Smoking affects gene expression in blood of patients with ischemic stroke.

ObjectiveThough cigarette smoking (CS) is a well-known risk factor for ischemic stroke (IS), there is no data on how CS affects the blood transcriptome in IS patients.MethodsWe recruited IS-current smokers (IS-SM), IS-never smokers (IS-NSM), control-smokers (C-SM), and control-never smokers (C-NSM). mRNA expression was assessed on HTA-2.0 microarrays and unique as well as commonly expressed genes identified for IS-SM versus IS-NSM and C-SM versus C-NSM.ResultsOne hundred and fifty-eight genes were differentially expressed in IS-SM versus IS-NSM; 100 genes were differentially expressed in C-SM versus C-NSM; and 10 genes were common to both IS-SM and C-SM (P < 0.01; |fold change| ≥ 1.2). Functional pathway analysis showed the 158 IS-SM-regulated genes were associated with T-cell receptor, cytokine-cytokine receptor, chemokine, adipocytokine, tight junction, Jak-STAT, ubiquitin-mediated proteolysis, and adherens junction signaling. IS-SM showed more altered genes and functional networks than C-SM.InterpretationWe propose some of the 10 genes that are elevated in both IS-SM and C-SM (GRP15, LRRN3, CLDND1, ICOS, GCNT4, VPS13A, DAP3, SNORA54, HIST1H1D, and SCARNA6) might contribute to increased risk of stroke in current smokers, and some genes expressed by blood leukocytes and platelets after stroke in smokers might contribute to worse stroke outcomes that occur in smokers

Characterizing the Distribution and Rates of Microbial Sulfate Reduction at Middle Valley Hydrothermal Vents

Few studies have directly measured sulfate reduction at hydrothermal vents, and relatively little is known about how environmental or ecological factors influence rates of sulfate reduction in vent environments. A better understanding of microbially mediated sulfate reduction in hydrothermal vent ecosystems may be achieved by integrating ecological and geochemical data with metabolic rate measurements. Here we present rates of microbially mediated sulfate reduction from three distinct hydrothermal vents in the Middle Valley vent field along the Juan de Fuca Ridge, as well as assessments of bacterial and archaeal diversity, estimates of total biomass and the abundance of functional genes related to sulfate reduction, and in situ geochemistry. Maximum rates of sulfate reduction occurred at $90^{\circ}C$ in all three deposits. Pyrosequencing and functional gene abundance data reveal differences in both biomass and community composition among sites, including differences in the abundance of known sulfate reducing bacteria. The abundance of sequences for Thermodesulfovibro-like organisms and higher sulfate reduction rates at elevated temperatures, suggests that Thermodesulfovibro-like organisms may play a role in sulfate reduction in warmer environments. The rates of sulfate reduction presented here suggest that - within anaerobic niches of hydrothermal deposits - heterotrophic sulfate reduction may be quite common and can contribute to secondary productivity, underscoring the potential role of this process in both sulfur and carbon cycling at vents.Organismic and Evolutionary Biolog

Elevating microRNA-122 in blood improves outcomes after temporary middle cerebral artery occlusion in rats.

Because our recent studies have demonstrated that miR-122 decreased in whole blood of patients and in whole blood of rats following ischemic stroke, we tested whether elevating blood miR-122 would improve stroke outcomes in rats. Young adult rats were subjected to a temporary middle cerebral artery occlusion (MCAO) or sham operation. A polyethylene glycol-liposome-based transfection system was used to administer a miR-122 mimic after MCAO. Neurological deficits, brain infarction, brain vessel integrity, adhesion molecule expression and expression of miR-122 target and indirect-target genes were examined in blood at 24 h after MCAO with or without miR-122 treatment. miR-122 decreased in blood after MCAO, whereas miR-122 mimic elevated miR-122 in blood 24 h after MCAO. Intravenous but not intracerebroventricular injection of miR-122 mimic decreased neurological deficits and brain infarction, attenuated ICAM-1 expression, and maintained vessel integrity after MCAO. The miR-122 mimic also down-regulated direct target genes (e.g. Vcam1, Nos2, Pla2g2a) and indirect target genes (e.g. Alox5, Itga2b, Timp3, Il1b, Il2, Mmp8) in blood after MCAO which are predicted to affect cell adhesion, diapedesis, leukocyte extravasation, eicosanoid and atherosclerosis signaling. The data show that elevating miR-122 improves stroke outcomes and we postulate this occurs via downregulating miR-122 target genes in blood leukocytes

American Geriatrics Society and National Institute on Aging Bench-to-Bedside conference: sensory impairment and cognitive decline in older adults

This article summarizes the presentations and recommendations of the tenth annual American Geriatrics Society and National Institute on Aging Bench‐to‐Bedside research conference, “Sensory Impairment and Cognitive Decline,” on October 2–3, 2017, in Bethesda, Maryland. The risk of impairment in hearing, vision, and other senses increases with age, and almost 15% of individuals aged 70 and older have dementia. As the number of older adults increases, sensory and cognitive impairments will affect a growing proportion of the population. To limit its scope, this conference focused on sensory impairments affecting vision and hearing. Comorbid vision, hearing, and cognitive impairments in older adults are more common than would be expected by chance alone, suggesting that some common mechanisms might affect these neurological systems. This workshop explored the mechanisms and consequences of comorbid vision, hearing, and cognitive impairment in older adults; effects of sensory loss on the aging brain; and bench‐to‐bedside innovations and research opportunities. Presenters and participants identified many research gaps and questions; the top priorities fell into 3 themes: mechanisms, measurement, and interventions. The workshop delineated specific research questions that provide opportunities to improve outcomes in this growing population.Funding was provided by National Institutes of Health (NIH) Grant U13 AG054139-01. Dr. Whitson's efforts and contributions were supported by R01AG043438, R24AG045050, UH2AG056925, and 5P30AG028716. Dr. Lin's effort and contributions were also supported by R01AG055426, R01HL096812, and R33DC015062. (U13 AG054139-01 - National Institutes of Health (NIH); R01AG043438; R24AG045050; UH2AG056925; 5P30AG028716; R01AG055426; R01HL096812; R33DC015062)Accepted manuscrip

When, where, and why should we look for vestibular dysfunction in people with diabetes mellitus?

The biochemistry of diabetes mellitus results in multi-system tissue compromise that reduces functional mobility and interferes with disease management. Sensory system compromise, such as peripheral neuropathy and retinopathy, are specific examples of tissue compromise detrimental to functional mobility. There is lack of clarity regarding if, when, and where parallel changes in the peripheral vestibular system, an additional essential sensory system for functional mobility, occur as a result of diabetes. Given the systemic nature of diabetes and the plasticity of the vestibular system, there is even less clarity regarding if potential vestibular system changes impact functional mobility in a meaningful fashion. This commentary will provide insight as to when we should employ diagnostic vestibular function tests in people with diabetes, where in the periphery we should look, and why testing may or may not matter. The commentary concludes with recommendations for future research and clinical care

An Open Pilot Study of Training Hostile Interpretation Bias to Treat Disruptive Mood Dysregulation Disorder

Objective: Irritability in disruptive mood dysregulation disorder (DMDD) may be associated with a biased tendency to judge ambiguous facial expressions as angry. We conducted three experiments to explore this bias as a treatment target. We tested: 1) whether youth with DMDD express this bias; 2) whether judgment of ambiguous faces can be altered in healthy youth by training; and 3) whether such training in youth with DMDD is associated with reduced irritability and associated changes in brain function. Methods: Participants in all experiments made happy versus angry judgments of faces that varied along a happy to angry continuum. These judgments were used to quantify a “balance point,” the facial expression at which a participant's judgment switches from predominantly happy to predominantly angry. We first compared balance points in youth with DMDD (n = 63) versus healthy youth (n = 26). We then conducted a double-blind, randomized controlled trial of active versus sham balance-point training in 19 healthy youth. Finally, we piloted open, active balance-point training in 14 youth with DMDD, with 10 completing an implicit functional MRI (fMRI) face-emotion processing task. Results: Relative to healthy youth, DMDD youth manifested a shifted balance point, expressed as a tendency to classify ambiguous faces as angry rather than happy. In both healthy and DMDD youth, active training is associated with a shift in balance point toward more happy judgments. In DMDD, evidence suggests that active training may be associated with decreased irritability and changes in activation in the lateral orbitofrontal cortex. Conclusions:These results set the stage for further research on computer-based treatment targeting interpretation bias of angry faces in DMDD. Such treatment may decrease irritability and alter neural responses to subtle expressions of happiness and anger

Ischaemic stroke, haemorrhage and mortality in elderly patients with chronic kidney disease newly started on anticoagulation for atrial fibrillation: a population-based study from UK primary care

Objective To assess the association between anticoagulation, ischaemic stroke, gastrointestinal and cerebral haemorrhage, and all cause mortality in older people with atrial fibrillation and chronic kidney disease. Design Propensity matched, population based, retrospective cohort analysis from January 2006 through December 2016. Setting The Royal College of General Practitioners Research and Surveillance Centre database population of almost 2.73 million patients from 110 general practices across England and Wales. Participants Patients aged 65 years and over with a new diagnosis of atrial fibrillation and estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73m2, calculated using the chronic kidney disease epidemiology collaboration creatinine equation. Patients with a previous diagnosis of atrial fibrillation or receiving anticoagulation in the preceding 120 days were excluded, as were patients requiring dialysis and recipients of renal transplants. Intervention Receipt of an anticoagulant prescription within 60 days of atrial fibrillation diagnosis. Main outcome measures Ischaemic stroke, cerebral or gastrointestinal haemorrhage, and all cause mortality. Results 6977 patients with chronic kidney disease and newly diagnosed atrial fibrillation were identified, of whom 2434 were on anticoagulants within 60 days of diagnosis and 4543 were not. 2434 pairs were matched using propensity scores by exposure to anticoagulant or none and followed for a median of 506 days. The crude rates for ischaemic stroke and haemorrhage were 4.6 and 1.2 after taking anticoagulants and 1.5 and 0.4 in patients who were not taking anticoagulant per 100 person years, respectively. The hazard ratios for ischaemic stroke, haemorrhage, and all cause mortality for those on anticoagulants were 2.60 (95% confidence interval 2.00 to 3.38), 2.42 (1.44 to 4.05), and 0.82 (0.74 to 0.91) compared with those who received no anticoagulation. Conclusion Giving anticoagulants to older people with concomitant atrial fibrillation and chronic kidney disease was associated with an increased rate of ischaemic stroke and haemorrhage but a paradoxical lowered rate of all cause mortality. Careful consideration should be given before starting anticoagulants in older people with chronic kidney disease who develop atrial fibrillation. There remains an urgent need for adequately powered randomised trials in this population to explore these findings and to provide clarity on correct clinical management