The biological foundation of the genetic association of TOMM40 with late-onset Alzheimer's disease.

A variable-length poly-T variant in intron 6 of the TOMM40 gene, rs10524523, is associated with risk and age-of-onset of sporadic (late-onset) Alzheimer's disease. In Caucasians, the three predominant alleles at this locus are Short (S), Long (L) or Very long (VL). On an APOE ε3/3 background, the S/VL and VL/VL genotypes are more protective than S/S.

An experimental canine patent ductus arteriosus occlusion device based on shape memory polymer foam in a nitinol cage.

Patent ductus arteriosus (PDA) is a congenital cardiovascular defect in which a fetal connection between the aorta and pulmonary artery does not spontaneously close shortly after birth. If left uncorrected serious complications and even death can occur. Surgical ligation is the traditional treatment method; however, it is an invasive procedure, that motivates development of a minimally invasive option.

APOE ε4-TOMM40 '523 haplotypes and the risk of Alzheimer's disease in older Caucasian and African Americans.

Patterns of linkage between the ε4 allele of Apolipoprotein E (APOE) and '523 poly-T alleles in the adjacent gene, TOMM40, differ between Caucasian and African Americans. The extent to which this difference affects the risk of Alzheimer's disease (AD) is unclear. We compared the APOE ε4-TOMM40 '523 haplotypes between older Caucasian and African Americans, and examined their relationship with AD dementia.

Asymptomatic Canine Degenerative Valve Disease: Current and Future Therapies.

Degenerative valve disease (DVD) is the leading cause of heart disease and congestive heart failure (CHF) in the dog. The first published consensus statement provided guidelines for the diagnosis and treatment of DVD. Although treatment was not recommended in stage B1 DVD, consensus was not reached regarding evidence-based recommendations for treatment of stage B2 DVD.

Neuropathologic features of TOMM40 '523 variant on late-life cognitive decline.

Introduction: The study investigated the role of neuropathologies in the relationship between TOMM40 '523 genotype and late-life cognitive decline.

Methods: Participants were community-dwelling older persons who had annual cognitive assessments and brain autopsies after death. Genotyping used DNA from peripheral blood or postmortem brain tissue.

Perceptions of transcatheter device closure of patent ductus arteriosus in veterinary cardiology and evaluation of a canine model to simulate device placement: a preliminary study.

Objectives: The purpose of this study was to evaluate a canine patent ductus arteriosus (PDA) model developed for practicing device placement and to determine practices and perceptions regarding transcatheter closure of PDA from the veterinary cardiology community.

Method: A silicone model was developed from images obtained from a dog with a PDA and device placement was performed with catheter equipment and a document camera to simulate fluoroscopy. A total of 36 individuals including 24 diplomates and 12 residents participated, and the feedback was obtained.

Real-time 3D transesophageal echocardiography-guided closure of a complicated patent ductus arteriosus in a dog.

Advanced imaging modalities are becoming more widely available in veterinary cardiology, including the use of transesophageal echocardiography (TEE) during occlusion of patent ductus arteriosus (PDA) in dogs. The dog in this report had a complex history of attempted ligation and a large PDA that initially precluded device placement thereby limiting the options for PDA closure. Following a second thoracotomy and partial ligation, the morphology of the PDA was altered and device occlusion was an option.

A new method for measuring the neutron lifetime using an in situ neutron detector.

In this paper, we describe a new method for measuring surviving neutrons in neutron lifetime measurements using bottled ultracold neutrons (UCN), which provides better characterization of systematic uncertainties and enables higher precision than previous measurement techniques. An active detector that can be lowered into the trap has been used to measure the neutron distribution as a function of height and measure the influence of marginally trapped UCN on the neutron lifetime measurement. In addition, measurements have demonstrated phase-space evolution and its effect on the lifetime measurement.

Impact of Chronic Renal Failure on Safety and Effectiveness of Paclitaxel-Eluting Stents for Femoropopliteal Artery Disease: Subgroup Analysis from Zilver PTX Post-Market Surveillance Study in Japan.

Purpose: Favorable long-term outcomes of the Zilver PTX drug-eluting stent (DES) in femoropopliteal lesions have been demonstrated. Chronic renal failure (CRF) has been shown to be a risk factor for restenosis and decreased limb salvage. The results of the DES in patients with CRF have not previously been reported.

Context-Dependent Functions of NANOG Phosphorylation in Pluripotency and Reprogramming.

The core pluripotency transcription factor NANOG is critical for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Although NANOG is phosphorylated at multiple residues, the role of NANOG phosphorylation in ESC self-renewal is incompletely understood, and no information exists regarding its functions during reprogramming. Here we report our findings that NANOG phosphorylation is beneficial, although nonessential, for ESC self-renewal, and that loss of phosphorylation enhances NANOG activity in reprogramming.

Observation of Betatron X-Ray Radiation in a Self-Modulated Laser Wakefield Accelerator Driven with Picosecond Laser Pulses.

We investigate a new regime for betatron x-ray emission that utilizes kilojoule-class picosecond lasers to drive wakes in plasmas. When such laser pulses with intensities of ∼5×10^{18}  W/cm^{2} are focused into plasmas with electron densities of ∼1×10^{19}  cm^{-3}, they undergo self-modulation and channeling, which accelerates electrons up to 200 MeV energies and causes those electrons to emit x rays. The measured x-ray spectra are fit with a synchrotron spectrum with a critical energy of 10-20 keV, and 2D particle-in-cell simulations were used to model the acceleration and radiation of the electrons in our experimental conditions.

Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia.

The basal ganglia (BG) integrate inputs from diverse sensorimotor, limbic, and associative regions to guide action-selection and goal-directed behaviors. The entopeduncular nucleus (EP) is a major BG output nucleus and has been suggested to channel signals from distinct BG nuclei to target regions involved in diverse functions. Here we use single-cell transcriptional and molecular analyses to demonstrate that the EP contains at least three classes of projection neurons-glutamate/GABA co-releasing somatostatin neurons, glutamatergic parvalbumin neurons, and GABAergic parvalbumin neurons.

Mechanisms that synergistically regulate η-secretase processing of APP and Aη-α protein levels: relevance to pathogenesis and treatment of Alzheimer's disease.

The pathophysiology of Alzheimer's disease (AD) is characterized by the formation of cerebral β-amyloid plaque from a small peptide amyloid-β (Aβ). Aβ is generated from the canonical amyloid-β precursor protein (APP) proteolysis pathway through β- and γ-secretases. Decreasing Aβ levels through targeting APP processing is a very promising direction in clinical trials for AD.

Clinical Characteristics of Adult Dogs More Than 5 Years of Age at Presentation for Patent Ductus Arteriosus.

Background: The median age at presentation for dogs with patent ductus arteriosus (PDA) is <6 months of age, and closure is associated with a decrease in heart size and increased survival time, which are not well described in older dogs.

Objectives: To describe the clinical characteristics of dogs with PDA ≥5 years of age at the time of presentation to a veterinary referral hospital.

Animals: 35 client-owned dogs.

Females exposed to 24 h of sleep deprivation do not experience greater physiological strain, but do perceive heat illness symptoms more severely, during exercise-heat stress.

There is limited and inconclusive evidence surrounding the physiological and perceptual responses to heat stress while sleep deprived, especially for females. This study aimed to quantify the effect of 24 h sleep deprivation on physiological strain and perceptual markers of heat-related illness in females. Nine females completed two 30-min heat stress tests (HST) separated by 48 h in 39°C, 41% relative humidity at a metabolic heat production of 10 W · kg.

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

Objective: Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe.

Study Design: The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine).

The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.

Although SIN3A is required for the survival of early embryos and embryonic stem cells (ESCs), the role of SIN3A in the maintenance and establishment of pluripotency remains unclear. Here, we find that the SIN3A/HDAC corepressor complex maintains ESC pluripotency and promotes the generation of induced pluripotent stem cells (iPSCs). Members of the SIN3A/HDAC corepressor complex are enriched in an extended NANOG interactome and function in transcriptional coactivation in ESCs.

Is Paternal Smoking at Conception a Risk for ADHD? A Controlled Study in Youth With and Without ADHD.

Based on emerging preclinical findings suggesting that paternal smoking at conception may be a risk for ADHD in the offspring, we investigated whether a similar effect can be observed in humans. We analyzed data from an opportunistic dataset of girl probands with ( = 140) and without ( = 122) ADHD with available information on paternal smoking at conception. Data were analyzed using Pearson's chi-square tests and multiple logistic regression.

Inverse-collimated proton radiography for imaging thin materials.

Relativistic, magnetically focused proton radiography was invented at Los Alamos National Laboratory using the 800 MeV LANSCE beam and is inherently well-suited to imaging dense objects, at areal densities >20 g cm. However, if the unscattered portion of the transmitted beam is removed at the Fourier plane through inverse-collimation, this system becomes highly sensitive to very thin media, of areal densities <100 mg cm. Here, this inverse-collimation scheme is described in detail and demonstrated by imaging Xe gas with a shockwave generated by an aluminum plate compressing the gas at Mach 8.

The association between cognitive impairment and functional outcome in hospitalised older patients: a systematic review and meta-analysis.

Background: in hospitalised older adults, cognitive impairments are common and may be associated with functional outcomes. Our aim was to systematically review this association.

Method: we systematically searched MEDLINE, CINAHL, AMED and PsycINFO from inception to April 2016.

Biologic variability of N-terminal pro-brain natriuretic peptide in healthy dogs and dogs with myxomatous mitral valve disease.

Introduction: To determine the biologic variability of N-terminal pro-brain natriuretic peptide (NTproBNP) in healthy dogs and dogs with various stages of myxomatous mitral valve disease (MMVD).

Animals: Thirty-eight privately owned dogs: 28 with MMVD and 10 healthy controls.

Materials And Methods: Prospective clinical study with comprehensive evaluation used to group dogs as healthy or into three stages of MMVD based on current guidelines.

'523 variant and cognitive decline in older persons with ε3/3 genotype.

Objective: To interrogate a poly-T variant (rs10524523, '523) in , a gene adjacent to the gene on chromosome 19, in older persons with ε3/3 homozygosity for association with cognitive decline, the clinical hallmark of Alzheimer disease (AD).

Methods: Data came from participants in 2 cohort studies of aging and dementia who underwent annual clinical evaluations for up to 21 years. and '523 genotypes were determined from DNA from blood or brain samples.