Improved left ventricular contractility with cool temperature hemodialysis

Improved left ventricular contractility with cool temperature hemodialysis. Cool temperature dialysis (CTD) has been shown to sharply decrease the frequency of intradialytic hemodialysis hypotension, but the mechanism of this hemodynamic protection is unknown. Therefore, we performed two-dimensional echocardiographic studies of left ventricular contractility in six stable hemodialysis patients before and after hemodialysis at 37°C (RTD) and 35°C (CTD). Left ventricular function was assessed by plotting the rate-corrected velocity of circumferential fiber shortening (Vcfc) against end-systolic wall stress (σes) at four different levels of afterload. Linear regression was used to calculate Vcfc at a common afterload of 50 g/cm2. Changes in weight and dialysis parameters were similar following RTD and CTD. Mean arterial pressure and heart rate did not change significantly following RTD or CTD. The Vcfc – σes relation was shifted upward in each patient after CTD, indicating increased contractility as compared to RTD or pre-dialysis baseline. Pre-dialysis Vcfc at an afterload of 50 g/cm2 was similar during RTD and CTD (0.94 ± 0.24 circ/sec vs. 0.92 ± 0.22 circ/sec). Post-dialysis Vcfc at an afterload of 50 g/cm2 was significantly higher for CTD than for RTD (1.13 ± 0.29 circ/sec vs. 0.98 ± 0.30 circ/sec, P = 0.0004). Thus, cool temperature dialysis increases left ventricular contractility in hemodialysis patients, which may be a potential mechanism whereby hemodynamic tolerance to the dialysis procedure is improved

Role of osmolality in blood pressure stability after dialysis and ultrafiltration

Role of osmolality in blood pressure stability after dialysis and ultrafiltration. To clarify the mechanisms involved in the stability of blood pressure during ultrafiltration (UF) alone versus regular dialysis, this study systematically examined the importance of changes in serum potassium, osmolality, and plasma norepinephrine during several dialysis maneuvers. Six stable, normotensive chronic dialysis patients were subjected to a uniform 2 to 3% decrease in body weight during the 2 hours of each dialysis maneuver. Supine to upright mean blood pressure (MBP) decreased (90 to 75 mm Hg, P < 0.05), and three patients became symptomatic after weight loss during regular dialysis, but orthostatic blood pressure was stable (89 to 86 mm Hg, NS) and the patients were asymptomatic after UF and weight loss. Isokalemic regular dialysis did not afford hemodynamic stability, as orthostatic MBP declined (85 to 56 mm Hg, P < 0.02), and four of the patients again were symptomatic after standing. A continuous hypertonic mannitol (25%) infusion during the 2-hour dialysis, however, kept osmolality from decreasing and was associated with a stable orthostatic MBP (89 to 83 mm Hg, NS). A continuous infusion of isotonic mannitol (5%) given in a volume five times that of the hypertonic mannitol failed to prevent orthostatic hypotension (89 to 60 mm Hg, P < 0.005). Plasma norepinephrine concentrations were high in these patients and increased only modestly after weight loss. These results implicate constant plasma osmolality as a critical protective factor of blood pressure during UF and further demonstrate that changes in blood pressure may be dissociated from changes in both serum potassium and plasma norepinephrine concentration.Rôle de l'osmolalité dans la stabilité de la pression artérielle après dialyse et ultrafiltration. Afin de clarifier les mécanismes impliqués dans la stabilité de la pression artérielle au cours de l'ultrafiltration (UF) seule par comparaison avec la dialyse habituelle ce travail évalue systématiquement l'importance des modifications de la kaliémie, de l'osmolalité et de la norépinéphrine plasmatique au cours de plusieurs tactiques de dialyse. Six sujets stables, normotendus, en hémodialyse chronique ont subi une diminution de poids corporel de 2 à 3% au cours des 2 heures de chaque tactique de dialyse. La pression artérielle moyenne a diminué de la position couchée à la position debout (de 90 à 75 mm Hg, P < 0,05) et trois patients sont devenus symptomatiques après la perte de poids au cours de la dialyse habituelle. Par contre la pression artérielle orthostatique a été stable (89 à 86 mm Hg, NS) et les malades ont été asymptomatiques après UF. La dialyse habituelle isokaliémique n'a pas déterminé de stabilité hémodynamique, la pression artérielle moyenne orthostatique a diminué (85 à 56 mm Hg, P < 0,02) et quatre malades ont été à nouveau symptomatiques quand ils se sont levés. Cependant quand une perfusion continue de mannitol hypertonique (25%) pendant les deux heures de la dialyse a empêché la baisse de l'osmolalité la pression artérielle moyenne orthostatique a été stable (89 à 83 mm Hg, NS). Une perfusion continue de mannitol isotonique (5%) apportant un volume cinq fois celui du mannitol hypertonique n'a pas empêché l'hypotention orthostatique (89 à 60 mm Hg, P < 0,005). Les concentrations plasmatiques de norépinéphrine étaient élevées chez ces malades et n'ont que peu augmenté après la perte de poids. Ces résultats impliquent qu'une osmolalité plasmatique constante est un facteur protecteur critique pour la pression artérielle au cours de UF et ils démontrent, de plus, que les modifications de la pression artérielle peuvent être dissociées des modifications du potassium plasmatique et de la concentration de norépinéphrine

Innovative Research Exploring the Effects of Physical Activity and Genetics on Cognitive Performance in Community-Based Older Adults

Physical activity is predictive of better cognitive performance and lower risk of Alzheimer’s disease (AD). The apolipoprotein E gene (APOE) is a susceptibility gene for AD with the e4 allele being associated with a greater risk of AD. Cross-sectional and prospective research shows that physical activity is predictive of better cognitive performance for those at greater genetic risk for AD. However, the moderating role of APOE on the effects of a physical activity intervention on cognitive performance has not been examined. The purpose of this manuscript is to justify the need for such research and to describe the design, methods, and recruitment tactics used in the conductance of a study designed to provide insight as to the extent to which cognitive benefits resulting from an 8-month physical activity program are differentiated by APOE e4 status. The effectiveness of the recruitment strategies and the feasibility of recruiting APOE e4 carriers are discussed

Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone

<p>Abstract</p> <p>Background</p> <p>The effect of neurotrophic factors in enhancing stroke-induced neurogenesis in the adult subventricular zone (SVZ) is limited by their poor blood-brain barrier (BBB) permeability.</p> <p>Intranasal administration is a noninvasive and valid method for delivery of neuropeptides into the brain, to bypass the BBB. We investigated the effect of treatment with intranasal transforming growth factor-β1 (TGF-β1) on neurogenesis in the adult mouse SVZ following focal ischemia. The modified Neurological Severity Scores (NSS) test was used to evaluate neurological function, and infarct volumes were determined from hematoxylin-stained sections. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) labeling was performed at 7 days after middle cerebral artery occlusion (MCAO). Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) and neuron- or glia-specific markers for identifying neurogenesis in the SVZ at 7, 14, 21, 28 days after MCAO.</p> <p>Results</p> <p>Intranasal treatment of TGF-β1 shows significant improvement in neurological function and reduction of infarct volume compared with control animals. TGF-β1 treated mice had significantly less TUNEL-positive cells in the ipsilateral striatum than that in control groups. The number of BrdU-incorporated cells in the SVZ and striatum was significantly increased in the TGF-β1 treated group compared with control animals at each time point. In addition, numbers of BrdU- labeled cells coexpressed with the migrating neuroblast marker doublecortin (DCX) and the mature neuronal marker neuronal nuclei (NeuN) were significantly increased after intranasal delivery of TGF-β1, while only a few BrdU labeled cells co-stained with glial fibrillary acidic protein (GFAP).</p> <p>Conclusion</p> <p>Intranasal administration of TGF-β1 reduces infarct volume, improves functional recovery and enhances neurogenesis in mice after stroke. Intranasal TGF-β1 may have therapeutic potential for cerebrovascular disorders.</p

Development of Social Variation in Reproductive Schedules: A Study from an English Urban Area

Background: There is striking social variation in the timing of the onset of childbearing in contemporary England, with the mean age at first motherhood about 8 years earlier in the most deprived compared to the least deprived neighbourhoods. However, relatively little is known about how these social differences in reproductive schedule develop in childhood. Methodology/Principal Findings: We studied the development of differences in reproductive schedules, using a crosssectional survey over 1000 school students aged 9–15 in the metropolitan borough of North Tyneside. Students from more deprived neighbourhoods had earlier ideal ages for parenthood than those from more affluent ones, and these differences were fully apparent by age 11. We found evidence consistent with three mechanisms playing a role in maintaining the socioeconomic gradient. These were: vertical intergenerational transmission (students whose own parents were younger at their birth wanted children younger); oblique intergenerational transmission (students in neighbourhoods where parents were younger in general wanted children earlier); and low parental investment (students who did not feel emotionally supported by their own parents wanted children at a younger age). Conclusions/Significance: Our results shed some light on the proximate factors which may be involved in maintaining early childbearing in disadvantaged communities. They help understand why educational initiatives aimed at adolescents tend to have no effect, whereas improving the well-being of poor families with young children may do so. Our results also sugges

The Spatial Heterogeneity between Japanese Encephalitis Incidence Distribution and Environmental Variables in Nepal

To identify potential environmental drivers of Japanese Encephalitis virus (JE) transmission in Nepal, we conducted an ecological study to determine the spatial association between 2005 Nepal JE incidence, and climate, agricultural, and land-cover variables at district level.District-level data on JE cases were examined using Local Indicators of Spatial Association (LISA) analysis to identify spatial clusters from 2004 to 2008 and 2005 data was used to fit a spatial lag regression model with climate, agriculture and land-cover variables.Prior to 2006, there was a single large cluster of JE cases located in the Far-West and Mid-West terai regions of Nepal. After 2005, the distribution of JE cases in Nepal shifted with clusters found in the central hill areas. JE incidence during the 2005 epidemic had a stronger association with May mean monthly temperature and April mean monthly total precipitation compared to mean annual temperature and precipitation. A parsimonious spatial lag regression model revealed, 1) a significant negative relationship between JE incidence and April precipitation, 2) a significant positive relationship between JE incidence and percentage of irrigated land 3) a non-significant negative relationship between JE incidence and percentage of grassland cover, and 4) a unimodal non-significant relationship between JE Incidence and pig-to-human ratio.JE cases clustered in the terai prior to 2006 where it seemed to shift to the Kathmandu region in subsequent years. The spatial pattern of JE cases during the 2005 epidemic in Nepal was significantly associated with low precipitation and the percentage of irrigated land. Despite the availability of an effective vaccine, it is still important to understand environmental drivers of JEV transmission since the enzootic cycle of JEV transmission is not likely to be totally interrupted. Understanding the spatial dynamics of JE risk factors may be useful in providing important information to the Nepal immunization program

The Availability Heuristic, Intuitive Cost-Benefit Analysis, and Climate Change

Because risks are on all sides of social situations, it is not possible to be “precautionary” in general. The availability heuristic ensures that some risks stand out as particularly salient, whatever their actual magnitude. Taken together with intuitive cost-benefit balancing, the availability heuristic helps to explain differences across groups, cultures, and even nations in the assessment of precautions to reduce the risks associated with climate change. There are complex links among availability, social processes for the spreading of information, and predispositions. If the United States is to take a stronger stand against climate change, it is likely to be a result of available incidents that seem to show that climate change produces serious and tangible harm