No Association Between Consumption of Sweetened Beverages and Risk of Later-Onset Crohn's Disease or Ulcerative Colitis

Background & Aims: Consumption of sweetened beverages has been associated with inflammation based on measurements of C-reactive protein and tumor necrosis factor, as well as immune-mediated disorders including rheumatoid arthritis. We investigated associations with Crohn's disease (CD) or ulcerative colitis (UC). Methods: We conducted a prospective cohort study of 83,042 participants (age, 44–83 y) enrolled in the Cohort of Swedish Men or the Swedish Mammography Study. Dietary and lifestyle data were collected using a validated food frequency questionnaire at baseline in 1997. Diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modeling to calculate hazard ratios and 95% CIs. Results: Through December of 2014, we confirmed 143 incident cases of CD (incidence rate, 11 cases/100,000 person-years) and 349 incident cases of UC (incidence rate, 28 cases/100,000 person-years) over 1,264,345 person-years of follow-up evaluation. Consumption of sweetened beverages was not associated with increased risk of CD (Ptrend = .34) or UC (Ptrend = .40). Compared with participants who reported no consumption of sweetened beverages, the multivariable-adjusted hazard ratios for 1 or more servings per day were 1.02 for CD (95% CI, 0.60–1.73) and 1.14 for UC (95% CI, 0.83–1.57). The association between consumption of sugar-sweetened beverages and risk of CD or UC were not modified by age, sex (cohort), body mass index, or smoking (all Pinteraction ≥ .12). Conclusions: In analyses of data from 2 large prospective cohort studies from Sweden, we observed no evidence for associations between consumption of sweetened beverages and later risk of CD or UC

How Changing the Inversion/ Eversion Foot Angle Affects the Nondriving Intersegmental Knee Moments and the Relative Activation of the Vastii Muscles in Cycling

Nondriving intersegmental knee moment components (i.e., varus/valgus and internal/ external axial moments) neutral). A previously described mathematical model was used to compute the nondriving intersegmental knee moments throughout the crank cycle. The excitations of the VMO, VL, and TFL muscles were measured with surface electromyography and the muscle activations were computed. On average, the 10-deg everted position decreased the peak varus moment by 55% and decreased the peak internal axial moment by 53% during the power stroke (crank cycle region where the knee moment is extensor). A correlation analysis revealed that the VMO/VL activation ratio increase

A major population of mucosal memory CD4⁺ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality

Mucosal tissues contain large numbers of memory CD4(+) T cells that, through T-cell receptor-dependent interactions with antigen-presenting cells, are believed to have a key role in barrier defense and maintenance of tissue integrity. Here we identify a major subset of memory CD4(+) T cells at barrier surfaces that coexpress interleukin-18 receptor alpha (IL-18Rα) and death receptor-3 (DR3), and display innate lymphocyte functionality. The cytokines IL-15 or the DR3 ligand tumor necrosis factor (TNF)-like cytokine 1A (TL1a) induced memory IL-18Rα(+)DR3(+)CD4(+) T cells to produce interferon-γ, TNF-α, IL-6, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα(+)DR3(+)CD4(+) T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively, these results suggest that human memory IL-18Rα(+)DR3(+) CD4(+) T cells may contribute to antigen-independent innate responses at barrier surfaces.Mucosal Immunology advance online publication, 1 October 2014; doi:10.1038/mi.2014.87

High-intensity interval training for reducing blood pressure: a randomized trial vs. moderate-intensity continuous training in males with overweight or obesity

The optimal exercise-training characteristics for reducing blood pressure (BP) are unclear. We investigated the effects of 6-weeks of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) on BP and aortic stiffness in males with overweight or obesity. Twenty-eight participants (18–45 years; BMI: 25–35 kg/m2) performed stationary cycling three times per week for 6 weeks. Participants were randomly allocated (unblinded) to work-matched HIIT (N = 16; 10 × 1-min intervals at 90–100% peak workload) or MICT (N = 12; 30 min at 65–75% peak heart rate). Central (aortic) and peripheral (brachial) BP and aortic stiffness was assessed before and after training. There were no significant group × time interactions for any BP measure (all p > 0.21). HIIT induced moderate reductions in central (systolic/diastolic ∆: −4.6/−3.5 mmHg, effect size d = −0.51/−0.40) and peripheral BP (−5.2/−4 mmHg, d = −0.45/−0.47). MICT induced moderate reductions in diastolic BP only (peripheral: −3.4 mmHg, d = −0.57; central: −3 mmHg, d = −0.50). The magnitude of improvement in BP was strongly negatively correlated with baseline BP (r = −0.66 to −0.78), with stronger correlations observed for HIIT (r = −0.73 to −0.88) compared with MICT (r = −0.43 to −0.61). HIIT was effective for reducing BP (~3–5 mmHg) in the overweight to obese cohort. Exercise training induced positive changes in central (aortic) BP. The BP-lowering effects of exercise training are more prominent in those with higher baseline BP, with stronger correlation in HIIT than MICT

The effect of high-intensity interval training and moderate-intensity continuous training on aerobic fitness and body composition in males with overweight or obesity: A randomized trial

The optimal exercise training characteristics for improving body composition in individuals with obesity are not clear. This study assessed the effects of 6-weeks of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) on aerobic fitness and body composition in males with overweight or obesity. Twenty-eight participants (18–45 years; BMI: 25–35 kg/m2) performed stationary cycling 3 times per week for 6 weeks. Participants were randomly allocated to work-matched HIIT (N = 16) (10 × 1-min intervals at ~90% peak heart rate) or MICT (N = 12) (30 min at 65–75% peak heart rate). Maximal aerobic capacity (VO2peak) and body composition were assessed before and after 6-week training. Both HIIT and MICT induced moderate increases in aerobic fitness (Δ% VO2peak: HIIT 9 ± 8%, ES = 0.42; MICT: 7 ± 13%, ES = 0.32) and work capacity (Δ% peak workload: HIIT 13 ± 10%, ES = 0.69: MICT 17 ± 15%, ES = 0.76), but these changes did not differ significantly between the groups (all p > 0.16). The effects of HIIT or MICT on body composition outcomes were negligible to small across whole-body and all regional-specific sites (all effect sizes ES = −0.19 to 0.38) and did not differ significantly between the groups (all p > 0.21). Short-term (6-weeks) cycling training did not improve body composition in males with overweight or obesity. Improvements in aerobic fitness were comparable between work-matched HIIT and MICT

Apoptosis-Like Death in Bacteria Induced by HAMLET, a Human Milk Lipid-Protein Complex

Background: Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. Methodology/Principal Findings: We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death. Conclusions/Significance: Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells

Universal Rights and Wrongs

This paper argues for the important role of customers as a source of competitive advantage and firm growth, an issue which has been largely neglected in the resource-based view of the firm. It conceptualizes Penrose’s (1959) notion of an ‘inside track’ and illustrates how in-depth knowledge about established customers combines with joint problem-solving activities and the rapid assimilation of new and previously unexploited skills and resources. It is suggested that the inside track represents a distinct and perhaps underestimated way of generating rents and securing long-term growth. This also implies that the sources of sustainable competitive advantage in important respects can be sought in idiosyncratic interfirm relationships rather than within the firm itself

Liquid Chromatography Electron Capture Dissociation Tandem Mass Spectrometry (LC-ECD-MS/MS) versus Liquid Chromatography Collision-induced Dissociation Tandem Mass Spectrometry (LC-CID-MS/MS) for the Identification of Proteins

Electron capture dissociation (ECD) offers many advantages over the more traditional fragmentation techniques for the analysis of peptides and proteins, although the question remains: How suitable is ECD for incorporation within proteomic strategies for the identification of proteins? Here, we compare LC-ECD-MS/MS and LC-CID-MS/MS as techniques for the identification of proteins.Experiments were performed on a hybrid linear ion trap–Fourier transform ion cyclotron resonance mass spectrometer. Replicate analyses of a six-protein (bovine serum albumin, apo-transferrin,lysozyme, cytochrome c, alcohol dehydrogenase, and β-galactosidase) tryptic digest were performed and the results analyzed on the basis of overall protein sequence coverage and sequence tag lengths within individual peptides. The results show that although protein coverage was lower for LC-ECDMS/MS than for LC-CID-MS/MS, LC-ECD-MS/MS resulted in longer peptide sequence tags,providing greater confidence in protein assignment

Electron Capture Dissociation Mass Spectrometry of Tyrosine Nitrated Peptides

In vivo protein nitration is associated with many disease conditions that involve oxidative stress and inflammatory response. The modification involves addition of a nitro group at the position ortho to the phenol group of tyrosine to give 3-nitrotyrosine. To understand the mechanisms and consequences of protein nitration, it is necessary to develop methods for identification of nitrotyrosine-containing proteins and localization of the sites of modification.Here, we have investigated the electron capture dissociation (ECD) and collision-induced association (CID) behavior of 3-nitrotyrosine-containing peptides. The presence of nitration did not affect the CID behavior of the peptides. For the doubly-charged peptides, addition of nitration severely inhibited the production of ECD sequence fragments. However, ECD of the triply-charged nitrated peptides resulted in some singly-charged sequence fragments. ECD of the nitrated peptides is characterized by multiple losses of small neutral species including hydroxyl radicals, water and ammonia. The origin of the neutral losses has been investigated by use of activated ion (AI) ECD. Loss of ammonia appears to be the result of non-covalent interactions between the nitro group and protonated lysine side-chains

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-α and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes (P=0.028), CD3 (P=0.017), CD57 (P=0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0.015), CD57 (P=0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 (P=0.047), baseline CD57 (P=0.035), CD3 at one month (P=0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients