Ageing effect on flicker-induced diameter changes in retinal microvessels of healthy individuals

Purpose: To compare flicker-induced retinal vessel diameter changes in varying age groups with low cardiovascular risk. Methods: Retinal vascular reactivity to flicker light was assessed by means of dynamic retinal vessel analysis in 57 participants aged 19-30 years, 75 participants aged 31-50 years and 62 participants aged 51-70 years participants. Other assessments included carotid intima-media thickness (c-IMT), augmentation index (AIx), blood pressure profiles, blood lipid metabolism markers and Framingham risk scores (FRS). Results: Retinal arterial dilation amplitude (DA) and postflicker percentage constriction (MC%) were significantly decreased in the oldest group compared to the middle-aged (p = 0.028; p = 0.021) and youngest group (p = 0.003; p = 0.026). The arterial constriction slope (SlopeAC) was also decreased in the oldest group compared to the youngest group (p = 0.027). On the venous side, MC% was decreased in the middle-aged and oldest groups in comparison with the youngest group (p = 0.015; p = 0.010, respectively). Additionally, men exhibited increased arterial DA (p = 0.007), and percentage dilation (MD%, p < 0.001) in comparison with women, but only in the youngest age group. Both AIx and c-IMT scores increased with age (both p < 0.001); however, no correlations were found between the observed differences in the measured retinal vascular function and systemic parameters. Conclusion: In individuals with low cardiovascular risk, there are age-related differences in flicker-induced retinal vessel diameter changes throughout the entire functional response curve for arteries and veins. Gender differences mainly affect the arterial dilatory phase and are only present in young individuals

Retinal Microvascular Abnormalities and Systemic Arterial Stiffness Are the First Manifestation of Cardiovascular Abnormalities in Patients with Untreated Moderate to Severe Obstructive Sleep Apnoea and with Low to Intermediate Cardiovascular Risk-A Pilot Study

This study aimed to investigate macro- and microvascular function parameters and their relationship with known markers of cardiovascular risk in patients with untreated moderate to severe obstructive sleep apnoea (OSA). Fourteen patients with moderate to severe OSA and fourteen controls were included in the present study. General assessments included BMI, systemic blood pressure (BP) and circulating markers for oxidative stress and endothelial function. Additional assessments included 24 h BP and heart rate monitoring, as well as the assessment of heart rate variability. Macro- and microvascular assessments included augmentation index, carotid intima-media thickness, brachial artery flow-mediated dilation, as well as various retinal microvascular function assessments, using the Dynamic Retinal Vessel Analyzer. All participants completed the Short Form Health Survey, Functional Outcomes of Sleep Questionnaire, and Epworth Sleepiness Scale. The results show that, in comparison to controls, BMI ( = 0.003) and AIx ( = 0.025) were significantly higher in the OSA group. There was, however, no significant difference between groups with regard to other measured systemic general, vascular and circulatory parameters (all > 0.05). Nevertheless, the retinal microvascular function showed various alterations in the OSA patients, including a delayed reaction time in response to flicker ( = 0.047), as well as a decreased dilation amplitude ( = 0.004), dilation slope ( = 0.004), and post-flicker constriction ( = 0.015). In addition, the observed Slope alterations correlated negatively with BMI values only in the OSA group (r = -0.46, = 0.045). In conclusion, individuals with untreated moderate to severe OSA but without overt CVD, exhibit signs of increased arterial stiffness and retinal microvascular dysfunction, which can be early indicators for future vascular complications

Infectious consequences of hematoma from cardiac implantable electronic device procedures and the role of the antibiotic envelope: A WRAP-IT trial analysis.

Hematoma is a complication of cardiac implantable electronic device (CIED) procedures and may lead to device infection. The TYRX antibacterial envelope reduced major CIED infection by 40% in the randomized WRAP-IT (World-wide Randomized Antibiotic Envelope Infection Prevention Trial) study, but its effectiveness in the presence of hematoma is not well understood.The purpose of this study was to evaluate the incidence and infectious consequences of hematoma and the association between envelope use, hematomas, and major CIED infection among WRAP-IT patients.All 6800 study patients were included in this analysis (control 3429; envelope 3371). Hematomas occurring within 30 days postprocedure (acute) were characterized and grouped by study treatment and evaluated for subsequent infection risk. Data were analyzed using Cox proportional hazard regression modeling.Acute hematoma incidence was 2.2% at 30 days, with no significant difference between treatment groups (envelope vs control hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.84-1.58; P = .39). Through all follow-up, the risk of major infection was significantly higher among control patients with hematoma vs those without (13.1% vs 1.6%; HR 11.3; 95% CI 5.5-23.2; P.001). The risk of major infection was significantly lower in the envelope vs control patients with hematoma (2.5% vs 13.1%; HR 0.18; 95% CI 0.04-0.85; P = .03).The risk of hematoma was 2.2% among WRAP-IT patients. Among control patients, hematoma carried a11-fold risk of developing a major CIED infection. This risk was significantly mitigated with antibacterial envelope use, with an 82% reduction in major CIED infection among envelope patients who developed hematoma compared to control

the world wide randomized antibiotic envelope infection prevention wrap it trial long term follow up

Abstract Background The WRAP-IT trial reported a 40% reduction in major CIED infection within 12 months of the procedure with the antibacterial-eluting envelope (TYRX). Objective This report describes the longer-term (>12 months) envelope effects on infection reduction and complications. Methods All trial patients that underwent CIED replacement, upgrade, revision, or initial CRT-D implant received standard-of-care infection prophylaxis and were randomized 1:1 to receive the envelope or not. CIED infection incidence, and procedure and system-related complications were characterized through all follow-up (36 months) using Cox proportional hazard regression modeling. Results In total, 6800 patients received their intended randomized treatment (3371 envelope; 3429 control; mean follow-up 21.0±8.3 months). Major CIED-related infection occurred in 32 envelope patients and 51 control patients (KM estimate, 1.3% vs. 1.9%; HR: 0.64, 95% CI: 0.41-0.99; P=0.046). Any CIED-related infection occurred in 57 envelope patients and 84 control patients (KM estimate, 2.1% vs. 2.8%; HR: 0.69, 95% CI: 0.49-0.97; P=0.030). System- or procedure-related complications occurred in 235 envelope patients and 252 control patients (KM estimate, 8.0% vs. 8.2%; HR, 0.95, 95% CI: 0.79-1.13; P Conclusions The effects of the TYRX envelope in reducing the risk of CIED infection are sustained beyond the first year post-procedure, without increased risk of complication

Retinal vascular function and cardiovascular risk factors

The current platform of conventional cardiovascular risk assessments tends to forsake the importance of endothelial function - a key biological mechanism by which cardiovascular risk factors exert their propensity for adverse vascular events. Moreover, the presence and severity of endothelial dysfunction in ‘low-risk’ individuals suggests considerable variability in pre-clinical risk that could potentially be detected well before the onset of disease. The aim of the present thesis was to investigate the presence and impact of retinal vascular dysfunction, as a barometer of endothelial function, in otherwise healthy individuals with one or more cardiovascular risk factors, but low to moderate cardiovascular risk. Systemic circulatory influences on retinal vascular function were also evaluated. The principle sections and findings of this work are: 1. Ageing effect on retinal vascular function • In low-risk individuals, there are age differences in retinal vascular function throughout the entire functional response curve for arteries and veins. Gender differences mainly affect the dilatory phase and are only present in young individuals. 2. Retinal vascular function in healthy individuals with a family history of cardiovascular disease • In low-risk individuals with a family history of cardiovascular disease, impairments in microvascular function at the retinal level correlate with established plasma markers for cardiovascular risk. 3. Ethnic differences in retinal vascular function • When compared to age-matched White Europeans, in low-risk middle-aged South Asians, there are impairments in retinal vascular function that correlate with established cardiovascular risk indicators. 4. Systemic circulatory influences on retinalµvascular function • Systemic antioxidant capacity (redox index) and plasma markers for cardiovascular risk (lipids) influence retinal microvascular function at both arterial and venous levels. 5. Retinal vascular function in individuals with obstructive sleep apnoea: a preliminarystudy • Patients with moderate to severe sleep apnoea exhibit attenuated retinal vascular function

Prostanoids, Diabetes and the Brain: unveiling a pathophysiological role for 15-deoxy-delta-12, 14-prostaglandin J2 in diabetes-related encephalopathy and cerebrovascular injury

Amongst a host of diabetes-related changes in the central nervous system (CNS) the cerebral microvesssels remain a susceptible target for detrimental effects of the disease associated with altered barrier transport and function of the cerebral microvasculature. While oxidative stress and the activation of COX enzymes emerge as two separate pathogenic mechanisms in a variety of CNS-related diseases, a common link between these presumably distinct processes is the oxidation of arachidonic acid and subsequent formation of bioactive prostaglandins. With basal levels of the parent compound, Prostaglandin D2, exceeding those of other prostaglandins in the brain, the liberation of 15-deoxy-?12, 14-Prostaglandin J2 (15d-PGJ2) may in turn be warranted. Irrespective of whether cerebrovascular dysfunction is a cause or consequence of diabetes-related encephalopathies, the current understanding of the molecular mechanisms leading to this detrimental process is limited. The present thesis attempts to characterize the role of one such arachidonic acid metabolite, 15d-PGJ2, as a potential mediator of neurovascular degeneration. The findings in effect unveil a pathophysiological role for 15d-PGJ2 in a deleterious state of untreated diabetes; corroborated by the Streptozotocin-induced mouse model of diabetes. With a near 8-fold increase in 15d-PGJ2 levels and concomitant reductions of cortical vessel density within the diabetic brain, pharmacological inhibition with the selenocompound SeCl4 appeared to partially rescue cortical capillary density subsequent to reductions in 15d-PGJ2. Furthermore, intracerebroventricular (ICV) administration of pathophysiological doses of 15d-PGJ¬2 in vivo and treatment of brain explants and aortic rings ex vivoLes plus fréquentes complications reliées au Diabète, au niveau du système nerveux central, sont associées aux microvaisseaux cérébraux; cible fragile et compromise. Les effets délétères du diabète causent un endommagement à la fonction de transport de la barrière hémato-encéphalique et des cellules endothéliales. L'augmentation du stress oxydatif et l'activation des cyclooxygenases jouent un rôle primordial dans la génèse de ces complications et entraînent la formation subséquente des prostaglandines. Les mécanismes moléculaires associés à la dysfonction de l'endothélium vasculaire cérébral demeurent indéterminés. Le contenu de cette thèse tentera de caractériser le rôle de la prostaglandine 15-deoxy-?12,14- J2 (15d-PGJ2), une potentielle médiatrice de la dégénérescence neuromicrovasculaire. Nos données révèlent un rôle pathologique de la 15d-PGJ2 dans un modèle animal de diabète induit à la streptozotocine. Les niveaux de 15d-PGJ2 augmentent de 8 fois chez les souris diabétiques par rapport aux souris contrôles et semblent induire une dégénérescence microvasculaire cérébrale. L'inhibition de la formation de 15d-PGJ2 dans ce modèle par SeCl4 prévient partiellement l'induction de ce phénomène. Par ailleurs, l'injection cérébroventriculaire de 15d-PGJ2 in vivo, le traitement d'explants cérébraux et d'anneaux aortiques ex vivo confirment les propriétés anti-angiogéniques. Finalement, nous démontrons que 15d-PGJ2 induit une surproduction d'espéces oxygénées activées suivie d'une mort cellulaire apoptotique indépendante des récepteurs DP1/DP2 et PPAR?. À travers cette thèse, nous avons réussi à dévoiler de nouveaux mécanismes induisant les lésions microvas

Handedness, Brain Lateralization, and Emotion

John Pellegrini, PhD, Associate Professor of Biology, and Swathi Seshadri, student researcher, received a $1,875 award from the 3M Small Scale Grant program to determine if left-handed individuals differ from right-handed individuals in their expression and perception of emotion. The study will compare the generation of facial expressions and the perception of such expressions in right and left-handed subjects

Choroidal Involution Is a Key Component of Oxygen-Induced Retinopathy

International audiencePurpose: Retinopathy of prematurity (ROP) is a major cause of visual handicap in the pediatric population. To date, this disorder is thought to stem from deficient retinal vascularization. Intriguingly, functional electrophysiological studies in patients with mild or moderate ROP and in the oxygen-induced retinopathy (OIR) model in rats reveal central photoreceptor disruption that overlies modest retinal vessel loss; a paucity of retinal vasculature occurs predominantly at the periphery. Given that choroidal circulation is the major source of oxygen and nutrients to the photoreceptors, the authors set out to investigate whether the choroidal vasculature system may be affected in OIR.Methods: Rat models of OIR treating newborn animals with 80% or 50/10% alternated oxygen level for the first two postnatal weeks were used to mimic ROP in humans. Immunohistology staining and vascular corrosion casts were used to investigate the vessel layout of the eye. To investigate the effect of 15-deoxy-Δ12,14-PGJ(2) (15d-PGJ(2); a nonenzymatic product of prostaglandin D(2)) on endothelial cells, in vitro cell culture and ex vivo choroid explants were employed and intravitreal injections were performed in animals.Results: The authors herein demonstrate that deficient vascularity occurs not only in the retinal plexus but also in the choroid. This sustained, marked choroidal degeneration is specifically confined to central regions of the retina that present persistent photoreceptor loss and corresponding functional deficits. Moreover, the authors show that 15d-PGJ(2) is a prominent contributor to this choroidal decay.Conclusions: The authors demonstrate for the first time pronounced, sustained choroidal vascular involution during the development of ROP. Findings also suggest that effective therapeutic strategies to counter ROP should consider choroidal preservation

Use of healthcare claims to validate the Prevention of Arrhythmia Device Infection Trial cardiac implantable electronic device infection risk score

AIM: The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims. METHODS AND RESULTS: Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P &lt; 0.0001) after adjusting for PADIT score. A Harrell's C-statistic for the PADIT score and history of prior CIED infection was 0.76. CONCLUSION: The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score