Ocrevus reduces TH40 cells, a biomarker of systemic inflammation, in relapsing multiple sclerosis (RMS) and in progressive multiple sclerosis (PMS).

Treating MS has been difficult. One successful drug is Ocrelizumab (anti-CD20), used for the chronic relapsing MS (RMS) and the progressive MS (PMS) forms. TH40 cells are pathogenic effector T cells that increase in percentage and numbers during chronic inflammation.

Small cell carcinoma of the ovary hypercalcemic type (SCCOHT): A review and novel case with dual germline SMARCA4 and BRCA2 mutations.

Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive disease. While classically linked to mutations in we describe a case in a patient with both and germline mutations. We describe her disease presentation, histopathology and treatment with adjuvant systemic chemotherapy, interval hyperthermic intraperitoneal chemotherapy, high dose chemotherapy with stem cell rescue, and maintenance with a poly-ADP-ribose polymerase inhibitor (PARPi).

ATF6-Mediated Signaling Contributes to PARP Inhibitor Resistance in Ovarian Cancer.

Unlabelled: High-grade serous ovarian cancer (HGSOC) is the deadliest ovarian cancer histotype due in-part to the lack of therapeutic options for chemotherapy-resistant disease. PARP inhibitors (PARPi) represent a targeted treatment. However, PARPi resistance is becoming a significant clinical challenge.

AST-487 Inhibits RET Kinase Driven TERT Expression in Bladder Cancer.

Mutations in the promoter of the human Telomerase Reverse Transcriptase (hTERT) gene are common and associated with its elevated expression in bladder cancer, melanoma, and glioblastoma. Though these mutations and TERT overexpression are associated with aggressive disease and poor outcome, an incomplete understanding of mutant TERT regulation limits treatment options directed at this gene. Herein, we unravel a signaling pathway that leads to upregulated hTERT expression resulting from the -124 bp promoter mutation, the most frequent variant across human cancer.

High-Content Drug Discovery Targeting Molecular Bladder Cancer Subtypes.

Molecular subtypes of muscle-invasive bladder cancer (MIBC) display differential survival and drug sensitivities in clinical trials. To date, they have not been used as a paradigm for phenotypic drug discovery. This study aimed to discover novel subtype-stratified therapy approaches based on high-content screening (HCS) drug discovery.

Between a Rock and a Hard Place: The Challenges of Caregiving During a Pandemic for Parkinson's Family Care Partners.

: To understand Parkinson's Disease (PD) care partners' a) challenges that led to worsening strain and b) their suggestions for supports to help them during the ongoing pandemic. : Using a qualitative descriptive design, semi-structured interviews with family care partners (n 19) were completed. Participants were recruited from 10 sites across the United States that varied in size, demographics of patient population served, and geographic location (urban, suburban, rural).

The CAPNET multi-center data set for child physical abuse: Rationale, methods and scope.

Background: The pediatric subspecialty of Child Abuse Pediatrics (CAP) was certified by the American Board of Medical Subspecialties in 2006. Relative to its impact on pediatric health, CAP-focused research has been relatively under-funded. Multi-center networks related to CAP-focused research have made important advances, but have been limited in scope and duration.

KDM5A Inhibits Antitumor Immune Responses Through Downregulation of the Antigen-Presentation Pathway in Ovarian Cancer.

The extent to which effector CD8+ T cells infiltrate into tumors is one of the major predictors of clinical outcome for patients with epithelial ovarian cancer (EOC). Immune cell infiltration into EOC is a complex process that could be affected by the epigenetic makeup of the tumor. Here, we have demonstrated that a lysine 4 histone H3 (H3K4) demethylase, (lysine-specific demethylase 5A; KDM5A) impairs EOC infiltration by immune cells and inhibits antitumor immune responses.

Emergency Department Child Abuse Evaluations During COVID-19: A Multicenter Study.

Background And Objective: The reported impacts of the COVID-19 pandemic on child maltreatment in the United States have been mixed. Encounter trends for child physical abuse within pediatric emergency departments may provide insights. Thus, this study sought to determine the change in the rate of emergency department encounters related to child physical abuse.

Targeting DUSP Activity as a Treatment for High-Grade Serous Ovarian Carcinoma.

Identifying novel, durable treatments for high-grade serous ovarian cancer (HGSOC) is paramount to extend both progression-free survival (PFS) and overall survival (OS) in patients afflicted with this disease. Dual-specificity phosphatase 1 (DUSP1) was identified as one of seven genes that may significantly affect prognosis in patients with HGSOC; however, the role of DUSP inhibition (DUSPi) in the treatment of HGSOC remains largely unknown. In this study, we show that DUSP1 is highly expressed in HGSOC and confers worse PFS and OS.

Common Ground: Primary Care and Specialty Clinicians' Perceptions of E-Consults in the Veterans Health Administration.

Objective: The US Department of Veterans Affairs (VA) introduced electronic consultation (e-consult) to increase access to specialty care. The objective of this study was to understand perceptions of e-consults that may be relevant to increasing adoption in the VA.

Methods: Deductive and inductive content analysis of semistructured qualitative telephone interviews with VA primary care practitioners (PCPs), specialists, and specialty division chiefs was performed.

Endoluminal vacuum closure of a duodenal perforation.

Perforation is a known complication of endoscopic resection and has been managed with endoscopic defect closure, antibiotics and close observation. Closure of duodenal perforations are more challenging due to the presence of gastric and pancreaticobiliary secretions. The use of endoluminal vacuum therapy (EVT) to divert flow and aid closure is increasingly prevalent and may avoid high-risk surgery.

Mild Cognitive Impairment and Donepezil Impact Mitochondrial Respiratory Capacity in Skeletal Muscle.

Alzheimer's Disease (ad) associates with insulin resistance and low aerobic capacity, suggestive of impaired skeletal muscle mitochondrial function. However, this has not been directly measured in AD. This study (   = 50) compared muscle mitochondrial respiratory function and gene expression profiling in cognitively healthy older adults (CH;  = 24) to 26 individuals in the earliest phase of ad-related cognitive decline, mild cognitive impairment (MCI;   = 11) or MCI taking the ad medication donepezil (MCI + med;   = 15).

The Spatial Context of Tumor-Infiltrating Immune Cells Associates with Improved Ovarian Cancer Survival.

Ovarian cancer is the deadliest gynecologic malignancy. Multi-omics techniques have provided a platform for improved predictive modeling of therapy response and patient outcomes. While high-grade serous carcinoma (HGSOC) tumors are immunogenic and numerous studies have defined positive correlation to immune cell infiltration, immunotherapies in clinical trials have exhibited low efficacy rates.

Mast Cells Promote Nitrogen Mustard-Mediated Toxicity in the Lung Associated With Proinflammatory Cytokine and Bioactive Lipid Mediator Production.

Sulfur mustard (SM) has been widely used as a chemical warfare agent including most recently in Syria. Mice exposed to SM exhibit an increase in pro-inflammatory cytokines followed by immune cell infiltration in the lung, however, the mechanisms leading to these inflammatory responses has not been completely elucidated. Mast cells are one of the first responding innate immune cells found at the mucosal surfaces of the lung and have been reported to be activated by SM in the skin.

Closed-loop automated reaching apparatus (CLARA) for interrogating complex motor behaviors.

Closed-loop neuromodulation technology is a rapidly expanding category of therapeutics for a broad range of indications. Development of these innovative neurological devices requires high-throughput systems for closed-loop stimulation of model organisms, while monitoring physiological signals and complex, naturalistic behaviors. To address this need, we developed CLARA, a closed-loop automated reaching apparatus.

Safety and effectiveness of a risk-stratified venous thromboembolism prophylaxis algorithm in young people with cystic fibrosis.

Background: People with cystic fibrosis (CF) have an increased risk of thrombosis due to acquired thrombophilia secondary to chronic systemic inflammation and central venous catheter use for treatment of pulmonary infections. The objective of this study is to determine the safety and effectiveness of a risk-stratified, venous thromboembolism (VTE) prophylaxis intervention.

Methods: This single-center, IRB-approved, retrospective study assessed patients with CF admitted to our institution for treatment of a pulmonary exacerbation from 2017 to 2019.