Frequency of anticholinergic drug use in patients treated with aripiprazole once-monthly: a 2-year cohort study using European healthcare databases.

Background: Extrapyramidal symptoms (EPS) in association with the long-acting, injectable, atypical antipsychotic aripiprazole once monthly (AOM) have been observed in clinical trials, but information on EPS requiring treatment with anticholinergic drugs in clinical practice is limited.

Objectives: The objective of this European post-authorisation safety study (PASS) was to assess the risk of EPS-related events, as defined by dispensings of anticholinergic drugs, linked to the use of AOM in routine clinical practice.

Design: This European cohort study was based on healthcare databases from Germany (German Pharmacoepidemiological Research Database GePaRD), Italy (Caserta and Palermo healthcare claims databases), and Sweden (National health registers).

Safety Evaluation in Iterative Development of Wearable Patches for Aripiprazole Tablets With Sensor: Pooled Analysis of Clinical Trials.

Background: Wearable sensors in digital health may pose a risk for skin irritation through the use of wearable patches. Little is known about how patient- and product-related factors impact the risk of skin irritation. Aripiprazole tablets with sensor (AS, Abilify MyCite; Otsuka America Pharmaceutical, Inc) is a digital medicine system indicated for the treatment of patients with schizophrenia, bipolar I disorder, and major depressive disorder.

A Randomized, Open-Label, Multiple-Dose, Parallel-Arm, Pivotal Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Aripiprazole 2-Month Long-Acting Injectable in Adults With Schizophrenia or Bipolar I Disorder.

Background: Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for gluteal administration every 2 months, currently being investigated for the treatment of schizophrenia and bipolar I disorder (BP-I). The objectives of this trial were to evaluate the safety and tolerability of Ari 2MRTU 960, and the similarity of aripiprazole plasma concentrations following administration of Ari 2MRTU 960 or aripiprazole once-monthly 400 mg (AOM 400), in adults with schizophrenia or BP-I.

Methods: This was a 32-week open-label study.

Using an Automated Algorithm to Identify Potential Drug-Induced Liver Injury Cases in a Pharmacovigilance Database.

Introduction: Drug-induced liver injury (DILI) is the most frequent cause of acute liver failure in North America and Europe, but it is often missed because of unstandardized diagnostic methods and criteria. This study aimed to develop and validate an automated algorithm to identify potential DILI cases in routine pharmacovigilance (PV) activities.

Methods: Post-marketing hepatic adverse events reported for a potentially hepatotoxic drug in a global PV database from 19 March 2017 to 18 June 2018 were assessed manually and with the automated algorithm.

Molecular processes mediating hyperhomocysteinemia-induced metabolic reprogramming, redox regulation and growth inhibition in endothelial cells.

Hyperhomocysteinemia (HHcy) is an established and potent independent risk factor for degenerative diseases, including cardiovascular disease (CVD), Alzheimer disease, type II diabetes mellitus, and chronic kidney disease. HHcy has been shown to inhibit proliferation and promote inflammatory responses in endothelial cells (EC), and impair endothelial function, a hallmark for vascular injury. However, metabolic processes and molecular mechanisms mediating HHcy-induced endothelial injury remains to be elucidated.

Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes.

Immobilization of proteins has been examined to improve implant surfaces. In this study, titanium surfaces were modified with nanofunctionalized denosumab (cDMAB), a human monoclonal anti-RANKL IgG. Noncoding DNA oligonucleotides (ODN) served as linker molecules between titanium and DMAB.

The roles of stress and social support in prostate cancer mortality.

Objective: This study aimed to evaluate the association between perceived stress, social support, disease progression and mortality in a nationwide population-based cohort of men with prostate cancer.

Materials And Methods: The study surveyed 4105 Swedish men treated for clinically localized prostate cancer regarding stress, grief, sleep habits and social support. Associations between these factors and mortality were assessed using multivariate Cox regression analysis.

Detonation nanodiamonds biofunctionalization and immobilization to titanium alloy surfaces as first steps towards medical application.

Due to their outstanding properties nanodiamonds are a promising nanoscale material in various applications such as microelectronics, polishing, optical monitoring, medicine and biotechnology. Beyond the typical diamond characteristics like extreme hardness or high thermal conductivity, they have additional benefits as intrinsic fluorescence due to lattice defects without photobleaching, obtained during the high pressure high temperature process. Further the carbon surface and its various functional groups in consequence of the synthesis, facilitate additional chemical and biological modification.

Early initiation of antiretroviral therapy in HIV-infected adults and adolescents: a systematic review.

Objectives: The objective of this review was to update evidence on when to initiate antiretroviral therapy (ART) to inform revision of the 2013 WHO guidelines for ART in low and middle-income countries.

Design: A systematic review and meta-analysis.

Methods: We comprehensively searchescohorts.

Homocysteine induces inflammatory transcriptional signaling in monocytes.

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. Here, we studied transcriptional regulation in homocysteine (Hcy)-induced gene expression in monocytes (MC). We identified 11 Hcy-induced genes, 17 anti-inflammatory cytokine interleukin 10-induced, 8 pro-inflammatory cytokine interferon gamma (IFN gamma)-induced and 8 pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha)-induced genes through literature search.

The Role of Immunogenicity in Cardiovascular Disease.

Recently, many of the complexities associated with cardiovascular diseases (CVD) have been unlocked. However, despite these breakthroughs, CVD and its related complications are the leading contributors of morbidity and mortality worldwide, which indicates the shortcomings of current treatment regimens and the need for continued research. Published data within the field clearly indicates that CVD are built on inflammation and autoimmune platforms, though a strong, fundamental understanding of the mechanisms remains elusive.

Inflammatory and autoimmune reactions in atherosclerosis and vaccine design informatics.

Atherosclerosis is the leading pathological contributor to cardiovascular morbidity and mortality worldwide. As its complex pathogenesis has been gradually unwoven, the regime of treatments and therapies has increased with still much ground to cover. Active research in the past decade has attempted to develop antiatherosclerosis vaccines with some positive results.

Biological nano-functionalization of titanium-based biomaterial surfaces: a flexible toolbox.

Surface functionalization with bioactive molecules (BAMs) on a nanometre scale is a main field in current biomaterial research. The immobilization of a vast number of substances and molecules, ranging from inorganic calcium phosphate phases up to peptides and proteins, has been investigated throughout recent decades. However, in vitro and in vivo results are heterogeneous.

The FOX transcription factors regulate vascular pathology, diabetes and Tregs.

A small number of upstream master genes in "higher hierarchy" controls the expression of a large number of downstream genes and integrates the signaling pathways underlying the pathogenesis of cardiovascular diseases with or without autoimmune inflammatory mechanisms. In this brief review, we organize our analysis of recent progress in characterization of forkhead (FOX) transcription factor family members in vascular pathology, diabetes and regulatory T cells into the following sections: (1) Overview of the FOX transcription factor superfamily; (2) Vascular pathology of mice deficient in FOX transcription factors; (3) Roles of FOX transcription factors in endothelial cell pathology; (4) Roles of FOX transcription factors in vascular smooth muscle cells; (5) Roles of FOX transcription factors in the pathogenesis of diabetes; and (6) Immune system phenotypes of mice deficient in FOX transcription factors. Advances in these areas suggest that the FOX transcription factor family plays important roles in vascular development and in the pathogenesis of autoimmune inflammatory cardiovascular diseases.

Oligonucleotide-RGD peptide conjugates for surface modification of titanium implants and improvement of osteoblast adhesion.

A new concept for modular biosurface engineering of titanium implants based on the self-assembly of complementary oligonucleotides was biochemically investigated and optimized. This study describes the synthesis and characterization (RP-HPLC and Sakaguchi assay) of oligodeoxyribonucleotide (ODN) conjugates of the hexapeptide GRGDSP containing the RGD sequence as the recognition motif for cellular adhesion receptors (integrins). The peptide was chosen exemplarily as a model molecule, because it is a simple but potent bioactive molecule and relatively well investigated.

Immobilization of oligonucleotides on titanium based materials by partial incorporation in anodic oxide layers.

This paper describes the immobilization of bioactive molecules on titanium based surfaces through a combination of nano-mechanical fixation of nucleic acid anchor strands (ASs) by partial and regioselective incorporation within an anodic oxide layer and their hybridization with complementary strands (CSs) intended to be conjugated to bioactive molecules. We focus on the interaction between the substrate surface and the anchor strands, the integrity of ASs and their hybridization ability. The observed dependence of adsorption on pH suggests that initial interaction of terminally phosphorylated ASs with the substrate surface is mediated by electrostatic interaction.

The forkhead transcription factors play important roles in vascular pathology and immunology.

Transcription factor families are a small number of upstream master genes in "higher hierarchy" that control the expression of a large number of downstream genes. These transcription factors have been found to integrate the signaling pathways underlying the pathogenesis of cardiovascular diseases with or without autoimmune inflammatory mechanisms. In this chapter, we organize our analysis of recent progress in characterization of forkhead (Fox) transcription factor family members in vascular pathology and immune regulation into the following sections: (1) Introduction of the FOX transcription factor superfamily; (2) FOX transcription factors and endotheial cell pathology; (3) FOX transcription factors and vascular smooth muscle cells; and (4) FOX transcription factors, inflammation and immune system.

Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin A gene.

We reported previously that homocysteine (Hcy) inhibits endothelial cell (EC) growth by transcriptional inhibition of the cyclin A gene via a hypomethylation-related mechanism. In this study, we examined the effect of Hcy on epigenetic modification of the cyclin A gene and its biologic role in human ECs. Cyclin A mRNA levels were significantly suppressed by Hcy and a DNA methyltransferase inhibitor.

Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery.

Background: Acute renal dysfunction (ARD) and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury. Recent studies showed that urinary neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) is up-regulated early (within 1-3 h) after murine renal injury and in pediatric ARD after cardiac surgery.

Anti-inflammatory and antinecrotic effects of the volatile anesthetic sevoflurane in kidney proximal tubule cells.

Renal ischemia-reperfusion (IR) injury is a major clinical problem without effective therapy. We recently reported that volatile anesthetics protect against renal IR injury, in part, via their anti-inflammatory properties. In this study, we demonstrate the anti-inflammatory and antinecrotic effects of sevoflurane in cultured kidney proximal tubule cells and probed the mechanisms of sevoflurane-induced renal cellular protection.

A1 adenosine receptor knockout mice are protected against acute radiocontrast nephropathy in vivo.

The role of renal A1 adenosine receptors (A1AR) in the pathogenesis of radiocontrast nephropathy is controversial. We aimed to further elucidate the role of A1AR in the pathogenesis of radiocontrast nephropathy and determine whether renal proximal tubule A1AR contribute to the radiocontrast nephropathy. To induce radiocontrast nephropathy, A1AR wild-type (WT) or knockout (KO) mice were injected with a nonionic radiocontrast (iohexol, 1.

Pharmacokinetics of fluvoxamine in relation to CYP2C19 phenotype and genotype.

Objective: To evaluate the pharmacokinetics of fluvoxamine (FLV) in poor metabolizers (PMs) versus extensive metabolizers (EMs) of cytochrome P450 (CYP)2C19.

Methods: This was a prospective, open-label study conducted at the Clinical Research Unit School of Pharmacy. Fifty-seven healthy, nonsmoking volunteers aged 21-40 years participated.