A randomized controlled trial: the effect of inulin on weight management and ectopic fat in subjects with prediabetes.

BACKGROUND: Fat infiltration of the liver, muscle and pancreas is associated with insulin resistance and risk of diabetes. Weight loss reduces ectopic fat deposition and risk of diabetes, but is difficult to sustain to due to compensatory increases in appetite. Fermentable carbohydrates have been shown to decrease appetite and food intake, and promote weight loss in overweight subjects. In animal studies, fermentable carbohydrate reduces ectopic fat independent of weight loss. We aimed to investigate the effect of the fermentable carbohydrate inulin on weight maintenance, appetite and ectopic fat in subjects with prediabetes. METHODS: Forty-four subjects with prediabetes were randomized to 18 weeks' inulin or cellulose supplementation. During weeks 1-9 (weight loss phase) all subjects had four visits with a dietitian to guide them towards a 5 % weight loss. During weeks 10-18 (weight maintenance phase) subjects continued taking their assigned supplementation and were asked to maintain the weight they had lost but were offered no further support. All subjects attended study sessions at baseline, 9 and 18 weeks for measurement of weight; assessment of adipose tissue and ectopic fat content by magnetic resonance imaging and magnetic resonance spectroscopy; glucose, insulin and GLP-1 levels following a meal tolerance test; and appetite by ad libitum meal test and visual analogue scales. RESULTS: Both groups lost approximately 5 % of their body weight by week nine (-5.3 ± 0.1 % vs -4.3 ± 0.4 %, p = 0.13, but the inulin group lost significantly more weight between 9 and 18 weeks (-2.3 ± 0.5 % vs -0.6 ± 0.4 %, p = 0.012). Subjects taking inulin had lower hepatic (p = 0.02) and soleus muscle (p < 0.05) fat content at 18 weeks compared to control even after controlling for weight loss and consumed less at the ad libitum meal test (p = 0.027). Fasting glucose significantly decreased at week nine only (p = 0.005), insulin concentrations did not change, and there was a significant increase in GLP-1 in the cellulose group at 9 and 18 weeks (p < 0.03, p < 0.00001). CONCLUSION: Inulin may have a two-pronged effect on the risk of diabetes by 1) promoting weight loss 2) reducing intrahepatocellular and intramyocellular lipid in people with prediabetes independent of weight loss

Different abundance and correlational patterns exist between total and presumed pathogenic Vibrio vulnificus and V. parahaemolyticus in shellfish and waters along the North Carolina coast

Monitoring of Vibrio vulnificus and V. parahaemolyticus abundance is pertinent due to the ability of these species to cause disease in humans through aquatic vectors. Previously, we performed a multiyear investigation tracking Vibrio spp. levels in five sites along the southeastern North Carolina coast. From February 2013 to October 2015, total V. vulnificus and V. parahaemolyticus abundance was measured in water, oysters and clams. In the current study, pathogenic subpopulations were identified in these isolates using molecular markers, revealing that 5.3% of V. vulnificus isolates possessed the virulence-correlated gene (vcgC), and 1.9% of V. parahaemolyticus isolates harbored one or both of the virulence-associated hemolysin genes (tdh and trh). Total V. parahaemolyticus abundance was not sufficient to predict the abundance of pathogenic subpopulations. Specifically, pathogenic V. parahaemolyticus isolates were more often isolated in cooler waters and were sometimes isolated when no other V. parahaemolyticus strains were detectable. Vibrio vulnificus clinical (C-) genotypes correlated with total V. vulnificus; however, salinity, water depth and total suspended solids influenced C- and E-genotypes differently. Lastly, we documented individual oysters harboring significantly higher V. vulnificus levels for which there was no ecological explanation, a phenomenon that deserves closer attention due to the potentially elevated health hazard associated with these 'hot' shellfish. We tested environmentally isolated Vibrio vulnificus and V. parahaemolyticus isolates for the presence of virulence markers and found that pathogenic subpopulations do not necessarily reflect total species abundance and correlation patterns

Madurella mycetomatis, the main causative agent of eumycetoma, is highly susceptible to olorofim

OBJECTIVES: Eumycetoma is currently treated with a combination of itraconazole therapy and surgery, with limited success. Recently, olorofim, the lead candidate of the orotomides, a novel class of antifungal agents, entered a Phase II trial for the treatment of invasive fungal infections. Here we determined the activity of olorofim against Madurella mycetomatis, the main causative agent of eumycetoma. METHODS: Activity of olorofim against M. mycetomatis was determined by in silico comparison of the target gene, dihydroorotate dehydrogenase (DHODH), and in vitro susceptibility testing. We also investigated the in vitro interaction between olorofim and itraconazole against M. mycetomatis. RESULTS: M. mycetomatis and Aspergillus fumigatus share six out of seven predicted binding residues in their DHODH DNA sequence, predicting susceptibility to olorofim. Olorofim demonstrated excellent potency against M. mycetomatis in vivo with MICs ranging from 0.004 to 0.125 mg/L and an MIC90 of 0.063 mg/L. Olorofim MICs were mostly one dilution step lower than the itraconazole M

Unified Dark Matter models with fast transition

We investigate the general properties of Unified Dark Matter (UDM) fluid models where the pressure and the energy density are linked by a barotropic equation of state (EoS) $p = p(\rho)$ and the perturbations are adiabatic. The EoS is assumed to admit a future attractor that acts as an effective cosmological constant, while asymptotically in the past the pressure is negligible. UDM models of the dark sector are appealing because they evade the so-called "coincidence problem" and "predict" what can be interpreted as $w_{\rm DE} \approx -1$, but in general suffer the effects of a non-negligible Jeans scale that wreak havoc in the evolution of perturbations, causing a large Integrated Sachs-Wolfe effect and/or changing structure formation at small scales. Typically, observational constraints are violated, unless the parameters of the UDM model are tuned to make it indistinguishable from $\Lambda$CDM. Here we show how this problem can be avoided, studying in detail the functional form of the Jeans scale in adiabatic UDM perturbations and introducing a class of models with a fast transition between an early Einstein-de Sitter CDM-like era and a later $\Lambda$CDM-like phase. If the transition is fast enough, these models may exhibit satisfactory structure formation and CMB fluctuations. To consider a concrete case, we introduce a toy UDM model and show that it can predict CMB and matter power spectra that are in agreement with observations for a wide range of parameter values.Comment: 30 pages, 15 figures, JHEP3 style, typos corrected; it matches the published versio

A Mathematical Model of Liver Cell Aggregation In Vitro

The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work

The Bristol CMIP6 Data Hackathon

The Bristol CMIP6 Data Hackathon formed part of the Met Office Climate Data Challenge Hackathon series during 2021, bringing together around 100 UK early career researchers from a wide range of environmental disciplines. The purpose was to interrogate the under-utilised but currently most advanced climate model inter-comparison project datasets to develop new research ideas, create new networks and outreach opportunities in the lead up to COP26. Experts in different science fields, supported by a core team of scientists and data specialists at Bristol, had the unique opportunity to explore together interdisciplinary environmental topics summarised in this article