Role of gut microbiota-generated short chain fatty acids in metabolic and cardiovascular health

Purpose of this Review: This review assesses the latest evidence linking short-chain fatty acids (SCFA) with host metabolic health and cardiovascular disease (CVD) risk and presents the latest evidence on possible biological mechanisms. Recent Findings: SCFA have a range of effects locally in the gut and at both splanchnic and peripheral tissues which together appear to induce improved metabolic regulation and have direct and indirect effects on markers of CVD risk. Summary: SCFA produced primarily from the microbial fermentation of dietary fibre appear to be key mediators of the beneficial effects elicited by the gut microbiome. Not only does dietary fibre fermentation regulate microbial activity in the gut, SCFA also directly modulate host health through a range of tissue-specific mechanisms related to gut barrier function, glucose homeostasis, immunomodulation, appetite regulation and obesity. With the increasing burden of obesity worldwide, the role for gut microbiota-generated SCFA in protecting against the effects of energy dense diets offers an intriguing new avenue for regulating metabolic health and CVD risk

What do we need for robust and quantitative health impact assessment?

Health impact assessment (HIA) aims to make the health consequences of decisions explicit. Decision-makers need to know that the conclusions of HIA are robust. Quantified estimates of potential health impacts may be more influential but there are a number of concerns. First, not everything that can be quantified is important. Second, not everything that is being quantified at present should be, if this cannot be done robustly. Finally, not everything that is important can be quantified; rigorous qualitative HIA will still be needed for a thorough assessment. This paper presents the first published attempt to provide practical guidance on what is required to perform robust, quantitative HIA. Initial steps include profiling the affected populations, obtaining evidence from for postulated impacts, and determining how differences in subgoups' exposures and suscepibilities affect impacts. Using epidemiological evidence for HIA is different from carrying out a new study. Key steps in quantifying impacts are mapping the causal pathway, selecting appropriate outcome measures and selecting or developing a statistical model. Evidence from different sources is needed. For many health impacts, evidence of an effect may be scarce and estimates of the size and nature of the relationship may be inadequate. Assumptions and uncertainties must therefore be explicit. Modelled data can sometimes be tested against empirical data but sensitivity analyses are crucial. When scientific problems occur, discontinuing the study is not an option, as HIA is usually intended to inform real decisions. Both qualitative and quantitative elements of HIA must be performed robustly to be of value

Identification of a lineage of multipotent hematopoietic progenitors

All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1^(lo) Sca-1^+ Lin^(-/lo) c-kit^+ cells: long-term reconstituting Mac-1^-CD4^-c-kit^+ cells and transiently reconstituting Mac-1^(lo)CD4^-or Mac-1^(lo) CD4^(lo) cells. This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopoietic stem cells after lethal irradiation. We demonstrate that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multipotent progenitor population. In reconstituted mice, Mac-1- CD4^-c-kit^+ cells gave rise to Mac-1^(lo)CD4^- cells, which gave rise to Mac-1^(lo)CD4^(lo) cells. Mac-1^- CD4^-c-kit^+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 10^4 functionally similar Mac-1^-CD4^-c-kit^+ cells. At least half of Mac-1^(lo)CD4^- cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1^(lo)CD4^(lo) cells did not have detectable self-renewal potential. The identification of a lineage of multipotent progenitors provides an important tool for identifying genes that regulate self-renewal and lineage commitment

Novel field theory phenomena from F theory and D-branes

Talk presented in the 97 Karpatcz winter school. We describe Sen's work on F theory on K3 and its reflection on the world-volume field theory on a D3-brane probe. Field theories on a multiple of probes are analyzed. We construct a 4d N=1 superconformal probe theory which is invariant under electric-magnetic duality via a compactification to six dimensions on T^6/Z_2 x Z_2.Comment: latex file, 14 pages, 15 figs, epsf.sty, espcrc2.st

Short chain fatty acid production from mycoprotein and mycoprotein fibre in an in vitro fermentation model

Dietary mycoprotein (marketed as QuornTM) has many health benefits, including reductions in energy intake. The majority of studies evaluating mycoprotein focus on the protein content and very few consider the fibre content. Fibre consumption is also associated with decreased energy intake, which is partly attributed to short chain fatty acids (SCFAs) from fibre fermentation by colonic bacteria. To study the SCFA-producing capability of mycoprotein, in vitro batch fermentations were conducted, and SCFA production compared with that from extracted mycoprotein fibre, oligofructose (OF), rhamnose, and laminarin. Mycoprotein and mycoprotein fibre were both fermentable, resulting in a total SCFA production of 24.9 (1.7) and 61.2 (15.7) mmol/L, respectively. OF led to a significantly higher proportion of acetate compared to all other substrates tested (92.6 (2.8)%, p < 0.01). Rhamnose generated the highest proportion of propionate (45.3 (2.0)%, p < 0.01), although mycoprotein and mycoprotein fibre yielded a higher proportion of propionate compared with OF and laminarin. Butyrate proportion was the highest with laminarin (28.0 (10.0)although mycoprotein fibre led to a significantly higher proportion than OF (p < 0.01). Mycoprotein is a valuable source of dietary protein, but its fibre content is also of interest. Further evaluation of the potential roles of the fibre content of mycoprotein is required

State Firearm Laws and Interstate Firearm Deaths From Homicide and Suicide in the United States: A Cross-Sectional Analysis of Data by County

In a cross-sectional analysis of deaths from 2010 through 2014, states with strong gun laws had lower rates of firearm-related homicide and suicide than states with less regulation. Counties in states with less restrictive firearms laws had relatively lower rates of firearm-related homicide when they bordered states with strict gun laws. In contrast, rates of gun violence in areas with strong gun laws were unaffected by lenient laws in neighboring states. Restrictions on the sale and ownership of firearms may have measurable effects on rates of firearm deaths, with potential spillover across state lines

Carbohydrate dose influences liver and muscle glycogenoxidation and performance during prolonged exercise

This study investigated the effect of carbohydrate (CHO) dose and composi-tion on fuel selection during exercise, specifically exogenous and endogenous(liver and muscle) CHO oxidation. Ten trained males cycled in a double-blindrandomized order on 5 occasions at 77%_VO2maxfor 2 h, followed by a30-min time-trial (TT) while ingesting either 60 g�h�1(LG) or 75 g�h�113C-glucose (HG), 90 g�h�1(LGF) or 112.5 g�h�113C-glucose-13C-fructose ([2:1]HGF) or placebo. CHO doses met or exceed reported intestinal transportersaturation for glucose and fructose. Indirect calorimetry and stable mass iso-tope [13C] tracer techniques were utilized to determine fuel use. TT perfor-mance was 93% “likely/probable” to be improved with LGF compared withthe other CHO doses. Exogenous CHO oxidation was higher for LGF andHGF compared with LG and HG (ES>1.34,P<0.01), with the relative con-tribution of LGF (24.5�5.3%)moderatelyhigher than HGF (20.6�6.2%,ES=0.68). Increasing CHO dose beyond intestinal saturation increased abso-lute (29.2�28.6 g�h�1,ES=1.28,P=0.06) and relative muscle glycogenutilization (9.2�6.9%, ES=1.68,P=0.014) for glucose-fructose ingestion.Absolute muscle glycogen oxidation between LG and HG was not significantlydifferent, but wasmoderatelyhigher for HG (ES=0.60). Liver glycogen oxida-tion was not significantly different between conditions, but absolute and rela-tive contributions weremoderatelyattenuated for LGF (19.3�9.4 g�h�1,6.8�3.1%) compared with HGF (30.5�17.7 g�h�1, 10.1�4.0%, ES=0.79& 0.98). Total fat oxidation was suppressed in HGF compared with all otherCHO conditions (ES>0.90,P=0.024–0.17). In conclusion, there was no lin-ear dose response for CHO ingestion, with 90 g�h�1of glucose-fructose beingoptimal in terms of TT performance and fuel selectio

The Breakdown of Topology at Small Scales

We discuss how a topology (the Zariski topology) on a space can appear to break down at small distances due to D-brane decay. The mechanism proposed coincides perfectly with the phase picture of Calabi-Yau moduli spaces. The topology breaks down as one approaches non-geometric phases. This picture is not without its limitations, which are also discussed.Comment: 12 pages, 2 figure

Definition of Nonresponse to Analgesic Treatment of Arthritic Pain: An Analytical Literature Review of the Smallest Detectable Difference, the Minimal Detectable Change, and the Minimal Clinically Important Difference on the Pain Visual Analog Scale

Our objective was to develop a working definition of nonresponse to analgesic treatment of arthritis, focusing on the measurement of pain on the 0–100 mm pain visual analog scale (VAS). We reviewed the literature to assess the smallest detectable difference (SDD), the minimal detectable change (MDC), and the minimal clinically important difference (MCID). The SDD for improvement reported in three studies of rheumatoid arthritis was 18.6, 19.0, and 20.0. The median MDC was 25.4 for 7 studies of osteoarthritis and 5 studies of rheumatoid arthritis (calculated for a reliability coefficient of 0.85). The MCID increased with increasing baseline pain score. For baseline VAS tertiles defined by scores of 30–49, 50–65, and >65, the MCID for improvement was, respectively, 7–11 units, 19–27 units, and 29–37 units. Nonresponse can thus be defined in terms of the MDC for low baseline pain scores and in terms of the MCID for high baseline scores