PP2A activation overcomes leptomeningeal dissemination in group 3 medulloblastoma.

Leptomeningeal dissemination (LMD) is the primary cause of treatment failure in children with group 3 medulloblastoma (MB). Building on our previous work on protein phosphatase 2A (PP2A) activation in MB, here we present preclinical and molecular data on the effects of two novel classes of PP2A activators on disease processes of LMD in group 3 MB. The PP2A activators used in this study are ATUX-6156 and ATUX-6954 (diarylmethylcycloamine sulfonylureas), and ATUX-1215 and ATUX-5800 (diarylmethyl-4-aminotetrahydropyran-sulfonamides).

Transforming Veteran Rehabilitation Care: Learnings from a Remote Digital Approach for Musculoskeletal Pain.

While musculoskeletal pain (MSP) stands as the most prevalent health condition among Veterans, timely and high-quality care is often hindered due to access barriers. Team Red, White & Blue (Team RWB), a nonprofit organization dedicated to promoting a healthier lifestyle among Veterans, aimed to assess innovative approaches to veteran care. This is a single-arm pilot study investigating the feasibility, clinical outcomes, engagement, and satisfaction of a remote multimodal digital care program among Veterans with MSP.

Using 3D-bioprinted models to study pediatric neural crest-derived tumors.

The use of three-dimensional (3D) bioprinting has remained at the forefront of tissue engineering and has recently been employed for generating bioprinted solid tumors to be used as cancer models to test therapeutics. In pediatrics, neural crest-derived tumors are the most common type of extracranial solid tumors. There are only a few tumor-specific therapies that directly target these tumors, and the lack of new therapies remains detrimental to improving the outcomes for these patients.

The Effects of Protein Phosphatase 2A Activation with Novel Tricyclic Sulfonamides on Hepatoblastoma.

Background: The tumor suppressor, protein phosphatase 2A (PP2A), is downregulated in hepatoblastoma. We aimed to examine the effects of two novel compounds of the tricyclic sulfonamide class, ATUX-3364 (3364) and ATUX-8385 (8385), designed to activate PP2A without causing immunosuppression, on human hepatoblastoma.

Methods: An established human hepatoblastoma cell line, HuH6, and a human hepatoblastoma patient-derived xenograft, COA67, were treated with increasing doses of 3364 or 8385, and viability, proliferation, cell cycle and motility were investigated.

Pre-Clinical Study Evaluating Novel Protein Phosphatase 2A Activators as Therapeutics for Neuroblastoma.

Background: Protein phosphatase 2A (PP2A) functions as an inhibitor of cancer cell proliferation, and its tumor suppressor function is attenuated in many cancers. Previous studies utilized FTY720, an immunomodulating compound known to activate PP2A, and demonstrated a decrease in the malignant phenotype in neuroblastoma. We wished to investigate the effects of two novel PP2A activators, ATUX-792 (792) and DBK-1154 (1154).

Targeting High-Risk Neuroblastoma Patient-Derived Xenografts with Oncolytic Virotherapy.

Cancer is the leading cause of death by disease in children, and over 15% of pediatric cancer-related mortalities are due to neuroblastoma. Current treatment options for neuroblastoma remain suboptimal as they often have significant toxicities, are associated with long-term side effects, and result in disease relapse in over half of children with high-risk disease. There is a dire need for new therapies, and oncolytic viruses may represent an effective solution.

Regional differences in BMI, obesity, and exercise frequency in a large veteran service organization: A secondary analysis of new veteran member surveys from Team Red, White & Blue.

The purpose of the present study was to examine regional differences in average self-reported BMI, obesity prevalence, and frequent exercise (FE) among members of Team Red, White, and Blue (Team RWB) - a military veteran service organization founded to increase physical activity in veterans. A total of 10,015 military veterans participated in a needs assessment conducted by Team RWB between December 2014 and August 2016. Multivariate regression analysis with bootstrapped coefficients revealed that: BMI was highest in the Midwest region ( = 28.

Team Red, White & Blue: a community-based model for harnessing positive social networks to enhance enrichment outcomes in military veterans reintegrating to civilian life.

Military service assimilates individuals into a socially cohesive force to address dangerous and traumatic situations that have no counterpart in civilian life. Upon leaving active duty, many veterans experience a "reverse culture shock" when trying to reintegrate into civilian institutions and cultivate supportive social networks. Poor social reintegration is associated with greater morbidity and premature mortality in part due to adoption of risky health behaviors, social isolation, and inadequate engagement in health care services.

Spatial Modeling of Wild Bird Risk Factors for Highly Pathogenic A(H5N1) Avian Influenza Virus Transmission.

One of the longest-persisting avian influenza viruses in history, highly pathogenic avian influenza virus (HPAIV) A(H5N1), continues to evolve after 18 yr, advancing the threat of a global pandemic. Wild waterfowl (family Anatidae) are reported as secondary transmitters of HPAIV and primary reservoirs for low-pathogenic avian influenza viruses, yet spatial inputs for disease risk modeling for this group have been lacking. Using geographic information software and Monte Carlo simulations, we developed geospatial indices of waterfowl abundance at 1 and 30 km resolutions and for the breeding and wintering seasons for China, the epicenter of H5N1.

Strong, safe, and secure: negotiating early fathering and military service across the deployment cycle.

Military fathers of young children often endure repeated separations from their children, and these may disrupt the early parent-child relationship. Postdeployment reunification also poses challenges; disruptions that have occurred must often be repaired in the context of heightened emotions on the part of each family member at a time when fathers are themselves readjusting to the routines and responsibilities of family life. The current study employed qualitative research with the central aim of informing a richer understanding of these experiences.

Fathering after military deployment: parenting challenges and goals of fathers of young children.

Although often eagerly anticipated, reunification after deployment poses challenges for families, including adjusting to the parent-soldier's return, re-establishing roles and routines, and the potentially necessary accommodation to combat-related injuries or psychological effects. Fourteen male service members, previously deployed to a combat zone, parent to at least one child under seven years of age, were interviewed about their relationships with their young children. Principles of grounded theory guided data analysis to identify key themes related to parenting young children after deployment.

Mapping avian influenza transmission risk at the interface of domestic poultry and wild birds.

Emergence of avian influenza viruses with high lethality to humans, such as the currently circulating highly pathogenic A(H5N1) (emerged in 1996) and A(H7N9) cause serious concern for the global economic and public health sectors. Understanding the spatial and temporal interface between wild and domestic populations, from which these viruses emerge, is fundamental to taking action. This information, however, is rarely considered in influenza risk models, partly due to a lack of data.

The use of novel biomarkers to determine dietary mercury accumulation in nestling waterbirds.

Mercury (Hg) depuration into growing feathers is a well-studied phenomenon in waterbirds. Although the kinetics of Hg excretion in relation to molt and diet has been studied extensively, the relationship between the individual nutritional condition of nestlings and dietary Hg accumulation has not been investigated. In the present study, a body-condition index (BCI) and nutritional condition index (NCI) for nestlings of two waterbird species occupying different trophic positions on the aquatic food web were determined and used to predict Hg accumulation through diet.

Antibiotic dosing during sustained low-efficiency dialysis: special considerations in adult critically ill patients.

Objective: To address issues of antibiotic dosing during sustained low-efficiency dialysis by using available pharmacokinetic data, intermittent and continuous renal replacement therapy dialysis guidelines, and our experience with sustained low-efficiency dialysis.

Data Resources: Published clinical trials, case reports, and reviews of antibiotic dosing in humans during sustained low-efficiency dialysis.

Data Extraction: A search of electronic databases (MEDLINE, PubMed, and Ovid) was conducted by using key words of extended daily dialysis, sustained low-efficiency dialysis, antibiotics, antimicrobial agents, and pharmacokinetics.

Effects of open marsh water management on numbers of larval salt marsh mosquitoes.

Open marsh water management (OMWM) is a commonly used approach to manage salt marsh mosquitoes than can obviate the need for pesticide application and at the same time, partially restore natural functions of grid-ditched marshes. OMWM includes a variety of hydrologic manipulations, often tailored to the specific conditions on individual marshes, so the overall effectiveness of this approach is difficult to assess. Here, we report the results of controlled field trials to assess the effects of two approaches to OMWM on larval mosquito production at National Wildlife Refuges (NWR).

Racial differences in the prevalence of cardiac sources of embolism in subjects with unexplained stroke or transient ischemic attack evaluated by transesophageal echocardiography.

Little is known about the distribution of cardiac sources of embolism among African-Americans with cryptogenic cerebrovascular events. We compared the prevalence of potential cardiac sources of embolism between black and white patients referred to our laboratory for transesophageal echocardiographic (TEE) evaluation of unexplained stroke or transient ischemic attack. Records were reviewed to exclude subjects with high-risk cardiac or vascular disorders likely to explain the index event.