Association between walking pace and stroke incidence: findings from the UK Biobank prospective cohort study

Background and Purpose— Stroke incidence in younger and middle-aged people is growing. Despite this, its associations in this subset of the stroke population are unknown, and prevention strategies are not tailored to meet their needs. This study examined the association between self-reported walking pace and incident stroke. Methods— Data from the UK Biobank were used in a prospective population-based study. Three hundred and sixty-three thousand, one hundred and thirty-seven participants aged 37 to 73 years (52% women) were recruited. The associations of self-reported walking pace with stroke incidence over follow-up were investigated using Cox proportional-hazard models. Results— Among 363,137 participants, 2705 (0.7%) participants developed a fatal or nonfatal stroke event over the mean follow-up period of 6.1 years (interquartile range, 5.4–6.7). Slow walking pace was associated with a higher hazard for stroke incidence (hazard ratio [HR], 1.45 [95% CI, 1.26–1.66]; P<0.0001). Stroke incidence was not associated with walking pace among people <65 years of age. However, slow walking pace was associated with a higher risk of stroke among participants aged ≥65 years (HR, 1.42 [95% CI, 1.17–1.72]; P<0.0001). A higher risk for stroke was observed on those with middle (HR, 1.28 [95% CI, 1.01–1.63]; P=0.039) and higher (HR, 1.29 [95% CI, 1.05–1.69]; P=0.012) deprivation levels but not in the least deprived individuals. Similarly, overweight (HR, 1.30 [95% CI, 1.04–1.63]; P=0.019) and obese (HR, 1.33 [95% CI, 1.09–1.63]; P=0.004) but not normal-weight individuals had a higher risk of stroke incidence. Conclusions— Slow walking pace was associated with a higher risk of stroke among participants over 64 years of age in this population-based cohort study. The addition of the measurement of self-reported walking pace to primary care or public health clinical consultations may be a useful screening tool for stroke risk

Short-Term Very High Carbohydrate Diet and Gut-Training Have Minor Effects on Gastrointestinal Status and Performance in Highly Trained Endurance Athletes

We implemented a multi-pronged strategy (MAX) involving chronic (2 weeks high carbohydrate [CHO] diet + gut-training) and acute (CHO loading + 90 g·h(−1) CHO during exercise) strategies to promote endogenous and exogenous CHO availability, compared with strategies reflecting lower ranges of current guidelines (CON) in two groups of athletes. Nineteen elite male race walkers (MAX: 9; CON:10) undertook a 26 km race-walking session before and after the respective interventions to investigate gastrointestinal function (absorption capacity), integrity (epithelial injury), and symptoms (GIS). We observed considerable individual variability in responses, resulting in a statistically significant (p < 0.001) yet likely clinically insignificant increase (Δ 736 pg·mL(−1)) in I-FABP after exercise across all trials, with no significant differences in breath H(2) across exercise (p = 0.970). MAX was associated with increased GIS in the second half of the exercise, especially in upper GIS (p < 0.01). Eighteen highly trained male and female distance runners (MAX: 10; CON: 8) then completed a 35 km run (28 km steady-state + 7 km time-trial) supported by either a slightly modified MAX or CON strategy. Inter-individual variability was observed, without major differences in epithelial cell intestinal fatty acid binding protein (I-FABP) or GIS, due to exercise, trial, or group, despite the 3-fold increase in exercise CHO intake in MAX post-intervention. The tight-junction (claudin-3) response decreased in both groups from pre- to post-intervention. Groups achieved a similar performance improvement from pre- to post-intervention (CON = 39 s [95 CI 15–63 s]; MAX = 36 s [13–59 s]; p = 0.002). Although this suggests that further increases in CHO availability above current guidelines do not confer additional advantages, limitations in our study execution (e.g., confounding loss of BM in several individuals despite a live-in training camp environment and significant increases in aerobic capacity due to intensified training) may have masked small differences. Therefore, athletes should meet the minimum CHO guidelines for training and competition goals, noting that, with practice, increased CHO intake can be tolerated, and may contribute to performance outcomes

Short-term very high carbohydrate diet and gut-training have minor effects on gastrointestinal status and performance in highly trained endurance athletes

We implemented a multi-pronged strategy (MAX) involving chronic (2 weeks high carbohydrate [CHO] diet + gut-training) and acute (CHO loading + 90 g·h−1 CHO during exercise) strategies to promote endogenous and exogenous CHO availability, compared with strategies reflecting lower ranges of current guidelines (CON) in two groups of athletes. Nineteen elite male race walkers (MAX: 9; CON:10) undertook a 26 km race-walking session before and after the respective interventions to investigate gastrointestinal function (absorption capacity), integrity (epithelial injury), and symptoms (GIS). We observed considerable individual variability in responses, resulting in a statistically significant (p < 0.001) yet likely clinically insignificant increase (Δ 736 pg·mL−1) in I-FABP after exercise across all trials, with no significant differences in breath H2 across exercise (p = 0.970). MAX was associated with increased GIS in the second half of the exercise, especially in upper GIS (p < 0.01). Eighteen highly trained male and female distance runners (MAX: 10; CON: 8) then completed a 35 km run (28 km steady-state + 7 km time-trial) supported by either a slightly modified MAX or CON strategy. Inter-individual variability was observed, without major differences in epithelial cell intestinal fatty acid binding protein (I-FABP) or GIS, due to exercise, trial, or group, despite the 3-fold increase in exercise CHO intake in MAX post-intervention. The tight-junction (claudin-3) response decreased in both groups from pre- to post-intervention. Groups achieved a similar performance improvement from pre- to post-intervention (CON = 39 s [95 CI 15–63 s]; MAX = 36 s [13–59 s]; p = 0.002). Although this suggests that further increases in CHO availability above current guidelines do not confer additional advantages, limitations in our study execution (e.g., confounding loss of BM in several individuals despite a live-in training camp environment and significant increases in aerobic capacity due to intensified training) may have masked small differences. Therefore, athletes should meet the minimum CHO guidelines for training and competition goals, noting that, with practice, increased CHO intake can be tolerated, and may contribute to performance outcomes

Tumor Invasion of Salmonella enterica Serovar Typhimurium Is Accompanied by Strong Hemorrhage Promoted by TNF-α

BACKGROUND:Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the tumors is still unclear. However, this is an important issue to be clarified when bacteria should be tailored for application in cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS:We describe the initial events of colonization of an ectopic transplantable tumor by Salmonella enterica serovar Typhimurium. Initially, after intravenous administration, bacteria were found in blood, spleen, and liver. Low numbers were also detected in tumors associated with blood vessels as could be observed by immunohistochemistry. A rapid increase of TNF-alpha in blood was observed at that time, in addition to other pro-inflammatory cytokines. This induced a tremendous influx of blood into the tumors by vascular disruption that could be visualized in H&E stainings and quantified by hemoglobin measurements of tumor homogenate. Most likely, together with the blood, bacteria were flushed into the tumor. In addition, blood influx was followed by necrosis formation, bacterial growth, and infiltration of neutrophilic granulocytes. Depletion of TNF-alpha retarded blood influx and delayed bacterial tumor-colonization. CONCLUSION:Our findings emphasize similarities between Gram-negative tumor-colonizing bacteria and tumor vascular disrupting agents and show the involvement of TNF-alpha in the initial phase of tumor-colonization by bacteria

Crohn's Disease and Early Exposure to Domestic Refrigeration

Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood.Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD.This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood

Geographical information system and environmental epidemiology: a cross-sectional spatial analysis of the effects of traffic-related air pollution on population respiratory health

<p>Abstract</p> <p>Background</p> <p>Traffic-related air pollution is a potential risk factor for human respiratory health. A Geographical Information System (GIS) approach was used to examine whether distance from a main road (the Tosco-Romagnola road) affected respiratory health status.</p> <p>Methods</p> <p>We used data collected during an epidemiological survey performed in the Pisa-Cascina area (central Italy) in the period 1991-93. A total of 2841 subjects participated in the survey and filled out a standardized questionnaire on health status, socio-demographic information, and personal habits. A variable proportion of subjects performed lung function and allergy tests. Highly exposed subjects were defined as those living within 100 m of the main road, moderately exposed as those living between 100 and 250 m from the road, and unexposed as those living between 250 and 800 m from the road. Statistical analyses were conducted to compare the risks for respiratory symptoms and diseases between exposed and unexposed. All analyses were stratified by gender.</p> <p>Results</p> <p>The study comprised 2062 subjects: mean age was 45.9 years for men and 48.9 years for women. Compared to subjects living between 250 m and 800 m from the main road, subjects living within 100 m of the main road had increased adjusted risks for persistent wheeze (OR = 1.76, 95% CI = 1.08-2.87), COPD diagnosis (OR = 1.80, 95% CI = 1.03-3.08), and reduced FEV₁/FVC ratio (OR = 2.07, 95% CI = 1.11-3.87) among males, and for dyspnea (OR = 1.61, 95% CI = 1.13-2.27), positivity to skin prick test (OR = 1.83, 95% CI = 1.11-3.00), asthma diagnosis (OR = 1.68, 95% CI = 0.97-2.88) and attacks of shortness of breath with wheeze (OR = 1.67, 95% CI = 0.98-2.84) among females.</p> <p>Conclusion</p> <p>This study points out the potential effects of traffic-related air pollution on respiratory health status, including lung function impairment. It also highlights the added value of GIS in environmental health research.</p

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.Swedish Research Council et al.Manuscrip

Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791

Towards the design of 3D multiscale instructive tissue engineering constructs: Current approaches and trends

The design of 3D constructs with adequate properties to instruct and guide cells both in vitro and in vivo is one of the major focuses of tissue engineering. Successful tissue regeneration depends on the favorable crosstalk between the supporting structure, the cells and the host tissue so that a balanced matrix production and degradation is achieved. Herein, the major occurring events and players in normal and regenerative tissue are overviewed. These have been inspiring the selection or synthesis of instructive cues to include into the 3D constructs. We further highlight the importance of a multiscale perception of the range of features that can be included on the biomimetic structures. Lastly, we focus on the current and developing tissue-engineering approaches for the preparation of such 3D constructs: top-down, bottom-up and integrative. Bottom-up and integrative approaches present a higher potential for the design of tissue engineering devices with multiscale features and higher biochemichal control than top-down strategies, and are the main focus of this review.The research leading to these results has received funding from the European Research Council grant agreement ERC-2012-ADG-20120216-321266 for the project ComplexiTE. Portuguese Foundation for Science and Technology is gratefully acknowledged for the fellowship of Sara M. Oliveira (SFRH/BD/70107/2010)