Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Eligibility and Prescription Rates in Patients Presenting With Recurrent Acute Coronary Syndromes.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel medications for reducing low-density lipoprotein cholesterol (LDL-C) levels. In 2020, the Australian Pharmaceutical Benefits Scheme (PBS) began subsidising PCSK9 inhibitors for secondary prevention of cardiovascular disease in patients with LDL-C >2.6 mmol/L despite statin and ezetimibe therapy.

CogWatch: An open-source platform to monitor physiological indicators for cognitive workload and stress.

Cognitive workload is a measure of the mental resources a user is dedicating to a given task. Low cognitive workload produces boredom and decreased vigilance, which can lead to an increase in response time. Under high cognitive workload the information processing burden of the user increases significantly, thereby compromising the ability to effectively monitor their environment for unexpected stimuli or respond to emergencies.

Perceptions of primary care patients on the use of electronic clinical decision support tools to facilitate health care: A systematic review.

Objective: Electronic clinical decision support tools (eCDSTs) are interventions designed to facilitate clinical decision-making using targeted medical knowledge and patient information. While eCDSTs have been demonstrated to improve quality of care, there is a paucity of research relating to the acceptability of eCDSTs in primary care from the patients' perspective. This study aims to summarize current evidence relating to primary care patients' perceptions and experiences on the use of eCDSTs by their clinician to provide care.

The Effects of Statins on Cardiovascular and Inflammatory Biomarkers in Primary Prevention: A Systematic Review and Meta-Analysis.

Background: Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting.

Methods: We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD.

Heterogeneous integration of a III-V quantum dot laser on high thermal conductivity silicon carbide.

Heat accumulation prevents semiconductor lasers from operating at their full potential. This can be addressed through heterogeneous integration of a III-V laser stack onto non-native substrate materials with high thermal conductivity. Here, we demonstrate III-V quantum dot lasers heterogeneously integrated on silicon carbide (SiC) substrates with high temperature stability.

Effect of inpatient antibiotic treatment among older adults with delirium found with a positive urinalysis: a health record review.

Background: Among older adults with delirium and positive urinalysis, antibiotic treatment for urinary tract infection is common practice, but unsupported by literature or guidelines. We sought to: i) determine the rate of antibiotic treatment and the proportion of asymptomatic patients (other than delirium) in this patient population, and ii) examine the effect of antibiotic treatment on delirium resolution and adverse outcomes.

Methods: A health record review was conducted at a tertiary academic centre from January to December 2020.

Association of Mitochondrial DNA Copy Number with Risk of Progression of Kidney Disease.

Background And Objectives: Mitochondrial DNA copy number is a biomarker of mitochondrial function, which has been hypothesized to contribute to pathogenesis of CKD through podocyte injury, tubular epithelial cell damage, and endothelial dysfunction. The prospective association of mitochondrial DNA copy number with CKD progression has not been previously evaluated.

Design, Setting, Participants, & Measurements: Chronic Renal Insufficiency Cohort study participants had serum levels of mitochondrial DNA copy number calculated from probe intensities of mitochondrial single nucleotide polymorphisms genotyped on the Illumina HumanOmni 1-Quad Array.

Metabolomics study of blood pressure salt-sensitivity and hypertension.

Background And Aims: Identify novel metabolite associations with blood pressure (BP) salt-sensitivity and hypertension.

Methods And Results: The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Replication study includes 698 Chinese participants who underwent a 3-day baseline examination followed by a 7-day low-sodium feeding and 7-day high-sodium feeding. Latent mixture models identified three trajectories of blood pressure (BP) responses to the sodium interventions.

Metabolites Associated with Coffee Consumption and Incident Chronic Kidney Disease.

Background And Objectives: Moderate coffee consumption has been associated with lower risk of CKD; however, the exact biologic mechanisms underlying this association are unknown. Metabolomic profiling may identify metabolic pathways that explain the association between coffee and CKD. The goal of this study was to identify serum metabolites associated with coffee consumption and examine the association between these coffee-associated metabolites and incident CKD.

Comparison of Radiation Exposure in Third-Generation Second-Generation Dual-Source Dual-Energy CT for Imaging Urinary Calculi.

To investigate the potential for decreasing radiation dose when utilizing a third-generation second-generation dual-source dual-energy CT (dsDECT) scanner, while maintaining diagnostic image quality and acceptable image noise. : Retrospective analysis of patients who underwent dsDECT for clinical suspicion of urolithiasis from October 2, 2017, to September 5, 2018. Patient demographics, body mass index, abdominal diameter, scanning parameters, and CT dose index volume (CTDIvol) were recorded.

An untargeted metabolomics study of blood pressure: findings from the Bogalusa Heart Study.

Objective: To identify novel and confirm previously reported metabolites associated with SBP, DBP, and hypertension in a biracial sample of Bogalusa Heart Study (BHS) participants.

Methods: We employed untargeted, ultra-high performance liquid chromatography tandem mass spectroscopy metabolomics profiling among 1249 BHS participants (427 African-Americans and 822 whites) with BP and covariable data collected during the 2013 to 2016 visit cycle. A total of 1202 metabolites were tested for associations with continuous and binary BP phenotypes using multiple linear and logistic regression models, respectively, in overall and race-stratified analyses.

Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer.

Objective: To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target.

Design: FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA.

The non-coding RNome after splenectomy.

Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non-infectious complications, with unknown mechanisms. In order to explore the role of the non-coding transcripts involved in these complications, we analysed a panel of circulating microRNAs (miRNAs), which were previously reported to be deregulated in sepsis, in the plasma of splenectomized patients.

Interleukin-18 up-regulates amino acid transporters and facilitates amino acid-induced mTORC1 activation in natural killer cells.

Upon inflammation, natural killer (NK) cells undergo metabolic changes to support their high energy demand for effector function and proliferation. The metabolic changes are usually accompanied by an increase in the expression of nutrient transporters, leading to increased nutrient uptake. Among various cytokines inducing NK cell proliferation, the mechanisms underlying the effect of interleukin (IL)-18 in promoting NK cell proliferation are not completely understood.

Circulating MiR-374a-5p is a potential modulator of the inflammatory process in obesity.

Obese individuals without expected metabolic co-morbidities are referred to as metabolically healthy obese (MHO). The molecular mechanisms underlying this phenotype remain elusive. MicroRNAs may be involved in the MHO phenotype.

Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

Background: We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP.

Methods: We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg.

Associations of Renin-Angiotensin-Aldosterone System Genes With Blood Pressure Changes and Hypertension Incidence.

Background: The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure (BP) regulation. The current study uses single-marker and gene-based analyses to examine the association between RAAS genes and longitudinal BP phenotypes in a Han Chinese population.

Methods: A total of 1,768 participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current study.

Expression of a CD200 transgene is necessary for induction but not maintenance of tolerance to cardiac and skin allografts.

CD200, a type 2 transmembrane molecule of the Ig supergene family, can induce immunosuppression in a number of biological systems, as well as promote increased graft acceptance, following binding to its receptors (CD200Rs). Skin and cardiac allograft acceptance are readily induced in transgenic mice overexpressing CD200 under control of a doxycycline-inducible promoter, both of which are associated with increased intragraft expression of mRNAs for a number of genes associated with altered T cell subset differentiation, including GATA-3, type 2 cytokines (IL-4, IL-13), GITR, and Foxp3. Interestingly, some 12-15 days after grafting, induction of transgenic CD200 expression can be stopped (by doxycycline withdrawal), without obvious significant effect on graft survival.

Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A/J mice.

Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease which has been difficult to study and treat because of the lack of a readily available animal model. Intranasal infection of A/J mice with the coronavirus murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features of SARS. All MHV-1-infected A/J mice developed progressive interstitial pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline membranes, resulting in death of all animals.

Targeted delivery of ribavirin improves outcome of murine viral fulminant hepatitis via enhanced anti-viral activity.

Side effects of interferon-ribavirin combination therapy limit the sustained viral response achievable in hepatitis C virus (HCV) patients. Coupling ribavirin to macromolecular carriers that target the drug to the liver would reduce systemic complications. The aim of this study was to evaluate the efficacy of a hemoglobin-ribavirin conjugate (HRC 203) in murine hepatitis virus strain 3 (MHV-3) induced viral hepatitis.

Role of fibrinogen-like protein 2 prothrombinase/fibroleukin in experimental and human allograft rejection.

Immune coagulation is a major contributor to the pathogenesis of xenograft rejection, viral-induced hepatocellular injury and cytokine-induced fetal loss syndrome. In this study, we investigated the contribution of the novel gene product, fibrinogen-like protein 2 (fgl2) prothrombinase, in mediating immune injury in experimental and human acute allograft rejection. Using a mouse heterotopic cardiac transplant model, mouse fgl2(mfgl2)/fibroleukin mRNA transcripts and protein were highly expressed in macrophages, CD4- and CD8-positive T lymphocytes, and endothelial cells in rejecting cardiac allografts in association with deposits of fibrin.