Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.

Parkinson's disease (PD) is a debilitating neurodegenerative disease affecting millions of individuals worldwide. Hallmark features of PD pathology are the formation of Lewy bodies in neuromelanin-containing dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc), and the subsequent irreversible death of these neurons. Although genetic risk factors have been identified, around 90 % of PD cases are sporadic and likely caused by environmental exposures and gene-environment interaction.

Astrocyte Mitochondria Are a Sensitive Target of PCB52 and its Human-Relevant Metabolites.

Polychlorinated biphenyls (PCBs) are industrial chemicals that are ubiquitously found in the environment. Exposure to these compounds has been associated with neurotoxic outcomes; however, the underlying mechanisms for such outcomes remain to be fully understood. Recent studies have shown that astrocytes, the most abundant glial cell type in the brain, are susceptible to PCB exposure as well as exposure to human-relevant metabolites of PCBs.

Thalamocortical organoids enable in vitro modeling of 22q11.2 microdeletion associated with neuropsychiatric disorders.

Thalamic dysfunction has been implicated in multiple psychiatric disorders. We sought to study the mechanisms by which abnormalities emerge in the context of the 22q11.2 microdeletion, which confers significant genetic risk for psychiatric disorders.

Structure-Activity Relationship of Lower Chlorinated Biphenyls and Their Human-Relevant Metabolites for Astrocyte Toxicity.

Exposure to polychlorinated biphenyls (PCBs) is associated with developmental neurotoxicity and neurodegenerative disorders; however, the underlying mechanisms of pathogenesis are unknown. Existing literature has focused mainly on using neurons as a model system to study mechanisms of PCB-mediated neurotoxicity, overlooking the role of glial cells, such as astrocytes. As normal brain function is largely astrocyte-dependent, we hypothesize that astrocytes play an important role in PCB-mediated injury to neurons.

A CRISPR-engineered isogenic model of the 22q11.2 A-B syndromic deletion.

22q11.2 deletion syndrome, associated with congenital and neuropsychiatric anomalies, is the most common copy number variant (CNV)-associated syndrome. Patient-derived, induced pluripotent stem cell (iPS) models have provided insight into this condition.

Outcomes and Adverse Effects of Baricitinib Versus Tocilizumab in the Management of Severe COVID-19.

Objectives: The National Institutes of Health and Infectious Diseases Society of America guidelines recommend tocilizumab or baricitinib in the management of severe COVID-19. Despite clinical trials on the individual agents, there are no large-scale studies comparing the two agents to guide the selection of one versus the other. The purpose of this study was to compare the outcomes and adverse effects of baricitinib versus tocilizumab in the management of severe COVID-19.

Paragonimiasis presenting as an acute hemorrhagic stroke.

Cerebral paragonimiasis is rare and is usually seen in younger patients. This is a case of a 19-year-old male presenting as a hemorrhagic stroke with headache and blurred vision. He was found to have cystic thick-walled spaces with focal linear tracking towards the pleural space on computed tomography of the chest.

Early Use of Remdesivir in Patients Hospitalized With COVID-19 Improves Clinical Outcomes: A Retrospective Observational Study.

Background: Remdesivir treatment, like most antiviral drugs, is likely to be most effective when used early in the course of coronavirus disease 2019 (COVID-19). Optimal timing of remdesivir for the treatment of COVID-19 remains unclear.

Objectives: The aim of this study was to determine whether early treatment with remdesivir improves clinical outcomes: length of stay, need for mechanical ventilation, and death.

Prolonged Detection of SARS-CoV-2 in a Patient With the Development of New Clinical Symptoms.

We present a case of a 65-year-old woman with a persistently positive nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 PCR who developed new complications of coronavirus disease 2019 (COVID-19) 63 days from illness onset. She presented with intermittent fevers, fluctuating disorientation, gait instability, diffuse corticospinal tract signs, and acute venous thromboembolism. No alternate diagnosis was identified.

Rhombencephalitis due to .

Brain stem encephalitis is an unusual form of CNS listeriosis that is associated with a high mortality. This is a case of a 46 year-old male with a history of dermatomyositis on methotrexate who presented with fever, headache, assymetrical cranial nerve palsy and right hemiparesis. MRI showed a ring-enhancing lesions in medulla oblongata.

Development and validation of a predictive model for critical illness in adult patients requiring hospitalization for COVID-19.

Background: Identifying factors that can predict severe disease in patients needing hospitalization for COVID-19 is crucial for early recognition of patients at greatest risk.

Objective: (1) Identify factors predicting intensive care unit (ICU) transfer and (2) develop a simple calculator for clinicians managing patients hospitalized with COVID-19.

Methods: A total of 2,685 patients with laboratory-confirmed COVID-19 admitted to a large metropolitan health system in Georgia, USA between March and July 2020 were included in the study.

The Histone Variant H3.3 Is Enriched at Drosophila Amplicon Origins but Does Not Mark Them for Activation.

Eukaryotic DNA replication begins from multiple origins. The origin recognition complex (ORC) binds origin DNA and scaffolds assembly of a prereplicative complex (pre-RC), which is subsequently activated to initiate DNA replication. In multicellular eukaryotes, origins do not share a strict DNA consensus sequence, and their activity changes in concert with chromatin status during development, but mechanisms are ill-defined.

DNA sequence templates adjacent nucleosome and ORC sites at gene amplification origins in Drosophila.

Eukaryotic origins of DNA replication are bound by the origin recognition complex (ORC), which scaffolds assembly of a pre-replicative complex (pre-RC) that is then activated to initiate replication. Both pre-RC assembly and activation are strongly influenced by developmental changes to the epigenome, but molecular mechanisms remain incompletely defined. We have been examining the activation of origins responsible for developmental gene amplification in Drosophila.

Swertisin an Anti-Diabetic Compound Facilitate Islet Neogenesis from Pancreatic Stem/Progenitor Cells via p-38 MAP Kinase-SMAD Pathway: An In-Vitro and In-Vivo Study.

Transplanting islets serves best option for restoring lost beta cell mass and function. Small bio-chemical agents do have the potential to generate new islets mass, however lack of understanding about mechanistic action of these small molecules eventually restricts their use in cell-based therapies for diabetes. We recently reported "Swertisin" as a novel islet differentiation inducer, generating new beta cells mass more effectively.