A double-blind randomized controlled trial of the effects of eicosapentaenoic acid supplementation on muscle inflammation and physical function in patients undergoing colorectal cancer resection

BackgroundResection of colorectal cancer (CRC) initiates inflammation, mediated at least partly by NFĸB (nuclear factor kappa-light-chain-enhancer of activated B-cells), leading to muscle catabolism and reduced physical performance. Eicosapentaenoic acid (EPA) has been shown to modulate NFĸB, but evidence for its benefit around the time of surgery is limited.ObjectiveTo assess the effect of EPA supplementation on muscle inflammation and physical function around the time of major surgery.DesignIn a double-blind randomized control trial, 61 patients (age: 68.3 ± 0.95 y; 42 male) scheduled for CRC resection, received 3 g per day of EPA (n = 32) or placebo (n = 29) for 5-days before and 21-days after operation. Lean muscle mass (LMM) (via dual energy X-ray absorptiometry (DXA)), anaerobic threshold (AT) (via cardiopulmonary exercise testing (CPET)) and hand-grip strength (HG) were assessed before and 4-weeks after surgery, with muscle biopsies (m. vastus lateralis) obtained for the assessment of NF-ĸB protein expression.ResultsThere were no differences in muscle NFĸB between EPA and placebo groups (mean difference (MD) −0.002; 95% confidence interval (CI) −0.19 to 0.19); p = 0.98). There was no difference in LMM (MD 704.77 g; 95% CI -1045.6 g–2455.13 g; p = 0.42) or AT (MD 1.11 mls/kg/min; 95% CI -0.52 mls/kg/min to 2.74 mls/kg/min; p = 0.18) between the groups. Similarly, there was no difference between the groups in HG at follow up (MD 0.1; 95% CI -1.88 to 2.08; p = 0.81). Results were similar when missing data was imputed.ConclusionEPA supplementation confers no benefit in terms of inflammatory status, as judged by NFĸB, or preservation of LMM, aerobic capacity or physical function following major colorectal surgery

Comprehensive, long-term evaluation of pancreatic exocrine insufficiency after pancreatoduodenectomy

AIMS: Treatment of pancreatic exocrine insufficiency (PEI) following pancreatoduodenectomy (PD) improves quality of life, clinical outcomes, and survival. However, diagnosing PEI following PD is challenging owing to the difficulties with current tests and often non-specific symptoms. This work aims to quantify the true rate of long-term PEI in patients following a PD.METHODS: Patients underwent a PEI screen approximately one to two years following PD for oncologic indication, including the 13C Mixed triglyceride breath test (13CMTGT), faecal elastase 1 (FE-1) and the PEI Questionnaire (PEI-Q). Four reviewers with expertise in PEI reviewed the results blinded to other decisions to classify PEI status; disagreements were resolved on consensus.RESULTS: 26 patients were recruited. Of those with valid test results, these were indicative of PEI based on pre-specified thresholds for 60 % (15/25) for the 13CMTGT, 82 % (18/22) for FE-1, and 88 % (22/25) for the PEI-Q. After discussion between reviewers, the consensus PEI prevalence was 81 % (95 % CI: 61-93 %; 21/26), with 50 % (N = 13) classified as having severe, 23 % (N = 6) moderate, and 8 % (N = 2) mild PEI.DISCUSSION: Since no ideal test exists for PEI, this collation of diagnostic modalities and blinded expert review was designed to ascertain the true rate of long-term PEI following PD. This required our cohort to survive a year, travel to hospital, and undergo a period of starvation and PERT hold, and therefore there is likely to be recruitment bias towards fitter, younger patients with less aggressive pathology. Despite this, over 80 % were deemed to have PEI, with over 90 % of these being considered moderate or severe.</p

Occludin Independently Regulates Permeability under Hydrostatic Pressure and Cell Division in Retinal Pigment Epithelial Cells

PURPOSE. The aim of this study was to determine the function of the tight junction protein occludin in the control of permeability, under diffusive and hydrostatic pressures, and its contribution to the control of cell division in retinal pigment epithelium. METHODS. Occludin expression was inhibited in the human retinal pigment epithelial cell line ARPE-19 by siRNA. Depletion of occludin was confirmed by Western blot, confocal microscopy, and RT-PCR. Paracellular permeability of cell monolayers to fluorescently labeled 70 kDa dextran, 10 kDa dextran, and 467 Da tetramethylrhodamine (TAMRA) was examined under diffusive conditions or after the application of 10 cm H 2 O transmural pressure. Cell division rates were determined by tritiated thymidine incorporation and Ki67 immunoreactivity. Cell cycle inhibitors were used to determine whether changes in cell division affected permeability. RESULTS. Occludin depletion increased diffusive paracellular permeability to 467 Da TAMRA by 15%, and permeability under hydrostatic pressure was increased 50% compared with control. Conversely, depletion of occludin protein with siRNA did not alter diffusive permeability to 70 kDa and 10 kDa RITCdextran, and permeability to 70 kDa dextran was twofold lower in occludin-depleted cells under hydrostatic pressure conditions. Occludin depletion also increased thymidine incorporation by 90% and Ki67-positive cells by 50%. Finally, cell cycle inhibitors did not alter the effect of occludin siRNA on paracellular permeability. CONCLUSIONS. The data suggest that occludin regulates tight junction permeability in response to changes in hydrostatic pressure. Furthermore, these data suggest that occludin also contributes to the control of cell division, demonstrating a novel function for this tight junction protein. (Invest Ophthalmol Vis Sci

Short-term, equipment-free high intensity interval training elicits significant improvements in the cardiorespiratory fitness of young adults irrespective of supervision

Introduction:Serious health implications from having low levels of cardiorespiratory fitness (CRF) and/or being overweight in young adulthood are carried forward into later life. High-intensity interval training (HIIT) is a time-effective, potent stimulus for improving CRF and indices of cardiometabolic health. To date, few studies have investigated the use of equipment-free HIIT or the impact of supervision for improving CRF via HIIT.Methods:Thirty healthy young adults (18-30 y) were randomised to 4 weeks equipment-free supervised HIIT (L-HIIT), unsupervised HIIT (H-HIIT) or no-intervention (CON). Measurements of CRF (anaerobic threshold (AT) and VO2peak (VO2)), blood pressure (BP), body mass index (BMI), blood glucose, plasma insulin and muscle architecture were performed at baseline and after the intervention.Results:Both HIIT protocols improved CRF (AT: L-HIIT mean difference (MD) +2.1 (95% CI: 0.34 to 4.03) ml/kg/min; p=0.02; H-HIIT MD +3.01 (1.17 to 4.85) ml/kg/min; p=0.002), VO2: L-HIIT MD +2.94 (0.64 to 5.25) ml/kg/min; p=0.01; H-HIIT MD +2.55 (0.34 to 4.76) ml/kg/min; p=0.03), BMI (L-HIIT MD 0.18 (-0.35 to 0.5) kg/m2; p=0.04; H-HIIT: MD 0.19 (-0.25 to 0.63) kg/m2; p=0.03) and m. vastus lateralis pennation angle (L-HIIT MD 0.2 (0.13 to 0.27)º; p[less than]0.001; H-HIIT MD 0.17 (0.09 to 0.24)º; p[less than]0.001). There was no significant change in BP, glucose or insulin in any of the groups.Conclusions:Four weeks’ time-efficient, equipment-free, bodyweight-based HIIT ais able to elicit improvements in CRF irrespective of supervision status. Unsupervised HIIT may be a useful tool for counteracting the rise of sedentary behaviours and consequent cardiometabolic disorders in young adults

Herschel observations of EXtraordinary Sources: Analysis of the full Herschel/HIFI molecular line survey of Sagittarius B2(N)

A sensitive broadband molecular line survey of the Sagittarius B2(N) star-forming region has been obtained with the HIFI instrument on the Herschel Space Observatory, offering the first high-spectral resolution look at this well-studied source in a wavelength region largely inaccessible from the ground (625-157 um). From the roughly 8,000 spectral features in the survey, a total of 72 isotopologues arising from 44 different molecules have been identified, ranging from light hydrides to complex organics, and arising from a variety of environments from cold and diffuse to hot and dense gas. We present an LTE model to the spectral signatures of each molecule, constraining the source sizes for hot core species with complementary SMA interferometric observations, and assuming that molecules with related functional group composition are cospatial. For each molecule, a single model is given to fit all of the emission and absorption features of that species across the entire 480-1910 GHz spectral range, accounting for multiple temperature and velocity components when needed to describe the spectrum. As with other HIFI surveys toward massive star forming regions, methanol is found to contribute more integrated line intensity to the spectrum than any other species. We discuss the molecular abundances derived for the hot core, where the local thermodynamic equilibrium approximation is generally found to describe the spectrum well, in comparison to abundances derived for the same molecules in the Orion KL region from a similar HIFI survey.Comment: Accepted to ApJ. 64 pages, 14 figures. Truncated abstrac

Irradiation of the secondary star in X-ray Nova Scorpii 1994 (=GRO J1655--40)

We have obtained intermediate resolution optical spectra of the black-hole candidate Nova Sco 1994 in June 1996, when the source was in an X-ray/optical active state (R~15.05). We measure the radial velocity curve of the secondary star and obtain a semi-amplitude of 279+/-10 km/s; a value which is 30 per cent larger than the value obtained when the source is in quiescence. Our large value for K_2 is consistent with 60 +9,-7 per cent of the secondary star's surface being heated; compared to 35 per cent, which is what one would expect if only the inner face of the secondary star were irradiated. Effects such as irradiation-induced flows on the secondary star may be important in explaining the observed large value for K_2.Comment: 5 pages, 2 figures, accepted by MNRA

Short-term (<8 weeks) high-intensity interval training in diseased cohorts

Background & Aim: Exercise training regimes can lead to improvements in measures of cardiorespiratory fitness (CRF), improved general health, and reduced morbidity and overall mortality risk. High intensity interval training (HIIT) offers a time-efficient approach to improve CRF in healthy individuals, but the relative benefits of HIIT compared to traditional training methods are unknown in across different disease cohorts. Methods: This systematic review and meta-analysis compares CRF gains in randomised controlled trials of short-term (<8 weeks) HIIT vs. either no exercise control (CON) or moderate continuous exercise training (MCT) within diseased cohorts. Literature searches of the following databases were performed: MEDLINE, EMBASE, CINAHL, AMED, and PubMed (all from inception to 1st December 2017), with further searches of Clinicaltrials.gov and citations via Google Scholar. Primary outcomes were effect upon CRF variables; VO2peak and Anaerobic Threshold (AT). Results: Thirty-nine studies met the inclusion criteria. HIIT resulted in a clinically significant increase in VO2peak compared with CON (mean difference (MD) 3.32 ml∙kg-1∙min-1; 95% CI 2.56 to 2.08). Overall HIIT provided added benefit to VO2peak over MCT (MD 0.79 ml∙kg-1∙min-1; 95% CI 0.20 to 1.39). The benefit of HIIT was most marked in patients with cardiovascular disease when compared to MCT (VO2peak (MD 1.66 ml∙kg-1∙min-1; 95% CI 0.60 to 2.73); AT (MD 1.61 ml∙kg-1∙min-1; 95% CI 0.33 to 2.90)). Conclusions: HIIT elicits improvements in objective measures of CRF within 8 weeks in diseased cohorts compared to no intervention. When compared to MCT, HIIT imparts statistically significant additional improvements in measures of CRF, with clinically important additional improvements in VO2peak in cardiovascular patients. Comparative efficacy of HIIT vs MCT combined with an often reduced time commitment may warrant HIIT’s promotion as a viable clinical exercise intervention

Short-term (less 8 wk) high-intensity interval training in diseased cohorts

Background and Aim: Exercise training regimes can lead to improvements in measures of cardiorespiratory fitness (CRF), improved general health, and reduced morbidity and overall mortality risk. High-intensity interval training (HIIT) offers a time-efficient approach to improve CRF in healthy individuals, but the relative benefits of HIIT compared with traditional training methods are unknown in across different disease cohorts. Methods: This systematic review and meta-analysis compares CRF gains in randomized controlled trials of short-term (G8 wk) HIIT versus either no exercise control (CON) or moderate continuous training (MCT) within diseased cohorts. Literature searches of the following databases were performed: MEDLINE, EMBASE, CINAHL, AMED, and PubMed (all from inception to December 1, 2017), with further searches of Clinicaltrials.gov and citations via Google Scholar.Primary outcomes were effect on CRF variables: V˙ O2peak and anaerobic threshold. Results: Thirty-nine studies met the inclusion criteria. HIIT resulted in a clinically significant increase in V˙ O2peak compared with CON (mean difference [MD] = 3.32 mLIkgj1 Iminj1, 95% confidence interval [CI] = 2.56–2.08). Overall HIIT provided added benefit to V˙ O2peak over MCT (MD = 0.79 mLIkgj1 Iminj1, 95% CI =0.20–1.39). The benefit of HIIT was most marked in patients with cardiovascular disease when compared with MCT (V˙ O2peak: MD =1.66 mLIkgj1 Iminj1, 95% CI = 0.60–2.73; anaerobic threshold: MD = 1.61 mLIkgj1 Iminj1, 95% CI = 0.33–2.90). Conclusions: HIIT elicits improvements in objective measures of CRF within 8 wk in diseased cohorts compared with no intervention. When compared with MCT, HIIT imparts statistically significant additional improvements in measures of CRF, with clinically important additional improvements in V˙ O2peak in cardiovascular patients. Comparative efficacy of HIIT versus MCT combined with an often reduced time commitment may warrant HIIT_s promotion as a viable clinical exercise intervention

Exercise and other nonpharmacological strategies to reduce blood pressure in older adults: a systematic review and meta-analysis

The incidence of hypertension increases with advancing age and represents a significant burden of disease. Lifestyle modification represents the first-line intervention in treatment algorithms; however, the majority of evidence for this comes from studies involving young participants using interventions that may not always be feasible in the elderly. This manuscript presents a systematic review of all randomized controlled trials involving participants with a mean age of 65 or over investigating nonpharmacological strategies to reduce blood pressure (BP). Fifty-three randomized controlled trials were included. The majority of interventions described aerobic exercise training, dynamic resistance exercise training, or combined aerobic and dynamic resistance exercise training (COM), with limited studies reporting isometric exercise training or alternative lifestyle strategies. Aerobic exercise training, dynamic resistance exercise training, COM, and isometric exercise training all elicited significant reductions in both systolic and diastolic BP, with no additional benefit of COM compared with single modality exercise training. Three months of traditional exercise-based lifestyle intervention may produce a reduction in BP of approximately 5 mmHg systolic and 3 mmHg diastolic in older individuals, similar to that expected in younger individuals