Remote Ischemic Pre-conditioning in the Management of Intermittent Claudication: A Pilot Randomized Controlled Trial.

BACKGROUND: Animal data suggest that remote ischemic conditioning (RIC) can improve blood flow in ischemic limbs and, consequently, may benefit claudication patients. Supervised exercise is the preferred first-line intervention for patients with intermittent claudication (IC) but is constrained by limited availability and logistical issues, particularly in rural settings. The aim of this study is to evaluate remote ischemic pre-conditioning in the management of intermittent claudication patients. METHODS: We undertook a randomized clinical trial to evaluate RIC's effect in claudication patients. Stable IC patients were randomly allocated to receive RIC alone, structured exercise (SE) alone, RIC plus SE, or to a control group which received standard advice and risk factor modification. Patients received their intervention over a 28-day period. RIC patients attended an RIC clinic every 3-4 days to undergo 4 cycles of 5-min upper limb ischemia followed by 5-min reperfusion induced with a standard blood pressure cuff. RESULTS: Forty-five patients were randomized, of whom 40 completed the trial (10 patients per group). The RIC alone, SE alone, and RIC plus SE groups all demonstrated significant improvements in pain-free walking distance and ankle-brachial pressure indices at 30 days. There were no differences in the magnitude of improvements between the groups. CONCLUSIONS: Compared with standard care RIC is promising as a home-delivered intervention. It appears to be equivalent to SE in the treatment of IC, with no apparent additive benefit to combining the 2 interventions in this small size sample. Large-scale randomized controlled trial is needed for validation.

Metagenome tracking biogeographic agroecology: Phytobiota of tomatoes from Virginia, Maryland, North Carolina and California.

Describing baseline microbiota associated with agricultural commodities in the field is an important step towards improving our understanding of a wide range of important objectives from plant pathology and horticultural sustainability, to food safety. Environmental pressures on plants (wind, dust, drought, water, temperature) vary by geography and characterizing the impact of these variable pressures on phyllosphere microbiota will contribute to improved stewardship of fresh produce for both plant and human health. A higher resolution understanding of the incidence of human pathogens on food plants and co-occurring phytobiota using metagenomic approaches (metagenome tracking) may contribute to improved source attribution and risk assessment in cases where human pathogens become introduced to agro-ecologies. Between 1990 and 2007, as many as 1990 culture-confirmed Salmonella illnesses were linked to tomatoes from as many as 12 multistate outbreaks (Bell et al., 2012; Bell et al., 2015; Bennett et al., 2014; CDC, 2004; CDC, 2007; Greene et al., 2005a; Gruszynski et al., 2014). When possible, source attribution for these incidents revealed a biogeographic trend, most events were associated with eastern growing regions. To improve our understanding of potential biogeographically linked trends in contamination of tomatoes by Salmonella, we profiled microbiota from the surfaces of tomatoes from Virginia, Maryland, North Carolina and California. Bacterial profiles from California tomatoes were completely different than those of Maryland, Virginia and North Carolina (which were highly similar to each other). A statistically significant enrichment of Firmicutes taxa was observed in California phytobiota compared to the three eastern states. Rhizobiaceae, Sphingobacteriaceae and Xanthobacteraceae were the most abundant bacterial families associated with tomatoes grown in eastern states. These baseline metagenomic profiles of phyllosphere microbiota may contribute to improved understanding of how certain ecologies provide supportive resources for human pathogens on plants and how components of certain agro-ecologies may play a role in the introduction of human pathogens to plants.

The Ingestion of 39 or 64 g·h(-1) of Carbohydrate is Equally Effective at Improving Endurance Exercise Performance in Cyclists.

In an investigator-blind, randomized cross-over design, male cyclists (mean± SD) age 34.0 (± 10.2) years, body mass 74.6 (±7.9) kg, stature 178.3 (±8.0) cm, peak power output (PPO) 393 (±36) W, and VO2max 62 (±9) ml·kg-1·min(-1) training for more than 6 hr/wk for more than 3y (n = 20) completed four experimental trials. Each trial consisted of a 2-hr constant load ride at 95% of lactate threshold (185 ± 25 W) then a work-matched time trial task (~30 min at 70% of PPO). Three commercially available carbohydrate (CHO) beverages, plus a control (water), were administered during the 2-hr ride providing 0, 20, 39, or 64 g·hr-1 of CHO at a fluid intake rate of 1L·hr(-1). Performance was assessed by time to complete the time trial task, mean power output sustained, and pacing strategy used. Mean task completion time (min:sec ± SD) for 39 g·hr(-1) (34:19.5 ± 03:07.1, p = .006) and 64 g·hr(-1) (34:11.3 ± 03:08.5 p = .004) of CHO were significantly faster than control (37:01.9 ± 05:35.0). The mean percentage improvement from control was -6.1% (95% CI: -11.3 to -1.0) and -6.5% (95% CI: -11.7 to -1.4) in the 39 and 64 g·hr(-1) trials respectively. The 20 g·hr(-1) (35:17.6 ± 04:16.3) treatment did not reach statistical significance compared with control (p = .126) despite a mean improvement of -3.7% (95% CI -8.8-1.5%). No further differences between CHO trials were reported. No interaction between CHO dose and pacing strategy occurred. 39 and 64 g·hr-1 of CHO were similarly effective at improving endurance cycling performance compared with a 0 g·hr(-1) control in our trained cyclists.

The Cholesterol, Hypertension, and Glucose Education (CHANGE) study for African Americans with diabetes: study design and methodology.

BACKGROUND: Cardiovascular disease (CVD) and diabetes account for over one third of the mortality difference between African Americans and white patients. The increased CVD risk in African Americans is due in large part to the clustering of multiple CVD risk factors. OBJECTIVES: The current study is aimed at improving CVD outcomes in African-American adults with diabetes by addressing the modifiable risk factors of systolic blood pressure , glycosylated hemoglobin, and low-density lipoprotein cholesterol. METHODS: A sample of African American patients with diabetes (N = 400) will receive written education material at baseline and be randomized to one of 2 arms: (1) usual primary care or (2) nurse-administered disease-management intervention combining patient self-management support and provider medication management. The nurse administered intervention is delivered monthly over the telephone. The nurses also interacts with the primary care providers at 3, 6, and 9 months to provide concise patient updates and facilitate changes in medical management. All patients are followed for 12 months after enrollment. The primary outcomes are change in glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol over 12-months. Secondary outcomes include change in overall cardiovascular risk, aspirin use, and health behaviors. CONCLUSION: Given the continued racial disparities in CVD, the proposed study could result in significant contributions to cardiovascular risk reduction in African-American patients.

Impact of organic and conventional management on the phyllosphere microbial ecology of an apple crop.

Bacterial communities associated with the phyllosphere of apple trees (Malus domestica cv. Enterprise) grown under organic and conventional management were assessed to determine if increased biological food safety risks might be linked with the bacterial communities associated with either treatment. Libraries of 16S rRNA genes were generated from phyllosphere DNA extracted from a wash made from the surfaces of leaves and apples from replicated organic and conventional treatments. 16S rRNA gene libraries were analyzed with software designed to identify statistically significant differences between bacterial communities as well as shared and unique phylotypes. The identified diversity spanned eight bacterial phyla and 14 classes in the pooled organic and conventional libraries. Significant differences between organic and conventional communities were observed at four of six time points (P < 0.05). Despite the identification of significantly diverse microfloras associated with organic and conventional treatments, no detectable differences in the presence of potential enteric pathogens could be associated with either organic or conventional management. Neither of the bacterial genera most commonly associated with produce-related illness outbreaks (Salmonella and Escherichia) was observed in any of the libraries. The impressive bacterial diversity that was documented in this study provides a valuable contribution to our developing understanding of the total microbial ecology associated with the preharvest phyllospheres of food crops. The fact that organic and conventional phyllosphere bacterial communities were significantly different at numerous time points suggests that crop management methods may influence the bacterial consortia associated with the surfaces of fruits and vegetables.

Metabolic Responses to Carbohydrate Ingestion during Exercise: Associations between Carbohydrate Dose and Endurance Performance.

Carbohydrate (CHO) ingestion during exercise lasting less than three hours improves endurance exercise performance but there is still debate about the optimal dose. We utilised stable isotopes and blood metabolite profiles to further examine metabolic responses to CHO (glucose only) ingestion in the 20-64 g·h-1 range, and to determine the association with performance outcome. In a double-blind, randomized cross-over design, male cyclists (n = 20, mean ± SD, age 34 ± 10 years, mass 75.8 ± 9 kg, peak power output 394 ± 36 W, VO2max 62 ± 9 mL·kg-1·min-1) completed four main experimental trials. Each trial involved a two-hour constant load ride (185 ± 25 W) followed by a time trial, where one of three CHO beverages, or a control (water), were administered every 15 min, providing 0, 20, 39 or 64 g CHO·h-1. Dual glucose tracer techniques, indirect calorimetry and blood analyses were used to determine glucose kinetics, exogenous CHO oxidation (EXO), endogenous CHO and fat oxidation; and metabolite responses. Regression analysis revealed that total exogenous CHO oxidised in the second hour of exercise, and suppression of serum NEFA concentration provided the best prediction model of performance outcome. However, the model could only explain ~19% of the variance in performance outcome. The present data demonstrate that consuming ~40 g·h-1 of CHO appears to be the minimum ingestion rate required to induce metabolic effects that are sufficient to impact upon performance outcome. These data highlight a lack of performance benefit and few changes in metabolic outcomes beyond an ingestion rate of 39 g·h-1. Further work is required to explore dose-response effects of CHO feeding and associations between multiple metabolic parameters and subsequent performance outcome.

Effect of exercise intensity on Nrf2 signalling in young men.

INTRODUCTION: The transcription factor Nrf2 is the master regulator of antioxidant defence. Recent data indicate a single bout of moderate-intensity stationary cycling at a constant workload upregulates Nrf2 signalling in young, but not older men; however, the role of exercise intensity on Nrf2 activation has not been tested. We hypothesised that a high-intensity interval session would elicit a greater Nrf2 response than moderate aerobic exercise. METHODS: Nrf2 signalling in response to two 30-min cycling protocols (high-intensity interval and constant workload) was compared in young men (25 ± 1y, n = 16). Participants completed exercise trials in random order with blood collected pre-, immediately post-, and 30-mins post exercise. Five participants completed a control trial without any physical activity. Nrf2 signalling was determined by measuring protein expression of Nrf2 in whole cell and nuclear fractions. Plasma 8-isoprostanes as well as peripheral mononuclear cell glutathione reductase (GR) and superoxide dismutase activity were measured as markers of oxidative stress. RESULTS: The exercise trials elicited significant increases in nuclear Nrf2 (p < .01), but increases in whole cell Nrf2 did not reach statistical significance. GR activity and plasma 8-isoprostanes increased significantly in response to exercise (p < .05), and GR response was higher in the high-intensity trial (p < .05). CONCLUSION: Our findings indicate that acute aerobic exercise elicits activation of nuclear Nrf2, regardless of exercise intensity, but that higher-intensity exercise results in greater activity of GR. Future experiments should explore the effect of exercise mode and duration on Nrf2 signalling, and the role of intensity in compromised populations.

Bioavailability and metabolism of phenolic compounds from wholegrain wheat and aleurone-rich wheat bread.

SCOPE: This work aimed at investigating absorption, metabolism, and bioavailability of phenolic compounds after consumption of wholegrain bread or bread enriched with an aleurone fraction. METHODS AND RESULTS: Two commercially available breads were consumed by 15 participants on three occasions and matched for either the amount of ferulic acid in the bread or the amount of bread consumed. Urine was collected for 48 h from all the volunteers for phenolic metabolite quantification. Blood samples were collected for 24 h following bread consumption in five participants. A total of 12 and 4 phenolic metabolites were quantified in urine and plasma samples, respectively. Metabolites were sulfate and glucuronic acid conjugates of phenolic acids, and high concentrations of ferulic acid-4'-O-sulfate, dihydroferulic acid-4'-O-sulfate, and dihydroferulic acid-O-glucuronide were observed. The bioavailability of ferulic acid was significantly higher from the aleurone-enriched bread when all ferulic acid metabolites were accounted for. CONCLUSIONS: The study shows that low amounts of aleurone-enriched bread resulted in equivalent plasma levels of ferulic acid as wholegrain bread. This could suggest that, if the absorbed phenolic metabolites after wholegrain product intake exert health benefits, equal levels could be reached through the consumption of lower doses of refined products enriched in aleurone fraction.

Using a Control to Better Understand Phyllosphere Microbiota.

An important data gap in our understanding of the phyllosphere surrounds the origin of the many microbes described as phyllosphere communities. Most sampling in phyllosphere research has focused on the collection of microbiota without the use of a control, so the opportunity to determine which taxa are actually driven by the biology and physiology of plants as opposed to introduced by environmental forces has yet to be fully realized. To address this data gap, we used plastic plants as inanimate controls adjacent to live tomato plants (phyllosphere) in the field with the hope of distinguishing between bacterial microbiota that may be endemic to plants as opposed to introduced by environmental forces. Using 16S rRNA gene amplicons to study bacterial membership at four time points, we found that the vast majority of all species-level operational taxonomic units were shared at all time-points. Very few taxa were unique to phyllosphere samples. A higher taxonomic diversity was consistently observed in the control samples. The high level of shared taxonomy suggests that environmental forces likely play a very important role in the introduction of microbes to plant surfaces. The observation that very few taxa were unique to the plants compared to the number that were unique to controls was surprising and further suggests that a subset of environmentally introduced taxa thrive on plants. This finding has important implications for improving our approach to the description of core phytobiomes as well as potentially helping us better understand how foodborne pathogens may become associated with plant surfaces.

Magnetic resonance myocardial perfusion imaging in the diagnosis of functionally significant obstructive coronary artery disease: a systematic review protocol.

BACKGROUND: Cardiac magnetic resonance (CMR) myocardial perfusion imaging has been suggested as a non-invasive alternative to pressure wire guided fractional flow reserve (FFR) in detecting haemodynamically significant obstructive coronary artery disease (CAD). The objective of this systematic review is to determine the diagnostic accuracy of CMR and to compare it to FFR. METHODS/DESIGN: A systematic review of diagnostic test accuracy of CMR and FFR will be conducted. Relevant English-language articles published before November 2013 in Medline, PubMed, EMBASE, Google scholar, Scopus and Cochrane databases will be identified. Relevant referenced articles from those selected will also be analysed. Articles describing diagnostic studies that compared CMR to FFR in patients with known or suspected coronary artery disease will be included. Two investigators will independently screen, assess quality and extract data from the selected articles. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool will be used to assess methodological quality. STATA 13 (the xtmelogit command) software will be used to calculate bivariate random effects models and estimate pooled sensitivity and specificity with 95% confidence intervals. Forests plots and summary receiver operating characteristics curves will also be generated. Sub-group pooled analyses using image quality of CMR (in terms of magnetic flux density - Tesla) and basis of analyses (coronary arterial territory vs. patients basis) at different FFR cutoffs (≤0.75 and ≤0.8) will also be performed. DISCUSSION: This systematic review will help to determine if CMR is an adequate alternative to FFR in the diagnosis of significant and obstructive CAD. We will also be able to assess diagnostic accuracy of specific types of CMR scan at different FFR cutoffs. SYSTEMATIC REVIEW REGISTRATION: This systematic review had been registered at PROSPERO and the registration number is CRD42013006180.

Comparing source of agricultural contact water and the presence of fecal indicator organisms on the surface of 'juliet' grape tomatoes.

Consumption of fresh tomatoes (Solanum lycopersicum) has been implicated as the cause of several foodborne illness outbreaks in the United States, most notably in cases of salmonellosis. How the levels of fecal indicator organisms (FIOs) in water relate to the counts of these microorganisms on the tomato fruit surface is unknown, although microbial water quality standards exist for agricultural use. This study utilized four types of FIOs currently and historically used in microbial water quality standards (Enterobacteriaceae, total coliforms, fecal coliforms, and Escherichia coli) to monitor the water quality of two surface ponds and a groundwater source. The groundwater tested contained significantly lower counts of all FIOs than the two surface water sources (P < 0.05). Considerable variability in bacterial counts was found in the surface water sources over the course of the season, perhaps explained by environmental variables, such as water temperature, pH, precipitation, and air temperature (R(2) of 0.13 to 0.27). We also monitored the fruit surface of grape tomatoes treated with overhead applications of the different water sources over the 2009 and 2010 growing seasons. The type of water source and time of year significantly affected the populations of FIOs in irrigation water (P < 0.05). Despite up to 5-log differences in fecal coliforms and 3-log differences in E. coli between the water sources, there was little difference in the populations measured in washes taken from tomato fruits. This lack of association between the aforementioned FIOs present in the water samples and on the tomato fruit surface demonstrates the difficulty in developing reliable metrics needed for testing of agricultural water to ensure the effectiveness of food safety programs.