Prehypertensive blood pressures and regional cerebral blood flow independently relate to cognitive performance in midlife

Background High blood pressure is thought to contribute to dementia in late life, but our understanding of the relationship between individual differences in blood pressure ( BP ) and cognitive functioning is incomplete. In this study, cognitive performance in nonhypertensive midlife adults was examined as a function of resting BP and regional cerebral blood flow ( rCBF ) responses during cognitive testing. We hypothesized that BP would be negatively related to cognitive performance and that cognitive performance would also be related to rCBF responses within areas related to BP control. We explored whether deficits related to systolic BP might be explained by rCBF responses to mental challenge. Methods and Results Healthy midlife participants (n=227) received neuropsychological testing and performed cognitive tasks in a magnetic resonance imaging scanner. A pseudocontinuous arterial spin labeling sequence assessed rCBF in brain areas related to BP in prior studies. Systolic BP was negatively related to 4 of 5 neuropsychological factors (standardized β&gt;0.13): memory, working memory, executive function, and mental efficiency. The rCBF in 2 brain regions of interest was similarly related to memory, executive function, and working memory (standardized β&gt;0.17); however, rCBF responses did not explain the relationship between resting systolic BP and cognitive performance. Conclusions Relationships at midlife between prehypertensive levels of systolic BP and both cognitive and brain function were modest but suggested the possible value of midlife intervention. </jats:sec

Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a 'treatabolome'.

BACKGROUND: Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking. OBJECTIVE: We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies. METHODS: We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale. RESULTS: Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH). CONCLUSIONS: The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies

Brachial vein transposition arteriovenous fistulas for hemodialysis access

BackgroundAn arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, offering lower morbidity, mortality, and cost compared with grafts or catheters. Patients with a difficult access extremity have often lost all superficial veins, and even basilic veins may be obliterated. We have used brachial vein transposition AVFs (BVT-AVFs) in these challenging patients and review our experience in this report.MethodsThe study reviewed consecutive patients in whom BVT-AVFs were created from September 2006 to March 2009. Most BVT-AVFs were created in staged procedures, with the second-stage transposition operations completed 4 to 6 weeks after the first-stage AVF operation. A single-stage BVT-AVF was created when the brachial vein diameter was ≥6 mm.ResultsWe identified 58 BVT-AVF procedures, comprising 41 women (71.0%), 28 diabetic patients (48.3%), and 29 (50.0%) had previous access surgery. The operation was completed in two stages in 45 operations (77.6%) and was a primary transposition in 13 patients. However, five of these were secondary AVFs with previous distal AV grafts or AVFs placed elsewhere; effectively, late staged procedures. Follow-up was a mean of 11 months (range, 2.0-31.7 months). Primary patency, primary-assisted patency, and cumulative (secondary) patency were 52.0%, 84.9%, and 92.4% at 12 months and 46.2%, 75.5%, and 92.4% at 24 months, respectively. Harvesting the brachial vein was tedious and more difficult than harvesting other superficial veins. No prosthetic grafts were used.ConclusionBVT-AVFs provide a suitable option for autogenous access when the basilic vein is absent in patients with difficult access extremities. Most patients required intervention for access maturation or maintenance. Most BVT-AVFs were created with staged procedures. Cumulative (secondary) patency was 92.4% at 24 months

Brachial vein transposition arteriovenous fistulas for hemodialysis access

BackgroundAn arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, offering lower morbidity, mortality, and cost compared with grafts or catheters. Patients with a difficult access extremity have often lost all superficial veins, and even basilic veins may be obliterated. We have used brachial vein transposition AVFs (BVT-AVFs) in these challenging patients and review our experience in this report.MethodsThe study reviewed consecutive patients in whom BVT-AVFs were created from September 2006 to March 2009. Most BVT-AVFs were created in staged procedures, with the second-stage transposition operations completed 4 to 6 weeks after the first-stage AVF operation. A single-stage BVT-AVF was created when the brachial vein diameter was ≥6 mm.ResultsWe identified 58 BVT-AVF procedures, comprising 41 women (71.0%), 28 diabetic patients (48.3%), and 29 (50.0%) had previous access surgery. The operation was completed in two stages in 45 operations (77.6%) and was a primary transposition in 13 patients. However, five of these were secondary AVFs with previous distal AV grafts or AVFs placed elsewhere; effectively, late staged procedures. Follow-up was a mean of 11 months (range, 2.0-31.7 months). Primary patency, primary-assisted patency, and cumulative (secondary) patency were 52.0%, 84.9%, and 92.4% at 12 months and 46.2%, 75.5%, and 92.4% at 24 months, respectively. Harvesting the brachial vein was tedious and more difficult than harvesting other superficial veins. No prosthetic grafts were used.ConclusionBVT-AVFs provide a suitable option for autogenous access when the basilic vein is absent in patients with difficult access extremities. Most patients required intervention for access maturation or maintenance. Most BVT-AVFs were created with staged procedures. Cumulative (secondary) patency was 92.4% at 24 months

Synthesis of High χ–Low N Diblock Copolymers by Polymerization-Induced Self-Assembly

Polymerization‐induced self‐assembly (PISA) enables the scalable synthesis of functional block copolymer nanoparticles with various morphologies. Herein we exploit this versatile technique to produce so‐called ‘high χ ‐low N ’ diblock copolymers that undergo nanoscale phase separation in the solid state to produce sub‐10 nm surface features. By varying the degree of polymerization of the stabilizer and core‐forming blocks, PISA provides rapid access to a wide range of diblock copolymers, and enables fundamental thermodynamic parameters to be determined. In addition, the pre‐organization of copolymer chains within sterically‐stabilized nanoparticles that occurs during PISA leads to enhanced phase separation relative to that achieved using solution‐cast molecularly‐dissolved copolymer chains

A Potent Fuel?: Faith Identity And Development Impact In World Vision Community Programming

This paper explores the role of faith identity on impact in development by looking at the programming of a major international faith‐based development organisation (FBDO). It argues that faith identity rests not only in the internal projected identity of the FBDO but also on perceptions of that identity in the community, highlighting the role context plays in the formulation of faith identity and its impact. Secondly, the paper argues that FBDOs possess not only a faith identity but also a development one and that it is the interplay between both that allows for the creation of engagement and trust in interventions

Hysteresis from Multiscale Porosity: Modeling Water Sorption and Shrinkage in Cement Paste

Cement paste has a complex distribution of pores and molecular-scale spaces. This distribution controls the hysteresis of water sorption isotherms and associated bulk dimensional changes (shrinkage). We focus on two locations of evaporable water within the fine structure of pastes, each having unique properties, and we present applied physics models that capture the hysteresis by dividing drying and rewetting into two related regimes based on relative humidity (RH). We show that a continuum model, incorporating a pore-blocking mechanism for desorption and equilibrium thermodynamics for adsorption, explains well the sorption hysteresis for a paste that remains above approximately 20% RH. In addition, we show with molecular models and experiments that water in spaces of ≲1  nm width evaporates below approximately 20% RH but reenters throughout the entire RH range. This water is responsible for a drying shrinkage hysteresis similar to that of clays but opposite in direction to typical mesoporous glass. Combining the models of these two regimes allows the entire drying and rewetting hysteresis to be reproduced accurately and provides parameters to predict the corresponding dimensional changes. The resulting model can improve the engineering predictions of long-term drying shrinkage accounting also for the history dependence of strain induced by hysteresis. Alternative strategies for quantitative analyses of the microstructure of cement paste based on this mesoscale physical model of water content within porous spaces are discussed.Portland Cement AssociationNational Ready Mixed Concrete Association (Research and Education Foundation)Schlumberger Foundatio

ChIP-Seq and RNA-Seq Reveal an AmrZ-Mediated Mechanism for Cyclic di-GMP Synthesis and Biofilm Development by Pseudomonas aeruginosa

The transcription factor AmrZ regulates genes important for P. aeruginosa virulence, including type IV pili, extracellular polysaccharides, and the flagellum; however, the global effect of AmrZ on gene expression remains unknown, and therefore, AmrZ may directly regulate many additional genes that are crucial for infection. Compared to the wild type strain, a ΔamrZ mutant exhibits a rugose colony phenotype, which is commonly observed in variants that accumulate the intracellular second messenger cyclic diguanylate (c-di-GMP). Cyclic di-GMP is produced by diguanylate cyclases (DGC) and degraded by phosphodiesterases (PDE). We hypothesized that AmrZ limits the intracellular accumulation of c-di-GMP through transcriptional repression of gene(s) encoding a DGC. In support of this, we observed elevated c-di-GMP in the ΔamrZ mutant compared to the wild type strain. Consistent with other strains that accumulate c-di-GMP, when grown as a biofilm, the ΔamrZ mutant formed larger microcolonies than the wild-type strain. This enhanced biofilm formation was abrogated by expression of a PDE. To identify potential target DGCs, a ChIP-Seq was performed and identified regions of the genome that are bound by AmrZ. RNA-Seq experiments revealed the entire AmrZ regulon, and characterized AmrZ as an activator or repressor at each binding site. We identified an AmrZ-repressed DGC-encoding gene (PA4843) from this cohort, which we named AmrZ dependent cyclase A (adcA). PAO1 overexpressing adcA accumulates 29-fold more c-di-GMP than the wild type strain, confirming the cyclase activity of AdcA. In biofilm reactors, a ΔamrZ ΔadcA double mutant formed smaller microcolonies than the single ΔamrZ mutant, indicating adcA is responsible for the hyper biofilm phenotype of the ΔamrZ mutant. This study combined the techniques of ChIP-Seq and RNA-Seq to define the comprehensive regulon of a bifunctional transcriptional regulator. Moreover, we identified a c-di-GMP mediated mechanism for AmrZ regulation of biofilm formation and chronicity

Influence of forest-to-silvopasture conversion and drought on components of evapotranspiration

The northeastern U.S. is projected to experience more frequent short-term (1-2 month) droughts interspersed among larger precipitation events. Agroforestry practices such as silvopasture may mitigate these impacts of climate change while maintaining economic benefits of both agricultural and forestry practices. This study evaluated the effects of forest-to-silvopasture (i.e., 50% thinning) conversion on the components of evapotranspiration (transpiration, rainfall interception, and soil evaporation) during the growing season of 2016. The study coincided with a late-summer drought throughout the northeastern U.S., which allowed us to also evaluate the effects of forest-to-silvopasture conversion on drought responses of multiple tree species, including Pinus strobus, Tsuga canadensis, and Quercus rubra. In the reference forest and silvopasture, we observed declining soil moisture and tree water use during the drought for all three tree species. However, the decline in P. strobus water use in response to declining soil moisture in the silvopasture was not as steep as compared with the reference forest, resulting in greater water use in the silvopasture for this species. In contrast, we did not detect different water-use responses between forest and silvopasture in T. canadensis or Q. rubra. This suggests that forest-to-silvopasture conversion via thinning can alleviate drought stress for P. strobus and that this species may be more sensitive to moisture stress when competition for water is high in denser stands. Evapotranspiration was 35% lower in the silvopasture compared with the reference forest, primarily a result of lower transpiration and rainfall interception. While soil evaporation was greater in the silvopasture, this was not enough to offset the considerably lower transpiration and interception. We observed greater radial tree growth 1-3 years following conversion in the silvopasture as compared with the reference forest for T. canadensis and Q. rubra, but not for P. strobus. Overall, our results suggest that forest conversion to silvopasture (in lieu of clearcutting for new pasture) may mitigate the impacts of agricultural land use intensification and climate change on ecosystem services, especially in terms of sustaining hydrologic regulation functions. Further study is required to determine the generality of these results and whether these benefits extend beyond the first few years post-conversion