Pyrimidine depletion enhances targeted and immune therapy combinations in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a fatal disease characterized by the accumulation of undifferentiated myeloblasts, and agents that promote differentiation have been effective in this disease but are not curative. Dihydroorotate dehydrogenase inhibitors (DHODHi) have the ability to promote AML differentiation and target aberrant malignant myelopoiesis. We introduce HOSU-53, a DHODHi with significant monotherapy activity, which is further enhanced when combined with other standard-of-care therapeutics.

Inhibition of Enhancer of Zeste Homolog 2 Induces Blast Differentiation, Impairs Engraftment and Prolongs Survival in Murine Models of Acute Myeloid Leukemia.

Background: Acute myeloid leukemia (AML) is the malignant proliferation of immature myeloid cells characterized by a block in differentiation. As such, novel therapeutic strategies to promote the differentiation of immature myeloid cells have been successful in AML, although these agents are targeted to a specific mutation that is only present in a subset of AML patients. In the current study, we show that targeting the epigenetic modifier enhancer of zeste homolog 2 (EZH2) can induce the differentiation of immature blast cells into a more mature myeloid phenotype and promote survival in AML murine models.

Differences in health care provider screening for tobacco use among youth in the United States: The National Youth Tobacco Survey, 2021.

Objective: Health care providers (HCP) are encouraged to screen youth for tobacco product use as a key step in preventing such use and associated health outcomes. However, recent data examining differences in HCP tobacco screening by sociodemographic characteristics and tobacco use is scant.

Methods: Data from the 2021 National Youth Tobacco Survey (N = 14,685) were analyzed.

Differences in health care provider advice on abstaining from tobacco use: Findings from the 2020 National Youth Tobacco Survey.

Background: Health care providers' (HCP) advice on tobacco prevention and cessation is critical in addressing the tobacco use epidemic among adolescents. However, examination of whether receiving advice from HCPs differs by adolescent sociodemographic characteristics and tobacco use is limited.

Methods: HCP advice to abstain from using tobacco was examined using the 2020 National Youth Tobacco Survey (N = 12,483).

Harm perceptions of secondhand e-cigarette aerosol among youth in the United States.

E-cigarette use among youth remains a public health concern. Although extant literature has examined the perceived harms of cigarette use and secondhand smoke, perceptions of harms associated with secondhand e-cigarette aerosol (SHA) are not well understood. Therefore, we used data from the 2020 U.

Workplace Culture and Biomarkers of Health Risk.

Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined associations between the work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic nervous system activity, indicative of stress. We recruited participants (n = 219; 2018-2019) from a cardiovascular risk cohort to investigate workplace culture, well-being, and stress.

P027 Brain Fog in Patients With Inflammatory Bowel Disease, and Association With Use of Probiotics.

Background: Brain fog has been minimally studied in patients with inflammatory bowel disease (IBD). IBD patients frequently consume probiotics, whether sanctioned by a physician or not. However, probiotic consumption in itself has been shown to increase the incidence of brain fog.

Tobacco Use Status and Temptation to Try E-Cigarettes among a Sample of Appalachian Youth.

E-cigarettes are commonly used tobacco products among youth populations, including Appalachian youth. However, knowledge of the extent to which tobacco use status relates to temptation to try e-cigarettes is limited. Data from the Youth Appalachian Tobacco Study ( = 1047) were used.

Associations between Appalachian youth tobacco consumption and communication channel use.

Introduction: Youth tobacco use rates in Appalachia exceed the US national average, and e-cigarette use has increased. Thus, further research is needed to understand how these youth receive and share product information.

Methods: Middle and high school students in rural Appalachia were surveyed (N=1103).

A Comparative Evaluation of Conventional and Staircase Modification of the Intraoral Mandibular Vestibular Incision Approach in Symphysis and Parasymphysis Fractures.

Aim: The aim of this study was therefore to evaluate the conventional intraoral mandibular vestibular incision approach in symphysis and parasymphysis fractures and compare prognosis of the incision site, fracture healing, and associated complications with the staircase modification of the intraoral mandibular vestibular incision approach for symphysis and parasymphysis fractures.

Materials And Methods: This study was conducted on 34 healthy individual of age 18-60 years, reporting to the department with a history of trauma having mandibular symphysis or parasymphysis fractures and underwent open reduction and internal fixation under either local or general anesthesia. The treated patients were prospectively followed and examined for the postoperative complications such as pain, swelling, infection, dehiscence, sensory disturbances, and nonunion/malunion of the fracture site.

Tobacco use and harm perceptions among Appalachian youth.

Appalachian youth tobacco use rates exceed the national average. Additional inquiry is needed to better understand youth product perceptions and use patterns. This study examined tobacco harm perceptions and their relationship with tobacco use among Appalachian youth.

Pyoderma Gangrenosum in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Background: Pyoderma gangrenosum (PG) is an uncommon but severe extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD). The incidence and risk factors for PG are disputed.

Aims: To assess the incidence of PG and identify factors associated with PG in IBD patients.

Microbiome data analysis with applications to pre-clinical studies using QIIME2: Statistical considerations.

Diversity analysis and taxonomic profiles can be generated from marker-gene sequence data with the help of many available computational tools. The Quantitative Insights into Microbial Ecology Version 2 (QIIME2) has been widely used for 16S rRNA data analysis. While many articles have demonstrated the use of QIIME2 with suitable datasets, the application to pre-clinical data has rarely been talked about.

Mitochondrial matrix metalloproteinase activation decreases myocyte contractility in hyperhomocysteinemia.

Cardiomyocyte N-methyl-d-aspartate receptor-1 (NMDA-R1) activation induces mitochondrial dysfunction. Matrix metalloproteinase protease (MMP) induction is a negative regulator of mitochondrial function. Elevated levels of homocysteine [hyperhomocysteinemia (HHCY)] activate latent MMPs and causes myocardial contractile abnormalities.