WRN inhibition leads to its chromatin-associated degradation via the PIAS4-RNF4-p97/VCP axis.

Synthetic lethality provides an attractive strategy for developing targeted cancer therapies. For example, cancer cells with high levels of microsatellite instability (MSI-H) are dependent on the Werner (WRN) helicase for survival. However, the mechanisms that regulate WRN spatiotemporal dynamics remain poorly understood.

Health inequities and marginalized groups: An overview for college student travelers and travel health professionals.

One of the main goals of college- and university-sponsored travel is to broaden the global perspectives of student travelers, thereby enhancing their ability to effectively communicate and work with people from different cultural backgrounds. Pre-travel consultations are important for all students traveling internationally, and especially for those facing current or past health inequities and marginalization. To offer high quality, inclusive services, college travel health clinicians must understand both the student traveler population and cultural norms at the travel destinations, especially those related to health and safety.

A Scoping Review of Self-Care Within the Context of Obesity-Related Outcomes Among Faith Leaders.

Objective: Faith leaders often serve as health-related role models yet many struggle with obesity and self-care engagement. The purpose of this scoping review was to examine how the faith leader literature has defined self-care and examined obesity and obesity-related chronic disease.

Data Source: Studies were identified through database (eg, PubMed, CINAHL, PsycINFO), backward, and grey literature (eg, dissertations) searches.

Mirizzi syndrome complicated by type IV cholecystobiliary fistula to the right hepatic duct.

Mirizzi syndrome is a rare complication of long-term chronic cholecystitis, characterized by extrinsic compression of the common hepatic duct that may progress to development of cholecystobiliary fistula. Here we report a case of a 38-year-old female patient who underwent laparoscopic cholecystectomy with intraoperative cholangiogram for acute cholecystitis and choledocholithiasis. Intraoperatively, the patient was found to have a Mirizzi syndrome complicated by cholecystobiliary fistula to the right hepatic duct.

The Impact of Smartphone Use on Course Comprehension and Psychological Well-Being in the College Classroom.

The present study explores the impact of smartphone use on course comprehension and the psychological well-being of students during class. Students in four classes ( = 106) were assigned to either a control group or quasi-experimental group. Students in the quasi-experimental group were instructed to place their smartphones on the front desk upon entering the class, while the control group had no instructions regarding smartphone use.

Resistance training protects against muscle pain through activation of androgen receptors in male and female mice.

Resistance training-based exercise is commonly prescribed in the clinic for the treatment of chronic pain. Mechanisms of aerobic exercise for analgesia are frequently studied, while little is known regarding resistance training mechanisms. We developed a resistance training model in mice and hypothesized resistance training would protect against development of muscle pain, mediated through the activation of androgen receptors.

UNC5293, a potent, orally available and highly MERTK-selective inhibitor.

Inhibition of MER receptor tyrosine kinase (MERTK) causes direct tumor cell killing and stimulation of the innate immune response. Therefore, MERTK has been identified as a therapeutic target in a wide variety of human tumors. Clinical trials targeting MERTK have recently been initiated, however, none of these drugs are MERTK-specific.

Self-Esteem Mediates Longitudinal Associations from Adolescent Perceptions of Parenting to Adjustment.

The present study examines direct and indirect associations between perceptions of parenting and adolescent adjustment. We focus on self-esteem as an intervening variable. Participants included 446 girls and 471 boys ages 14 to 17 (M = 15.

Data-Driven Construction of Antitumor Agents with Controlled Polypharmacology.

Controlling which particular members of a large protein family are targeted by a drug is key to achieving a desired therapeutic response. In this study, we report a rational data-driven strategy for achieving restricted polypharmacology in the design of antitumor agents selectively targeting the TYRO3, AXL, and MERTK (TAM) family tyrosine kinases. Our computational approach, based on the concept of fragments in structural environments (FRASE), distills relevant chemical information from structural and chemogenomic databases to assemble a three-dimensional inhibitor structure directly in the protein pocket.

Norovirus outbreaks on college and university campuses.

To describe norovirus outbreaks at colleges and universities. None. Conducted September 2016 to March 2018.

Viewpoint: Why you should provide HIV pre-exposure prophylaxis (PrEP) at your college health center.

By providing HIV pre-exposure prophylaxis, or PrEP (a single daily oral pill), in a primary care college health setting, clinical providers can make a dramatic contribution to the current and long-term health and well-being of the students they see. This viewpoint article describes the approach taken to instituting primary care PrEP services at two college health programs. It delineates which students might benefit from PrEP and how to prescribe/monitor PrEP over time.

MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity.

MERTK is ectopically expressed and promotes survival in acute lymphoblastic leukemia (ALL) cells and is thus a potential therapeutic target. Here we demonstrate both direct therapeutic effects of MERTK inhibition on leukemia cells and induction of anti-leukemia immunity via suppression of the coinhibitory PD-1 axis. A MERTK-selective tyrosine kinase inhibitor, MRX-2843, mediated therapeutic anti-leukemia effects in immunocompromised mice bearing a MERTK-expressing human leukemia xenograft.

Parent contributions to friendship stability during the primary school years.

The present study examines whether characteristics of parents predict the stability of a child's best friendships across the primary school years. Participants included 1,523 Finnish children (766 boys) who reported involvement in a total of 1,326 reciprocated friendship dyads in the 1st grade (M = 7.16 years old).

Residual hormone levels in used contraceptive rings as a measurement of adherence to vaginal ring use.

Objective: This study sought to measure residual contraceptive hormone levels in vaginal rings as an adherence marker for monitoring product use in clinical trials.

Study Design: Residual etonogestrel and ethinyl estradiol levels from used NuvaRings® of 26 self-reported adherent women enrolled in a clinical trial of vaginal ring acceptability were compared to those from 16 women who used NuvaRing® as their contraceptive choice.

Results: Twenty-one (81%) clinical trial rings had contraceptive hormone levels within the range of those used as a contraceptive choice.

Mother-adolescent conflict types and adolescent adjustment: A person-oriented analysis.

This investigation was designed to identify dyadic differences in mother-adolescent conflict. In 2 studies (N = 131 and N = 147), adolescents (M = 13.88 and 14.

Targeting the TAM Receptors in Leukemia.

Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma.

UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with Methotrexate in Leukemia Models.

MERTK tyrosine kinase is ectopically expressed in 30% to 50% of acute lymphoblastic leukemias (ALL) and more than 80% of acute myeloid leukemias (AML) and is a potential therapeutic target. Here, we evaluated the utility of UNC2025, a MERTK tyrosine kinase inhibitor, for treatment of acute leukemia. Preclinical and assays using cell lines and primary leukemia patient samples were used to evaluate antileukemic effects of UNC2025.

The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia.

FMS-like tyrosine kinase 3-targeted (FLT3-targeted) therapies have shown initial promise for the treatment of acute myeloid leukemia (AML) expressing FLT3-activating mutations; however, resistance emerges rapidly. Furthermore, limited options exist for the treatment of FLT3-independent AML, demonstrating the need for novel therapies that reduce toxicity and improve survival. MERTK receptor tyrosine kinase is overexpressed in 80% to 90% of AMLs and contributes to leukemogenesis.

Activation of adult rat CNS endothelial cells by opioid-induced toll-like receptor 4 (TLR4) signaling induces proinflammatory, biochemical, morphological, and behavioral sequelae.

CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance, reward, and dependence/withdrawal. Such effects are mediated by opioid signaling at toll-like receptor 4 (TLR4), presumptively of glial origin. Whether CNS endothelial cells express TLR4 is controversial.

Hepatitis B vaccination coverage and documented seroprotection among matriculating healthcare students at an academic institution in the United States.

We evaluated hepatitis B vaccination coverage and documentation of antibody to hepatitis B surface antigen (anti-HBs) concentration among a cohort of healthcare students. Of 4,075 students, 59.8% had documentation of vaccination and 83.

Pseudoepidemic of Q fever at an animal research facility.

Serum samples from people exposed to sheep at a research facility were evaluated by a commercial laboratory and resulted in an overall Coxiella burnetii seroprevalence of 75%. We interviewed individuals to determine exposure history and compatible illness, and retested their sera. Analysis indicated that the commercial laboratory was misinterpreting its results; when corrected, the seroprevalence dropped to 27%.

Vascular endothelial growth factor induces abnormal microvasculature in the endoglin heterozygous mouse brain.

Hereditary hemorrhagic telangiectasia (HHT), associated with brain arteriovenous malformations, is caused by a loss of function mutation in either the endoglin (HHT1) or activin receptor-like kinase 1 gene (ALK-1, HHT2). Endoglin heterozygous (Eng+/-)mice have been proposed as a disease model. To better understand the role of endoglin in vascular malformation development, we examined the effect of vascular endothelial growth factor (VEGF) hyperstimulation on microvessels in adult endoglin heterozygous (Eng+/-) mice using an adenoviral vector to deliver recombinant human VEGF165 cDNA (AdhVEGF) into basal ganglia.

Induction of focal angiogenesis through adenoviral vector mediated vascular endothelial cell growth factor gene transfer in the mature mouse brain.

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and morphogen, which stimulates angiogenesis in a wide variety of tissues and lesions in vivo. In this study, we applied adenoviral vector delivered human VEGF165 cDNA to develop focal non-tumor angiogenesis in the mature mouse brain. Seventy-two adult CD-1 mice underwent Ad h VEGF, Ad lacZ, and saline injection for up to fourweeks.