Independent Effects of Blood Pressure on Intraocular Pressure and Retinal Ganglion Cell Degeneration: A Mendelian Randomization Study.

Purpose: To investigate the causal effect of elevated blood pressure on primary open-angle glaucoma (POAG) and POAG endophenotypes.

Methods: Two-sample Mendelian randomization (MR) was performed to investigate the causal effect of elevated systolic blood pressure (SBP) (N = 757,601) and diastolic blood pressure (DBP) (N = 757,601) on intraocular pressure (IOP) (N = 139,555), macular retinal nerve fiber layer (mRNFL) thickness (N = 33,129), ganglion cell complex (GCC) thickness (N = 33,129), vertical cup-to-disc ratio (VCDR) (N = 111,724), and POAG liability (Ncases = 16,677, Ncontrols = 199,580). The primary analysis was conducted using the inverse-variance weighted approach.

A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study.

Objective: To investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile dysfunction, with fertility, sexual behaviour, and subjective wellbeing.

Design: Two sample cis-mendelian randomisation study.

Setting: Summary data on genetic associations obtained from the International Consortium for Blood Pressure and UK Biobank.

TIE1 and TEK signalling, intraocular pressure, and primary open-angle glaucoma: a Mendelian randomization study.

Background: In primary open-angle glaucoma (POAG), lowering intraocular pressure (IOP) is the only proven way of slowing vision loss. Schlemm's canal (SC) is a hybrid vascular and lymphatic vessel that mediates aqueous humour drainage from the anterior ocular chamber. Animal studies support the importance of SC endothelial angiopoietin-TEK signalling, and more recently TIE1 signalling, in maintaining normal IOP.

A Mendelian randomization study of genetic liability to post-traumatic stress disorder and risk of ischemic stroke.

Observational studies have shown an association between post-traumatic stress disorder (PTSD) and ischemic stroke (IS) but given the susceptibility to confounding it is unclear if these associations represent causal effects. Mendelian randomization (MR) facilitates causal inference that is robust to the influence of confounding. Using two sample MR, we investigated the causal effect of genetic liability to PTSD on IS risk.

Safety of beta-blocker and calcium channel blocker antihypertensive drugs in pregnancy: a Mendelian randomization study.

Background: Beta-blocker (BB) and calcium channel blocker (CCB) antihypertensive drugs are commonly used in pregnancy. However, data on their relative impact on maternal and foetal outcomes are limited. We leveraged genetic variants mimicking BB and CCB antihypertensive drugs to investigate their effects on risk of pre-eclampsia, gestational diabetes and birthweight using the Mendelian randomization paradigm.

Sodium-glucose cotransporter 1 inhibition and gout: Mendelian randomisation study.

Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce serum urate, but their efficacy depends on renal function which is often impaired in people with gout. SGLT1 is primarily expressed in the small intestine and its inhibition may be a more suitable therapeutic target. We aimed to investigate the association of genetically proxied SGLT1i with gout risk, serum urate levels and cardiovascular safety using Mendelian randomisation (MR).

Lipid traits and type 2 diabetes risk in African ancestry individuals: A Mendelian Randomization study.

Background: Dyslipidaemia is highly prevalent in individuals with type 2 diabetes mellitus (T2DM). Numerous studies have sought to disentangle the causal relationship between dyslipidaemia and T2DM liability. However, conventional observational studies are vulnerable to confounding.

Morning Cortisol and Circulating Inflammatory Cytokine Levels: A Mendelian Randomisation Study.

Cortisol exerts a broad anti-inflammatory effect on the immune system. Inflammatory cytokines contribute to the molecular signalling pathways implicated in various autoimmune and inflammatory conditions. However, the mechanisms by which cortisol modulates such signalling pathways remain uncertain.

Ultrasound- Versus Fluoroscopy-Guided Strategy for Transfemoral Transcatheter Aortic Valve Replacement Access: A Systematic Review and Meta-Analysis.

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IP-mediated Ca release regulates atrial Ca transients and pacemaker function by stimulation of adenylyl cyclases.

Inositol trisphosphate (IP) is a Ca-mobilizing second messenger shown to modulate atrial muscle contraction and is thought to contribute to atrial fibrillation. Cellular pathways underlying IP actions in cardiac tissue remain poorly understood, and the work presented here addresses the question whether IP-mediated Ca release from the sarcoplasmic reticulum is linked to adenylyl cyclase activity including Ca-stimulated adenylyl cyclases (AC1 and AC8) that are selectively expressed in atria and sinoatrial node (SAN). Immunocytochemistry in guinea pig atrial myocytes identified colocalization of type 2 IP receptors with AC8, while AC1 was located in close vicinity.

Transcatheter aortic valve replacement and percutaneous coronary intervention versus surgical aortic valve replacement and coronary artery bypass grafting in patients with severe aortic stenosis and concomitant coronary artery disease: A systematic review and meta-analysis.

Objectives: We performed a systematic review and meta-analysis to evaluate the early and midterm outcomes of patients who underwent surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) against patients who had transcatheter aortic valve replacement (TAVR) and percutaneous coronary intervention (PCI).

Background: Contemporary guidelines suggest that surgical or percutaneous revascularization of significant coronary artery disease (CAD) in patients with severe aortic stenosis (AS) is a reasonable strategy.

Methods: We conducted a comprehensive search of Medline and Embase to identify studies comparing a percutaneous transcatheter versus a surgical approach.

Ultrasound guided vascular access site management and left ventricular pacing are associated with improved outcomes in contemporary transcatheter aortic valve replacement: Insights from the OxTAVI registry.

Objectives: To identify clinical and procedural practice predictors of avoidable complications during transcatheter aortic valve replacement (TAVR).

Background: TAVR is evolving as a viable strategy for treatment of aortic stenosis (AS). Vascular complications, major bleeding, or pericardial tamponade may be influenced by procedural practice.

Transcatheter Aortic Valve Replacement Influence on Coronary Hemodynamics: A Quantitative Meta-Analysis and Proposed Decision-Making Algorithm.

Background: As transcatheter aortic valve replacement (TAVR) expands to younger and lower-risk severe aortic stenosis patients, appropriate coronary artery disease treatment is key to reducing long-term adverse cardiovascular outcomes. Recently, studies have been exploring the role of coronary-physiology guided revascularization strategies. Our aim was to investigate whether TAVR influences coronary physiology measurements using quantitative meta-analytic methods.

Safety of Rotational Atherectomy Using the Radial Access in Patients With Severe Aortic Stenosis.

Despite frequent percutaneous coronary intervention (PCI) in calcified vessels of older patients, rotational atherectomy (RA) has not been endorsed in patients with severe aortic stenosis (AS) due to safety concerns and lack of data. We explored periprocedural safety and mortality in severe AS patients undergoing RA. Prospective anonymized clinical, echocardiographic, procedural and outcome data of patients undergoing RA PCI between January 2012 and July 2018 were retrospectively extracted from the institutional coronary database.

Adenosine A2A Receptor Signaling in the Immunopathogenesis of Experimental Autoimmune Encephalomyelitis.

Our increasing appreciation of adenosine as an endogenous signaling molecule that terminates inflammation has generated excitement regarding the potential to target adenosine receptors (ARs) in the treatment of multiple sclerosis (MS), a disease of chronic neuroinflammation. Of the four G protein-coupled ARs, A2ARs are the principal mediator of adenosine's anti-inflammatory effects and accordingly, there is a growing body of evidence surrounding the role of A2ARs in experimental autoimmune encephalomyelitis (EAE), the dominant animal model of MS. Such evidence points to a complex, often paradoxical role for A2ARs in the immunopathogenesis of EAE, where they have the ability to both exacerbate and alleviate disease severity.