Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington's Disease.

Background: Huntington's disease is marked by progressive neuroanatomical changes, assumed to underlie the development of the disease's characteristic symptoms. Previous work has demonstrated longitudinal macrostructural white-matter atrophy, with some evidence of microstructural change focused in the corpus callosum.

Objective: To more accurately characterise longitudinal patterns, we examined white matter microstructural change using Diffusion Tensor Imaging (DTI) data from three timepoints over a 15 month period.

Effect of Rifampin on the Pharmacokinetics of Apixaban, an Oral Direct Inhibitor of Factor Xa.

Objective: Apixaban is a substrate of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein. The effects of rifampin, a strong inducer of CYP3A4 and P-glycoprotein, on the pharmacokinetics of oral and intravenous apixaban were evaluated in an open-label, randomized, sequential crossover study.

Methods: Twenty healthy participants received single doses of apixaban 5 mg intravenously on day 1 and 10 mg orally on day 3, followed by rifampin 600 mg once daily on days 5-15.

A Metabolic Study of Huntington's Disease.

Background: Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III) and controls.

Methods: Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period.

Dynamics of Seeded Aβ40-Fibril Growth from Atomistic Molecular Dynamics Simulations: Kinetic Trapping and Reduced Water Mobility in the Locking Step.

Filamentous β-amyloid aggregates are crucial for the pathology of Alzheimer's disease. Despite the tremendous biomedical importance, the molecular pathway of growth propagation is not completely understood and remains challenging to investigate by simulations due to the long time scales involved. Here, we apply extensive all-atom molecular dynamics simulations in explicit water to obtain free energy profiles and kinetic information from position-dependent diffusion profiles for three different Aβ9-40-growth processes: fibril elongation by single monomers at the structurally unequal filament tips and association of larger filament fragments.

Remedial after-school support classes offered in rural Gambia (The SCORE trial): study protocol for a cluster randomized controlled trial.

Background: Low education levels are endemic in much of the developing world, particularly in rural areas where traditional government-provided public services often have difficulty reaching beneficiaries. Providing trained para-teachers to teach regular after-school remedial education classes has been shown to improve literacy and numeracy in children of primary school age residing in such areas in India. This trial investigates whether such an intervention can also be effective in a West African setting with similarly low learning levels and difficult geographic access.

Upper Cervical Epidural Abscess in a Patient With Parkinson Disease: A Case Report and Review.

To our knowledge, there are no reports in the literature of patients with Parkinson disease (PD) developing upper cervical spine infections. Our objective is to present a case of upper cervical epidural abscess in a patient with PD and to review upper cervical spine infection. We present the patient's presentation, physical examination, imaging findings, and management as well a review of the literature.

Reproductive Health in the United States: A Review of the Recent Social Work Literature.

Reproductive health is an important area affecting a woman's overall health and well-being. The examination of reproductive health and barriers to care is pertinent to the social work profession and should be a focus of social work practice, education, research, and advocacy. The authors conducted a literature search of articles published in the social work literature from 2010 to 2014.

Psychosocial Adjustment in School-age Girls With a Family History of Breast Cancer.

Objective: Understanding how young girls respond to growing up with breast cancer family histories is critical given expansion of genetic testing and breast cancer messaging. We examined the impact of breast cancer family history on psychosocial adjustment and health behaviors among >800 girls in the multicenter LEGACY Girls Study.

Methods: Girls aged 6 to 13 years with a family history of breast cancer or familial BRCA1/2 mutation (BCFH+), peers without a family history (BCFH-), and their biological mothers completed assessments of psychosocial adjustment (maternal report for 6- to 13-year-olds, self-report for 10- to 13-year-olds), breast cancer-specific distress, perceived risk of breast cancer, and health behaviors (10- to 13-year-olds).

A 24-Hour Study of the Hypothalamo-Pituitary Axes in Huntington's Disease.

Background: Huntington's disease is an inherited neurodegenerative disorder characterised by motor, cognitive and psychiatric disturbances. Patients exhibit other symptoms including sleep and mood disturbances, muscle atrophy and weight loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo-pituitary axes.

Methods: We studied neuroendocrine profiles of corticotropic, somatotropic and gonadotropic hypothalamo-pituitary axes hormones over a 24-hour period in controlled environment in 15 healthy controls, 14 premanifest and 13 stage II/III Huntington's disease subjects.

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban.

This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr ) as a measure of renal function. The relationships between 24-hour CLcr and iohexol clearance, estimated CLcr (Cockcroft-Gault equation), and estimated glomerular filtration rate (modification of diet in renal disease [MDRD] equation) were also assessed.

The proteolytic profile of human cancer procoagulant suggests that it promotes cancer metastasis at the level of activation rather than degradation.

Proteases are essential for tumour progression and many are over-expressed during this time. The main focus of research was the role of these proteases in degradation of the basement membrane and extracellular matrix (ECM), thereby enabling metastasis to occur. Cancer procoagulant (CP), a protease present in malignant tumours, but not normal tissue, is a known activator of coagulation factor X (FX).

Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis.

An open-label, parallel-group, single-dose study was conducted to assess the pharmacokinetics, pharmacodynamics, and safety of apixaban in 8 subjects with end-stage renal disease (ESRD) on hemodialysis compared with 8 subjects with normal renal function. A single oral 5-mg dose of apixaban was administered once to healthy subjects and twice to subjects with ESRD, separated by ≥7 days: 2 hours before (on hemodialysis) and immediately after a 4-hour hemodialysis session (off hemodialysis). Blood samples were collected for determination of apixaban pharmacokinetic parameters, measures of clotting (prothrombin time, international normalized ratio, activated partial thromboplastin time), and anti-factor Xa (FXa) activity.

Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge.

Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models.

Community-level net spillover of natural enemies from managed to natural forest.

Edge effects in fragmented natural habitats may De exaceroateci by intensive land use in the surrounding landscape. Given that most managed systems have higher primary productivity than adjacent natural systems, theory suggests that bottom-up subsidized consumers are likely to spill over from managed to natural habitats. Furthermore, the magnitude of spillover is likely to differ between generalist and specialist consumers, because of differences in their ability to use the full spectrum of resources.

Signal transduction and amplification through enzyme-triggered ligand release and accelerated catalysis.

Signal transduction and signal amplification are both important mechanisms used within biological signalling pathways. Inspired by this process, we have developed a signal amplification methodology that utilises the selectivity and high activity of enzymes in combination with the robustness and generality of an organometallic catalyst, achieving a hybrid biological and synthetic catalyst cascade. A proligand enzyme substrate was designed to selectively self-immolate in the presence of the enzyme to release a ligand that can bind to a metal pre-catalyst and accelerate the rate of a transfer hydrogenation reaction.

Ruthenium-Catalyzed O- to S-Alkyl Migration: A Pseudoreversible Barton-McCombie Pathway.

A practical ruthenium-catalyzed O- to S-alkyl migration affords structurally diverse thiooxazolidinones in excellent yields. Our studies suggest this catalytic transformation proceeds through a pseudoreversible radical pathway drawing mechanistic parallels to the classic Barton-McCombie reaction.

Relative Bioavailability of Apixaban Solution or Crushed Tablet Formulations Administered by Mouth or Nasogastric Tube in Healthy Subjects.

Purpose: Crushed tablet and solution formulations of apixaban administered orally or via a nasogastric tube (NGT) may be useful in patients unable to swallow solid dose formulations. It is important to understand whether new formulations and/or methods of administration impact apixaban bioavailability and pharmacokinetic properties. These studies evaluated the relative bioavailability (Frel) of apixaban solution administered orally; oral solution administered via NGT flushed with either 5% dextrose in water (D5W) or with infant formula; oral solution via NGT with a nutritional supplement; and crushed tablet suspended in D5W and administered via NGT.

U.S. Men's Perceptions and Experiences of Emergency Contraceptives.

Research suggests that men should be included in reproductive health decision making to help enhance positive health outcomes for their partners. Men affect the use of contraception and what method is used. Men's decisions may be affected by different factors such as gender, education, and the nature of their sexual relationship.

Catalytic meta-selective C-H functionalization to construct quaternary carbon centres.

A catalytic meta-selective C-H functionalization of 2-phenylpyridines using a range of tertiary halides is described. The protocol is simple to perform and uses commercially available reagents to construct challenging quaternary carbon centres in a regioselective manner. Preliminary studies suggest the C-H functionalization proceeds through a radical process directed via a remote σ-activation.

Reproductive parasitism: maternally inherited symbionts in a biparental world.

Most species of insect, and many other plants and animals, carry maternally heritable microorganisms-viruses, bacteria, unicellular eukaryotes, and fungi that pass from a female host to her progeny. Maternal inheritance establishes a correlation between the fitness of symbiont and host female, which can select for the symbiont to contribute to host fitness. Nevertheless, its lack of transmission through male hosts places the symbiont in conflict with biparentally inherited nuclear genes.

Alzheimer's disease first symptoms are age dependent: Evidence from the NACC dataset.

Introduction: Determining the relationship between age and Alzheimer's disease (AD) presentation is important to improve understanding and provide better patient services.

Methods: We used AD patient data (N = 7815) from the National Alzheimer Coordinating Center database and multinomial logistic regression to investigate presentation age and first cognitive/behavioral symptoms.

Results: The odds of having a nonmemory first cognitive symptom (including impairment in judgment and problem solving, language, and visuospatial function) increased with younger age (P < .

Online reviews of orthopedic surgeons: an emerging trend.

Various websites are dedicated to rating physicians. The goals of this study were to: (1) evaluate the prevalence of orthopedic surgeon ratings on physician rating websites in the United States and (2) evaluate factors that may affect ratings, such as sex, practice sector (academic or private), years of practice, and geographic location. A total of 557 orthopedic surgeons selected from the 30 most populated US cities were enrolled.

Acute Invasive Fungal Rhinosinusitis: A Comprehensive Update of CT Findings and Design of an Effective Diagnostic Imaging Model.

Background And Purpose: Acute invasive fungal rhinosinusitis carries a high mortality rate. An easy-to-use and accurate predictive imaging model is currently lacking. We assessed the performance of various CT findings for the identification of acute invasive fungal rhinosinusitis and synthesized a simple and robust diagnostic model to serve as an easily applicable screening tool for at-risk patients.