Review of: Leonard W. Doob, Sustainers and Sustainability

Review of: Leonard W. Doob, Sustainers and Sustainability (Praeger Publishers 1995). Bibliography, index, notes. LC 95-7982; ISBN 0-275-95314-9 [167 pp. $52.95 Cloth, .88 Post Road West, Westport, CT 06881.

Acute Beetroot Juice Ingestion Increases Nitric Oxide Bioavailability Without Changing Oral Microbial Composition in Healthy Young Women

Dietary nitrate supplementation can elicit beneficial health and exercise performance effects. Oral microbiota are critical for the metabolism of exogenously consumed nitrate; however, limited data are available on the influence of dietary nitrate ingestion on bacterial taxa and in women. PURPOSE: To investigate if acute dietary nitrate ingestion alters the oral microbiota in young healthy women compared to a nitrate-depleted placebo. METHODS: In a randomized double-blinded crossover design, fifteen recreationally active women (mean ± SD: age 20 ± 1 years; body mass 63 ± 10 kg; height 1.68 ± 0.1 m) participated in two conditions to ingest nitrate-rich beetroot juice (BR; 12 mmol of nitrate) and nitrate-depleted beetroot juice (PL, negligible nitrate), 2.5 hours prior to a resting blood draw and buccal swab sample. Plasma [nitrate] and [nitrite] were analyzed using gas phase chemiluminescence. Buccal swab samples were used for DNA extraction and isolation. DNA was amplified using polymerase chain reaction targeting the V3 - V4 region of the 16S rRNA gene. Following index PCR, amplicons were pooled and sequenced using the iSeq Illumina NGS sequencer. Reads were clustered into amplicon sequence variants and analyzed for alpha and beta diversity and relative abundance. RESULTS: BR increased plasma [nitrate] (PL: 52 ± 14 µM vs. BR: 629 ± 132 µM, P \u3c 0.001) and plasma [nitrite] (PL: 276 ± 286 nM vs. BR: 703 ± 391 nM, P \u3c 0.001). One sample had insufficient DNA and thus, a subset of samples was analyzed for oral microbial composition (n = 14). Alpha (i.e., species richness or evenness) and beta diversity was not different between PL and BR (P \u3e 0.05). The relative abundance of the phylum and genus were not influenced by BR (P \u3e 0.05). CONCLUSION: Acute nitrate ingestion did not improve or worsen the composition of global or lower taxonomic levels of bacteria in young recreationally active women. These data indicate that acute nitrate ingestion is an intervention to rapidly increase nitric oxide bioavailability in young recreationally active women, which is an effect that did not require changes to the oral microbial community. Further research is required to understand the impact of dosing regimen and population on oral bacterial taxa and the efficacy of nitrate on nitrate-induced effects

Angiotensin II and angiotensin-(1-7) decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study

<p>Abstract</p> <p>Background</p> <p>During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF), placental growth factor (PLGF), soluble VEGF receptor 1 (sFlt1), and soluble endoglin (sEng) are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy.</p> <p>Methods</p> <p>We evaluated the effects of angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)] on the release of VEGF, PLGF, sFlt1, and sEng from placental chorionic villi (CV). CV were collected from nulliparous third-trimester normotensive and preeclamptic subjects. CV were incubated for 0, 2, 4, and 16 hours with or without Ang II (1 nM and 1 microM) or Ang-(1-7) (1 nM and 1 microM). The release of VEGF, PLGF, sFlt1, sEng, lactate dehydrogenase (LDH), and human placenta lactogen (HPL) was measured by ELISA.</p> <p>Results</p> <p>The release of sFlt1, PLGF, sEng from normal and preeclamptic CV increased over time. Release of sFlt1 and sEng was significantly higher from preeclamptic CV. VEGF was below the detectable level of the assay in normal and preeclamptic CV. After 2 hours, sFlt1 release from normal CV was significantly inhibited with Ang II (1 nM and 1 microM) and Ang-(1-7) (1 nM and 1 microM). There was a time-dependent increase in HPL indicating that the CV were functioning normally.</p> <p>Conclusions</p> <p>Our study demonstrates a critical inhibitory role of angiotensin peptides on sFlt1 in normal pregnancy. Loss of this regulation in preeclampsia may allow sFlt1 to increase resulting in anti-angiogenesis and end organ damage in the mother.</p

The effect of a single dose of beetroot juice on speed, strength, and power in healthy recreationally active females.

Nitrate-rich beetroot juice (BR) improves muscle contraction which is relevant for intense intermittent-type sports. However, few studies have examined the effect of BR ingestion on performance using sport-specific exercise protocols. Moreover, there is a scarcity of research that include female participants which limits real world application given that females potentially have different responses to BR ingestion. The purpose of the present study was to examine the effect of BR supplementation on speed, acceleration, strength and power before and after fatigue in females. In a double-blind, randomized crossover design, 15 recreationally active females consumed BR and nitrate-depleted placebo juice (PL) ~2.5 hours prior to exercise testing. Measurements included 20 m sprint and acceleration using timing gates, strength using isokinetic handgrip dynamometry, and upper and lower body power using the medicine ball power throw and countermovement jump (CMJ) before and after a fatiguing running protocol. Data from a subset of participants (n=15) were analyzed and revealed no significant difference between PL and BR for 20 m speed and 10 m acceleration (P\u3e0.05), isokinetic handgrip dynamometry (PL: PRE: 76±10 vs POST: 76±13; BR: PRE: 78±12 vs POST: 78±12 lb; P\u3e0.05), medicine ball power throw (PL: PRE: 4.45±0.48 vs POST: 4.35±0.48; BR: PRE: 4.41±0.38 vs POST: 4.49±0.47 m; P\u3e0.05) or CMJ (PL: PRE: 1.72±0.27 vs POST: 1.7±0.26; BR: PRE: 1.77±0.25 vs POST: 1.73±0.28 m; P\u3e0.05). These results indicate that there are no effects of BR supplementation on exercise performance in female athletes; however, this study is currently underpowered, and research is still in progress

The effects of nitrate-rich beetroot juice supplementation on nonverbal executive function in healthy recreationally active females

Nitrate-rich beetroot juice (BR) supplementation has been reported to preserve executive function (i.e. decision making and reaction time) before and after a simulated soccer match in recreationally active males, which may be due to enhanced cerebral blood flow. However, the literature examining the physiological response following BR ingestion in females is scarce, which hampers the extrapolation of results since physiological sex-differences may exist. Therefore, the purpose of this study was to assess if BR ingestion influenced executive function in an unfatigued and fatigued state in healthy recreationally active females. In a double-blind, randomized crossover design, 20 females consumed 140 mL of concentrated BR or nitrate-depleted placebo juice (PL) approximately 2.5 hours prior to each experimental visit. The Delis-Kaplan Executive Function (D-KEF) test, used for assessing higher-level cognitive function, was administered before and after completing a high-intensity intermittent running protocol. The D-KEF test involved 3 x 60-s conditions evaluating various cognitive tasks. A two-way repeated measures analysis of variance was conducted (n=15) and revealed no significant differences in executive function between PL (PRE: 15.27 ± 32.71 vs. POST: 16.93 ± 1.44) and BR (PRE: 15.80 ± 2.65 vs. POST: 16.60 ± 1.88). These preliminary data suggest that acute BR ingestion does not have an influence on processing and creative thinking of nonverbal executive function in an unfatigued or fatigued state in healthy recreationally active females, although importantly, the study is still in progress

The Effects of Acute Beetroot Juice Ingestion on Exercise and Cognitive Performance in Female Athletes

Nitrate-rich beetroot juice can enhance intense exercise performance which is attributed to enhanced skeletal muscle contractility. However, limited data exist in females and it is unknown whether dietary nitrate has an ergogenic effect in this population. PURPOSE: To investigate the potential effects of acute nitrate ingestion on a battery of exercise performance and cognitive tests before and after fatiguing intermittent running exercise. METHODS: Fifteen female team-sport athletes were assigned in a randomized, double-blind, crossover design to consume nitrate-rich beetroot juice (BR; 12 mmol of nitrate) and nitrate-depleted beetroot juice (PL; 0.10 mmol of nitrate) 2.5 h prior to performing the exercise protocol, with a washout period of 7 days between trials. Running 10 m and 20 m sprint split times, sprint reaction time, upper- and lower-body power, handgrip strength, and cognitive flexibility were measured before and after the Yo-Yo intermittent recovery level 1 (Yo-Yo IR1) test, during which performance and rate of perceived exertion were recorded. RESULTS: There were no significant differences in any performance outcome or cognitive flexibility (P \u3e 0.05). CONCLUSION: These findings indicate that acute nitrate ingestion does not influence performance in sprints, intermittent running, power, strength, or cognitive function in young adult female team-sport athletes

Behind the screen: drug discovery using the big data of phenotypic analysis

Technological advances in drug discovery are exciting to students, but it is challenging for faculty to maintain the pace with these developments, particularly within undergraduate courses. In recent years, a High-throughput Discovery Science and Inquiry-based Case Studies for Today’s Students (HITS) Research Coordination Network has been assembled to address the mechanism of how faculty can, on-pace, introduce these advancements. As a part of HITS, our team has developed “Behind the Screen: Drug Discovery using the Big Data of Phenotypic Analysis” to introduce students and faculty to phenotypic screening as a tool to identify inhibitors of diseases that do not have known cellular targets. This case guides faculty and students though current screening methods using statistics and can be applied at undergraduate and graduate levels. Tested across 70 students at three universities and a variety of courses, our case utilizes datasets modeled on a real phenotypic screening method as an accessible way to teach students about current methods in drug discovery. Students will learn how to identify hit compounds from a dataset they have analyzed and understand the biological significance of the results they generate. They are guided through practical statistical procedures, like those of researchers engaging in a novel drug discovery strategy. Student survey data demonstrated that the case was successful in improving student attitudes in their ability to discuss key topics, with both undergraduate and graduate students having a significant increase in confidence. Together, we present a case that uses big data to examine the utility of a novel phenotypic screening strategy, a pedagogical tool that can be customized for a wide variety of courses

Trans-Ethnic Mapping of BANK1 Identifies Two Independent SLE-Risk Linkage Groups Enriched for Co-Transcriptional Splicing Marks

BANK1 is a susceptibility gene for several systemic autoimmune diseases in several populations. Using the genome-wide association study (GWAS) data from Europeans (EUR) and African Americans (AA), we performed an extensive fine mapping of ankyrin repeats 1 (BANK1). To increase the SNP density, we used imputation followed by univariate and conditional analysis, combinedwith a haplotypic and expression quantitative trait locus (eQTL) analysis. The data from Europeans showed that the associated region was restricted to a minimal and dependent set of SNPs covering introns two and three, and exon two. In AA, the signal found in the Europeans was split into two independent effects. All of the major risk associated SNPs were eQTLs, and the risks were associated with an increased BANK1 gene expression. Functional annotation analysis revealed the enrichment of repressive B cell epigenomicmarks (EZH2 and H3K27me3) and a strong enrichment of splice junctions. Furthermore, one eQTL located in intron two, rs13106926, was found within the binding site for RUNX3, a transcriptional activator. These results connect the local genome topography, chromatin structure, and the regulatory landscape of BANK1 with co-transcriptional splicing of exon two. Our data defines a minimal set of risk associated eQTLs predicted to be involved in the expression of BANK1 modulated through epigenetic regulation and splicing. These findings allow us to suggest that the increased expression of BANK1 will have an impact on B-cell mediated disease pathways.The work presented in this paper has been supported by the Ministerio de Economía y Competitividad, Spain (SAF2016-78631-P), partly co-financed by FEDER funds of the European Union, the Gustaf den V:e-80-års Fond and the Swedish Association against Rheumatism to M.E.A-R. In addition, this work was financed by the NIH P01 grant P01-AI-083194 to C.D.L., J.B.H., R.K., and M.E.A-R. JBH: NIH grants: R01 AI024717, U01 HG00866, P30 AR070549 and U01 AI130830 and the US Department of Veterans Affairs: I01 BX001834.C.D.L.: Center for Public Health Genomics. R.K.: NIH grant R01-AR33062. J.A.J.: NIH grants U54GM104938, P30AR053483

A randomised controlled trial to prevent hospital readmissions and loss of functional ability in high risk older adults: a study protocol

Background Older people have higher rates of hospital admission than the general population and higher rates of readmission due to complications and falls. During hospitalisation, older people experience significant functional decline which impairs their future independence and quality of life. Acute hospital services comprise the largest section of health expenditure in Australia and prevention or delay of disease is known to produce more effective use of services. Current models of discharge planning and follow-up care, however, do not address the need to prevent deconditioning or functional decline. This paper describes the protocol of a randomised controlled trial which aims to evaluate innovative transitional care strategies to reduce unplanned readmissions and improve functional status, independence, and psycho-social well-being of community-based older people at risk of readmission. Methods/Design The study is a randomised controlled trial. Within 72 hours of hospital admission, a sample of older adults fitting the inclusion/exclusion criteria (aged 65 years and over, admitted with a medical diagnosis, able to walk independently for 3 meters, and at least one risk factor for readmission) are randomised into one of four groups: 1) the usual care control group, 2) the exercise and in-home/telephone follow-up intervention group, 3) the exercise only intervention group, or 4) the in-home/telephone follow-up only intervention group. The usual care control group receive usual discharge planning provided by the health service. In addition to usual care, the exercise and in-home/telephone follow-up intervention group receive an intervention consisting of a tailored exercise program, in-home visit and 24 week telephone follow-up by a gerontic nurse. The exercise only and in-home/telephone follow-up only intervention groups, in addition to usual care receive only the exercise or gerontic nurse components of the intervention respectively. Data collection is undertaken at baseline within 72 hours of hospital admission, 4 weeks following hospital discharge, 12 weeks following hospital discharge, and 24 weeks following hospital discharge. Outcome assessors are blinded to group allocation. Primary outcomes are emergency hospital readmissions and health service use, functional status, psychosocial well-being and cost effectiveness. Discussion The acute hospital sector comprises the largest component of health care system expenditure in developed countries, and older adults are the most frequent consumers. There are few trials to demonstrate effective models of transitional care to prevent emergency readmissions, loss of functional ability and independence in this population following an acute hospital admission. This study aims to address that gap and provide information for future health service planning which meets client needs and lowers the use of acute care services

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery