Reimagining the Role of Health Departments and Their Partners in Addressing Climate Change: Revising the Building Resilience against Climate Effects (BRACE) Framework.

Public health departments have important roles to play in addressing the local health impacts of climate change, yet are often not well prepared to do so. The Climate and Health Program (CHP) at the Centers for Disease Control and Prevention (CDC) created the Building Resilience Against Climate Effects (BRACE) framework in 2012 as a five-step planning framework to support public health departments and their partners to respond to the health impacts of climate change. CHP has initiated a process to revise the framework to address learnings from a decade of experience with BRACE and advances in the science and practice of addressing climate and health.

Determination of metarrestin (ML-246) in human plasma for a first-in-human clinical pharmacokinetic application by a simple and efficient uHPLC-MS/MS assay.

Metarrestin is a first-in-class small molecule inhibitor targeting the perinucleolar compartment, a subnuclear body associated with metastatic capacity. Promising preclinical results led to the clinical translation of the compound into a first-in-human phase I trial (NCT04222413). To characterize metarrestin's pharmacokinetic profile in humans, a uHPLC-MS/MS assay was developed and validated to determine the disposition of the drug in human plasma.

A Phase II Trial of Guadecitabine in Children and Adults with SDH-Deficient GIST, Pheochromocytoma, Paraganglioma, and HLRCC-Associated Renal Cell Carcinoma.

Purpose: Succinate dehydrogenase (dSDH)-deficient tumors, including pheochromocytoma/paraganglioma, hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinoma (HLRCC-RCC), and gastrointestinal stromal tumors (GIST) without KIT or platelet-derived growth factor receptor alpha mutations are often resistant to cytotoxic chemotherapy, radiotherapy, and many targeted therapies. We evaluated guadecitabine, a dinucleotide containing the DNA methyltransferase inhibitor decitabine, in these patient populations.

Patients And Methods: Phase II study of guadecitabine (subcutaneously, 45 mg/m2/day for 5 consecutive days, planned 28-day cycle) to assess clinical activity (according to RECISTv.

Male and female rats exhibit comparable gaping behavior but activate brain regions differently during expression of conditioned nausea.

Twenty-five to fifty percent of patients undergoing chemotherapy will develop anticipatory nausea and vomiting (ANV), in which symptoms occur in anticipation of treatment. ANV is triggered by environmental cues and shows little response to traditional antiemetic therapy, suggesting that unique neural pathways mediate this response. Understanding the underlying neural mechanisms of this disorder is critical to the development of novel therapeutic interventions.

Quantitation of the next-generation imipridone ONC206 in human plasma by a simple and sensitive UPLC-MS/MS assay for clinical pharmacokinetic application.

ONC206 is an imipridone derivative that is being developed clinically as a single agent given orally in a first-in-human trial (NCT04541082). This ongoing clinical trial requires pharmacokinetic analysis of ONC206 to fully characterize its pharmacologic profile. There is currently no published bioanalytical method for ONC206 quantitation.

Behavior and Fos activation reveal that male and female rats differentially assess affective valence during CTA learning and expression.

Females are more affected by psychiatric illnesses including eating disorders, depression, and post-traumatic stress disorder than males. However, the neural mechanisms mediating these sex differences are poorly understood. Animal models can be useful in exploring such neural mechanisms.

Vertical Inhibition of the RAF-MEK-ERK Cascade Induces Myogenic Differentiation, Apoptosis, and Tumor Regression in Mutant Rhabdomyosarcoma.

Oncogenic RAS signaling is an attractive target for fusion-negative rhabdomyosarcoma (FN-RMS). Our study validates the role of the ERK MAPK effector pathway in mediating RAS dependency in a panel of mutant RMS cells and correlates efficacy of the MEK inhibitor trametinib with pharmacodynamics of ERK activity. A screen is used to identify trametinib-sensitizing targets, and combinations are evaluated in cells and tumor xenografts.

Ibrutinib's off-target mechanism: cause for dose optimization.

Ibrutinib (Imbruvica®, 2013) is a Bruton's tyrosine kinase (BTK) inhibitor approved for multiple B-cell malignancies and cGVHD. Its treatment is associated with increased risk of cardiac adverse events. Atrial fibrillation is a common cause of therapy discontinuation and interruptions, which have been correlated with shorter progression-free survival in chronic lymphocyte leukemia (CLL) patients.

Development and validation of a simple, selective, and sensitive LC-MS/MS assay for the quantification of remdesivir in human plasma.

Remdesivir, formerly GS-5734, has recently become the first antiviral drug approved by the U.S. Food and Drug Administration (FDA) to treat COVID-19, the disease caused by SARS-CoV-2.

Walking School Bus Programs: Implementation Factors, Implementation Outcomes, and Student Outcomes, 2017-2018.

Purpose And Objectives: Walking school bus programs increase children's physical activity through active travel to school; however, research to inform large-scale implementation of such programs is limited. We investigated contextual factors, implementation outcomes, and student outcomes in existing walking school bus programs in the United States and internationally.

Intervention Approach: Walking school bus programs involve a group of children walking to school together with an adult leader.

Overcoming legal liability concerns for school-based physical activity promotion.

Schools have been identified as a priority environment for physical activity promotion as a component of efforts to help prevent childhood obesity. A variety of school-based environmental and programmatic strategies have been proven effective in promoting physical activity both on-site and in the surrounding community. However, many schools are deterred by fears of increased risk of legal liability for personal injuries.

Calorie and protein intake in acute rehabilitation inpatients with traumatic spinal cord injury versus other diagnoses.

Background: Obesity and its consequences affect patients with spinal cord injury (SCI). There is a paucity of data with regard to the dietary intake patterns of patients with SCI in the acute inpatient rehabilitation setting. Our hypothesis is that acute rehabilitation inpatients with SCI consume significantly more calories and protein than other inpatient rehabilitation diagnoses.

Reorganization in coping behavior at 1 1/2 years: dynamic systems and normative change.

By the age of 1 year toddlers demonstrate distinct coping habits for dealing with frustration. However, these habits may be open to change and reorganization at subsequent developmental junctures. We investigated change in coping habits at 18-20 months, a normative age for major advances in social cognition, focusing on the dynamic systems principles of fluctuation and novelty at transitions.