The effect of short-chain fatty acids on glycemic control in humans: A systematic review and meta-analysis

Background: Non-communicable disease development is related to impairments in glycaemic and insulinemic response, which can be modulated by fiber intake. Fiber's beneficial effect upon metabolic health can be partially attributed to the production of short-chain fatty acids (SCFAs) via microbial fermentation of fiber in the gastrointestinal tract. Objective: We aimed to determine the effect of the SCFAs, acetate, propionate, and butyrate on glycemic control in humans. Methods: CENTRAL, Embase, PubMed, Scopus and Web of Science databases were searched from inception to the 07/12/2021. Papers were included if they reported a randomized, controlled trial measuring glucose and/or insulin compared to a placebo in adults. Studies were categorized by the type of SCFA and intervention duration. Random effects meta-analyses were performed for glucose and insulin for those subject categories with ≥3 studies, or a narrative review was performed. Results: We identified 43 eligible papers, with 46 studies within those records (n = 913), 44 studies were included in the meta-analysis. Vinegar intake decreased acute glucose response, standard mean difference (SMD) and (95% CI) –0.53 (–0.92, –0.14) (n = 67) in individuals with impaired glucose tolerance or type 2 diabetes and in healthy (SMD) –0.27 (–0.54, 0.00) (n = 186). The meta-analyses for acute acetate as well as acute and chronic propionate studies had no significant effect. Conclusions: Vinegar decreased glucose response acutely in healthy and non-healthy. Acetate, propionate, butyrate, and mixed SCFAs had no effect on blood glucose and insulin in humans. Significant heterogeneity, risk of bias, and publication bias were identified in several study categories, including acute vinegar glucose response. As evidence was very uncertain, caution is urged when interpreting these results. Further high-quality research is required to determine the effect of SCFAs on glycemic control

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

Squatter settlements and slums and sustainable development

Squatter settlement is defined as a low residential area, which has developed without legal right to the land or permission from the concerned authorities to build, and as a result, of their illegal status, infrastructure and services are usually inadequate (UN-Habitat 2003). On the other hand, slums are contiguous settlements where inhabitants are characterized by insecure residential status, inadequate access to safe water, inadequate access to sanitation and other basic infrastructure and services, poor housing quality, and overcrowding (UN-Habitat 2003). Both are form of informal settlements that are not formally planned

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Automatic Calibration of Artificial Neural Networks for Zebrafish Collective Behaviours using a Quality Diversity Algorithm

During the last two decades, various models have been proposed for fish collective motion. These models are mainly developed to decipher the biological mechanisms of social interaction between animals. They consider very simple homogeneous unbounded environments and it is not clear that they can simulate accurately the collective trajectories. Moreover when the models are more accurate, the question of their scalability to either larger groups or more elaborate environments remains open. This study deals with learning how to simulate realistic collective motion of collective of zebrafish, using real-world tracking data. The objective is to devise an agent-based model that can be implemented on an artificial robotic fish that can blend into a collective of real fish. We present a novel approach that uses Quality Diversity algorithms, a class of algorithms that emphasise exploration over pure optimisation. In particular, we use CVT-MAP-Elites, a variant of the state-of-the-art MAP-Elites algorithm for high dimensional search space. Results show that Quality Diversity algorithms not only outperform classic evolutionary reinforcement learning methods at the macroscopic level (i.e. group behaviour), but are also able to generate more realistic biomimetic behaviours at the microscopic level (i.e. individual behaviour).Comment: 8 pages, 4 figures, 1 tabl

Suicide-related behaviors in older patients with new anti-epileptic drug use: data from the VA hospital system

<p>Abstract</p> <p>Background</p> <p>The U.S. Food and Drug Administration (FDA) recently linked antiepileptic drug (AED) exposure to suicide-related behaviors based on meta-analysis of randomized clinical trials. We examined the relationship between suicide-related behaviors and different AEDs in older veterans receiving new AED monotherapy from the Veterans Health Administration (VA), controlling for potential confounders.</p> <p>Methods</p> <p>VA and Medicare databases were used to identify veterans 66 years and older, who received a) care from the VA between 1999 and 2004, and b) an incident AED (monotherapy) prescription. Previously validated ICD-9-CM codes were used to identify suicidal ideation or behavior (suicide-related behaviors cases), epilepsy, and other conditions previously associated with suicide-related behaviors. Each case was matched to controls based on prior history of suicide-related behaviors, year of AED prescription, and epilepsy status.</p> <p>Results</p> <p>The strongest predictor of suicide-related behaviors (N = 64; Controls N = 768) based on conditional logistic regression analysis was affective disorder (depression, anxiety, or post-traumatic stress disorder (PTSD); Odds Ratio 4.42, 95% CI 2.30 to 8.49) diagnosed before AED treatment. Increased suicide-related behaviors were not associated with individual AEDs, including the most commonly prescribed AED in the US - phenytoin.</p> <p>Conclusion</p> <p>Our extensive diagnostic and treatment data demonstrated that the strongest predictor of suicide-related behaviors for older patients newly treated with AED monotherapy was a previous diagnosis of affective disorder. Additional, research using a larger sample is needed to clearly determine the risk of suicide-related behaviors among less commonly used AEDs.</p

In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

© 2008 Garvin and Dabrosin; licensee BioMed Central Ltd

Review of the literature and suggestions for the design of rodent survival studies for the identification of compounds that increase health and life span

Much of the literature describing the search for agents that increase the life span of rodents was found to suffer from confounds. One-hundred-six studies, absent 20 contradictory melatonin studies, of compounds or combinations of compounds were reviewed. Only six studies reported both life span extension and food consumption data, thereby excluding the potential effects of caloric restriction. Six other studies reported life span extension without a change in body weight. However, weight can be an unreliable surrogate measure of caloric consumption. Twenty studies reported that food consumption or weight was unchanged, but it was unclear whether these data were anecdotal or systematic. Twenty-nine reported extended life span likely due to induced caloric restriction. Thirty-six studies reported no effect on life span, and three a decrease. The remaining studies suffer from more serious confounds. Though still widely cited, studies showing life span extension using short-lived or “enfeebled” rodents have not been shown to predict longevity effects in long-lived animals. We suggest improvements in experimental design that will enhance the reliability of the rodent life span literature. First, animals should receive measured quantities of food and its consumption monitored, preferably daily, and reported. Weights should be measured regularly and reported. Second, a genetically heterogeneous, long-lived rodent should be utilized. Third, chemically defined diets should be used. Fourth, a positive control (e.g., a calorically restricted group) is highly desirable. Fifth, drug dosages should be chosen based on surrogate endpoints or accepted cross-species scaling factors. These procedures should improve the reliability of the scientific literature and accelerate the identification of longevity and health span-enhancing agents

Diagnostic and mechanistic implications of serum free light chains, albumin and alpha-fetoprotein in hepatocellular carcinoma

Background: Mass spectroscopy analysis suggested low serum albumin and high immunoglobulin free light chain (sFLC) levels may have diagnostic value in hepatocellular carcinoma (HCC). Our aims were to apply quantitative assays to confirm these observations, determine their diagnostic utility, and investigate the mechanisms involved. Methods: Albumin, sFLC, routine liver and renal function tests were measured in patients with chronic liver disease with (n=102) and without (n=113) HCC. The discriminant performance was compared with the current standard serological test alpha-fetoprotein (AFP) using receiver operating characteristic (ROC) and area under the curve (AUC) analyses. Results: sFLC and serum albumin were each confirmed to have discriminatory utility in HCC with AUC values of 0.7 and 0.8, respectively. sFLC were strongly correlated with gammaglobulin levels and both these were inversely related to serum albumin levels. The discriminatory utility of sFLC was retained after adjusting for renal and liver function. Conclusions: Serum levels of sFLC and albumin were strongly associated with HCC as predicted by mass spectroscopy. Discrimination of HCC by AFP was improved by the addition of either albumin or sFLC. Larger prospective studies are required to determine how AFP, sFLC and albumin might be combined in a useful diagnostic approach for HCC