Neuroprotective Role of SRT1720 Against Hydrogen Peroxide Induced Oxidative Stress in NT2 Cells

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by a significant increase in neuronal loss. Oxidative stress (OS) plays a significant role on neuronal damage. Reactive oxygen species (ROS) generated from agents such as hydrogen peroxide (H2O2) leads to cell damage and reduction of cell viability. Sirtuin 1 (SIRT1) is a therapeutic target for neurodegenerative disorders because it regulates several cellular functions and biological processes that promote cellular longevity. This study was undertaken to examine the role of SRT1720 in protecting cells from H2O2 induced stress in Ntera-2 cl.D1(NT2), which has been proven to be a useful in vitro system for the investigation of functions related to human neuronal and glial systems. The results provide evidence that H2O2 significantly induced oxidative stress in a concentration dependent manner. Moreover, pre-treatment with low concentrations of SRT1720 for 48 hours protected against the effects of H2O2. Also, a combination of H2O2 and SRT1720 improved cell viability. Interestingly, apoptotic or necrotic cell death was not detected after H2O2 treatment in the cell culture model system employed

Steady improvement in renal allograft survival among North American children: A five year appraisal by the North American Pediatric Renal Transplant Cooperative Study

Steady improvement in renal allograft survival among North American children. From 1987 through 1994, the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) has enrolled 1641 cadaver donor transplants. For this study, we have analyzed one and two year graft survival by annual cohorts for the years 1987 through 1991. For the 1987 cohort one and two year graft survival was 72% and 65%, respectively, and for the 1991 cohort it was 83% and 78%, respectively. Using a proportional hazards model, and comparing the 1987 cohort to the 1991 cohort, the relative risk for graft failure was 1.40 (P = 0.02). Analysis of practice patterns revealed the following changes which may have been associated with this improved graft survival: (1) use of T cell induction antibody, 38% in 1987 and 67% in 1991 (P ≤ 0.001); (2) the increased use of cyclosporine (CsA) post-transplant: in 1987, 87% were maintained on CsA at day 30 compared to 97% in 1991 (P < 0.001); (3) the mean higher daily maintenance CsA dose at 12 months post-transplant which in 1987 was 6.5 mg/kg compared to 7.5 mg/kg in 1991 (P = 0.03); (4) the decreased use of random transfusions, 54% receiving >5 transfusions in 1987 compared to 37% in 1991 (P < 0.001); and (5) decreased use of younger cadaver donors between 1987 and 1991 (P < 0.001)

iPose: Instance-Aware 6D Pose Estimation of Partly Occluded Objects

We address the task of 6D pose estimation of known rigid objects from single input images in scenarios where the objects are partly occluded. Recent RGB-D-based methods are robust to moderate degrees of occlusion. For RGB inputs, no previous method works well for partly occluded objects. Our main contribution is to present the first deep learning-based system that estimates accurate poses for partly occluded objects from RGB-D and RGB input. We achieve this with a new instance-aware pipeline that decomposes 6D object pose estimation into a sequence of simpler steps, where each step removes specific aspects of the problem. The first step localizes all known objects in the image using an instance segmentation network, and hence eliminates surrounding clutter and occluders. The second step densely maps pixels to 3D object surface positions, so called object coordinates, using an encoder-decoder network, and hence eliminates object appearance. The third, and final, step predicts the 6D pose using geometric optimization. We demonstrate that we significantly outperform the state-of-the-art for pose estimation of partly occluded objects for both RGB and RGB-D input

Recovering 6D Object Pose: A Review and Multi-modal Analysis

A large number of studies analyse object detection and pose estimation at visual level in 2D, discussing the effects of challenges such as occlusion, clutter, texture, etc., on the performances of the methods, which work in the context of RGB modality. Interpreting the depth data, the study in this paper presents thorough multi-modal analyses. It discusses the above-mentioned challenges for full 6D object pose estimation in RGB-D images comparing the performances of several 6D detectors in order to answer the following questions: What is the current position of the computer vision community for maintaining "automation" in robotic manipulation? What next steps should the community take for improving "autonomy" in robotics while handling objects? Our findings include: (i) reasonably accurate results are obtained on textured-objects at varying viewpoints with cluttered backgrounds. (ii) Heavy existence of occlusion and clutter severely affects the detectors, and similar-looking distractors is the biggest challenge in recovering instances' 6D. (iii) Template-based methods and random forest-based learning algorithms underlie object detection and 6D pose estimation. Recent paradigm is to learn deep discriminative feature representations and to adopt CNNs taking RGB images as input. (iv) Depending on the availability of large-scale 6D annotated depth datasets, feature representations can be learnt on these datasets, and then the learnt representations can be customized for the 6D problem

Virtual Immortality: Reanimating Characters from TV Shows.

The objective of this work is to build virtual talking avatars of characters fully automatically from TV shows. From this unconstrained data, we show how to capture a character's style of speech, visual appearance and language in an e ort to construct an interactive avatar of the person and e ectively immortalize them in a computational model. We make three contributions (i) a complete framework for producing a generative model of the audiovisual and language of characters from TV shows; (ii) a novel method for aligning transcripts to video using the audio; and (iii) a fast audio segmentation system for silencing nonspoken audio from TV shows. Our framework is demonstrated using all 236 episodes from the TV series Friends [34] ( 97hrs of video) and shown to generate novel sentences as well as character specific speech and video

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

Morphological and Pathological Evolution of the Brain Microcirculation in Aging and Alzheimer’s Disease

Key pathological hallmarks of Alzheimer’s disease (AD), including amyloid plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles do not completely account for cognitive impairment, therefore other factors such as cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to elucidate the microvascular changes that contribute to aging and disease, direct neuropathological staining and immunohistochemistry, were used to quantify the structural integrity of the microvasculature and its innervation in three oldest-old cohorts: 1) nonagenarians with AD and a high amyloid plaque load; 2) nonagenarians with no dementia and a high amyloid plaque load; 3) nonagenarians without dementia or amyloid plaques. In addition, a non-demented (ND) group (average age 71 years) with no amyloid plaques was included for comparison. While gray matter thickness and overall brain mass were reduced in AD compared to ND control groups, overall capillary density was not different. However, degenerated string capillaries were elevated in AD, potentially suggesting greater microvascular “dysfunction” compared to ND groups. Intriguingly, apolipoprotein ε4 carriers had significantly higher string vessel counts relative to non-ε4 carriers. Taken together, these data suggest a concomitant loss of functional capillaries and brain volume in AD subjects. We also demonstrated a trend of decreasing vesicular acetylcholine transporter staining, a marker of cortical cholinergic afferents that contribute to arteriolar vasoregulation, in AD compared to ND control groups, suggesting impaired control of vasodilation in AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic vascular innervation, was reduced which may also contribute to a loss of control of vasoconstriction. The data highlight the importance of the brain microcirculation in the pathogenesis and evolution of AD

Early Infant Morbidity in the City of São Paulo, Brazil

BACKGROUND: Early infant morbidities may produce adverse outcomes in subsequent life. A low Apgar score is a convenient measure of early infant morbidity. We study determinants of early infant morbidity (sex, plurality, mode of delivery, prior losses, gestational age, prenatal care and birth weight, parity and maternal age, race, maternal education and community development) for the 1998-birth cohort, City of São Paulo, Brazil. METHODS: This study identified all deliveries that took place in the City of São Paulo during 1998. Information was extracted from 209,628 birth records. We used multivariate logistic regression to assess the effect of each independent variable on Apgar score less than seven at one minute and Apgar score less than seven at five minutes. RESULTS: Low birth weight, prematurity and community development were found to be strong predictors of morbidity. Maternal education showed strong negative correlation with both Apgar scores. The negative correlations between maternal schooling and Apgar scores were observed after prenatal care, parity and maternal age were included in the model. Unmeasured proximate factors may thus be the true source of disparity between educational groups. Children of very young adolescent mothers had lower Apgar scores at one minute (but not at five minutes) than those born to mothers 15 to 19. Parity one or higher was associated with decreased odds of low Apgar scores. Cesarean section and operative delivery were associated with higher odds of early infant morbidity. CONCLUSION: Education may allow mothers to have better care in the peripartum period. More educated mothers may be more likely to recognize certain morbidities through the pregnancy period and the monitoring of such morbidities yields better infant outcomes. Also, having less than seven prenatal care visits was found to predict early infant morbidity and one way to increase the use of such services is to focus on aspects of care that may lead to easier accessibility and continuity of prenatal care. Physicians should inform mothers about the risks associated with high number of children for a next infant and also about the risks for the infant associated with unnecessary cesarean sections. Special attention should be paid to adolescent mothers, since much of their increased risk is likely to be minimized by counseling

Effects of caffeine intake prior to stress cardiac magnetic resonance perfusion imaging on regadenoson- versus adenosine-induced hyperemia as measured by T1 mapping

The antagonistic effects of caffeine on adenosine receptors are a possible cause of false-negative stress perfusion imaging. The purpose of this study was to determine the effects of coffee intake <4 h prior to stress perfusion cardiac magnetic resonance imaging (CMR) in regadenoson- versus adenosine-induced hyperemia as measured with T1-mapping. 98 consecutive patients with suspected coronary artery disease referred for either adenosine or regadenoson perfusion CMR were included in this analysis. Twenty-four patients reported coffee consumption <4 h before CMR (15 patients with adenosine, and 9 patients with regadenoson); 74 patients reported no coffee intake (50 patients with adenosine, and 24 patients with regadenoson). T1 mapping was performed using a modified look-locker inversion recovery sequence. T1 reactivity was determined by subtracting T1(rest) from T1(stress). T1(rest), T1(stress), and T1 reactivity in patients referred for regadenoson perfusion CMR were not significantly different when comparing patients with <4 h coffee intake and patients who reported no coffee intake (976 +/- 4 ms, 1019 +/- 48 ms, and 4.4 +/- 3.2% vs 971 +/- 33 ms, 1023 +/- 43 ms, and 5.4 +/- 2.4%) (p = 0.70, 0.79, and 0.40), and similar to values in patients without coffee intake undergoing adenosine CMR. In patients with <4 h coffee intake, T1(stress), and T1 reactivity were significantly lower for adenosine (898 +/- 51 ms, and -7.8 +/- 5.0%) compared to regadenoson perfusion CMR (p <0.001). Coffee intake <4 h prior to regadenoson perfusion CMR has no effect on stress-induced hyperemia as measured with T1 mapping