Development of Novel Analogs of the Monocarboxylate Transporter Ligand FACH and Biological Validation of One Potential Radiotracer for Positron Emission Tomography (PET) Imaging.

Monocarboxylate transporters 1-4 (MCT1-4) are involved in several metabolism-related diseases, especially cancer, providing the chance to be considered as relevant targets for diagnosis and therapy. [F]FACH was recently developed and showed very promising preclinical results as a potential positron emission tomography (PET) radiotracer for imaging of MCTs. Given that [F]FACH did not show high blood-brain barrier permeability, the current work is aimed to investigate whether more lipophilic analogs of FACH could improve brain uptake for imaging of gliomas, while retaining binding to MCTs.

Regular cannabis use is associated with blunted affective, but not cardiovascular, stress responses.

Aims: To examine the potential impact of regular cannabis use on cardiovascular and subjective responses to acute stress.

Design: We used a quasi-experimental design in which subjective states and cardiovascular measures were obtained during rest and in response to acute stress challenges in a sample of regular cannabis users and non-users.

Participants: Seventy-nine adults (forty-five cannabis users and thirty-four non-users).

First year allopathic medical student attitudes about vaccination and vaccine hesitancy.

First year medical students at an allopathic medical school regional campus were asked to complete a 10-question survey at both the beginning and the conclusion of a required course on immunology, hematology and oncology. The survey was designed to solicit student attitudes about vaccination and the students' level of comfort with and exposure to vaccine hesitant patients. Surveys were administered to five consecutive classes from 2013 to 2017.

Alignment of roles of near-peer mentors for medical students underrepresented in medicine with medical education competencies: a qualitative study.

Background: Medical student learning experiences should facilitate progressive development of competencies required for practice. Medical school training opportunities have traditionally focused on acquiring medical knowledge and patient care competencies while affording less opportunity to receive feedback on practice-based improvement and system-based practice competencies. The Prematriculation program at the University of Minnesota Medical School Duluth Campus (UM MSD) utilized near-peer mentors to support the transition of students underrepresented in medicine, including American Indian/ Alaska Natives (AI/AN) and those from rural backgrounds, into medical school.

Longitudinal Mechanisms Linking Perceived Racial Discrimination to Aggressive Delinquency among North American Indigenous Youth.

Objectives: Drawing from an integrated general strain theory framework, the purpose of the study is to examine the longitudinal mediating and moderating mechanisms linking perceived racial discrimination with aggressive delinquency among North American Indigenous (i.e., American Indian and Canadian First Nations) youth.

Interactions between the complement and endothelin systems in normal pregnancy and following placental ischemia.

Preeclampsia is characterized by new onset hypertension and fetal growth restriction and is associated with aberrant activation of the innate immune complement system and stressed or ischemic placenta. Previous studies have suggested a role for both endothelin and complement system activation products in new onset hypertension in pregnancy, but inter-relationships of the pathways are unclear. We hypothesized that complement activation following placental ischemia stimulates the endothelin pathway to cause hypertension and impair fetal growth.

Maternal confidence for physiologic birth: Associated prenatal characteristics and outcomes.

Objectives: Pregnancy, labor, and birth are normal, physiologic processes. Women often seek information during pregnancy to enhance their confidence for physiologic birth. Little is known about confidence for physiologic birth and associated prenatal characteristics and birth outcomes such as provider type, source of labor and birth information, mode of birth, and use of pain medication in labor.

Teaching Community Health Needs Assessment to First Year Medical Students: Integrating with Longitudinal Clinical Experience in Rural Communities.

Community health education is especially important for physicians who will practice in rural communities. However, the majority of efforts to teach community and population health in medical school appear in later years and focus on non-rural contexts. This article presents data from a formative evaluation of a newly developed curricular component on population health and community health assessment for first year medical students in a rural longitudinal clinical preceptorship.

Timing constraints of action potential evoked Ca current and transmitter release at a central nerve terminal.

The waveform of presynaptic action potentials (APs) regulates the magnitude of Ca currents (I) and neurotransmitter release. However, how APs control the timing of synaptic transmission remains unclear. Using the calyx of Held synapse, we find that Na and K channels affect the timing by changing the AP waveform.

Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules.

Synaptic heterogeneity is widely observed but its underpinnings remain elusive. We addressed this issue using mature calyx of Held synapses whose numbers of bouton-like swellings on stalks of the nerve terminals inversely correlate with release probability (Pr). We examined presynaptic Ca currents and transients, topology of fluorescently tagged knock-in Ca channels, and Ca channel-synaptic vesicle (SV) coupling distance using Ca chelator and inhibitor of septin cytomatrix in morphologically diverse synapses.

Onset, Comorbidity, and Predictors of Nicotine, Alcohol, and Marijuana Use Disorders Among North American Indigenous Adolescents.

North American Indigenous (i.e., American Indian and Canadian First Nations) youth experience inequities in rates of substance abuse and dependence.

Stressful life events are associated with perinatal cigarette smoking.

Perinatal smoking, including smoking during pregnancy and postpartum smoking relapse, is a persistent public health problem. While childhood trauma has been linked to perinatal smoking, less is known about the association with more proximal stressful life events (SLEs). The objective of this study was to examine the association between SLEs that occurred during the year prior to childbirth with perinatal smoking.

Identification of a functional antioxidant response element at the HIF1A locus.

Reactive oxygen species (ROS), which are a byproduct of oxidative metabolism, serve as signaling molecules in a number of physiological settings. However, if their levels are not tightly maintained, excess ROS lead to potentially cytotoxic oxidative stress. Accordingly, several transcriptional regulatory networks have evolved to include components that are highly ROS-responsive.

Identification of a molecular locus for normalizing dysregulated GABA release from interneurons in the Fragile X brain.

Principal neurons encode information by varying their firing rate and patterns precisely fine-tuned through GABAergic interneurons. Dysregulation of inhibition can lead to neuropsychiatric disorders, yet little is known about the molecular basis underlying inhibitory control. Here, we find that excessive GABA release from basket cells (BCs) attenuates the firing frequency of Purkinje neurons (PNs) in the cerebellum of Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mice, a model of Fragile X Syndrome (FXS) with abrogated expression of the Fragile X Mental Retardation Protein (FMRP).

Association of exercise with smoking-related symptomatology, smoking behavior and impulsivity in men and women.

Introduction: Despite extensive efforts to develop effective smoking cessation interventions, 70-85% of American cigarette smokers who quit relapse within one year. Exercise has shown promise as an intervention; however, many results have been equivocal. This study explored how exercise is associated with smoking-related symptomatology, smoking behavior and impulsivity in male and female smokers.

Pathways of Adaptation: Two Case Studies with One Evidence-Based Substance Use Prevention Program Tailored for Indigenous Youth.

Indigenous communities often face disproportionate challenges across a variety of health domains, and effective prevention strategies are sorely needed. Unfortunately, evidence is scant regarding what approaches are effective for these communities. A common approach is to take an evidence-based practice or program with documented effectiveness in other populations and implement it with Indigenous populations.

Microaggressions, diabetes distress, and self-care behaviors in a sample of American Indian adults with type 2 diabetes.

American Indian/Alaska Native people experience the highest age-adjusted prevalence of type 2 diabetes of any racial group in the United States, as well as high rates of related health problems. Chronic stressors such as perceived discrimination are important contributors to these persistent health disparities. The current study used structural equation modeling to examine the relationships between racial microaggressions, diabetes distress, and self-care behaviors (diet and exercise) in a sample of 192 American Indians with type 2 diabetes from the northern United States.

Hormonal contraceptive use in smokers: Prevalence of use and associations with smoking motives.

Introduction: While endogenous sex hormones influence smoking-related outcomes, little is known about the role of hormonal contraceptives (HCs). This is despite dated estimates suggesting that HC use is prevalent among female smokers. Therefore, we sought to update estimates of the prevalence of HC use among female smokers and explore the association of HC use with various smoking motives (SMs).

The Complement System and Preeclampsia.

Purpose Of Review: Preeclampsia affects 3-4% of pregnancies with few treatment options to reduce maternal and fetal harm. Recent evidence that targeting the complement system may be an effective therapeutic strategy in prevention or treatment of preeclampsia will be reviewed.

Recent Findings: Studies in humans confirm the safety and efficacy of C5 blockade in complement-mediated disorders of pregnancy, including preeclampsia.

Stress Exposure and Physical, Mental, and Behavioral Health among American Indian Adults with Type 2 Diabetes.

American Indian (AI) communities experience disproportionate exposure to stressors and health inequities including type 2 diabetes. Yet, we know little about the role of psychosocial stressors for AI diabetes-related health outcomes. We investigated associations between a range of stressors and psychological, behavioral, and physical health for AIs with diabetes.

A method for extracting and characterizing RNA from urine: For downstream PCR and RNAseq analysis.

Readily accessible samples such as urine or blood are seemingly ideal for differentiating and stratifying patients; however, it has proven a daunting task to identify reliable biomarkers in such samples. Noncoding RNA holds great promise as a source of biomarkers distinguishing physiologic wellbeing or illness. Current methods to isolate and characterize RNA molecules in urine are limited.

Correlates of khat use during pregnancy: A cross-sectional study.

Objectives: Khat is widely used in East African countries including Ethiopia. A growing body of evidence indicates that long-term khat use is associated with various health consequences. The aim of this study was to examine the magnitude and correlates of khat use in pregnant women.

Alaska Native Elders in Recovery: Linkages between Indigenous Cultural Generativity and Sobriety to Promote Successful Aging.

This article builds on the People Awakening (PA) Project, which explored an Alaska Native (AN) understanding of the recovery process from alcohol use disorder and sobriety. The aim of this study is to explore motivating and maintenance factors for sobriety among older AN adult participants (age 50+) from across Alaska. Ten life history narratives of Alaska Native older adults, representing Alutiiq, Athabascan, Tlingit, Yup'ik/Cup'ik Eskimos, from the PA sample were explored using thematic analysis.