Epigenetic Regulation of Multidrug Resistance Protein 1 and Breast Cancer Resistance Protein Transporters by Histone Deacetylase Inhibition.

Multidrug resistance protein 1 (MDR1, , P-glycoprotein) and breast cancer resistance protein (BCRP, ) are key efflux transporters that mediate the extrusion of drugs and toxicants in cancer cells and healthy tissues, including the liver, kidneys, and the brain. Altering the expression and activity of MDR1 and BCRP influences the disposition, pharmacodynamics, and toxicity of chemicals, including a number of commonly prescribed medications. Histone acetylation is an epigenetic modification that can regulate gene expression by changing the accessibility of the genome to transcriptional regulators and transcriptional machinery.

Pharmacological inhibition of CSF1R by GW2580 reduces microglial proliferation and is protective against neuroinflammation and dopaminergic neurodegeneration.

Increased pro-inflammatory cytokine levels and proliferation of activated microglia have been found in Parkinson's disease (PD) patients and animal models of PD, suggesting that targeting of the microglial inflammatory response may result in neuroprotection in PD. Microglial proliferation is regulated by many factors, but colony stimulating factor-1 receptor (CSF1R) has emerged as a primary factor. Using data mining techniques on existing microarray data, we found that mRNA expression of the CSF1R ligand, CSF-1, is increased in the brain of PD patients compared to controls.

Nerve Growth Factor Protects Against Pyrethroid-Induced Endoplasmic Reticulum (ER) Stress in Primary Hippocampal Neurons.

Neurotrophins are a family of growth factors crucial for growth and survival of neurons in the developing and adult brain. Reduction in neurotrophin levels is associated with reduced neurogenesis and cognitive deficits in rodents. Recently, we demonstrated that long-term exposure to low levels of the pyrethroid pesticide deltamethrin causes hippocampal endoplasmic reticulum (ER) stress and learning deficits in mice.

An institutional ethnography of prevention and treatment services for substance use disorders in the Dominican Republic.

The Dominican Republic is thought to have significant epidemics of illicit drug use but lacks surveillance and formal analyses of the policy context of drug prevention and treatment services. We conducted an institutional ethnography of 15 drug service organisations in Santo Domingo and Boca Chica, Dominican Republic, to explore barriers and resources for drug abuse prevention and treatment. Here, we present a typology of drug service organisations based on their services, methods, and approach.

Epigenetic Regulation of the Ontogenic Expression of the Dopamine Transporter.

The dopamine transporter (DAT) is a plasma membrane transport protein responsible for regulating the duration and intensity of dopaminergic signaling. Altered expression of DAT is linked to neurodevelopmental disorders, including attention deficit hyperactivity disorder and autism spectrum disorder, and is shown to contribute to the response of psychotropic drugs and neurotoxicants. Although the postnatal levels of DAT have been characterized, there are few data regarding the mechanisms that regulate postnatal DAT expression.

An ethnographic study of 'touristic escapism' and health vulnerability among Dominican male tourism workers.

Health research on tourism has expanded over the past two decades, focusing on understanding how the social, economic, and political configuration of tourism zones might contribute to health vulnerabilities among the diverse populations that interact in these areas. While there are few studies of HIV and drug use interactions in the region, research has indicated that these two outcomes are often interwoven in tourism zones, potentially producing 'syndemics' of HIV infection and problematic drug use. One framework that has been used in public health research on tourism is one that we refer to as touristic escapism or situational disinhibition that may be heightened for some tourists while on vacation, potentially leading to the abandonment of normative constraints on behaviour and contributing to health risks such as unprotected sex or binge drinking.

Neurotoxicity of pesticides.

Pesticides are unique environmental contaminants that are specifically introduced into the environment to control pests, often by killing them. Although pesticide application serves many important purposes, including protection against crop loss and against vector-borne diseases, there are significant concerns over the potential toxic effects of pesticides to non-target organisms, including humans. In many cases, the molecular target of a pesticide is shared by non-target species, leading to the potential for untoward effects.

Microglial proliferation and monocyte infiltration contribute to microgliosis following status epilepticus.

Microglial activation has been recognized as a major contributor to inflammation of the epileptic brain. Seizures are commonly accompanied by remarkable microgliosis and loss of neurons. In this study, we utilize the CX3CR1 CCR2 genetic mouse model, in which CX3CR1 resident microglia and CCR2 monocytes are labeled with GFP and RFP, respectively.

Increased MDR1 Transporter Expression in Human Brain Endothelial Cells Through Enhanced Histone Acetylation and Activation of Aryl Hydrocarbon Receptor Signaling.

Multidrug resistance protein 1 (MDR1, ABCB1, P-glycoprotein) is a critical efflux transporter that extrudes chemicals from the blood-brain barrier (BBB) and limits neuronal exposure to xenobiotics. Prior studies in malignant cells demonstrated that MDR1 expression can be altered by inhibition of histone deacetylases (HDAC), enzymes that modify histone structure and influence transcription factor binding to DNA. Here, we sought to identify the mechanisms responsible for the up-regulation of MDR1 by HDAC inhibitors in human BBB cells.

Brain region-specific regulation of histone acetylation and efflux transporters in mice.

Multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) protect the brain by restricting the passage of chemicals across the blood-brain barrier. Prior studies have demonstrated the epigenetic regulation of MDR1 and BCRP in cancer cells treated with histone deacetylase (HDAC) inhibitors that enhance histone acetylation and gene transcription. In the present study, we tested the in vivo effects of two HDAC inhibitors, valproic acid (VPA; 400 mg/kg) and apicidin (5 mg/kg), on Mdr1 and Bcrp transporter expression in brain regions of adult male mice injected intraperitoneally daily for 7 days.

Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine.

Alzheimer's disease (AD) is the leading cause of dementia in the United States and afflicts >5.7 million Americans in 2018. Therapeutic options remain extremely limited to those that are symptom targeting, while no drugs have been approved for the modification or reversal of the disease itself.

Hepatic carboxylesterases are differentially regulated in PPARα-null mice treated with perfluorooctanoic acid.

Hepatic carboxylesterases (Ces) catalyze the metabolism of drugs, environmental toxicants, and endogenous lipids and are known to be regulated by multiple nuclear receptors. Perfluorooctanoic acid (PFOA) is a synthetic fluorochemical that has been associated with dyslipidemia in exposed populations. In liver, PFOA can activate nuclear receptors such as PPARα, and alter the metabolism and excretion of chemicals.

Regional Susceptibility to ER Stress and Protection by Salubrinal Following a Single Exposure to Deltamethrin.

Endoplasmic reticulum (ER) stress is a significant contributor to neurodegeneration and cognitive dysfunction. Recently, we reported that repeated exposure to the pyrethroid insecticide deltamethrin caused ER stress in the hippocampus of adult mice, which was accompanied by deficits in learning (Hossain et al., 2015).

Knockdown of Butyrylcholinesterase but Not Inhibition by Chlorpyrifos Alters Early Differentiation Mechanisms in Human Neural Stem Cells.

Butyrylcholinesterase (BChE) is the evolutionary counterpart to acetylcholinesterase (AChE). Both are expressed early in nervous system development prior to cholinergic synapse formation. The organophosphate pesticide chlorpyrifos (CPF) primarily exerts toxicity through the inhibition of AChE, which results in excess cholinergic stimulation at the synapse.

'What's my risk of sustaining an ACL injury while playing football (soccer)?' A systematic review with meta-analysis.

Objective: To estimate the incidence proportion (IP) and incidence rate (IR) of ACL injury in football players.

Design: Systematic review with meta-analysis.

Data Sources: PubMed, CINAHL and SPORTDiscus electronic databases were searched from inception to 20 January 2017.

"What's my risk of sustaining an ACL injury while playing sports?" A systematic review with meta-analysis.

Objective: To estimate the incidence proportion (IP) and incidence rate (IR) for ACL injury in athletes.

Design: Systematic review with meta-analysis DATA SOURCES: The PubMed, CINAHL and SPORTDiscus electronic databases were searched from inception to 20 January 2017.

Eligibility Criteria For Selecting Studies: Studies were included if they reported total number of participants/population by sex, total number of ACL injuries by sex and total person-time by sex.

Oxidative Stress in HIV Infection and Alcohol Use: Role of Redox Signals in Modulation of Lipid Rafts and ATP-Binding Cassette Transporters.

Aims: Human immunodeficiency virus (HIV) infection induces oxidative stress and alcohol use accelerates disease progression, subsequently causing immune dysfunction. However, HIV and alcohol impact on lipid rafts-mediated immune dysfunction remains unknown. In this study, we investigate the modulation by which oxidative stress induces reactive oxygen species (ROS) affecting redox expression, lipid rafts caveiloin-1, ATP-binding cassette (ABC) transporters, and transcriptional sterol regulatory element-binding protein (SREBP) gene and protein modification and how these mechanisms are associated with arachidonic acid (AA) metabolites in HIV positive alcohol users, and how they escalate immune dysfunction.

The Impact of Red Light Cameras on Crashes Within Miami-Dade County, Florida.

Objective: To determine the safety effect of red light camera (RLC) programs, this study attempted to estimate its impact on collisions within Miami-Dade County, Florida Methods: A before-after evaluation using a comparison group along with traffic control correction was employed. Twenty signalized intersections with RLCs that began enforcement on January 1, 2011, were matched to 2 comparison sites located at least 2 miles from camera sites to minimize spillover effect. An empirical Bayes analysis was used to account for potential regression to the mean effects.

Validation of a Sun Exposure Questionnaire Among Subjects with Type 2 Diabetes Residing in South Florida.

To validate a sun exposure questionnaire against objective measures of change in skin color and to assess its validity in predicting 25(OH)D in a sample of African Americans and Hispanics with type 2 diabetes. Ninety subjects were enrolled. The sun exposure score was calculated by multiplying the time spent outdoors times the skin exposed score.

Interhemispheric Asymmetries and Theta Activity in the Rostral Anterior Cingulate Cortex as EEG Signature of HIV-Related Depression: Gender Matters.

Resting EEGs of 40 people living with HIV (PLWH) on long-term antiretroviral treatment were examined for z-scored deviations from a healthy control (normative database) to examine the main and interaction effects of depression and gender. Regions of interest were frontal (alpha) and central (all bands) for interhemispheric asymmetries in quantitative EEGs and theta in the rostral anterior cingulate cortex (rACC) in low-resolution electromagnetic tomography (LORETA). Z-scored normed deviations of depressed PLWH, compared with nondepressed, showed right-dominant interhemispheric asymmetries in all regions.

Immediate rather than delayed memory impairment in older adults with latent toxoplasmosis.

The neurotropic parasite Toxoplasma gondii infects one third of the world population, but its effect on memory remains ambiguous. To examine a potential relationship of the infection with immediate and delayed memory, a population-based study was conducted in 4485 participants of the Third National Health and Nutrition Examination Survey aged 60years and older. Serum anti-Toxoplasma IgG antibodies were measured by enzyme immune assay and verbal memory was assessed using the Mini-Mental State Examination and the East Boston Memory Test.

Use of Homeostatic Model Assessment Indexes for the Identification of Metabolic Syndrome and Insulin Resistance among Cuban-Americans: A Cross Sectional Study.

Aim: to determine cut off points for The Homeostatic Model Assessment Index 1 and 2 (HOMA-1 and HOMA-2) for identifying insulin resistance and metabolic syndrome among a Cuban-American population.

Study Design: Cross sectional.

Place And Duration Of Study: Florida International University, Robert Stempel School of Public Health and Social Work, Department of Dietetics and Nutrition, Miami, FL from July 2010 to December 2011.

Eating disorder risk and body dissatisfaction based on muscularity and body fat in male university students.

Objective: To investigate the relationship between risk of eating disorders, body dissatisfaction, and perceptual attractiveness in male university students.

Participants: Research was conducted January-April 2012 and involved 339 male and 441 female students.

Methods: Eating disorder risk was assessed with the Eating Attitudes Test (EAT) and body dissatisfaction and perceptual attractiveness determined with the Bodybuilder Image Grid (BIG).

A comparison of the nutritional quality of organic and conventional ready-to-eat breakfast cereals based on NuVal scores.

Objective: To identify whether there were differences in nutritional quality between organic and conventional ready-to-eat breakfast cereals of similar types, based on NuVal scores.

Design: The current descriptive study analysed NuVal scores for 829 ready-to-eat breakfast cereals and eighteen different cereal types. ANOVA was used to compare the mean NuVal scores of 723 conventional cereals with those of 106 organic cereals.