Decreased pH in the aging brain and Alzheimer's disease.

Using publicly available data sets, we compared pH in the human brain and the cerebrospinal fluid (CSF) of postmortem control and Alzheimer's disease cases. We further investigated the effects of long-term acidosis in vivo in the APP-PS1 mouse model of Alzheimer's disease. We finally examined in vitro whether low pH exposure could modulate the release of proinflammatory cytokines and the uptake of amyloid beta by microglia.

Remote monitoring and clinical outcomes: details on information flow and workflow in the IN-TIME study.

Aims: Randomized clinical trials investigating a possible outcome effect of remote monitoring in patients with implantable defibrillators have shown conflicting results. This study analyses the information flow and workflow details from the IN-TIME study and discusses whether differences of message content, information speed and completeness, and workflow may contribute to the heterogeneous results.

Methods And Results: IN-TIME randomized 664 patients with an implantable cardioverter/defibrillator indication to daily remote monitoring vs.

Journey of Excellence: Implementing a Shared Decision-Making Model.

Research has shown that nurses who participate in shared decision making (SDM) have more control over their practice and greater job satisfaction, and hospitals that have instituted SDM have lower rates of nurse turnover and better patient outcomes. The purpose of this article is to describe the implementation of an SDM structure at a pediatric hospital. The hospital's chief nurse officer charged a group of nurses with developing SDM guidelines to outline the purpose, structure, and function of unit councils.

Abnormal galactosylation of immunoglobulin G in cerebrospinal fluid of multiple sclerosis patients.

Background: Glycosylation alterations have been associated with the development of several human diseases and their animal models, including multiple sclerosis.

Objectives: We aimed to determine whether immunoglobulin G galactosylation might be changed in multiple sclerosis.

Methods: Immunoglobulin G was isolated from serum and cerebrospinal fluid of patients with multiple sclerosis or viral meningitis and control patients without history of inflammatory or autoimmune disease.

IKKβ deficiency in myeloid cells ameliorates Alzheimer's disease-related symptoms and pathology.

Alzheimer's disease (AD) is characterized by extracellular amyloid-β (Aβ) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and Aβ clearance. However, studies examining innate immunity in Aβ pathology and neuronal degeneration have produced conflicting results.

Fluid status monitoring with a wireless network to reduce cardiovascular-related hospitalizations and mortality in heart failure: rationale and design of the OptiLink HF Study (Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink).

Aims: The Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink (OptiLink HF) study is designed to investigate whether OptiVol fluid status monitoring with an automatically generated wireless CareAlert notification via the CareLink Network can reduce all-cause death and cardiovascular hospitalizations in an HF population, compared with standard clinical assessment. Methods Patients with newly implanted or replacement cardioverter-defibrillator devices with or without cardiac resynchronization therapy, who have chronic HF in New York Heart Association class II or III and a left ventricular ejection fraction ≤35% will be eligible to participate. Following device implantation, patients are randomized to either OptiVol fluid status monitoring through CareAlert notification or regular care (OptiLink 'on' vs.

Doxepin concentrations in plasma and cerebrospinal fluid.

Doxepin--like other antidepressant drugs (ADs)--shows a variable antidepressant effect in clinical practice. The cause for this variability is as yet unclear; however, pharmacokinetic factors such as the variable permeability of doxepin into the cerebrospinal fluid (CSF), may contribute to the difference in therapeutic efficacy. We measured and correlated the concentration of doxepin and its active metabolite nordoxepin in both the plasma and CSF.

Width of the third ventricle assessed by transcranial sonography can monitor brain atrophy in a time- and cost-effective manner--results from a longitudinal study on 500 subjects.

Ventricular width and its enlargement over time are discussed as promising markers for preclinical brain atrophy. The aim of our study was to define whether brain atrophy can reliably be monitored by transcranial ultrasound (TCS). In a prospective longitudinal trial over 5years, 500 healthy persons were examined by a standardized protocol with TCS in addition to an extensive cognitive testing using the Consortium to Establish a Registry of Alzheimer's Disease - Neuropsychological Testing (CERAD-NP).

Termination of ventricular tachycardia with antitachycardia pacing after ineffective shock therapy in an ICD recipient with hypertrophic cardiomyopathy.

Implantable Cardioverter Defibrillator (ICD) implantation is the only established therapy for primary or secondary prevention of sudden cardiac death in patients with Hypertrophic Cardiomyopathy (HCM). Ineffectiveness of shock therapy for the termination of potentially fatal ventricular arrhythmias in ICD recipients is rare in the presence of appropriate arrhythmia detection by the device. We report the case of a 48-year-old woman with HCM and a single chamber ICD, who received five inefficient high-energy (35 Joules) shocks for the termination of an appropriately detected episode of Ventricular Tachycardia (VT).

Regulation of gene expression by the amyloid precursor protein: inhibition of the JNK/c-Jun pathway.

The amyloid precursor protein (APP) has been suggested to regulate gene expression. GeneChip analysis and in vitro kinase assays revealed potent APP-dependent repression of c-Jun, its target gene SPARC and reduced basal c-Jun N-terminal kinase (JNK) activity in PC12 cells overexpressing APP. UV-induced activation of the JNK signalling pathway and subsequent apoptosis were likewise reduced by APP and this effect could be mimicked by the indirect JNK inhibitor CEP-11004.

The amyloid precursor protein protects PC12 cells against endoplasmic reticulum stress-induced apoptosis.

Endoplasmic reticulum (ER) stress is believed to play an important role in neurodegenerative disorders such as Alzheimer's disease. In the present study, we investigated the effect of the human amyloid precursor protein (APP) on the ER stress response in PC12 cells. Tunicamycin, an inhibitor of N-glycosylation, rapidly induced the expression of the ER-resident chaperone Bip/grp78, a known target gene of the unfolded protein response.