Moderate exercise increases affinity of large very low density lipoproteins for hydrolysis by lipoprotein lipase

Context: Postprandial triglyceride (TG) concentration is independently associated with cardiovascular disease risk. Exercise reduces postprandial TG concentrations but the mechanisms responsible are unclear. Objective: To determine the effects of exercise on affinity of chylomicrons, large very low density lipoproteins (VLDL1) and smaller VLDL (VLDL2) for lipoprotein lipase (LPL) mediated TG hydrolysis. Design: Within-participant cross-over study. Setting: A University metabolic investigation unit. Participants: Ten overweight/obese men. Interventions: Participants undertook two oral fat tolerance tests, separated by 7–14 days, in which they had blood taken fasting and for 4 hours after a high-fat mixed meal. On the afternoon before one test, they performed a 90-minute treadmill walk at 50% maximal oxygen uptake (EX); no exercise was performed before the control test (CON). Main outcome measures: Circulating TG-rich lipoprotein concentrations; affinity of chylomicrons, VLDL1, VLDL2 for LPL-mediated TG hydrolysis. Results: Exercise significantly reduced fasting VLDL1-TG concentration (CON: 0.49(0.33–0.72) mmol.l−1, EX: 0.36(0.22–0.59) mmol.l−1, [geometric means (95% confidence interval)]; p=0.04). Time-averaged postprandial chylomicron-TG (CON: 0.55±0.10 mmol.l−1, EX: 0.39±0.08 mmol.l−1, [mean±SEM], p=0.03) and VLDL1-TG (CON: 0.85±0.13 mmol.l−1, EX: 0.66±0.10 mmol.l−1, p=0.01) concentrations were both lower in EX than CON. Affinity of VLDL1 for LPL-mediated TG hydrolysis increased by 2.2(1.3–3.7) fold (geometric mean (95% confidence interval)) (p=0.02) in the fasted state and 2.6(1.8–2.6) fold (p=0.001) postprandially. Affinity of chylomicrons and VLDL2 was not significantly different between trials. Conclusions: Exercise increases affinity of VLDL1 for LPL-mediated TG hydrolysis both fasting and postprandially. This mechanism is likely to contribute to exercise's TG-lowering effect

Bacteriophages of Erwinia amylovora and their potential use in biological control

Forty-four bacteriophage isolates of Erwinia amy/ovora, the causal agent of fire blight, were collected from sites in and around the Niagara Region of Southern Ontario in the summer of 1998. Phages were isolated only from sites where fire blight was present. Thirty-seven of these phages were isolated from the soil surrounding infected trees, with the remainder isolated from aerial plant tissue samples. A mixture of six E. amy/ovora bacterial host strains was used to enrich field samples in order to avoid the selection bias of a single-host system. Molecular characterization of the phages with a combination of peR and restriction endonuclease digestions showed that six distinct phage types were isolated. Ten phage isolates related to the previously characterized E. amy/ovora phage PEa1 were isolated, with some divergence of molecular markers between phages isolated from different sites. The host ranges of the phages revealed that certain types were unable to efficiently lyse some E. amy/ovora strains, and that some types were able to lyse the epiphytic bacterium Pantoea agg/omerans. Biological control of E. amy/ovora by the bacteriophages was assessed in a bioassay using discs of immature pear fruit. Twenty-three phage isolates were able to significantly suppress the incidence of bacterial exudate on the pear disc surface. Quantification of the bacterial population remaining on the disc surface indicated that population reductions of up to 97% were obtainable by phage treatment, but that elimination of bacteria from the surface was not possible with this model system

Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge

Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages - GordTnk2, Gmala1, and GordDuk1 - had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5–15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment

The habits of highly effective phages: population dynamics as a framework for identifying therapeutic phages

The use of bacteriophages as antibacterial agents is being actively researched on a global scale. Typically, the phages used are isolated from the wild by plating on the bacteria of interest, and a far larger set of candidate phages is often available than can be used in any application. When an excess of phages is available, how should the best phages be identified? Here we consider phage-bacterial population dynamics as a basis for evaluating and predicting phage success. A central question is whether the innate dynamical properties of phages are the determinants of success, or instead, whether extrinsic, indirect effects can be responsible. We address the dynamical perspective, motivated in part by the absence of dynamics in previously suggested principles of phage therapy. Current mathematical models of bacterial-phage dynamics do not capture the realities of in vivo dynamics, nor is this likely to change, but they do give insight to qualitative properties that may be generalizable. In particular, phage adsorption rate may be critical to treatment success, so understanding the effects of the in vivo environment on host availability may allow prediction of useful phages prior to in vivo experimentation. Principles for predicting efficacy may be derived by developing a greater understanding of the in vivo system, or such principles could be determined empirically by comparing phages with known differences in their dynamic properties. The comparative approach promises to be a powerful method of discovering the key to phage success. We offer five recommendations for future study: (i) compare phages differing in treatment efficacy to identify the phage properties associated with success, (ii) assay dynamics in vivo, (iii) understand mechanisms of bacterial escape from phages, (iv) test phages in model infections that are relevant to the intended clinical applications, and (v) develop new classes of models for phage growth in spatially heterogeneous environments

Effects of diabetes family history and exercise training on the expression of adiponectin and leptin and their receptors

The daughters of patients with diabetes have reduced insulin sensitivity index (ISI) scores compared with women with no family history of diabetes, but their ISI increase more in response to exercise training(1). The present study aimed to determine whether differences between these groups in exercise-induced changes in circulating adiponectin and leptin concentrations and expression of their genes and receptors in subcutaneous adipose tissue (SAT), could explain differences in the exercise-induced changes in ISI between women with and without a family history of diabetes

Non-exercise equations to estimate fitness in white European and South Asian men

Cardiorespiratory fitness is a strong, independent predictor of health, whether it is measured in an exercise test or estimated in an equation. The purpose of this study was to develop and validate equations to estimate fitness in middle-aged white European and South Asian men.Multiple linear regression models (n=168, including 83 white European and 85 South Asian men) were created using variables that are thought to be important in predicting fitness (VO2 max, mL⋅kg⋅min): age (years); BMI (kg·m); resting heart rate (beats⋅min); smoking status (0=never smoked, 1=ex or current smoker); physical activity expressed as quintiles (0=quintile 1, 1=quintile 2, 2=quintile 3, 3=quintile 4, 4=quintile 5), categories of moderate- to vigorous-intensity physical activity (0=<75 min⋅wk, 1=75-150 min⋅wk, 2=>150-225 min⋅wk, 3=>225-300 min⋅wk, 4=>300 min⋅wk), or minutes of moderate- to vigorous-intensity physical activity (min⋅wk); and, ethnicity (0=South Asian, 1=white). The leave-one-out-cross-validation procedure was used to assess the generalizability and the bootstrap and jackknife resampling techniques were used to estimate the variance and bias of the models.Around 70% of the variance in fitness was explained in models with an ethnicity variable, such as: VO2 max = 77.409 - (age*0.374) - (BMI*0.906) - (ex or current smoker*1.976) + (physical activity quintile coefficient) - (resting heart rate*0.066) + (white ethnicity*8.032), where physical activity quintile 1 is 1, 2 is 1.127, 3 is 1.869, 4 is 3.793, and 5 is 3.029. Only around 50% of the variance was explained in models without an ethnicity variable. All models with an ethnicity variable were generalizable and had low variance and bias.These data demonstrate the importance of incorporating ethnicity in non-exercise equations to estimate cardiorespiratory fitness in multi-ethnic populations

Biosecurity for Beef Cattle Operations

4 pp., 4 photosBiosecurity in the beef cattle industry involves understanding disease transmission and animal immunity, and then establishing a sound program for disease prevention. This publication explains general biosecurity practices

Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study

Objectives: While bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity. Design: Observational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively. Setting Multinational study of 9306 participants. Participants: Participants with biochemically confirmed impaired glucose tolerance had annual measurements of both weight and step count using research grade pedometers, worn for 7 days consecutively. Along with randomisation to valsartan or placebo plus nateglinide or placebo, participants took part in a lifestyle modification programme. Outcome measures: Longitudinal regression using weight as response value and physical activity as predictor value was conducted, adjusted for baseline covariates. Analysis was then repeated with physical activity as response value and weight as predictor value. Only participants with a response value preceded by at least three annual response values were included. Results: Adequate data were available for 2811 (30%) of NAVIGATOR participants. Previous weight (χ2=16.8; p<0.0001), but not change in weight (χ2=0.1; p=0.71) was inversely associated with subsequent step count, indicating lower subsequent levels of physical activity in heavier individuals. Change in step count (χ2=5.9; p=0.02) but not previous step count (χ2=0.9; p=0.34) was inversely associated with subsequent weight. However, in the context of trajectories already established for weight (χ2 for previous weight measurements 747.3; p<0.0001) and physical activity (χ2 for previous step count 432.6; p<0.0001), these effects were of limited clinical importance. Conclusions: While a prospective bidirectional relationship was observed between weight and physical activity, the magnitude of any effect was very small in the context of natural trajectories already established for these variables

Therapeutic Potential of Intravenous Phage as Standalone Therapy for Recurrent Drug-Resistant Urinary Tract Infections

Recurrent urinary tract infections (rUTI) are common in kidney transplant recipients (KTR) and are associated with multidrug resistance and increased morbidity/mortality. Novel antibiotic alternatives to reduce UTI recurrence are critically needed. We describe a case of rUTI due to extended spectrum beta lactamase (ESBL) Klebsiella pneumoniae in a KTR that was treated successfully with 4 weeks of adjunctive intravenous bacteriophage therapy alone, without concomitant antibiotics, and with no recurrence in a year of follow-up

Red and processed meat consumption and breast cancer: UK Biobank cohort study and meta-analysis

Aim: Red and processed meat may be risk factors for breast cancer due to their iron content, administration of oestrogens to cattle or mutagens created during cooking. We studied the associations in UK Biobank and then included the results in a meta-analysis of published cohort studies. Methods: UK Biobank, a general population cohort study, recruited participants aged 40–69 years. Incident breast cancer was ascertained via linkage to routine hospital admission, cancer registry and death certificate data. Univariate and multivariable Cox proportional hazard models were used to explore the associations between red and processed meat consumption and breast cancer. Previously published cohort studies were identified from a systematic review using PubMed and Ovid and a meta-analysis conducted using a random effects model. Results: Over a median of 7 years follow-up, 4819 of the 262,195 women developed breast cancer. The risk was increased in the highest tertile (>9 g/day) of processed meat consumption (adjusted hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.08–1.35, p = 0.001). Collation with 10 previous cohort studies provided data on 40,257 incident breast cancers in 1.65 million women. On meta-analysis, processed meat consumption was associated with overall (relative risk [RR] 1.06, 95% CI 1.01–1.11) and post-menopausal (RR 1.09, 95% CI 1.03–1.15), but not pre-menopausal (RR 0.99, 95% CI 0.88–1.10), breast cancer. In UK Biobank and the meta-analysis, red meat consumption was not associated with breast cancer (adjusted HR 0.99 95% CI 0.88–1.12 and RR 1.03, 95% CI 0.99–1.08, respectively). Conclusions: Consumption of processed meat, but not red meat, may increase the risk of breast cancer