Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner.

PURPOSE: To examine the dose-response effects of acute glutamine supplementation on markers of gastrointestinal (GI) permeability, damage and, secondary, subjective symptoms of GI discomfort in response to running in the heat. METHODS: Ten recreationally active males completed a total of four exercise trials; a placebo trial and three glutamine trials at 0.25, 0.5 and 0.9 g kg(-1) of fat-free mass (FFM) consumed 2 h before exercise. Each exercise trial consisted of a 60-min treadmill run at 70% of [Formula: see text] in an environmental chamber set at 30 °C. GI permeability was measured using ratio of lactulose to rhamnose (L:R) in serum. Plasma glutamine and intestinal fatty acid binding protein (I-FABP) concentrations were determined pre and post exercise. Subjective GI symptoms were assessed 45 min and 24 h post-exercise. RESULTS: Relative to placebo, L:R was likely lower following 0.25 g kg(-1) (mean difference: - 0.023; ± 0.021) and 0.5 g kg(-1) (- 0.019; ± 0.019) and very likely following 0.9 g kg(- 1) (- 0.034; ± 0.024). GI symptoms were typically low and there was no effect of supplementation. DISCUSSION: Acute oral glutamine consumption attenuates GI permeability relative to placebo even at lower doses of 0.25 g kg(-1), although larger doses may be more effective. It remains unclear if this will lead to reductions in GI symptoms. Athletes competing in the heat may, therefore, benefit from acute glutamine supplementation prior to exercise in order to maintain gastrointestinal integrity

Probiotic supplementation increases carbohydrate metabolism in trained male cyclists: a randomized, double-blind, placebo-controlled cross-over trial.

We hypothesised that probiotic supplementation (PRO) increases the absorption and oxidation of orally ingested maltodextrin during 2h endurance cycling, thereby sparing muscle glycogen for a subsequent time trial (simulating a road race). Measurements were made of lipid and carbohydrate oxidation, plasma metabolites and insulin, gastrointestinal permeability, and subjective symptoms of discomfort. Seven male cyclists were randomized to PRO (bacterial composition given in methods) or placebo (PLC) for four weeks, separated by a 14-day washout period. After each period, cyclists consumed a 10% maltodextrin solution (initial 8 mL·kg-1 bolus and 2 mL·kg-1 every 15 min) while exercising for 2h at 55% Wmax followed by a 100 kJ time trial. PRO resulted in small increases in peak oxidation rates of the ingested maltodextrin (0.84 ± 0.10 vs 0.77 ± 0.09 g·min-1, P = 0.016), and mean total carbohydrate oxidation (2.20 ± 0.25 vs 1.87 ± 0.39 g·min-1, P = 0.038), while fat oxidation was reduced (0.40 ± 0.11 vs 0.55 ± 0.10 g·min-1, P = 0.021) . During PRO small but significant increases were seen in glucose absorption, plasma glucose and insulin concentration and decreases in NEFA and glycerol. Differences between markers of GI damage and permeability and time trial performance were not significant (P > 0.05). In contrast to the hypothesis, PRO led to minimal increases in absorption and oxidation of the ingested maltodextrin and small reductions in fat oxidation, while having no effect on subsequent time trial performance

Developing Single-Molecule TPM Experiments for Direct Observation of Successful RecA-Mediated Strand Exchange Reaction

RecA recombinases play a central role in homologous recombination. Once assembled on single-stranded (ss) DNA, RecA nucleoprotein filaments mediate the pairing of homologous DNA sequences and strand exchange processes. We have designed two experiments based on tethered particle motion (TPM) to investigate the fates of the invading and the outgoing strands during E. coli RecA-mediated pairing and strand exchange at the single-molecule level in the absence of force. TPM experiments measure the tethered bead Brownian motion indicative of the DNA tether length change resulting from RecA binding and dissociation. Experiments with beads labeled on either the invading strand or the outgoing strand showed that DNA pairing and strand exchange occurs successfully in the presence of either ATP or its non-hydrolyzable analog, ATPγS. The strand exchange rates and efficiencies are similar under both ATP and ATPγS conditions. In addition, the Brownian motion time-courses suggest that the strand exchange process progresses uni-directionally in the 5′-to-3′ fashion, using a synapse segment with a wide and continuous size distribution

Does the surgeon still have a role to play in the diagnosis and management of lymphomas?

<p>Abstract</p> <p>Background</p> <p>Over the course of the past 40 years, there have been a significant number of changes in the way in which lymphomatous disease is diagnosed and managed. With the advent of computed tomography, there is little role for staging laparotomy and the surgeon's role may now more diagnostic than therapeutic.</p> <p>Aims</p> <p>To review all cases of lymphoma diagnosed at a single institution in order determine the current role of the surgeon in the diagnosis and management of lymphoma.</p> <p>Patients and methods</p> <p>Computerized pathology records were reviewed for a five-year period 1996 to 2000 to determine all cases of lymph node biopsy (incisional or excisional) in which tissue was obtained as part of a planned procedure. Cases of incidental lymphadenopathy were thus excluded.</p> <p>Results</p> <p>A total of 297 biopsies were performed of which 62 (21%) yielded lymphomas. There were 22 females and 40 males with a median age of 58 years (range: 19–84 years). The lymphomas were classified as 80% non-Hodgkin's lymphoma, 18% Hodgkin's lymphoma and 2% post-transplant lymphoproliferative disorder. Diagnosis was established by general surgeons (n = 48), ENT surgeons (n = 9), radiologists (n = 4) and ophthalmic surgeons (n = 1). The distribution of excised lymph nodes was: cervical (n = 23), inguinal (n = 15), axillary (n = 11), intra-abdominal (n = 6), submandibular (n = 2), supraclavicular (n = 2), periorbital (n = 1), parotid (n = 1) and mediastinal (n = 1). Fine needle aspiration cytology had been performed prior to biopsy in only 32 (52%) cases and had suggested: lymphoma (n = 10), reactive changes (n = 13), normal (n = 5), inadequate (n = 4). The majority (78%) of cervical lymph nodes were subjected to FNAC prior to biopsy whilst this was performed in only 36% of non-cervical lymphadenopathy.</p> <p>Conclusion</p> <p>The study has shown that lymphoma is a relatively common cause of surgical lymphadenopathy. Given the limitations of FNAC, all suspicious lymph nodes should be biopsied following FNAC even if the FNAC is reported normal or demonstrating reactive changes only. With the more widespread application of molecular techniques, and the development of improved minimally-invasive procedures, percutaneous and endoscopic techniques may come to dominate, however, at present; the surgeon still has an important role to play in the diagnosis if not treatment of lymphomas.</p

Snake Envenoming: A Disease of Poverty

Every year snake envenoming kills more people in the tropics than some of the world's recognised neglected tropical diseases (NTDs), including schistosomiasis and leishmaniasis. While lacking the epidemic potential of an infectious/vector-borne disease, snake envenoming in rural tropical communities has as great a medical mortality, if not morbidity, as the NTDs. The recent categorisation of snake envenoming as an NTD is an important advance that hopefully will result in the wider recognition and allocation of resources, particularly since death from snake envenoming is preventable; antivenom is very effective when the appropriate antivenom is correctly administered. Snake envenoming urgently requires international support to instigate the epidemiological, health education, and effective treatment initiatives that proved so potent in addressing the medical burden of NTDs such as leprosy and dracunculosis. All the global estimates of snake envenoming and deaths from snakebite indicate that mortality is highest in the world's tropical countries. Here we examined associations between the globally available data on (i) snakebite-induced mortality and (ii) socioeconomic markers of poverty. Our data unequivocally establishes that snake envenoming is globally associated with poverty, a distinctive characteristic of the neglected tropical diseases

Dynamics and Regulation of RecA Polymerization and De-Polymerization on Double-Stranded DNA

10.1371/journal.pone.0066712PLoS ONE86

A Powerful Test of Parent-of-Origin Effects for Quantitative Traits Using Haplotypes

Imprinting is an epigenetic phenomenon where the same alleles have unequal transcriptions and thus contribute differently to a trait depending on their parent of origin. This mechanism has been found to affect a variety of human disorders. Although various methods for testing parent-of-origin effects have been proposed in linkage analysis settings, only a few are available for association analysis and they are usually restricted to small families and particular study designs. In this study, we develop a powerful maximum likelihood test to evaluate the parent-of-origin effects of SNPs on quantitative phenotypes in general family studies. Our method incorporates haplotype distribution to take advantage of inter-marker LD information in genome-wide association studies (GWAS). Our method also accommodates missing genotypes that often occur in genetic studies. Our simulation studies with various minor allele frequencies, LD structures, family sizes, and missing schemes have uniformly shown that using the new method significantly improves the power of detecting imprinted genes compared with the method using the SNP at the testing locus only. Our simulations suggest that the most efficient strategy to investigate parent-of-origin effects is to recruit one parent and as many offspring as possible under practical constraints. As a demonstration, we applied our method to a dataset from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to test the parent-of-origin effects of the SNPs within the PPARGC1A, MTP and FABP2 genes on diabetes-related phenotypes, and found that several SNPs in the MTP gene show parent-of-origin effects on insulin and glucose levels

Are antifibrinolytic drugs equivalent in reducing blood loss and transfusion in cardiac surgery? A meta-analysis of randomized head-to-head trials

BACKGROUND: Aprotinin has been shown to be effective in reducing peri-operative blood loss and the need for re-operation due to continued bleeding in cardiac surgery. The lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) are cheaper, but it is not known if they are as effective as aprotinin. METHODS: Studies were identified by searching electronic databases and bibliographies of published articles. Data from head-to-head trials were pooled using a conventional (Cochrane) meta-analytic approach and a Bayesian approach which estimated the posterior probability of TXA and EACA being equivalent to aprotinin; we used as a non-inferiority boundary a 20% increase in the rates of transfusion or re-operation because of bleeding. RESULTS: Peri-operative blood loss was significantly greater with TXA and EACA than with aprotinin: weighted mean differences were 106 mls (95% CI 37 to 227 mls) and 185 mls (95% CI 134 to 235 mls) respectively. The pooled relative risks (RR) of receiving an allogeneic red blood cell (RBC) transfusion with TXA and EACA, compared with aprotinin, were 1.08 (95% CI 0.88 to 1.32) and 1.14 (95% CI 0.84 to 1.55) respectively. The equivalent Bayesian posterior mean relative risks were 1.15 (95% Bayesian Credible Interval [BCI] 0.90 to 1.68) and 1.21 (95% BCI 0.79 to 1.82) respectively. For transfusion, using a 20% non-inferiority boundary, the posterior probabilities of TXA and EACA being non-inferior to aprotinin were 0.82 and 0.76 respectively. For re-operation the Cochrane RR for TXA vs. aprotinin was 0.98 (95% CI 0.51 to 1.88), compared with a posterior mean Bayesian RR of 0.63 (95% BCI 0.16 to 1.46). The posterior probability of TXA being non-inferior to aprotinin was 0.92, but this was sensitive to the inclusion of one small trial. CONCLUSION: The available data are conflicting regarding the equivalence of lysine analogues and aprotinin in reducing peri-operative bleeding, transfusion and the need for re-operation. Decisions are sensitive to the choice of clinical outcome and non-inferiority boundary. The data are an uncertain basis for replacing aprotinin with the cheaper lysine analogues in clinical practice. Progress has been hampered by small trials and failure to study clinically relevant outcomes

The importance of organizational characteristics for improving outcomes in patients with chronic disease: a systematic review of congestive heart failure

Luci K. Leykum, Jacqueline Pugh, Valerie Lawrence, and Polly H. Noel are with the South Texas Veterans Health Care System and Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio TX, 78229, USA -- Michael Parchman is with the South Texas Veterans Health Care System and Department of Family and Community Medicine, University of Texas Health Science Center at San Antonio, San Antonio TX, 78229, USA -- Reuben R. McDaniel Jr. is with the McComb's School of Business, University of Texas at Austin, Austin TX, USABackground: Despite applications of models of care and organizational or system-level interventions to improve patient outcomes for chronic disease, consistent improvements have not been achieved. This may reflect a mismatch between the interventions and the nature of the settings in which they are attempted. The application of complex adaptive systems (CAS) framework to understand clinical systems and inform efforts to improve them may lead to more successful interventions. We performed a systematic review of interventions to improve outcomes of patients with congestive heart failure (CHF) to examine whether interventions consistent with CAS are more likely to be effective. We then examine differences between interventions that are most effective for improving outcomes for patients with CHF versus previously published data for type 2 diabetes to explore the potential impact of the nature of the disease on the types of interventions that are more likely to be effective. Methods: We conducted a systematic review of the literature between 1998 and 2008 of organizational interventions to improve care of patients with CHF. Two independent reviewers independently assessed studies that met inclusion criteria to determine whether each reported intervention reflected one or more CAS characteristics. The effectiveness of interventions was rated as either 0 (no effect), 0.5 (mixed effect), or 1.0 (effective) based on the type, number, and significance of reported outcomes. Fisher's exact test was used to examine the association between CAS characteristics and intervention effectiveness. Specific CAS characteristics associated with intervention effectiveness for CHF were contrasted with previously published data for type 2 diabetes. Results and discussion: Forty-four studies describing 46 interventions met eligibility criteria. All interventions utilized at least one CAS characteristic, and 85% were either 'mixed effect' or 'effective' in terms of outcomes. The number of CAS characteristics present in each intervention was associated with effectiveness (p < 0.001), supporting the idea that interventions consistent with CAS are more likely to be effective. The individual CAS characteristics associated with CHF intervention effectiveness were learning, self-organization, and co-evolution, a finding different from our previously published analysis of interventions for diabetes. We suggest this difference may be related to the degree of uncertainty involved in caring for patients with diabetes versus CHF. Conclusion: These results suggest that for interventions to be effective, they must be consistent with the CAS nature of clinical systems. The difference in specific CAS characteristics associated with intervention effectiveness for CHF and diabetes suggests that interventions must also take into account attributes of the disease.McCombs School of [email protected]