Toidulisandite mõju hindamine vastupidavuslikule töövõimele kõrge temperatuuriga keskkonnas

Väitekirja elektrooniline versioon ei sisalda publikatsiooneToidulisandite kasutamine kehalise töövõime ja kognitiivse võimekuse parandamiseks on laialdaselt levinud sportlaste seas, aga ka rahvastikus laiemalt. Paraku on kontroll toidulisandite tootmise üle nõrk ning tõenduspõhine teave turul pakutavate toodete toime ja ohutuse kohta napp. Nii otsustatakse toidulisandite kasutamise üle sageli info põhjal, millel puudub teaduslik taust. Kofeiini kui toidulisandi vastupidavuslikku töövõimet parandav mõju on teaduslikult tõendatud. Naatriumtsitraadi toimet on uuritud vähe ja senised andmed on vastuolulised. Samas inimese organismi reaktsioon kehalisele koormusele, aga ka toidulisandite toime, sõltuvad keskkonnateguritest. Senised teadmised kofeiini, eriti aga naatriumtsitraadi toime kohta pärinevad valdavalt normaalsetes keskkonnatingimustes tehtud uuringutest. Käesoleva uurimistöö peamiseks eesmärgiks oli välja selgitada nende manustamise mõju treenitud indiviidide vastupidavuslikule töövõimele kõrge temperatuuriga keskkonnas. Kofeiini uuringus kõndisid noored mehed ja naised pärast kofeiini või platseebo manustamist jooksulindil kõrge temperatuuriga (42 °C) kuivas (suhteline õhuniiskus 20%) keskkonnas suutlikkuseni. Naatriumtsitraadi uuringus, mis teatud määral imiteeris jalgratturite mitmepäevavõistlust kõrge temperatuuriga keskkonnas (32 °C; suhteline õhuniiskus 46%), pedaalisid treenitud mehed veloergomeetril esmalt 4%-lise kehakaalu languseni. Pärast 16 h taastumisperioodi koos naatriumtsitraadi või platseebo manustamisega läbiti samades keskkonnatingimustes 40 km aja peale. Kumbki manustatud toidulisanditest võrreldes platseeboga vastupidavuslikku töövõimet ei parandanud. Kofeiin vähendas pingutuse subjektiivselt tajutud raskusastet ja väsimuse taju meestel, aga mitte naistel. Kofeiini mõjul suurenes südame löögisagedus ja ilmnes ulatuslikum laktaadi taseme tõus veres, kuid keha soojusregulatsiooni kofeiin ei mõjutanud. Naatriumtsitraat stimuleeris organismi veestaatuse normaliseerumist ja vereplasma mahu suurenemist, kuid ei mõjutanud pingutuse subjektiivselt tajutavat raskusastet järgnenud 40 km ajasõidul. Keha süvatemperatuur ning kortisooli ja aldosterooni tase veres 40 km ajasõidu lõpus osutusid naatriumtsitraadi kasutamisel võrreldes platseeboga madalamaks.Dietary supplements are widely used by athletes with the aim of improving physical and cognitive performance and this practice has increasingly spread among general population. However, the production of dietary supplements is loosely regulated and there is insufficient evidence-based information on the effect and safety of the marketed products. The intake of dietary supplements is thus often decided solely on the basis of information that lacks any scientific background. There is research-based evidence that caffeine as dietary supplement improves endurance ability. Current data on the effect of sodium citrate are scarce and the study results have been controversial. Both the reaction of the human organism to exercise and the effect of dietary supplements depend on environmental factors. However, the knowledge on the effect of caffeine, and especially sodium citrate has been obtained from the studies carried out predominantly in normal environmental conditions. The main aim of this research was to determine the impact of their administration on endurance ability of trained individuals in high-temperature environments. In caffeine study, young men and women were administered either caffeine or placebo, and then walked on treadmill to exhaustion in high-temperature (42 °C) dry (relative humidity 20%) environment. The study concerning sodium citrate imitated to some extent multi-stage cycling competitions in high-temperature environment (32 °C; relative humidity 46%): trained men exercised on cycle ergometer until they lost 4% of body mass. Following the 16 h recovery period, including the administration of either sodium citrate or placebo, the subjects cycled in the same environmental conditions 40-km as fast as possible. Neither of the administered dietary supplements improved endurance ability, compared to placebo. Caffeine decreased ratings of perceived exertion and fatigue in males, but not in females. Caffeine induced greater increases in heart rate and blood lactate concentrations, but did not have any impact on thermoregulation. Sodium citrate enhanced rehydration and increased blood plasma volume, but did not have any impact on the ratings of perceived exertion during the 40-km time-trial. The core body temperature and the level of cortisol and aldosterone in blood at the end of 40-km time-trial occurred to be lower in case of sodium citrate administration compared to placebo.https://www.ester.ee/record=b526434

Kofeiini manustamine ei paranda aklimatiseerumata noorte naiste vastupidavuslikku töövõimet kõrge temperatuuriga kuivas keskkonnas

http://tartu.ester.ee/record=b2654826~S1*es

Impact of sodium citrate ingestion during recovery after strenuous exercise in the heat on heart rate variability: A randomized, crossover study

Changes in hydration status influence plasma volume (PV) which is associated with post-exercise parasympathetic reactivation. The present study hypothesized that, after dehydrating cycling exercise in the heat (DE), stimulation of PV expansion with sodium citrate (CIT) supplementation would promote heart rate variability (HRV) recovery in endurance-trained men. Twelve participants lost 4% of body mass during DE. During subsequent 16-h recovery, participants consumed water ad libitum (CIT =5.5-L, PLC =5.1-L) and ate prescribed food supplemented with CIT or placebo in a randomized, double-blind, crossover manner. Relative changes in PV were assessed across DE and 16-h recovery. HRV was analyzed before and 16 h after DE in three conditions for altogether four 5-min periods: supine in a thermoneutral environment, supine in the heat (32°C, 46% relative humidity; 2 periods), and standing in the heat. A larger expansion of PV across 16-h recovery occurred in CIT compared to placebo trial (p 0.05). Increases in HR (p < 0.001) and lnLF/HF (p = 0.005) and decreases in lnRMSSD (p < 0.001) and lnSDNN (p < 0.001) occurred following DE in both trials. Larger PV expansion induced by CIT supplementation after DE does not improve recovery of HRV at rest and has no influence on HRV responsiveness in endurance-trained men

The Dynamics of the Human Infant Gut Microbiome in Development and in Progression toward Type 1 Diabetes

SummaryColonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors

The SOS-framework (Systems of Sedentary behaviours): an international transdisciplinary consensus framework for the study of determinants, research priorities and policy on sedentary behaviour across the life course: a DEDIPAC-study.

BACKGROUND: Ecological models are currently the most used approaches to classify and conceptualise determinants of sedentary behaviour, but these approaches are limited in their ability to capture the complexity of and interplay between determinants. The aim of the project described here was to develop a transdisciplinary dynamic framework, grounded in a system-based approach, for research on determinants of sedentary behaviour across the life span and intervention and policy planning and evaluation. METHODS: A comprehensive concept mapping approach was used to develop the Systems Of Sedentary behaviours (SOS) framework, involving four main phases: (1) preparation, (2) generation of statements, (3) structuring (sorting and ranking), and (4) analysis and interpretation. The first two phases were undertaken between December 2013 and February 2015 by the DEDIPAC KH team (DEterminants of DIet and Physical Activity Knowledge Hub). The last two phases were completed during a two-day consensus meeting in June 2015. RESULTS: During the first phase, 550 factors regarding sedentary behaviour were listed across three age groups (i.e., youths, adults and older adults), which were reduced to a final list of 190 life course factors in phase 2 used during the consensus meeting. In total, 69 international delegates, seven invited experts and one concept mapping consultant attended the consensus meeting. The final framework obtained during that meeting consisted of six clusters of determinants: Physical Health and Wellbeing (71% consensus), Social and Cultural Context (59% consensus), Built and Natural Environment (65% consensus), Psychology and Behaviour (80% consensus), Politics and Economics (78% consensus), and Institutional and Home Settings (78% consensus). Conducting studies on Institutional Settings was ranked as the first research priority. The view that this framework captures a system-based map of determinants of sedentary behaviour was expressed by 89% of the participants. CONCLUSION: Through an international transdisciplinary consensus process, the SOS framework was developed for the determinants of sedentary behaviour through the life course. Investigating the influence of Institutional and Home Settings was deemed to be the most important area of research to focus on at present and potentially the most modifiable. The SOS framework can be used as an important tool to prioritise future research and to develop policies to reduce sedentary time

EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation

Mitochondria are subcellular organelles critical for meeting the bioenergetic and biosynthetic needs of the cell. Mitochondrial function relies on genes and RNA species encoded both in the nucleus and mitochondria, as well as their coordinated translation, import and respiratory complex assembly. Here we describe the characterization of exonuclease domain like 2 (EXD2), a nuclear encoded gene that we show is targeted to the mitochondria and prevents the aberrant association of mRNAs with the mitochondrial ribosome. The loss of EXD2 resulted in defective mitochondrial translation, impaired respiration, reduced ATP production, increased reactive oxygen species and widespread metabolic abnormalities. Depletion of EXD2/CG6744 in D.melanogaster caused developmental delays and premature female germline stem cell attrition, reduced fecundity and a dramatic extension of lifespan that could be reversed with an anti-oxidant diet. Our results define a conserved role for EXD2 in mitochondrial translation that influences development and aging

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival