Effects of candesartan, an angiotensin II receptor type I blocker, on atrial remodeling in spontaneously hypertensive rats

Hypertension-induced structural remodeling of the left atrium (LA) has been suggested to involve the renin–angiotensin system. This study investigated whether treatment with an angiotensin receptor blocker, candesartan, regresses atrial remodeling in spontaneously hypertensive rats (SHR). Effects of treatment with candesartan were compared to treatment with a nonspecific vasodilatator, hydralazine. Thirty to 32-week-old adult male SHR were either untreated (n = 15) or received one of either candesartan cilexetil (n = 9; 3 mg/kg/day) or hydralazine (n = 10; 14 mg/kg/day) via their drinking water for 14 weeks prior to experiments. Untreated age- and sex-matched Wistar- Kyoto rats (WKY; n = 13) represented a normotensive control group. Untreated SHR were hypertensive, with left ventricular hypertrophy (LVH) compared to WKY, but there were no differences in systolic pressures in excised, perfused hearts. LA from SHR were hypertrophied and showed increased fibrosis compared to those from WKY, but there was no change in connexin-43 expression or phosphorylation. Treatment with candesartan reduced systolic tail artery pressures of conscious SHR below those of normotensive WKY and caused regression of both LVH and LA hypertrophy. Although hydralazine reduced SHR arterial pressures to those of WKY and led to regression of LA hypertrophy, it had no significant effect on LVH. Notably, LA fibrosis was unaffected by treatment with either agent. These data show that candesartan, at a dose sufficient to reduce blood pressure and LVH, did not cause regression of LA fibrosis in hypertensive rats. On the other hand, the data also suggest that normalization of arterial pressure can lead to the regression of LA hypertrophy

Determining Consistency of Surrogate Decisions and End-of-Life Care Received with Patient Goals-of-Care Preferences

Background: Care consistent with preferences is the goal of advance care planning (ACP). However, comparing written preferences to actual end-of-life care may not capture consistency of care with preferences

Implementing Behavior Analysis and Intervention for Individuals with Cognitive Impairments in Skilled Nursing Facilities: Summary of Results

Summary of Purpose The purpose of the project was to provide behavioral consultation and services to aging persons with cognitive impairment at skilled nursing facilities in Michigan. The goal was to use empirically supported non-pharmacological approaches to reduce behavioral and psychological symptoms of dementia (BPSD; wandering, agitation, disruptive vocalizations, etc.) and help slow down or remediate lost skills, reduce the use of medication to manage BPSD, to improve staff knowledge and abilities, and to develop modules that can be adopted and used by other skilled nursing facilities.The project was led by Dr. Janet Hahn, a social gerontologist with extensive experience studying nursing home culture change and the quality of long-term care services. The intervention project team consisted of doctoral, masters and undergraduate level behavior analysts with advanced training in working with aging populations, under the direction of Dr. Jonathan Baker (doctoral level board certified behavior analyst and behavioral gerontologist). The project was funded by the Civil Money Penalties fund of the Michigan Department of Health and Human Services from May 2016 and to April 2019. The project was conducted with oversight by the Western Michigan University Human Subjects Institutional Review Board, under approved protocol HSIRB Project Number 16-09-07, titled Implementing Behavior Analysis and Intervention for Individuals with Cognitive Impairment in Skilled Nursing Facilities

Accuracy of the CT numbers of simulated lung nodules imaged with multiâ detector CT scanners

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135050/1/mp9332.pd

Sub-microsecond temporal evolution of edge density during edge localized modes in KSTAR tokamak plasmas inferred from ion cyclotron emission

During edge localised mode (ELM) crashes in KSTAR deuterium plasmas, bursts of spectrally structured ion cyclotron emission (ICE) are detected. Usually the ICE spectrum chirps downwards during an ELM crash, on sub-microsecond timescales. For KSTAR ICE where the separation of spectral peak frequencies is close to the proton cyclotron frequency Ω<sub>cp</sub> at the outer plasma edge, we show that the driving population of energetic ions is likely to be a subset of the 3MeV fusion protons, born centrally on deeply passing orbits which drift from the core to the edge plasma. We report first principles modelling of this scenario using a particle-in-cell code, which evolves the full orbit dynamics of large numbers of energetic protons, thermal deuterons, and electrons self-consistently with the electric and magnetic fields. The Fourier transform of the excited fields in the nonlinear saturated regime of the simulations is the theoretical counterpart to the measured ICE spectra. Multiple simulation runs for different, adjacent, values of the plasma density under KSTAR edge conditions enable us to infer the theoretical dependence of ICE spectral structure on the local electron number density. By matching this density dependence to the observed time-dependence of chirping ICE spectra in KSTAR, we obtain sub-microsecond time resolution of the evolving local electron number density during the ELM crash

Interpretation of suprathermal emission at deuteron cyclotron harmonics from deuterium plasmas heated by neutral beam injection in the KSTAR tokamak

Intense bursts of suprathermal radiation, with spectral peaks at
 frequencies corresponding to the deuteron cyclotron frequency in the outer
 midplane edge region, are often detected from deuterium plasmas in the KSTAR
 tokamak that are heated by tangential neutral beam injection (NBI) of deuterons
 at 100 keV. Identifying the physical process by which this deuterium ion cyclotron
 emission (ICE) is generated, typically during the crash of edge localised modes
 (ELMs), assists the understanding of collective energetic ion behaviour in tokamak
 plasmas. In the context of KSTAR deuterium plasmas, it is also important to
 distinguish deuterium ICE from the ICE at cyclotron harmonics of fusion-born
 protons examined by B. Chapman et al., Nucl. Fusion 57, 124004 (2017) and 58,
 096027 (2018). We use particle orbit studies in KSTAR-relevant magnetic field
 geometry, combined with a linear analytical treatment of the magnetoacoustic
 cyclotron instability (MCI), to identify the sub-population of freshly ionised
 NBI deuterons that is likely to excite deuterium ICE. These deuterons are
 then represented as an energetic minority, together with the majority thermal
 deuteron population and electrons, in first principles kinetic particle-in-cell (PIC)
 computational studies. By solving the Maxwell-Lorentz equations directly for
 hundreds of millions of interacting particles with resolved gyro-orbits, together
 with the self-consistent electric and magnetic fields, the PIC approach enables us
 to study the collective relaxation of the energetic deuterons through the linear
 phase and deep into the saturated regime. The Fourier transform of the excited
 fields displays strong spectral peaks at multiple successive deuteron cyclotron
 harmonics, mapping well to the observed KSTAR deuterium ICE spectra. This
 outcome, combined with the time-evolution of the energy densities of the different
 particle populations and electric and magnetic field components seen in the PIC
 computations, supports our identification of the driving sub-population of NBI
 deuterons, and the hypothesis that its relaxation through the MCI generates the
 observed deuterium ICE signal. We conclude that the physical origin of this
 signal in KSTAR is indeed distinct from that of KSTAR proton ICE, and is in
 the same category as the NBI-driven ICE seen notably in TFTR tokamak and
 LHD heliotron-stellarator plasmas. ICE has been proposed as a potential passive
 diagnostic of energetic particle populations in ITER plasmas; this is assisted by
 clarifying and extending the physics basis of ICE in contemporary magnetically
 confined plasmas

Adsorption of 2,2 '-dithiodipyridine as a tool for the assembly of silver nanoparticles

Silver nanostructured thin films stabilized by 2,2’-dithiodipyridine (2dtpy) were prepared. The Ag nanoparticles were obtained by treating the complex [Ag(2dtpy)]NO3 with NaBH4 in a methanol–toluene mixture. The films were transferred to borosilicate glass slips by a dip-coating method and were found to consist of Ag nanoparticles possibly linked via 2dtpy molecules. Surface-enhanced Raman scattering (SERS) studies have offered the possibility of investigating the adsorption modes of 2dtpy at the Ag nanoparticle surfaces in the fil

15-Deoxy-Δ 12,14 -prostaglandin J 2 -mediated ERK Signaling Inhibits Gram-negative Bacteria-induced RelA Phosphorylation and Interleukin-6 Gene Expression in Intestinal Epithelial Cells through Modulation of Protein Phosphatase 2A Activity

We have previously shown that non-pathogenic Gram-negative Bacteroides vulgatus induces transient RelA phosphorylation (Ser-536), NF-kappaB activity, and pro-inflammatory gene expression in native and intestinal epithelial cell (IEC) lines. We now demonstrate that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) but not prostaglandin E(2) inhibits lipopolysaccharide (LPS) (B. vulgatus)/LPS (Escherichia coli)-induced RelA phosphorylation and interleukin-6 gene expression in the colonic epithelial cell line CMT-93. This inhibitory effect of 15d-PGJ(2) was mediated independently of LPS-induced IkappaBalpha phosphorylation/degradation and RelA nuclear translocation as well as RelA DNA binding activity. Interestingly, although B. vulgatus induced nuclear expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in native epithelium of monoassociated Fisher rats, PPARgamma-specific knock-down in CMT-93 cells using small interference RNA failed to reverse the inhibitory effects of PPARgamma agonist 15d-PGJ(2), suggesting PPARgamma-independent mechanisms. In addition, 15d-PGJ(2) but not the synthetic high affinity PPARgamma ligand rosiglitazone triggered ERK1/2 phosphorylation in IEC, and most importantly, MEK1 inhibitor PD98059 reversed the inhibitory effect of 15dPGJ(2) on LPS-induced RelA phosphorylation and interleukin-6 gene expression. Calyculin A, a specific phosphoserine/phospho-threonine phosphatase inhibitor increased the basal phosphorylation of RelA and reversed the inhibitory effect of 15d-PGJ(2) on LPS-induced RelA phosphorylation. We further demonstrated in co-immunoprecipitation experiments that 15d-PGJ(2) triggered protein phosphatase 2A activity, which directly dephosphorylated RelA in LPS-stimulated CMT-93 cells. We concluded that 15d-PGJ(2) may help to control NF-kappaB signaling and normal intestinal homeostasis to the enteric microflora by modulating RelA phosphorylation in IEC through altered protein phosphatase 2A activity

Interprofessional Education in U.S. and Canadian Dental Schools: An ADEA Team Study Group Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153755/1/jddj002203372012769tb05381x.pd

Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway

OBJECTIVE—Protein kinase C (PKC)-δ, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-δ in neuronal apoptosis through Akt in the retinas of diabetic rats