Polygenic impact of common genetic risk loci for Alzheimer's disease on cerebral blood flow in young individuals.

Genome-wide association studies (GWAS) show that many common alleles confer risk for developing Alzheimer's disease (AD). These risk loci may contribute to MRI alterations in young individuals, preceding the clinical manifestations of AD. Prior evidence identifies vascular dysregulation as the earliest marker of disease progression.

Comparison of peak oxygen consumption response to aquatic and robotic therapy in individuals with chronic motor incomplete spinal cord injury: a randomized controlled trial.

Study Design: Randomized dual center controlled clinical trial.

Objective: To determine and compare the cardiorespiratory impact of 3 months of aquatic and robotic therapy for individuals with chronic motor incomplete spinal cord injury (CMISCI).

Settings: Two rehabilitation specialty hospitals.

Convergent Evidence That ZNF804A Is a Regulator of Pre-messenger RNA Processing and Gene Expression.

Genome-wide association studies have linked common variation in ZNF804A with an increased risk of schizophrenia. However, little is known about the biology of ZNF804A and its role in schizophrenia. Here, we investigate the function of ZNF804A using a variety of complementary molecular techniques.

Autoimmunity-associated intronic SNP (rs2281808) detected by a simple phenotypic assay: Unique case or broader opportunity?

Multiple genome-wide association studies have shown that the single-nucleotide polymorphism (SNP) rs2281808 TT variant, present within the signal regulatory protein gamma (SIRPG) gene, is associated with autoimmune diseases, such as type 1 diabetes. SIRPγ is the only SIRP expressed on T cells. The role of SIRPγ in human T-cells or the effect of the TT variant are poorly understood.

Chronic adolescent stress sex-specifically alters central and peripheral neuro-immune reactivity in rats.

Adversity during development is a reliable predictor of psychiatric disorders such as depression and anxiety which are increasingly recognized to have an immune component. We have previously demonstrated that chronic adolescent stress (CAS) in rats leads to depressive-like behavior in adulthood along with long-lasting changes to the hypothalamic-pituitary-adrenal axis and pro-inflammatory cytokine induction in the hippocampus. However, the mechanisms by which CAS promotes hippocampal inflammation are not yet defined.

Immune system responses in Parkinson's disease: Early and dynamic.

The neuropathological hallmarks of Parkinson's disease (PD) are the degeneration and death of dopamine-producing neurons in the ventral midbrain, the widespread intraneuronal aggregation of alpha-synuclein (α) in Lewy bodies and neurites, neuroinflammation, and gliosis. Signs of microglia activation in the PD brain postmortem as well as during disease development revealed by neuroimaging, implicate immune responses in the pathophysiology of the disease. Intensive research during the last two decades has advanced our understanding of the role of these responses in the disease process, yet many questions remain unanswered.

Individual glucose responses to prolonged moderate intensity aerobic exercise in adolescents with type 1 diabetes: The higher they start, the harder they fall.

Objective: To evaluate the pattern of change in blood glucose concentrations and hypoglycemia risk in response to prolonged aerobic exercise in adolescents with type 1 diabetes (T1D) that had a wide range in pre-exercise blood glucose concentrations.

Methods: Individual blood glucose responses to prolonged (~60 minutes) moderate-intensity exercise were profiled in 120 youth with T1D.

Results: The mean pre-exercise blood glucose concentration was 178 ± 66 mg/dL, ranging from 69 to 396 mg/dL, while the mean change in glucose during exercise was -76 ± 55 mg/dL (mean ± SD), ranging from +83 to -257 mg/dL.

Evaluation of owners' attitudes towards veterinarian attire in the small animal specialty setting in North America.

Previous studies in human medicine have found that patients prefer their doctors to be more formally attired, and that this influences their trust and confidence in their physician. The purpose of this study was to evaluate how veterinarians' attire affected owners' impressions and trust in the small animal specialty medicine setting. A questionnaire based study conducted during a 2-month period at an urban based small animal private practice specialty hospital.

Assessing stakeholder perceptions of the american society for biochemistry and molecular biology accreditation program for baccalaureate degrees.

The American Society for Biochemistry and Molecular Biology (ASBMB) began an accreditation program in 2013. The criteria for accreditation of undergraduate programs include sufficient infrastructure - number and expertise of faculty, physical space and equipment, support for faculty and students - and incorporation of core concepts in the curriculum - structure and function of biomolecules; information storage; energy transfer; and quantitative skills. Students in accredited programs are able to have their degrees ASBMB certified by taking an exam focused on knowledge or skills across the four core concept areas.

An autoimmune disease risk SNP, rs2281808, in SIRPG is associated with reduced expression of SIRPγ and heightened effector state in human CD8 T-cells.

Multiple GWAS studies have shown that the SNP rs2281808 TT variant, present within the SIRPG gene, is associated with autoimmune diseases, such as type 1 diabetes. However, the role of SIRPγ in human T-cells is not known, neither is the functional significance of TT variant. Here we investigated SIRPG genotypes and their effects on the fate and function of human T-cells.

Effect of client complaints on small animal veterinary internists.

Objectives: To investigate the effect of client complaints on small animal veterinary internists' welfare, job satisfaction and medical practices.

Materials And Methods: Cross-sectional anonymous survey study. Between February 1 and March 31, 2017, a web-based questionnaire was made available through the American College Veterinary Internal Medicine sub-specialty Small Animal Internal Medicine E-mail List Serve.

α-Synuclein and Noradrenergic Modulation of Immune Cells in Parkinson's Disease Pathogenesis.

α-synuclein (α-syn) pathology and loss of noradrenergic neurons in the locus coeruleus (LC) are among the most ubiquitous features of Parkinson's disease (PD). While noradrenergic dysfunction is associated with non-motor symptoms of PD, preclinical research suggests that the loss of LC norepinephrine (NE), and subsequently its immune modulatory and neuroprotective actions, may exacerbate or even accelerate disease progression. In this review, we discuss the mechanisms by which α-syn pathology and loss of central NE may directly impact brain health by interrupting neurotrophic factor signaling, exacerbating neuroinflammation, and altering regulation of innate and adaptive immune cells.

Earthquakes to Floods: A Scoping Review of Health-related Disaster Research in Low- and Middle-income Countries.

Introduction: Health-related disaster research is a relatively small; but growing field of inquiry.  A better understanding of the scope and scale of health-related disaster research that has occurred in low- and middle-income countries (LMICs) would be useful to funders, researchers, humanitarian aid organizations, and governments as they strive to identify gaps, disparities, trends, and needs of populations affected by disasters.

Methodology: We performed a scoping review using the process outlined by Arksey & O'Malley to assess the characteristics of peer-reviewed publications of empirical health-related disaster research conducted in LMICs and published in the years 2003-2012.

Effect of cytochrome CYP2C19 metabolizing activity on antidepressant response and side effects: Meta-analysis of data from genome-wide association studies.

Cytochrome (CYP) P450 enzymes have a primary role in antidepressant metabolism and variants in these polymorphic genes are targets for pharmacogenetic investigation. This is the first meta-analysis to investigate how CYP2C19 polymorphisms predict citalopram/escitalopram efficacy and side effects. CYP2C19 metabolic phenotypes comprise poor metabolizers (PM), intermediate and intermediate+ metabolizers (IM; IM+), extensive and extensive+ metabolizers (EM [wild type]; EM+) and ultra-rapid metabolizers (UM) defined by the two most common CYP2C19 functional polymorphisms (rs4244285 and rs12248560) in Caucasians.

Fractional anisotropy of the uncinate fasciculus and cingulum in bipolar disorder type I, type II, unaffected siblings and healthy controls.

Background: Fractional anisotropy in the uncinate fasciculus and the cingulum may be biomarkers for bipolar disorder and may even be distinctly affected in different subtypes of bipolar disorder, an area in need of further research.AimsThis study aims to establish if fractional anisotropy in the uncinate fasciculus and cingulum shows differences between healthy controls, patients with bipolar disorder type I (BD-I) and type II (BD-II), and their unaffected siblings.

Method: Fractional anisotropy measures from the uncinate fasciculus, cingulum body and parahippocampal cingulum were compared with tractography methods in 40 healthy controls, 32 patients with BD-I, 34 patients with BD-II, 17 siblings of patients with BD-I and 14 siblings of patients with BD-II.

Clients' attitudes toward veterinarians' attire in the small animal emergency medicine setting.

OBJECTIVE To determine how veterinarians' attire affected clients' perceptions and trust in the small animal emergency medicine setting. DESIGN Cross-sectional study. SAMPLE 154 clients of a 24-hour small animal emergency clinic in a rural location.

Sustainability issues of commercial non-timber forest product extraction in West Suriname.

Background: Non-timber forest products (NTFPs) have been traded for millennia by indigenous communities. Current increased demands driven by globalisation, however, put more pressure on local harvesters and their surrounding ecosystems. The safeguarding of indigenous access rights to harvesting grounds is needed, either through communal land titles or collaborative management agreements, both to secure prior indigenous rights and to minimise further negative ecological impacts.

A framework for measurement and harmonization of pediatric multiple sclerosis etiologic research studies: The Pediatric MS Tool-Kit.

Background: While studying the etiology of multiple sclerosis (MS) in children has several methodological advantages over studying etiology in adults, studies are limited by small sample sizes.

Objective: Using a rigorous methodological process, we developed the Pediatric MS Tool-Kit, a measurement framework that includes a minimal set of core variables to assess etiological risk factors.

Methods: We solicited input from the International Pediatric MS Study Group to select three risk factors: environmental tobacco smoke (ETS) exposure, sun exposure, and vitamin D intake.

Potential Role of the Gut Microbiome in ALS: A Systematic Review.

Amyotrophic lateral sclerosis (ALS) etiology and pathophysiology are not well understood. Recent data suggest that dysbiosis of gut microbiota may contribute to ALS etiology and progression. This review aims to explore evidence of associations between gut microbiota and ALS etiology and pathophysiology.

What does plasma CRP tell us about peripheral and central inflammation in depression?

Peripheral blood C-reactive protein (CRP) is a biomarker used clinically to measure systemic inflammation and is reproducibly increased in a subset of patients with major depressive disorder (MDD). Furthermore, increased peripheral blood CRP in MDD has been associated with altered reward circuitry and increased brain glutamate in relation with symptoms of anhedonia. Nevertheless, the relationship between peripheral CRP and other peripheral and central markers of inflammation in depressed patients has not been established.

Discovery of Potent 2-Aryl-6,7-dihydro-5 H-pyrrolo[1,2- a]imidazoles as WDR5-WIN-Site Inhibitors Using Fragment-Based Methods and Structure-Based Design.

WDR5 is a chromatin-regulatory scaffold protein overexpressed in various cancers and a potential epigenetic drug target for the treatment of mixed-lineage leukemia. Here, we describe the discovery of potent and selective WDR5-WIN-site inhibitors using fragment-based methods and structure-based design. NMR-based screening of a large fragment library identified several chemically distinct hit series that bind to the WIN site within WDR5.