Exploring the co-occurrence of depression, anxiety and insomnia symptoms, diagnoses and treatments in primary care: observational study using UK primary care data.

BACKGROUND: Depression, anxiety and insomnia often co-occur. However, there is a lack of research regarding how they cluster and how this is related to medication used to treat them. AIMS: To describe the frequencies and associations between depression, anxiety and insomnia, and treatment for these conditions in primary care. METHOD: A retrospective cohort study using UK electronic primary care records. We included individuals aged between 18 and 99 years old with one or more records suggesting they had a diagnosis, symptom or drug treatment for anxiety, depression or insomnia between 2015 and 2017. We report the conditional probabilities of having different combinations of diagnoses, symptoms and treatments recorded. RESULTS: There were 1 325 960 records indicative of depression, anxiety or insomnia, for 739 834 individuals. Depression was the most common condition (n = 106 117 records), and SSRIs were the most commonly prescribed medication (n = 347 751 records). Overall, individuals with a record of anxiety were most likely to have co-occurring symptoms and diagnoses of other mental health conditions. For example, of the individuals with a record of generalised anxiety disorder (GAD), 24% also had a diagnosis of depression. In contrast, only 0.6% of those who had a diagnosis of depression had a diagnosis or symptom of GAD. Prescribing of more than one psychotropic medication within the same year was common. For example, of those who were prescribed an SNRI (serotonin-norepinephrine reuptake inhibitor), 40% were also prescribed an SSRI (selective serotonin reuptake inhibitor). CONCLUSIONS: The conditional probabilities of co-occurring anxiety, depression and insomnia symptoms, diagnoses and treatments are high

Evaluation of decellularization protocols for production of tubular small intestine submucosa scaffolds for use in oesophageal tissue engineering.

Small intestine submucosa (SIS) has emerged as one of a number of naturally derived extracellular matrix (ECM) biomaterials currently in clinical use. In addition to clinical applications, ECM materials form the basis for a variety of approaches within tissue engineering research. In our preliminary work it was found that SIS can be consistently and reliably made into tubular scaffolds which confer certain potential advantages. Given that decellularization protocols for SIS are applied to sheet-form SIS, it was hypothesized that a tubular-form SIS would behave differently to pre-existing protocols. In this work, tubular SIS was produced and decellularized by the conventional peracetic acid-agitation method, peracetic acid under perfusion along with two commonly used detergent-perfusion protocols. The aim of this was to produce a tubular SIS that was both adequately decellularized and possessing the mechanical properties which would make it a suitable scaffold for oesophageal tissue engineering, which was one of the goals of this work. Analysis was carried out via mechanical tensile testing, DNA quantification, scanning electron and light microscopy, and a metabolic assay, which was used to give an indication of the biocompatibility of each decellularization method. Both peracetic acid protocols were shown to be unsuitable methods with the agitation-protocol-produced SIS, which was poorly decellularized, and the perfusion protocol resulted in poor mechanical properties. Both detergent-based protocols produced well-decellularized SIS, with no adverse mechanical effects; however, one protocol emerged, SDS/Triton X-100, which proved superior in both respects. However, this SIS showed reduced metabolic activity, and this cytotoxic effect was attributed to residual reagents. Consequently, the use of SIS produced using the detergent SD as the decellularization agent was deemed to be the most suitable, although the elimination of the DNase enzyme would give further improvement

Strontium- and calcium-containing, titanium-stabilised phosphate-based glasses with prolonged degradation for orthopaedic tissue engineering.

Strontium- and calcium-releasing, titanium-stabilised phosphate-based glasses with a controlled degradation rate are currently under development for orthopaedic tissue engineering applications. Ca and/or Sr were incorporated at varying concentrations in quaternary phosphate-based glasses, in order to promote osteoinduction. Ti was incorporated at a fixed concentration in order to prolong degradation. Glasses of the general formula (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) were prepared via the melt-quench technique. The materials were characterised by energy-dispersive X-ray spectroscopy, X-ray diffraction, (31)P magic angle spinning nuclear magnetic resonance, Fourier transform infrared spectroscopy, differential thermal analysis and density determination. The dissolution rate in distilled water was determined by measuring mass loss, ion release and pH change over a two-week period. In addition, the cytocompatibility and alkaline phosphatase activity of an osteoblast-like cell line cultured on the surface of glass discs was assessed. The glasses were shown to be amorphous and contained Q(1), Q(2) and Q(3) species. Fourier transform infrared spectroscopy revealed small changes in the glass structure as Ca was substituted with Sr and differential thermal analysis confirmed a decrease in crystallisation temperature with increasing Sr content. Degradation and ion release studies also showed that mass loss was positively correlated with Sr content. These results were attributed to the lower electronegativity of Sr in comparison to Ca favouring the formation of phosphate-based mineral phases. All compositions supported cell proliferation and survival and induced at least 2.3-fold alkaline phosphatase activity relative to the control. Glass containing 17.5 mol% Sr had 3.6-fold greater alkaline phosphatase activity than the control. The gradual release of Ca and Sr supported osteoinduction, indicating their potential suitability in orthopaedic tissue engineering applications

Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

Vessel-Associated Transforming Growth Factor-Beta1 (TGF-β1) Is Increased in the Bronchial Reticular Basement Membrane in COPD and Normal Smokers

BACKGROUND: Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity. There are only limited data about its role in airway remodeling in COPD. We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD). This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls. The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups. Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3. Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls. TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs. 0.0 (0.0-7.0), p<0.05]. Percentage of vessels stained was also increased in these clinical groups. Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation. CONCLUSIONS/SIGNIFICANCE: Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD

GHOSTM: A GPU-Accelerated Homology Search Tool for Metagenomics

A large number of sensitive homology searches are required for mapping DNA sequence fragments to known protein sequences in public and private databases during metagenomic analysis. BLAST is currently used for this purpose, but its calculation speed is insufficient, especially for analyzing the large quantities of sequence data obtained from a next-generation sequencer. However, faster search tools, such as BLAT, do not have sufficient search sensitivity for metagenomic analysis. Thus, a sensitive and efficient homology search tool is in high demand for this type of analysis.We developed a new, highly efficient homology search algorithm suitable for graphics processing unit (GPU) calculations that was implemented as a GPU system that we called GHOSTM. The system first searches for candidate alignment positions for a sequence from the database using pre-calculated indexes and then calculates local alignments around the candidate positions before calculating alignment scores. We implemented both of these processes on GPUs. The system achieved calculation speeds that were 130 and 407 times faster than BLAST with 1 GPU and 4 GPUs, respectively. The system also showed higher search sensitivity and had a calculation speed that was 4 and 15 times faster than BLAT with 1 GPU and 4 GPUs.We developed a GPU-optimized algorithm to perform sensitive sequence homology searches and implemented the system as GHOSTM. Currently, sequencing technology continues to improve, and sequencers are increasingly producing larger and larger quantities of data. This explosion of sequence data makes computational analysis with contemporary tools more difficult. We developed GHOSTM, which is a cost-efficient tool, and offer this tool as a potential solution to this problem

Processes Controlling Tropical Tropopause Temperature and Stratospheric Water Vapor in Climate Models

A warm bias in tropical tropopause temperature is found in the Met Office Unified Model (MetUM), in common with most models from phase 5 of CMIP (CMIP5). Key dynamical, microphysical, and radiative processes influencing the tropical tropopause temperature and lower-stratospheric water vapor concentrations in climate models are investigated using the MetUM. A series of sensitivity experiments are run to separate the effects of vertical advection, ice optical and microphysical properties, convection, cirrus clouds, and atmospheric composition on simulated tropopause temperature and lower-stratospheric water vapor concentrations in the tropics. The numerical accuracy of the vertical advection, determined in the MetUM by the choice of interpolation and conservation schemes used, is found to be particularly important. Microphysical and radiative processes are found to influence stratospheric water vapor both through modifying the tropical tropopause temperature and through modifying upper-tropospheric water vapor concentrations, allowing more water vapor to be advected into the stratosphere. The representation of any of the processes discussed can act to significantly reduce biases in tropical tropopause temperature and stratospheric water vapor in a physical way, thereby improving climate simulations

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides