Targeted long-read sequencing captures CRISPR editing and AAV integration outcomes in brain.

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing is an emerging therapeutic modality that shows promise in Huntington's disease and spinocerebellar ataxia (SCA) mouse models. However, advancing CRISPR-based therapies requires methods to fully define in vivo editing outcomes. Here, we use polymerase-free, targeted long-read nanopore sequencing and evaluate single- and dual-gRNA AAV-CRISPR editing of human ATXN2 in transgenic mouse models of SCA type 2 (SCA2).

Monitoring the use of dabigatran etexilate for stroke prevention: compliance with renal function guidelines.

INTRODUCTION Dabigatran etexilate has become widely used in New Zealand, but information relating to when renal function monitoring is being undertaken is lacking. AIM To investigate if clinically appropriate renal function monitoring is being undertaken in New Zealand primary care for stroke prevention in non-valvular atrial fibrillation patients prescribed dabigatran etexilate. METHODS New Zealand non-valvular atrial fibrillation patients' prescription and primary care health data were extracted from national administrative databases for the period 1 July 2011 to 31 December 2015.

Exposure Response Supports Therapeutic Drug Monitoring for Dabigatran Etexilate in Patients with Atrial Fibrillation.

 Dabigatran etexilate has become widely used for the prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF). Currently, there is limited information in real-world patients relating to dabigatran etexilate exposure and response.  This retrospective cohort study used administrative health data for NVAF patients dispensed dabigatran etexilate between July 1, 2011 and December 31, 2015.

Choice of Renal Function Estimator Influences Adverse Outcomes with Dabigatran Etexilate in Patients with Atrial Fibrillation.

 Clinical significance of dosing dabigatran with different estimates of renal function for treatment of atrial fibrillation (AF) is unknown. Renal function is routinely estimated by the chronic kidney disease epidemiology initiative equation (CKD-EPI) and used to guide dosing. The aim of this study was to investigate the risk of adverse outcomes for patients with AF when different estimators of renal function are used.

Deprivation and inequalities lead to worse outcomes with dabigatran etexilate.

INTRODUCTION Dabigatran etexilate is now prescribed for 51% of the patients receiving oral anticoagulation treatment in New Zealand. Its prescribing trends in relation to patient outcomes are, however, largely unknown for these patients. AIM To describe patient characteristics, effectiveness and safety of treatment with dabigatran etexilate in the New Zealand population.

Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain.

Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination-based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations in vivo.

Undetected, uncontrolled blood pressure in type 2 diabetes: self-monitored blood pressure profiles.

Objectives: To construct a novel and clinically relevant means of representing self-monitored blood pressure (SMBP).

Methods: Patients treated to an office blood pressure (BP) < 130/80 mmHg measured their BP at home for 14 days using an Omron IC semi-automatic portable monitor with memory. SMBP data were transferred from the monitor to a computer to produce graphic profiles (SMBPp) that depict the hourly variation in BP throughout a "typical" or modal day.