Phenotypic Differences Between the Epidemic Strains of Vesicular Stomatitis Virus Serotype Indiana 98COE and IN0919WYB2 Using an In-Vivo Pig () Model.

During the past 25 years, vesicular stomatitis virus (VSV) has produced multiple outbreaks in the US, resulting in the emergence of different viral lineages. Currently, very little is known about the pathogenesis of many of these lineages, thus limiting our understanding of the potential biological factors favoring each lineage in these outbreaks. In this study, we aimed to determine the potential phenotypic differences between two VSV Indiana (VSIV) serotype epidemic strains using a pig model.

Spatial analysis of microRNA regulation at defined tumor hypoxia levels reveals biological traits of aggressive prostate cancer.

Mechanisms regulating the gene expression program at different hypoxia severity levels in patient tumors are not understood. We aimed to determine microRNA (miRNA) regulation of this program at defined hypoxia levels from moderate to severe in prostate cancer. Biopsies from 95 patients were used, where 83 patients received the hypoxia marker pimonidazole before prostatectomy.

The V-ATPase/ATG16L1 axis is controlled by the VH subunit.

Defects in organellar acidification indicate compromised or infected compartments. Recruitment of the autophagy-related ATG16L1 complex to pathologically neutralized organelles targets ubiquitin-like ATG8 molecules to perturbed membranes. How this process is coupled to proton gradient disruption is unclear.

Combined effect of CYP2C19 and CYP2D6 genotypes on escitalopram serum concentration and its metabolic ratio in a European patient population.

Aims: The aim of the present study was to investigate the impact of CYP2D6 genotype on exposure and metabolism of escitalopram in patients stratified by CYP2C19 genotype in a large real-world population.

Methods: Patients were included from a therapeutic drug monitoring service if they had measured serum concentration of escitalopram and the metabolite, N-desmethyl escitalopram, and performed CYP2C19 and CYP2D6 genotyping. Patients were divided into 16 combined genotype-predicted phenotype subgroups (poor [PM], intermediate [IM], normal [NM] and ultrarapid metabolizers [UM]) of CYP2C19/CYP2D6.

Tau disengages from the proteosome core complex and neurogranin coincident with enhanced neuronal network excitability.

Tauopathies are characterised by the pathological accumulation of misfolded tau. The emerging view is that toxic tau species drive synaptic dysfunction and potentially tau propagation before measurable neurodegeneration is evident, but the underlying molecular events are not well defined. Human non-mutated 0N4R tau (tau) and P301L mutant 0N4R tau (tau) were expressed in mouse primary cortical neurons using adeno-associated viruses to monitor early molecular changes and synaptic function before the onset of neuronal loss.

Access to a tailored mobile application enhances medication adherence among young users of antidepressants.

Introduction: Patients' adherence to antidepressants is generally reported to be poor. This study examined whether users of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) enhance medication adherence following access to a mobile application (app) tailored for this patient group. The study addresses the implementation phase of medication adherence.

Dose-dependent effect of lamotrigine on quetiapine serum concentration in patients using instant release tablets.

Purpose: Lamotrigine was previously reported to reduce serum concentration of quetiapine. The aim of this study was to investigate whether lamotrigine dose or quetiapine formulation was of importance for the drug interaction.

Methods: Patients combining lamotrigine with quetiapine (cases) were included retrospectively from a routine therapeutic drug monitoring (TDM) service, as were a control group of patients using quetiapine without any interacting drugs.

Age of onset for increased dose-adjusted serum concentrations of antidepressants and association with sex and genotype: An observational study of 34,777 individuals.

Purpose: The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the potential association with sex and CYP2C19/CYP2D6 genotype.

Methods: Serum concentrations and prescribed daily doses for citalopram, escitalopram, sertraline, venlafaxine and mirtazapine, and CYP genotypes, were obtained from a therapeutic drug monitoring (TDM) service. Segmented linear regression analysis was used to examine the relationship between age and antidepressant log C/D ratio in (i) all individuals, (ii) men and women, and (iii) CYP2D6/CYP2C19 normal metabolizers (NMs) and CYP2D6/CYP2C19 intermediate or poor metabolizers (IMs/PMs).

Epigallocatechin Gallate Modulates Microglia Phenotype to Suppress Pro-inflammatory Signalling Cues and Inhibit Phagocytosis.

Microglia are crucial players in the pathogenesis of late-onset Alzheimer's disease (AD), with evidence for both deleterious and beneficial effects. Identifying interventions to modulate microglial responsiveness, promote amyloid β (Aβ) clearance, disrupt plaque formation, or dampen excessive inflammation has therapeutic potential. Bioavailable flavonoids, such as the flavan 3-ols, are of interest due to their antioxidant, metal chelating, signalling, and anti-inflammatory potential.

Multiparametric Magnetic Resonance Imaging of Penile Cancer: A Pictorial Review.

The role of multiparametric magnetic resonance imaging (mpMRI) in assessing penile cancer is not well defined. However, this modality may be successfully applied for preoperative staging and patient selection; postoperative local and regional surveillance; and assessments of treatment response after oncological therapies. Previous studies have been mostly limited to a few small series evaluating the accuracy of MRI for the preoperative staging of penile cancer.

Effect of CYP2D6 genotype on duloxetine serum concentration.

Duloxetine is metabolized by cytochrome P450 (CYP)1A2 and CYP2D6. The aim of this study was to investigate the effect of the CYP2D6 genotype on duloxetine serum concentration adjusting for age and sex. Patients were included retrospectively from a therapeutic drug monitoring service.

MRI Assessment of Changes in Tumor Vascularization during Neoadjuvant Anti-Angiogenic Treatment in Locally Advanced Breast Cancer Patients.

Anti-VEGF (vascular endothelial growth factor) treatment improves response rates, but not progression-free or overall survival in advanced breast cancer. It has been suggested that subgroups of patients may benefit from this treatment; however, the effects of adding anti-VEGF treatment to a standard chemotherapy regimen in breast cancer patients are not well studied. Understanding the effects of the anti-vascular treatment on tumor vasculature may provide a selection of patients that can benefit.

Prostate cancer radiogenomics reveals proliferative gene expression programs associated with distinct MRI-based hypoxia levels.

Background And Purpose: The biology behind individual hypoxia levels in patient tumors is poorly understood. Here, we used radiogenomics to identify associations between magnetic resonance imaging (MRI)-based hypoxia levels and biological processes derived from gene expression data in prostate cancer.

Materials And Methods: For 85 prostate cancer patients, MRI-based hypoxia images were constructed by combining diffusion-weighted images reflecting oxygen consumption and supply.

Pro-arrhythmic effect of escitalopram and citalopram at serum concentrations commonly observed in older patients - a study based on a cohort of 19,742 patients.

Background: For a decade, patients have been advised against using high citalopram- and escitalopram-doses due to risk for ventricular arrhythmia and cardiac arrest. Still, these drugs are widely used to treat depression and anxiety especially in older patients. It is unclear why they are cardiotoxic and at what serum concentrations patients are at risk for arrhythmias.

Impact of CYP2D6 Genotype on Paroxetine Serum Concentration.

Background: Paroxetine is a selective serotonin reuptake inhibitor metabolized by cytochrome P450 (CYP)2D6. Only small-scale studies have reported the impact of CYP2D6 genotype on paroxetine exposure, and international guidelines differ in their recommendations on whether paroxetine should be administered according to CYP2D6 genotype. To clarify this issue, the aim of the present study was to investigate the impact of CYP2D6 genotype on paroxetine serum concentration in a large population of patients after adjusting for CYP2C19 genotype, age, and sex.

Monoparametric high-resolution diffusion weighted MRI as a possible first step in an MRI-directed diagnostic pathway for men with suspicion of prostate cancer.

Purpose: To explore if a high-resolution diffusion weighted MRI sequence (DWI-only) could be used as a first step in an MRI-directed diagnostic pathway.

Methods: Prospective single center study that between December 2017 and August 2018 included 129 consecutive patients with suspicion of prostate cancer into a PI-RADS-based MRI-directed diagnostic pathway. All patients had multiparametric MRI (mpMRI).

Multi-parametric MRI without artificial erection for preoperative assessment of primary penile carcinoma: A pilot study on the correlation between imaging and histopathological findings.

Purpose: We aimed to evaluate the diagnostic potential of non-erectile multi-parametric magnetic resonance imaging (mpMRI) for preoperative assessment of primary penile squamous cell carcinoma (SCC).

Method: Twenty-five patients who underwent surgery for penile SCC were included. Preoperative mpMRI without artificial erection was performed in all patients.

Impact of human telomerase reverse transcriptase peptide vaccine combined with androgen deprivation therapy and radiotherapy in de novo metastatic prostate cancer: Long-term clinical monitoring.

Prostate cancer is considered as poorly immunogenic. In a phase I/II study on de novo metastatic prostate cancer we found that a human telomerase reverse transcriptase (hTERT) vaccine induced an early immune response in most of the patients. Here we present the results from the long-term monitoring of the immune responses and clinical outcomes.

Identification of Escitalopram Metabolic Ratios as Potential Biomarkers for Predicting CYP2C19 Poor Metabolizers.

Background: Escitalopram is metabolized by CYP2C19 to N-desmethyl escitalopram and escitalopram propionic acid. The primary aims of this study were to investigate the impact of the CYP2C19 phenotype on metabolic ratios of escitalopram in vivo and propose a biomarker for the CYP2C19 phenotype in patients treated with escitalopram.

Methods: Median steady-state serum metabolite/parent drug ratio of N-desmethyl escitalopram and escitalopram propionic acid was investigated across CYP2C19 genotype-translated phenotype groups.

Development of reverse-transcriptase, real-time PCR assays to distinguish the Southern African Territories (SAT) serotypes 1 and 3 and topotype VII of SAT2 of Foot-and-Mouth Disease Virus.

Foot-and-Mouth Disease Virus (FMDV), the causative agent of Foot-and-Mouth Disease, is a highly feared, economically devastating transboundary pathogen. This is due to the virus' extremely contagious nature and its ability to utilize multiple transmission routes. As such, rapid and accurate diagnostic testing is imperative to the control of FMD.

Evaluating the quality of the economic evidence in colorectal cancer genomics studies.

The increase in the use of genome-based screening and diagnostic tests adds to the overall costs of oncologic care for colorectal cancer. This, in turn, has resulted in an increase in published economic analyses. To perform a systematic literature review of the available economic evidence evaluating the value of genomic testing for colorectal cancer and appraise the quality of the economic studies conducted to date.

Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range.

Purpose: Variability in cytochrome P450 3A4 (CYP3A4) metabolism is mainly caused by non-genetic factors, hence providing a need for accurate phenotype biomarkers. Although 4β-hydroxycholesterol (4βOHC) is a promising endogenous CYP3A4 biomarker, additional investigations are required to evaluate its ability to predict CYP3A4 activity. This study investigated the correlations between 4βOHC concentrations and hepatic and intestinal CYP3A4 protein expression and ex vivo microsomal activity in paired liver and jejunum samples, as well as in vivo CYP3A4 phenotyping (midazolam) in patients with a wide body weight range.

A Prospective Study of High Dose-Rate Brachytherapy or Stereotactic Body Radiotherapy of Intra-Prostatic Recurrence: Toxicity and Long Term Clinical Outcome.

Background: Up to half of patients with localized prostate cancer experience biochemical relapse within 10 years after definitive radiotherapy. The aim of this prospective study was to investigate the toxicity, dose to the organs at risk (OARs), and efficacy of dose-intensified focal salvage radiotherapy.

Methods And Material: Thirty-three patients (median age 68.