Design of a pragmatic randomized implementation effectiveness trial testing a health system wide hypertension program for older adults.

Hypertension control remains poor. Multiple barriers at the level of patients, providers, and health systems interfere with implementation of hypertension guidelines and effective lowering of BP. Some strategies such as self-measured blood pressure (SMBP) and remote management by pharmacists are safe and effectively lower BP but have not been effectively implemented.

Differential Effects of Human P301L Tau Expression in Young versus Aged Mice.

The greatest risk factor for developing Alzheimer's disease (AD) is increasing age. Understanding the changes that occur in aging that make an aged brain more susceptible to developing AD could result in novel therapeutic targets. In order to better understand these changes, the current study utilized mice harboring a regulatable mutant P301L human transgene (rTg(TauP301L)4510), in which P301L tau expression can be turned off or on by the addition or removal of doxycycline in the drinking water.

Cross-Presentation of Soluble and Cell-Associated Antigen by Murine Hepatocytes Is Enhanced by Collectrin Expression.

Cross-presentation is a modular series of intracellular events dictating the internalization and subsequent MHC class I (MHC I) display of extracellular Ags. This process has been defined in dendritic cells and plays a fundamental role in the induction of CD8 T cell immunity during viral, intracellular bacterial, and antitumor responses. Herein, acute viral infection of murine liver with adenovirus, a model for intrahepatic cross-presentation, confirms hepatocytes directly contribute to cross-presentation of Ags and priming the pool of naive CD8 T cells within the liver microenvironment.

Platypnea-Orthodeoxia Syndrome: A Case of Chronic Paroxysmal Hypoxemia.

A 75-year-old man with chronic (30-year) unexplained paroxysmal hypoxemia presented with postural hypoxemia and desaturation consistent with a clinical manifestation of platypnea-orthodeoxia syndrome. His history included a lack of significant past pulmonary disease, yet with intermittent need for oxygen supplementation. On admission he was found to have an interatrial shunt through a patent foramen ovale.

Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression.

Hyperexcitability of the hippocampus is a commonly observed phenomenon in the years preceding a diagnosis of Alzheimer's disease (AD). Our previous work suggests a dysregulation in glutamate neurotransmission may mediate this hyperexcitability, and glutamate dysregulation correlates with cognitive deficits in the rTg(TauP301L)4510 mouse model of AD. To determine whether improving glutamate regulation would attenuate cognitive deficits and AD-related pathology, TauP301L mice were treated with riluzole (~ 12.

The role of the tripartite glutamatergic synapse in the pathophysiology of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia in individuals over 65 years of age and is characterized by accumulation of beta-amyloid (Aβ) and tau. Both Aβ and tau alter synaptic plasticity, leading to synapse loss, neural network dysfunction, and eventually neuron loss. However, the exact mechanism by which these proteins cause neurodegeneration is still not clear.

P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway.

Individuals at risk of developing Alzheimer's disease (AD) often exhibit hippocampal hyperexcitability. A growing body of evidence suggests that perturbations in the glutamatergic tripartite synapse may underlie this hyperexcitability. Here, we used a tau mouse model of AD (rTg(TauP301L)4510) to examine the effects of tau pathology on hippocampal glutamate regulation.

Effects of an α5GABAA inverse agonist on MK-801-induced learning deficits in an incremental repeated acquisition task.

N-methyl-D-aspartate receptors (NMDARs) are essential for several kinds of synaptic plasticity and play a critical role in learning and memory. Deficits in NMDAR functioning may be partially responsible for the learning and memory deficits associated with aging and numerous diseases. Administration of MK-801, a noncompetitive NMDAR antagonist, is commonly used as a preclinical model of NMDAR dysfunction.

Effect size of memory deficits in mice with adult-onset P301L tau expression.

Transgenic mice expressing mutations in tau have yielded essential discoveries for Alzheimer's disease. One of the most commonly used tau mouse models is the tet-off Tg(tauP301L)4510 model that expresses P301L human tau driven by the calcium-calmodulin kinase IIα (CaMKIIα) promoter system. Tau expression in this model is regulatable, allowing for suppression of mutant tau expression until adulthood and prevention of possible developmental alterations resulting from P301L tau expression during development.

Imaging flow cytometry elucidates limitations of microparticle analysis by conventional flow cytometry.

Microparticles (MPs) are submicron vesicles released from cell membranes in response to activation, cell injury, or apoptosis. The clinical importance of MPs has become increasingly recognized, although no standardized method exists for their measurement. Flow cytometry (FCM) is the most commonly used technique, however, because of the small size of MPs, and the limitations of current FCM instrumentation, accurate identification is compromised by this methodology.

Fractional-length sync-pumped degenerate optical parametric oscillator for 500-MHz 3-μm mid-infrared frequency comb generation.

We demonstrate a mid-IR frequency comb centered at 3120 nm with 650-nm (20-THz) bandwidth at a comb-teeth spacing of 500 MHz. The generated comb is based on a compact ring-type synchronously pumped optical parametric oscillator (SPOPO) operating at degeneracy and pumped by a mode-locked Er-doped 1560 nm fiber laser at a repetition rate of 100 MHz. We achieve high-repetition rate by using a fractional-length cavity with a roundtrip length of 60 cm, which is one-fifth of the length dictated by conventional synchronous pumping.

Demonstration of a Ge/GeSn/Ge quantum-well microdisk resonator on silicon: enabling high-quality Ge(Sn) materials for micro- and nanophotonics.

We theoretically study and experimentally demonstrate a pseudomorphic Ge/Ge0.92Sn0.08/Ge quantum-well microdisk resonator on Ge/Si (001) as a route toward a compact GeSn-based laser on silicon.

Loss of collectrin, an angiotensin-converting enzyme 2 homolog, uncouples endothelial nitric oxide synthase and causes hypertension and vascular dysfunction.

Background: Collectrin is an orphan member of the renin-angiotensin system and is a homolog of angiotensin-converting enzyme 2, sharing ≈50% sequence identity. Unlike angiotensin-converting enzyme 2, collectrin lacks any catalytic domain. Collectrin has been shown to function as a chaperone of amino acid transporters.

Octave-spanning supercontinuum generation in in situ tapered As₂S₃ fiber pumped by a thulium-doped fiber laser.

We report a supercontinuum spanning well over an octave of measurable bandwidth from about 1 to 3.7 μm in a 2.1 mm long As₂S₃ fiber taper using the in situ tapering method.

In-situ tapering of chalcogenide fiber for mid-infrared supercontinuum generation.

Supercontinuum generation (SCG) in a tapered chalcogenide fiber is desirable for broadening mid-infrared (or mid-IR, roughly the 2-20 μm wavelength range) frequency combs(1, 2) for applications such as molecular fingerprinting, (3) trace gas detection, (4) laser-driven particle acceleration, (5) and x-ray production via high harmonic generation. (6) Achieving efficient SCG in a tapered optical fiber requires precise control of the group velocity dispersion (GVD) and the temporal properties of the optical pulses at the beginning of the fiber, (7) which depend strongly on the geometry of the taper. (8) Due to variations in the tapering setup and procedure for successive SCG experiments-such as fiber length, tapering environment temperature, or power coupled into the fiber, in-situ spectral monitoring of the SCG is necessary to optimize the output spectrum for a single experiment.

Sub-50 fs pulses around 2070 nm from a synchronously-pumped, degenerate OPO.

We report generation of 48 fs pulses at a center wavelength of 2070 nm using a degenerate optical parametric oscillator (OPO) synchronously-pumped with a commercially available 36-MHz, femtosecond, mode-locked, Yb-doped fiber laser. The spectral bandwidth of the output is ~137 nm, corresponding to a theoretical, transform-limited pulse width of 33 fs. The threshold of the OPO is less than 10 mW of average pump power.

Mid-infrared supercontinuum generation in tapered chalcogenide fiber for producing octave-spanning frequency comb around 3 μm.

We demonstrate mid-infrared (mid-IR) supercontinuum generation (SCG) with instantaneous bandwidth from 2.2 to 5 μm at 40 dB below the peak, covering the wavelength range desirable for molecular spectroscopy and numerous other applications. The SCG occurs in a tapered As(2)S(3) fiber prepared by in-situ tapering and is pumped by femtosecond pulses from the subharmonic of a mode-locked Er-doped fiber laser.

HCV infection of the transplanted liver: changing CD81 and HVR1 variants immediately after liver transplantation.

The second envelope protein at hypervariable region 1 (HVR1) has been implicated in contributing to hepatitis C virus (HCV)-host cell interactions and CD81 (a multifunctional protein) has been demonstrated to act as a cell surface receptor for HCV and may interact directly with HVR1. The purpose of the current study was to determine if certain HVR1 quasispecies variants more effectively associate with and infect allografts after liver transplantation than other HVR1 variants and whether CD81 receptor expression changes after transplantation. Blood and allograft samples were obtained from the peritransplant period in seven patients.

Primary human hepatocytes in spheroid formation to study hepatitis C infection.

Background: Hepatitis C (HCV) is a worldwide health problem, affecting nearly 170 million people. Current models for studying Hepatitis C have focused primarily on the use of poorly permissive cell lines and viral constructs, because of the lack of a suitable animal model or an in vitro system for studying functional infection. As hepatocytes are the primary reservoir for the virus in vivo, we report on a model using primary human hepatocytes cultured in spheroid formation.