The Novel, Nicotinic Alpha7 Receptor Partial Agonist, BMS-933043, Improves Cognition and Sensory Processing in Preclinical Models of Schizophrenia.

The development of alpha7 nicotinic acetylcholine receptor agonists is considered a promising approach for the treatment of cognitive symptoms in schizophrenia patients. In the present studies we characterized the novel agent, (2R)-N-(6-(1H-imidazol-1-yl)-4-pyrimidinyl)-4'H-spiro[4-azabicyclo[2.2.

Exploiting Interkingdom Interactions for Development of Small-Molecule Inhibitors of Candida albicans Biofilm Formation.

A rapid decline in the development of new antimicrobial therapeutics has coincided with the emergence of new and more aggressive multidrug-resistant pathogens. Pathogens are protected from antibiotic activity by their ability to enter an aggregative biofilm state. Therefore, disrupting this process in pathogens is a key strategy for the development of next-generation antimicrobials.

Development of a high-throughput mass spectrometry based analytical method to support an in vitro OATP1B1 inhibition screening assay.

Rationale: It is well known that the organic anion transporting polypeptide 1B1 (OATP1B1) plays a major role in the hepatic uptake of a range of drugs. To this end, it is pivotal that the potential for new molecular entities (NMEs) to inhibit OATP1B1 activity be assessed during early drug discovery. The work reported herein describes the development of a high-throughput analytical method to measure the clinically relevant probe substrate, pitavastatin, for the in vitro assessment of OATP1B1 inhibition.

Testosterone Treatment and Sexual Function in Older Men With Low Testosterone Levels.

Context: The Testosterone Trials are a coordinated set of seven trials to determine the efficacy of T in symptomatic men ≥65 years old with unequivocally low T levels. Initial results of the Sexual Function Trial showed that T improved sexual activity, sexual desire, and erectile function.

Objective: To assess the responsiveness of specific sexual activities to T treatment; to relate hormone changes to changes in sexual function; and to determine predictive baseline characteristics and T threshold for sexual outcomes.

Long-term Neurotoxic Effects of Early-life Exposure to Tetrachloroethylene-contaminated Drinking Water.

Background: Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983, widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes.

Widespread Disrupted White Matter Microstructure in Autism Spectrum Disorders.

Autism Spectrum Disorders (ASDs) are characterised by impaired social communication and restricted repetitive behaviours. Researchers posit that these core features may be underpinned by disrupted structural connectivity. A tract based spatial statistical analysis of diffusion MRI data was performed to investigate white matter organisation (an indication of structural connectivity) in a well-defined cohort of 45 ASD and 45 age and IQ matched control participants.

Advances in Autophagy Regulatory Mechanisms.

Autophagy plays a critical role in cell metabolism by degrading and recycling internal components when challenged with limited nutrients. This fundamental and conserved mechanism is based on a membrane trafficking pathway in which nascent autophagosomes engulf cytoplasmic cargo to form vesicles that transport their content to the lysosome for degradation. Based on this simple scheme, autophagy modulates cellular metabolism and cytoplasmic quality control to influence an unexpectedly wide range of normal mammalian physiology and pathophysiology.

A Four-Way Comparison of Cardiac Function with Normobaric Normoxia, Normobaric Hypoxia, Hypobaric Hypoxia and Genuine High Altitude.

Background: There has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses.

Materials And Methods: This was a prospective observational study of 14 healthy subjects aged 22-35 years. Echocardiography was performed at rest and at 15 and 120 minutes following two hours exercise under normobaric normoxia (NN) and under similar PiO2 following genuine high altitude (GHA) at 3,375 m, normobaric hypoxia (NH) and hypobaric hypoxia (HH) to simulate the equivalent hypoxic stimulus to GHA.

It's Time for the Genetic Counseling Profession to Embrace Social Media.

Social Media is a powerful and emerging method of communication that is becoming increasingly popular in genetic counseling and other health care communities. Despite its multiple benefits, the Social Media revolution has been met with some resistance in the healthcare setting. Herein, we will describe the potential benefits of Social Media for the genetic counseling profession specifically and explore ways in which any risks can be mitigated and barriers overcome to ensure responsible Social Media use by the profession.

Dysregulated bioenergetics: a key regulator of joint inflammation.

Objectives: This study examines the relationship between synovial hypoxia and cellular bioenergetics with synovial inflammation.

Methods: Primary rheumatoid arthritis synovial fibroblasts (RASF) were cultured with hypoxia, dimethyloxalylglycine (DMOG) or metabolic intermediates. Mitochondrial respiration, mitochondrial DNA mutations, cell invasion, cytokines, glucose and lactate were quantified using specific functional assays.

Polish women's experiences of breastfeeding in Ireland.

Exclusive breastfeeding among Polish mothers at three-four months (38.6 per cent) is in keeping with the low rates of breastfeeding in Ireland overall (Begley et al 2008), and suggests that Polish women have begun to adopt the infant feeding practices of Irish women. Therefore, the aim of this study was to explore the factors that influence Polish women's decisions to initiate and continue breastfeeding in Ireland.

Risk of Pancreatic Cancer in Female Textile Workers in Shanghai, China, Exposed to Metals, Solvents, Chemicals, and Endotoxin: Follow-Up to a Nested Case-Cohort Study.

Objective: We studied associations between pancreatic cancer and occupational exposures to metals, solvents, chemicals, and endotoxin in a cohort of female textile workers in Shanghai, China. To assess the longer-term influences of these agents on pancreatic cancer we extended follow-up of this previously studied cohort.

Methods: We utilized a job exposure matrix to assess occupational exposures for 481 pancreatic cancer cases and a randomly selected sub-cohort of 3191 non-cases.

Biomaterial-Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives.

Heart failure is a significant clinical issue. It is the cause of enormous healthcare costs worldwide and results in significant morbidity and mortality. Cardiac regenerative therapy has progressed considerably from clinical and preclinical studies delivering simple suspensions of cells, macromolecule, and small molecules to more advanced delivery methods utilizing biomaterial scaffolds as depots for localized targeted delivery to the damaged and ischemic myocardium.

Essential Genome of the Metabolically Versatile Alphaproteobacterium Rhodopseudomonas palustris.

Unlabelled: Rhodopseudomonas palustris is an alphaproteobacterium that has served as a model organism for studies of photophosphorylation, regulation of nitrogen fixation, production of hydrogen as a biofuel, and anaerobic degradation of aromatic compounds. This bacterium is able to transition between anaerobic photoautotrophic growth, anaerobic photoheterotrophic growth, and aerobic heterotrophic growth. As a starting point to explore the genetic basis for the metabolic versatility of R.

Joint Transcriptional Control of Virulence and Resistance to Antibiotic and Environmental Stress in Acinetobacter baumannii.

Unlabelled: The increasing emergence of antibiotic-resistant bacterial pathogens represents a serious risk to human health and the entire health care system. Many currently circulating strains of Acinetobacter baumannii exhibit resistance to multiple antibiotics. A key limitation in combating A.

Biochemical and behavioral effects of PDE10A inhibitors: Relationship to target site occupancy.

Phosphodiesterase 10A (PDE10A) inhibitors increase the functionality of striatal medium spiny neurons and produce antipsychotic-like effects in rodents by blocking PDE10A mediated hydrolysis of cAMP and/or cGMP. In the current study, we characterized a radiolabeled PDE10A inhibitor, [(3)H]BMS-843496, and developed an ex vivo PDE10 binding autoradiographic assay to explore the relationship between PDE10 binding site occupancy and the observed biochemical and behavioral effects of PDE10 inhibitors in mice. [(3)H]BMS-843496 is a potent PDE10A inhibitor with a binding affinity (KD) of 0.

Performance of the CLSI Carba NP and the Rosco Carb Screen Assays Using North American Carbapenemase-Producing Enterobacteriaceae and Pseudomonas aeruginosa Isolates.

This study compared the performance of the Carba NP assay, published by the Clinical and Laboratory Standards Institute, and the Rosco Rapid Carb Screen kit. Carba NP had superior sensitivity, but both assays required an increased inoculum to detect carbapenemase production in isolates with blaNDM, blaIMP, and blaOXA-48.

Determinants of breastfeeding initiation in Ireland.

Background: Ireland continues to rank among countries with the lowest breastfeeding initiation rates. National and regional studies also show that few women in Ireland who initiate exclusive breastfeeding continue to breastfeed for the recommended 6 months.

Aim: To assess the rate of exclusive and partial breastfeeding in Ireland at three time periods: birth to 48 h, 3-4 months following birth, and when the infant was 6-7 months old.

Synchronous Gastric Metastasis of Renal Cell Carcinoma With Absence of Gastrointestinal Symptoms.

Renal cell carcinoma (RCC) is a rare adult malignancy, and one-third of cases present with distant metastases at the time of diagnosis. Early gastric metastasis is exceedingly rare. We describe an adult male with synchronous gastric metastasis of RCC at the time of diagnosis in the absence of gastrointestinal symptoms.

Gait deviations in children with autism spectrum disorders: a review.

In recent years, it has become clear that children with autism spectrum disorders (ASDs) have difficulty with gross motor function and coordination, factors which influence gait. Knowledge of gait abnormalities may be useful for assessment and treatment planning. This paper reviews the literature assessing gait deviations in children with ASD.

Use of early intervention for young children with autism spectrum disorder across Europe.

Little is known about use of early interventions for autism spectrum disorder in Europe. Parents of children with autism spectrum disorder aged 7 years or younger (N = 1680) were recruited through parent organisations in 18 European countries and completed an online survey about the interventions their child received. There was considerable variation in use of interventions, and in some countries more than 20% of children received no intervention at all.

Long-term health effects of early life exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

Background: While adult exposure to PCE is known to have toxic effects, there is little information on the long-term impact of prenatal and early childhood exposure. We undertook a retrospective cohort study to examine the effects of their early life exposure to PCE-contaminated drinking water. This retrospective cohort study examined whether prenatal and early childhood exposure to PCE-contaminated drinking water influenced the risk of a variety of chronic conditions among adults who were born between 1969 and 1983 in the Cape Cod area of Massachusetts.