methods: We performed an open-label, phase 1 trial at the University of Maryland (Baltimore, MD, USA).

RNA Interference Therapeutics for Chronic Hepatitis B: Progress, Challenges, and Future Prospects.

Chronic hepatitis B (CHB) is a global health challenge that can result in significant liver-related morbidity and mortality. Despite a prophylactic vaccine being available, patients already living with CHB often must engage in lifelong therapy with nucleoside analogues. However, the potential of RNA interference (RNAi) therapeutics as a promising avenue for CHB treatment is being explored.

Are Biodegradable Calcium Sulfate Antibiotic Beads Effective and Safe Adjuvants for Diabetic Foot Osteomyelitis?

Introduction:  Diabetic foot osteomyelitis (DFO) is a highly morbid condition that commonly affects diabetic patients. Biodegradable calcium-sulfate antibiotic beads (CaSO4) are theoretical adjuvant agents to reduce morbidity in DFO. However, there is a paucity of research on the safety and effectiveness of CaSO4 beads in DFO.

A rare case of ventriculitis.

Introduction: Nosocomial ventriculitis is a severe infection that habitually plagues neurological intensive care units. It is usually associated with external ventricular drains. Unfortunately, classic cerebral spinal fluid parameters are less specific and sensitive compared to community acquired meningitis.

Increased risk of severe COVID-19 in pregnancy in a multicenter propensity score-matched study.

Objectives: To explore the association between COVID-19 severity and pregnancy using measures such as COVID-19 ordinal scale severity score, hospitalization, intensive care unit (ICU) admission, oxygen supplementation, invasive mechanical ventilation, and death.

Methods: We conducted a retrospective, multicenter cohort study to understand the association between COVID-19 severity and pregnancy. We reviewed consecutive charts of adult females, ages 18-45, with laboratory testing for SARS-CoV-2 infection between March 1, 2020, and August 31, 2020.

A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains.

Humanized mice are an invaluable tool for investigating human diseases such as cancer, infectious diseases, and graft-versus-host disease (GvHD). However, it is crucial to understand the strengths and limitations of humanized mice and select the most appropriate model. In this study, we describe the development of the human lymphoid and myeloid lineages using a flow cytometric analysis in four humanized mouse models derived from NOD mice xenotransplanted with CD34 fetal cord blood from a single donor.

Blockade of CCR4 breaks immune tolerance in chronic hepatitis B patients by modulating regulatory pathways.

Background: Immunotargets including checkpoint inhibitors and toll-like receptor 8 agonists have recently gained attention for the recovery of hepatitis B virus (HBV)-specific T cell exhaustion in chronic hepatitis B(CHB). Chemokine receptors have a similar significant role during viral infections; however, their role in CHB remains poorly understood. Therefore, in this study we evaluated the role of chemokine receptor 4 (CCR4) in deriving immunosuppression during CHB.

COVID-19 Vaccines-All You Want to Know.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has led to an unprecedented public health crisis. The collective global response has led to production of multiple safe and effective vaccines utilizing novel platforms to combat the virus that have propelled the field of vaccinology forward. Significant challenges to universal vaccine effectiveness remain, including immune evasion by SARS-CoV-2 variants, waning of immune response, inadequate knowledge of correlates of protection, and dosing in special populations.

Immune-Mediated Pathogenesis in Dengue Virus Infection.

Dengue virus (DENV) infection is one of the major public health concerns around the globe, especially in the tropical regions of the world that contribute to 75% percent of dengue cases. While the majority of DENV infections are mild or asymptomatic, approximately 5% of the cases develop a severe form of the disease that is mainly attributed to sequential infection with different DENV serotypes. The severity of dengue depends on many immunopathogenic mechanisms involving both viral and host factors.

A Phase 2 open label study of ledipasvir/sofosbuvir for 12 weeks in subjects with hepatitis B virus infection.

Retrospective data showed that when we administered ledipasvir/sofosbuvir (LDV/SOF) to patients with hepatitis B and C coinfection, there was a modest reduction in hepatitis B surface antigen (HBsAg). Therefore, we hypothesize that similar HBsAg reduction can be seen in hepatitis B virus (HBV) monoinfected subjects. Primary and secondary efficacy endpoints are the decline in HBsAg and HBV DNA at Week 12 from baseline, respectively.

Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study.

Background: Non-antiviral therapeutic options are required for the treatment of hospitalised patients with COVID-19. CD24Fc is an immunomodulator with potential to reduce the exaggerated inflammatory response to tissue injuries. We aimed to evaluate the safety and efficacy of CD24Fc in hospitalised adults with COVID-19 receiving oxygen support.

Assessment of coronary inflammation in antiretroviral treated people with HIV infection and active HIV/hepatitis C virus co-infection.

Objective: People with HIV (PWH) and co-infected with hepatitis C virus (PWH + HCV) have increased risk of cardiovascular disease (CVD). Peri-coronary inflammation, measured by fat attenuation index (FAI) on coronary computed tomography angiography (CCTA), independently predicts cardiovascular risk in the general population but has not been studied in the PWH + HCV population. We tested whether peri-coronary inflammation is increased in PWH or PWH + HCV, and whether inflammation changes over time.

Humanized Mice for the Study of Dengue Disease Pathogenesis: Biological Assays.

Dengue is one of the most prevalent infectious diseases around the world, present in all continents and mainly affecting developing countries. With few tools to fight and study this disease, it is imperative to have reliable animal models that not only recapitulate human disease but also contain human components to understand the pathogenic mechanism and immune responses, allowing the development of new treatments and vaccines against dengue. Humanized mice are a significant advance in the development of in vivo models to understanding the relation of the human immune system and target organs such as the liver during the infection by dengue virus, allowing basic and preclinical research.

Current Trends and Limitations in Dengue Antiviral Research.

Dengue is the most prevalent arthropod-borne viral disease worldwide and affects approximately 2.5 billion people living in over 100 countries. Increasing geographic expansion of mosquitoes (which transmit the virus) has made dengue a global health concern.

Coronavirus Disease 2019-Associated Mucormycosis: Risk Factors and Mechanisms of Disease.

The severe surge of coronavirus disease 2019 (COVID-19) cases on the Indian subcontinent in early 2021 was marked by an unusually high number of COVID-19-associated mucormycosis (CAM) cases reported during this same period. This is significantly higher than predicted based on available data about prevalence and risk factors for this condition. This may be due to an unusual alignment of multiple risk factors for this condition.

Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial.

A major challenge for HIV vaccine development is to raise anti-envelope antibodies capable of recognizing and neutralizing diverse strains of HIV-1. Accordingly, a full length single chain (FLSC) of gp120-CD4 chimeric vaccine construct was designed to present a highly conserved CD4-induced (CD4i) HIV-1 envelope structure that elicits cross-reactive anti-envelope humoral responses and protective immunity in animal models of HIV infection. IHV01 is the FLSC formulated in aluminum phosphate adjuvant.

aortitis in a patient with HIV.

A 36-year-old man with well controlled HIV developed aortitis. To prevent aortic rupture, emergent surgical resection and neo-aortoiliac replacement with his left femoral vein was conducted. After surgical intervention, he was successfully treated with intravenous ertapenem for 6 weeks followed by oral amoxicillin for 3 months.

Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression.

More than 250 million people are living with chronic hepatitis B despite the availability of highly effective vaccines and oral antivirals. Although innate and adaptive immune cells play crucial roles in controlling hepatitis B virus (HBV) infection, they are also accountable for inflammation and subsequently cause liver pathologies. During the initial phase of HBV infection, innate immunity is triggered leading to antiviral cytokines production, followed by activation and intrahepatic recruitment of the adaptive immune system resulting in successful virus elimination.

Evolution of Nipah Virus Infection: Past, Present, and Future Considerations.

Nipah virus (NiV) is a zoonotic paramyxovirus of the genus first identified in Malaysia in 1998. Henipaviruses have bat reservoir hosts and have been isolated from fruit bats found across Oceania, Asia, and Africa. Bat-to-human transmission is thought to be the primary mode of human NiV infection, although multiple intermediate hosts are described.

Short-duration treatment with the novel non-nucleoside inhibitor CDI-31244 plus sofosbuvir/velpatasvir for chronic hepatitis C: An open-label study.

Combination regimens of direct-acting antiviral agents (DAAs) for chronic genotype 1 hepatitis C virus (HCV) infection given for 8 or 12 weeks have high cure rates. Shortened treatment durations that maintain high cure rates may lessen treatment barriers related to affordability and drug adherence. We enrolled 12 treatment-naïve adults with chronic genotype 1 HCV infection without cirrhosis in a single-center, open-label trial to receive 2 weeks of the highly potent and selective non-nucleoside inhibitor (NNI) CDI-31244 concurrent with 6 weeks of sofosbuvir/velpatasvir.

Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial.

Objectives: Primary Objective: To evaluate the efficacy and safety of oral administration of imatinib combined with the Best Conventional Care (BCC) versus placebo plus BCC in hospitalized patients with COVID-19.

Hypothesis: Addition of imatinib to the BCC will provide a superior clinical outcome for patients with COVID-19 compared with BCC plus placebo. This hypothesis is on the basis of 1) intralysosomal entrapment of imatinib will increase endosomal pH and effectively decrease SARS-CoV-2/cell fusion, 2) kinase inhibitory activity of imatinib will interfere with budding/release or replication of SARS-CoV-2, and 3) because of the critical role of mechanical ventilation in the care of patients with ARDS, imatinib will have a significant clinical impact for patients with critical COVID-19 infection in Intensive Care Unit (ICU).

Dengue Infections in Colombia: Epidemiological Trends of a Hyperendemic Country.

Dengue is a major public health problem in hyperendemic countries like Colombia, the understanding of the epidemiological trends is important for the development of efficient public health policies. We conducted a systematic review of the epidemiologic data on dengue in Colombia from 1971 to 2020. A total of 375 relevant citations were identified, 36 of which fulfilled the inclusion criteria.

Variability of CD4+ Cell Counts in HIV-1-Uninfected Volunteers Who Are Eligible for a Phase I HIV Vaccine Study.

Objective: Vaccines and biologics containing CD4 molecules or HIV-1 gp120 might induce antibodies targeting CD4. We evaluated temporal variability of CD4 levels in healthy volunteers to quantify declines that could indicate true adverse events.

Design: Prospective observational cohort study of 100 healthy adults without HIV-1 infection from the Baltimore region.