miR-217-5p NanomiRs Inhibit Glioblastoma Growth and Enhance Effects of Ionizing Radiation via EZH2 Inhibition and Epigenetic Reprogramming.

: CSCs are critical drivers of the tumor and stem cell phenotypes of glioblastoma (GBM) cells. Chromatin modifications play a fundamental role in driving a GBM CSC phenotype. The goal of this study is to further our understanding of how stem cell-driving events control changes in chromatin architecture that contribute to the tumor-propagating phenotype of GBM.

A model of lymphocryptovirus-associated post-transplant lymphoproliferative disorder in immunosuppressed Mauritian cynomolgus macaques.

Immunocompromised individuals are at risk for developing lymphocryptovirus-associated lymphoproliferative diseases, such as Epstein Barr virus (EBV)-associated B cell lymphomas and post-transplant lymphoproliferative disorder (PTLD). We previously reported development of cynomolgus lymphocryptovirus (CyLCV)-associated PTLD in Mauritian cynomolgus macaques (MCMs) undergoing hematopoietic stem cell transplantation (HSCT), which mirrored EBV-PTLD in transplant patients. Here, we sought to develop a MCM model of lymphocryptovirus-associated lymphoproliferative disease in immunosuppressed MCMs without HSCT.

A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation.

The salivary glands are often damaged during head and neck cancer radiotherapy. This results in chronic dry mouth, which adversely affects quality of life and for which there is no long-term cure. Mouse models of salivary gland injury are routinely used in regenerative research.

Development of a hydrogen peroxide-inactivated vaccine that protects against viscerotropic yellow fever in a non-human primate model.

Yellow fever virus (YFV) is endemic in >40 countries and causes viscerotropic disease with up to 20%-60% mortality. Successful live-attenuated yellow fever (YF) vaccines were developed in the mid-1930s, but their use is restricted or formally contraindicated in vulnerable populations including infants, the elderly, and people with compromised immune systems. In these studies, we describe the development of a next-generation hydrogen peroxide-inactivated YF vaccine and determine immune correlates of protection based on log neutralizing index (LNI) and neutralizing titer-50% (NT) studies.

Cellular diversity through space and time: adding new dimensions to GBM therapeutic development.

The current median survival for glioblastoma (GBM) patients is only about 16 months, with many patients succumbing to the disease in just a matter of months, making it the most common and aggressive primary brain cancer in adults. This poor outcome is, in part, due to the lack of new treatment options with only one FDA-approved treatment in the last decade. Advances in sequencing techniques and transcriptomic analyses have revealed a vast degree of heterogeneity in GBM, from inter-patient diversity to intra-tumoral cellular variability.

Subcutaneous choriocarcinomas in captive Amargosa voles ().

Spontaneous choriocarcinomas are rare, highly vascular, malignant trophoblastic tumors that occur in humans and animals. This report describes the unusual spontaneous presentation of 4 choriocarcinomas within the subcutaneous tissues of 4, multiparous but nongravid, Amargosa voles () from a captive breeding colony. Two subcutaneous neoplasms were composed of multifocal discohesive and infiltrative aggregates of medium to large trophoblasts and cytotrophoblasts within a fibrovascular stroma.

Use of a Novel Hypercrosslinked Carbohydrate Scaffold for Vocal Fold Medialization in an Ovine Model.

Objectives: Vocal fold medialization is commonly performed for glottic insufficiency and vocal fold immobility. Currently available materials are temporary injectables or synthetic implants. Acellular scaffolds may allow vocal fold augmentation with autologous tissue via host cell migration.

The Role of Supporting Cell Populations in Satellite Cell Mediated Muscle Repair.

Skeletal muscle has a high capacity to repair and remodel in response to damage, largely through the action of resident muscle stem cells, termed satellite cells. Satellite cells are required for the proper repair of skeletal muscle through a process known as myogenesis. Recent investigations have observed relationships between satellite cells and other cell types and structures within the muscle microenvironment.

Exploring glioblastoma stem cell heterogeneity: Immune microenvironment modulation and therapeutic opportunities.

Despite its growing use in cancer treatment, immunotherapy has been virtually ineffective in clinical trials for gliomas. The inherently cold tumor immune microenvironment (TIME) in gliomas, characterized by a high ratio of pro-tumor to anti-tumor immune cell infiltrates, acts as a seemingly insurmountable barrier to immunotherapy. Glioma stem cells (GSCs) within these tumors are key contributors to this cold TIME, often functioning indirectly through activation and recruitment of pro-tumor immune cell types.

Synthesis and Evaluation of Functionalized Aryl and Biaryl Isothiocyanates against Human MCF-7 Cells.

Organic isothiocyanates (ITCs) are a class of anticancer agents which naturally result from the enzymatic degradation of glucosinolates produced by Brassica vegetables. Previous studies have demonstrated that the structure of an ITC impacts its potency and mode(s) of anticancer properties, opening the way to preparation and evaluation of synthetic, non-natural ITC analogues. This study describes the preparation of a library of 79 non-natural ITC analogues intended to probe further structure-activity relationships for aryl ITCs and second-generation, functionalized biaryl ITC variants.

Birth Outcomes Associated With E-Cigarette and Non-E-Cigarette Tobacco Product Use During Pregnancy: An Examination of PATH Data Waves 1-5.

Objectives: To examine associations of prenatal e-cigarette use to pregnancy and birth outcomes.

Methods: Currently pregnant women (n = 1 037) from Waves 1 through 4 of the Population Assessment of Tobacco and Health Study who had pregnancy or live birth outcome data in a subsequent wave (Waves 2-5; 2013 to 2019). Weighted bivariate and multivariable models\ examined associations between past 30-day tobacco use assessed during pregnancy (any past 30-day e-cigarette use, any past 30-day non-e-cigarette tobacco use, or no past 30-day tobacco use) with adverse pregnancy (miscarriage, abortion, ectopic or tubal pregnancy, stillbirth) and birth outcomes (preterm birth, low birth weight, birth defect, placenta previa, placental abruption, pre-eclampsia) reported in the subsequent wave.

Common and Not-So-Common Pathologic Findings of the Gastrointestinal Tract of Rhesus and Cynomolgus Macaques.

Rhesus and cynomolgus macaques are the most frequently used nonhuman primate (NHP) species for biomedical research and toxicology studies of novel therapeutics. In recent years, there has been a shortage of laboratory macaques due to a variety of competing factors. This was most recently exacerbated by the surge in NHP research required to address the severe acute respiratory syndrome (SARS)-coronavirus 2 pandemic.

A novel non-human primate model of Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disorder of the central nervous system (CNS) linked to mutations in the proteolipid protein-1 (PLP1) gene. Although there are multiple animal models of PMD, few of them fully mimic the human disease. Here, we report three spontaneous cases of male neonatal rhesus macaques with the clinical symptoms of hypomyelinating disease, including intention tremors, progressively worsening motor dysfunction, and nystagmus.

Predictors of Subcutaneous Injection Site Reactions to Sustained-Release Buprenorphine in Rhesus Macaques ().

Subcutaneous injection site reactions to sustained-release buprenorphine hydrochloride (Buprenorphine SR) in macaques have been reported in only a single case report. In the current study, we evaluated the incidence rate and predictors of buprenorphine SR reactions in the subcutaneous tissue of rhesus macaques (M) based on retrospective review of macaque buprenorphine SR injection records. Potentially predictive variables were identified with logistic regression modeling and were evaluated using model selection based on Akaike information criterion.

People in E-Cigarette Ads Attract More Attention: An Eye-Tracking Study.

Objectives: Minimally regulated electronic cigarettes (e-cigarette) advertising may be one potential factor driving the increasing prevalence of young adult e-cigarette use. Using eye-tracking, the current study examined which e-cigarette advertising features were the most appealing to young adults as a first step to examine how e-cigarette advertising may be regulated.

Methods: Using a within-subjects design, 30 young adults ( = 20.

Differences in reasons for little cigar/cigarillo use across white and black/African American young adult users.

Introduction: The prevalence of little cigar and cigarillo (LCC) use among young adults is high. Research shows there are racial/ethnic differences in this prevalence, with Black/African American users more likely to report current LCC use. Given these discrepancies in LCC use, the present study aimed to assess potential differences in reasons for LCC use between White and Black/African American young adult ever and past 30-day users.

Colon volvulus in rhesus macaques (Macaca mulatta) at the Oregon National Primate Research Center-Retrospective analysis.

Colonic volvulus is an uncommon, often life-threatening condition, in non-human primates. Twenty-six cases of colonic volvulus in rhesus macaques (Macaca mulatta) were identified in necropsy records spanning 38 years at the Oregon National Primate Research Center (ONPRC). This report represents the largest collection of colonic volvuli in rhesus macaques.

Urothelial carcinoma in the urinary bladder of a Japanese macaque (Macaca fuscata).

Tumors of urinary origin are infrequently reported in non-human primates. Urothelial carcinoma involving the urinary bladder was diagnosed in an adult female Japanese macaque that extended transmurally to the uterus and cervix. To our knowledge, this is the first report of a primary cystic urothelial carcinoma in a Japanese macaque.

Two cases of cryptococcus gattii infection in the rhesus macaque (Macaca Mulatta).

Cryptococcus gattii was diagnosed in two female indoor-housed rhesus macaques. Gross and histopathologic findings included an isolated pulmonary cryptococcoma in a non-SIV-infected macaque and disseminated disease centered on the lungs of an SIV-infected macaque. Fungal yeast were positive with special stains, and the diagnoses were confirmed with a lateral flow assay and PCR.

Adolescent Susceptibility to E-Cigarettes: An Update From the 2018 National Youth Tobacco Survey.

Purpose: Examine correlates of e-cigarette susceptibility among adolescents.

Design: Secondary data analyses using the 2018 National Youth Tobacco Survey, excluding participants under 12 and over 17.

Setting: United States middle and high schools.

Menthol and Mint Cigarettes and Cigars: Initiation and Progression in Youth, Young Adults and Adults in Waves 1-4 of the PATH Study, 2013-2017.

Introduction: This study examined in youth (12-17 years), young adults (18-24 years), and adults (25+ years): (1) the prevalence of the first menthol cigarette and menthol/mint cigar use among new tobacco users; (2) association between the first menthol/mint use, subsequent tobacco use, and nicotine dependence ~1 year later compared with the first non-menthol/mint use.

Aims And Methods: Longitudinal analysis of data from Waves 1 to 4 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2017; 10 086 youth and 21 281 adults). Main outcome measures were past 12-month and past 30-day cigarette and cigar use, and nicotine dependence.

Heterologous Expression and Functional Characterization of Novel CYP2C9 Variants Identified in the Alaska Native People.

CYP2C9 is a major form of human liver cytochrome P450 that is responsible for the oxidative metabolism of several widely used low-therapeutic index drugs, including ()-warfarin and phenytoin. In a cohort of Alaska Native people, ultrarare or novel CYP2C9 protein variants, M1L (rs114071557), N218I (rs780801862), and P279T (rs182132442, CYP2C9*29), are expressed with higher frequencies than the well characterized and alleles. We report here on their relative expression in lentivirus-infected HepG2 cells and the functional characterization of purified reconstituted enzyme variants expressed in toward ()-warfarin, phenytoin, flurbiprofen, and ()-naproxen.

Impact of flavors and humectants on waterpipe tobacco smoking topography, subjective effects, toxicant exposure and intentions for continued use.

Introduction: The present study examined how the lack of characterising flavours and low levels of humectants may affect users' waterpipe tobacco (WT) smoking topography, subjective effects, toxicant exposure and intentions for continued use.

Methods: 89 WT smokers completed four ad libitum smoking sessions (characterising flavor/high humectant (+F+H); characterising flavor/low humectant (+F-H); no characterising flavor/high humectant (-F+H); no characterising flavor/low humectant (-F-H)) in a randomised cross-over design. WT was commercially available; same brand but nicotine levels were not held constant.