The Human Gut Microbiome – A Potential Controller of Wellness and Disease

Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them

HERITABILITY OF SALT INTAKE USING HALF-DAY URINE SAMPLES: THE HEALTHY TWIN STUDY

Salt is essential for both life and diet, but excess consumption of salt is an established risk factor of hypertension. Historically, salt intake has increased along with civilization, and the traditional Korean diet, although generally considered to be healthier than westernized one, has been reported to contain high level of salt on average about 13.5g/day which is 2.7-fold higher than the recommended values of WHO. Whether there is a genetic predisposition toward sodium intake level is a basic but interesting question to ponder in the Korean population.A half-day urine (HU) samples were collected for all participants of the Healthy Twin Study. HU collection starts around 7 pm of the day before visit, after completely voiding when time record starts. All the urine after then was collected in a bag until the next day visit for health examination. On site, in the morning, remaining urine was further voided and the time was recorded as final. We selected samples collected more than 8 hours. Urine samples with less than 8 hours collection were not included as these samples require a special formula to estimate 24 hour levels using sodium, potassium and creatinine concentrations. Among 3079 participants of the Healthy Twin Study, urine samples from 1312 individuals (143 pairs of MZ twins, 31 pairs of DZ twins and 961 singletons) sufficed both accurate information on volume and more than 8 hours collection, which were included in the analyses after projecting 24 hour sodium excretion level from simple volume-time calculation.Heritability of 24 hour sodium intake was estimated using a variance components model (SOLAR). The crude heritability of 24 hour sodium intake was 0.34±0.05. After further adjustment for household income which is one of the main factors of socio-economic status (SES) the heritability was not materially changed (0.28±0.1 p=0.007). Various types of shared environments, such as overall household effects, sibling effects, and generation effects, were included in ACE model, but did not account significant contribution to the variation of salt intake. We concluded that although salt intake is mediated through diet and meals are shared among families, genetic predisposition will play an important role in controlling salt intake. Analysis on the preference for salty food and on total amount of food intake is ongoing which will further dissect the genetics and shared environments related to salt intake.OAIID:oai:osos.snu.ac.kr:snu2012-01/102/0000040632/8SEQ:8PERF_CD:SNU2012-01EVAL_ITEM_CD:102USER_ID:0000040632ADJUST_YN:NEMP_ID:A077602DEPT_CD:902CITE_RATE:1.635FILENAME:abstract_heritablity of salt intake using half-day urine samples the healthy twin study.pdfDEPT_NM:보건학과EMAIL:[email protected]_YN:YCONFIRM:

Fluvial organic carbon fluxes from oil palm plantations on tropical peatland

Intact tropical peatlands are dense long-term stores of carbon. However, the future security of these ecosystems is at risk from land conversion and extensive peatland drainage. This can enhance peat oxidation and convert long-term carbon sinks into significant carbon sources. In Southeast Asia, the largest land use on peatland is for oil palm plantation agriculture. Here, we present the first annual estimate of exported fluvial organic carbon in the drainage waters of four peatland oil palm plantation areas in Sarawak, Malaysia. Total organic carbon (TOC) fluxes from the plantation second- and third-order drains were dominated (91 %) by dissolved organic carbon (DOC) and ranged from 34.4 ± 9.7 C m−2 yr−1 to 57.7 %, 16.3 g C m−2 yr−1 (± 95 % confidence interval). These fluxes represent a single-year survey which was strongly influenced by an El Ninõ event and therefore lower discharge than usual was observed. The magnitude of the flux was found to be influenced by water table depth, with higher TOC fluxes observed from more deeply drained sites. Radiocarbon dating on the DOC component indicated the presence of old (pre-1950s) carbon in all samples collected, with DOC at the most deeply drained site having a mean age of 735 years. Overall, our estimates suggest fluvial TOC contributes ∼ 5 % of total carbon losses from oil palm plantations on peat. Maintenance of high and stable water tables in oil palm plantations appears to be key to minimising TOC losses. This reinforces the importance of considering all carbon loss pathways, rather than just CO2 emissions from the peat surface, in studies of tropical peatland land conversion

A unified approach for the solution of the Fokker-Planck equation

This paper explores the use of a discrete singular convolution algorithm as a unified approach for numerical integration of the Fokker-Planck equation. The unified features of the discrete singular convolution algorithm are discussed. It is demonstrated that different implementations of the present algorithm, such as global, local, Galerkin, collocation, and finite difference, can be deduced from a single starting point. Three benchmark stochastic systems, the repulsive Wong process, the Black-Scholes equation and a genuine nonlinear model, are employed to illustrate the robustness and to test accuracy of the present approach for the solution of the Fokker-Planck equation via a time-dependent method. An additional example, the incompressible Euler equation, is used to further validate the present approach for more difficult problems. Numerical results indicate that the present unified approach is robust and accurate for solving the Fokker-Planck equation.Comment: 19 page

Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study.

BACKGROUND: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. DISCUSSION: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for \u3e4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. CONCLUSIONS: In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured

A Protocol for the Secure Linking of Registries for HPV Surveillance

In order to monitor the effectiveness of HPV vaccination in Canada the linkage of multiple data registries may be required. These registries may not always be managed by the same organization and, furthermore, privacy legislation or practices may restrict any data linkages of records that can actually be done among registries. The objective of this study was to develop a secure protocol for linking data from different registries and to allow on-going monitoring of HPV vaccine effectiveness.A secure linking protocol, using commutative hash functions and secure multi-party computation techniques was developed. This protocol allows for the exact matching of records among registries and the computation of statistics on the linked data while meeting five practical requirements to ensure patient confidentiality and privacy. The statistics considered were: odds ratio and its confidence interval, chi-square test, and relative risk and its confidence interval. Additional statistics on contingency tables, such as other measures of association, can be added using the same principles presented. The computation time performance of this protocol was evaluated.The protocol has acceptable computation time and scales linearly with the size of the data set and the size of the contingency table. The worse case computation time for up to 100,000 patients returned by each query and a 16 cell contingency table is less than 4 hours for basic statistics, and the best case is under 3 hours.A computationally practical protocol for the secure linking of data from multiple registries has been demonstrated in the context of HPV vaccine initiative impact assessment. The basic protocol can be generalized to the surveillance of other conditions, diseases, or vaccination programs

Hydrogen Sulfide Protects HUVECs against Hydrogen Peroxide Induced Mitochondrial Dysfunction and Oxidative Stress

10.1371/journal.pone.0053147PLoS ONE82