Risk Factors for Fracture in Patients with Coexisting Chronic Kidney Disease and Type 2 Diabetes: An Observational Analysis from the CREDENCE Trial.

Background: The fracture pathophysiology associated with type 2 diabetes and chronic kidney disease (CKD) is incompletely understood. We examined individual fracture predictors and prediction sets based on different pathophysiological hypotheses, testing whether any of the sets improved prediction beyond that based on traditional osteoporotic risk factors.

Methods: Within the CREDENCE cohort with adjudicated fracture outcomes, we assessed the association of individual factors with fracture using Cox regression models.

The impact of canagliflozin on the risk of neuropathy events: A post-hoc exploratory analysis of the CREDENCE trial.

Aim: Canagliflozin reduces the risk, and progression, of diabetic kidney disease. We hypothesized that it may improve the microvascular complication of neuropathy.

Methods: The CREDENCE trial randomized participants with type 2 diabetes and kidney disease to canagliflozin 100 mg daily or placebo.

Aging influence on pulmonary and systemic inflammation and neural metabolomics arising from pulmonary multi-walled carbon nanotube exposure in apolipoprotein E-deficient and C57BL/6 female mice.

Objective: Environmental exposures exacerbate age-related pathologies, such as cardiovascular and neurodegenerative diseases. Nanoparticulates, and specifically carbon nanomaterials, are a fast-growing contributor to the category of inhalable pollutants, whose risks to health are only now being unraveled. The current study assessed the exacerbating effect of age on multiwalled-carbon nanotube (MWCNT) exposure in young and old C57BL/6 and ApoE mice.

Serum peptidome: diagnostic window into pathogenic processes following occupational exposure to carbon nanomaterials.

Background: Growing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals along with a significant release of bioactive peptides into the circulation, the augmented serum peptidome. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up.

Pulmonary delivery of the broad-spectrum matrix metalloproteinase inhibitor marimastat diminishes multiwalled carbon nanotube-induced circulating bioactivity without reducing pulmonary inflammation.

Background: Multiwalled carbon nanotubes (MWCNT) are an increasingly utilized engineered nanomaterial that pose the potential for significant risk of exposure-related health outcomes. The mechanism(s) underlying MWCNT-induced toxicity to extrapulmonary sites are still being defined. MWCNT-induced serum-borne bioactivity appears to dysregulate systemic endothelial cell function.

Effects of canagliflozin compared with placebo on major adverse cardiovascular and kidney events in patient groups with different baseline levels of HbA, disease duration and treatment intensity: results from the CANVAS Program.

Aims/hypothesis: Type 2 diabetes mellitus can manifest over a broad clinical range, although there is no clear consensus on the categorisation of disease complexity. We assessed the effects of canagliflozin, compared with placebo, on cardiovascular and kidney outcomes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program over a range of type 2 diabetes mellitus complexity, defined separately by baseline intensity of treatment, duration of diabetes and glycaemic control.

Methods: We performed a post hoc analysis of the effects of canagliflozin on major adverse cardiovascular events (MACE) according to baseline glucose-lowering treatments (0 or 1, 2 or 3+ non-insulin glucose-lowering treatments, or insulin-based treatment), duration of diabetes (<10, 10 to 16, >16 years) and HbA (≤53.

Prevalence, incidence and risk factors of diabetes in Australian adults aged ≥45 years: A cohort study using linked routinely-collected data.

Aims: To use linked routinely-collected health data to estimate diabetes prevalence and incidence in an Australian cohort of adults aged ≥45 years, and examine risk factors associated with incident disease.

Research Design And Methods: The EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45) Study is a linked data study that combines baseline questionnaire responses from the population-based (2006-2009,  = 267,153) with multiple routinely-collected health databases up to December 2014. Among participants with ≥1 linked result for any laboratory test, diabetes status was determined from multiple data sources according to standard biochemical criteria, use of glucose-lowering medication or self-report, and the prevalence and incidence rate calculated.

How Do the Recent Major Randomized Controlled Trials Inform Best Use of the Novel Glucose-Lowering Agents?

Background: Type 2 diabetes mellitus (T2DM) is frequently associated with the development of cardiovascular disease and chronic kidney disease (CKD). Some newer glucose-lowering agents confer both cardiac and kidney benefits, as supported by robust data from recent high-quality randomized controlled trials. The decision-making process when selecting glucose-lowering medications for T2DM now extends beyond glycaemia and metabolic effects, and towards additional benefits such as prevention of other complications.

Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function.

Exposure to air pollutants such as ozone (O3) is associated with adverse pregnancy outcomes, including higher incidence of gestational hypertension, preeclampsia, and peripartum cardiomyopathy; however, the underlying mechanisms of this association remain unclear. We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4 h) to either filtered air (FA) or O3 (0.

Risk factors for incident kidney disease in older adults: an Australian prospective population-based study.

Background And Aim: To determine risk factors for incident chronic kidney disease (CKD) in a large population-based cohort.

Methods: This prospective opt-in population-based cohort study is based on the 45 and Up Study, where New South Wales residents aged ≥45 years were randomly sampled from the Services Australia database and agreed to complete the 45 and Up Study baseline questionnaire and have their responses linked to their health data in routinely collected databases. The primary outcome was the development of incident CKD, defined as eGFR < 60 mL/min/1.

Sodium-glucose co-transporter-2 inhibition and ocular outcomes in patients with type 2 diabetes: A systematic review and meta-analysis.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are effective for the treatment of macrovascular complications and nephropathy in type 2 diabetes, but effects on microvascular eye outcomes are unclear. We conducted a systematic review and meta-analysis of randomized placebo-controlled trials to evaluate the effect of SGLT2 inhibition on total ocular events and retinopathy in patients with type 2 diabetes. We searched MEDLINE and Embase for the period from database inception date to October 11, 2019.

EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (the EXTEND45 Study): Protocol for an Australian Linked Cohort Study.

Background: Chronic kidney disease (CKD) and diabetes are the major causes of death and disability worldwide. They are associated with high health service utilization persisting over many years. Their slow progression and wide clinical variation make them eminently suitable for study in population-based cohorts.

Incidence and Associations of Chronic Kidney Disease in Community Participants With Diabetes: A 5-Year Prospective Analysis of the EXTEND45 Study.

Objective: To determine the incidence of and factors associated with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m in people with diabetes.

Research Design And Methods: We identified people with diabetes in the EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45), a population-based cohort study (2006-2014) that linked the Sax Institute's 45 and Up Study cohort to community laboratory and administrative data in New South Wales, Australia.

SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis.

Background: The effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on kidney failure, particularly the need for dialysis or transplantation or death due to kidney disease, is uncertain. Additionally, previous studies have been underpowered to robustly assess heterogeneity of effects on kidney outcomes by different levels of estimated glomerular filtration rate (eGFR) and albuminuria. We aimed to do a systematic review and meta-analysis to assess the effects of SGLT2 inhibitors on major kidney outcomes in patients with type 2 diabetes and to determine the consistency of effect size across trials and different levels of eGFR and albuminuria.

Childhood and adolescent television viewing and internalising disorders in adulthood.

Time spent watching television during childhood and adolescence has been linked to socio-emotional and physical health problems in adulthood. It is unclear whether excessive television viewing is a risk factor for internalising mental health disorders such as anxiety and depression. Longitudinal associations between television viewing in childhood and adult diagnoses of anxiety and depression were investigated in a population-based birth cohort from Dunedin, New Zealand.

Nanoparticle exposure driven circulating bioactive peptidome causes systemic inflammation and vascular dysfunction.

Background: The mechanisms driving systemic effects consequent pulmonary nanoparticle exposure remain unclear. Recent work has established the existence of an indirect process by which factors released from the lung into the circulation promote systemic inflammation and cellular dysfunction, particularly on the vasculature. However, the composition of circulating contributing factors and how they are produced remains unknown.

A high ankle-brachial index is associated with obesity and low serum 25-hydroxyvitamin D in patients with diabetes.

Peripheral artery disease (PAD), when present with diabetes, is associated with significant morbidity and mortality. The spectrum of PAD in diabetes includes atherosclerosis with stenotic disease; and diffuse medial calcification with non-compliant arteries, as reflected by high ankle brachial index. The clinical characteristics of a high ABI are less well characterized than that of low ABI.

Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure.

The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O3) exposure in aged mice, where increased blood-brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C57BL/6 male mice, aged 8-10 weeks or 12-18 months were exposed to either filtered air or 1.

Peer-led, transformative learning approaches increase classroom engagement in care self-management classes during inpatient rehabilitation of individuals with spinal cord injury.

Objective: Evaluate effects of revised education classes on classroom engagement during inpatient rehabilitation for individuals with spinal cord injury/disease (SCI/D).

Design: Multiple-baseline, quasi-experimental design with video recorded engagement observations during conventional and revised education classes; visual and statistical analysis of difference in positive engagement responses observed in classes using each approach.

Participants/setting: 81 patients (72% male, 73% white, mean age 36 SD 15.

Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment.

Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration.

Claudins 1, 3, and 4 protein expression in ER negative breast cancer correlates with markers of the basal phenotype.

In the present study we investigated the protein expression of claudins 1, 3, and 4 and their relationship to clinical variables and outcome in a cohort of ER-ve and ER+ve human invasive breast cancers. Immunohistochemical analysis was performed on tissue microarrays representing a total of 412 tumors and interpretable data was derived from 314, 299, and 306 tumors for claudins 1, 3, and 4, respectively. In the ER+ve subset, 5%, 89%, and 52%, and in the ER-ve subset, 39%, 79%, and 79% of tumors stained positively for claudins 1, 3, and 4, respectively (p < 0.

MKP-1 switches arginine metabolism from nitric oxide synthase to arginase following endotoxin challenge.

L-Arginine (L-arg) is metabolized to nitric oxide (NO) by inducible NO synthase (iNOS) or to urea and L-ornithine (L-orn) by arginase. NO is involved in the inflammatory response, whereas arginase is the first step in polyamine and proline synthesis necessary for tissue repair and wound healing. Mitogen-activated protein kinases (MAPK) mediate LPS-induced iNOS expression, and MAPK phosphatase-1 (MKP-1) plays a crucial role in limiting MAPK signaling in macrophages.

Hyperoxia increases hepatic arginase expression and ornithine production in mice.

Hyperoxic exposure affects the levels and activities of some hepatic proteins. We tested the hypothesis that hyperoxic exposure would result in greater hepatic .NO concentrations.

Gene transfer with inducible nitric oxide synthase decreases production of urea by arginase in pulmonary arterial endothelial cells.

Nitric oxide (NO) is a vasodilator produced from L-arginine (L-Arg) by NO synthase (NOS). Gene therapy for hypertensive disorders has been proposed using the inducible isoform of NOS (iNOS). L-Arg also can be metabolized to urea and L-ornithine (L-Orn) by arginase, and L-Orn can be metabolized to proline and/or polyamines, which are vital for cellular proliferation.