Butyrate and tributyrin reduce LPS-induced inflammatory cytokine production from human visceral fat.

INTRODUCTION: The current obesity crisis has resulted in many people with excess adipose tissue suffering from chronic inflammation. This inflammation is largely due to the release of cytokines and chemokines from visceral fat. The aim of this study was to identify potential anti-inflammatory agents that might alleviate obesity-induced chronic inflammation. METHODS: To identify agents that might alleviate this obesity-induced chronic inflammation we have developed a simple protocol for incubating intact pieces of human visceral adipose tissue in 35 mm tissue culture plates, in the presence of low-dose lipopolysaccharide (LPS) and co-incubating these samples with potential anti-inflammatory agents. RNA-Seq analysis was performed to identify enriched gene expression signatures among the most significantly differentially expressed genes. RESULTS: From this screen, we have identified the short-chain fatty acid (SCFA) sodium butyrate and its triacylglyceride form, tributyrin, as effective agents, significantly reducing the production of LPS-induced inflammatory cytokines and chemokines from all adipose tissue samples tested. As well, these agents appear to be non-toxic at the concentrations tested. RNA-Seq analysis has revealed that IL36γ is one of the most upregulated genes in response to LPS and one of the most downregulated when sodium butyrate is added to human fat samples stimulated with LPS. IL-36γ ELISAs confirmed this holds true at the protein level as well. CONCLUSIONS: These studies suggest that the short-chain fatty acid, sodium butyrate, and its triacylglyceride form, tributyrin, might alleviate the chronic inflammation that is associated with many individuals with obesity.

California School Staff Reports of Seeing Students Vaping at School and Disciplinary Actions.

Youth vaping is a concern and schools may use many approaches to discipline students caught vaping at school. This study identified the prevalence of school staff seeing vaping in schools and the measures used to discipline students. A state-wide sample of 7,938 staff from 255 middle and high schools reported whether they saw any students vaping at school in the last 30 days, whether they have caught any students vaping during class in the last semester, and what happened after catching a student vaping in class. Open-text responses were coded and themes were identified related to disciplinary approaches. 31.9% of staff reported seeing students vaping at school, and 11.9% of teachers reported catching a student vaping during class. Teachers described four categories of disciplinary approaches after catching students vaping in class: no consequences, punitive approaches, restorative approaches, and mixed approaches. Additional support is necessary to help schools address student vaping.

Psychosocial interventions for people with young onset dementia and their carers: a systematic review.

BACKGROUND: Dementia in younger people, known as young (YOD) or early onset dementia (EOD), can pose significant challenges. YOD is often diagnosed in those in paid employment who have relatively young children, leading to different challenges to those for older people. It is therefore very important to provide support tailored to their specific needs. This systematic review aimed to synthesize the literature investigating the impact of psychosocial interventions for people with YOD and their family carers. METHOD: Eight electronic databases were searched and three key journals were also hand searched. Narrative synthesis of the selected articles was undertaken. RESULTS: Of the 498 records identified, 495 were ineligible after application of the exclusion criteria. The final sample included three studies, all of which were employment-based. Two were qualitative and one used mixed methods. Study quality was mixed. People with YOD and their carers reported benefits from participating in work-based interventions designed for those with YOD, including improved self-esteem and sense of purpose. Social contact was highlighted. Despite cognitive decline, maintenance in well-being was also reported. Carers described benefits for people with YOD, which extended outside the intervention, e.g. enhanced sleep and mood. The impact of the interventions on carers was not assessed. CONCLUSIONS: This review suggests work-based interventions providing supported, meaningful work outside the home can be beneficial. However, the dearth of studies, the lack of focus on family carers and their mixed quality demonstrate the need for better quality, mixed methods research with larger sample sizes.

A Monte Carlo study to investigate the feasibility of an on-board SPECT/spectral-CT/CBCT imager for medical linear accelerator.

PURPOSE: The on-board flat-panel cone-beam computed tomography (CBCT) lacks molecular/functional information for current online image-guided radiation therapy (IGRT). It might not be adequate for adaptive radiation therapy (ART), particularly for biologically guided tumor delineation and targeting which might be shifted and/or distorted during the course of RT. A linear accelerator (Linac) gantry-mounted on-board imager (OBI) was proposed using a single photon counting detector (PCD) panel to achieve single photon emission computed tomography (SPECT), energy-resolved spectral CT, and conventional CBCT triple on-board imaging, which might facilitate online ART with an addition of volumetric molecular/functional imaging information. METHODS: The system was designed and evaluated in the GATE Monte Carlo platform. The OBI system including a kV-beam source and a pixelated cadmium zinc telluride (CZT) detector panel mounted on a medical Linac orthogonally to the MV beam direction was designed to obtain online CBCT, spectral CT, and SPECT tri-modal imaging of patients in the treatment room. The spatial resolutions of the OBI system were determined by imaging simulated phantoms. The CBCT imaging was evaluated by a simulated contrast phantom. A PMMA phantom containing gadolinium was imaged to demonstrate quantitative imaging of spectral-CT/CBCT of the system. The capability of tri-modal imaging of the OBI was demonstrated using three different spectral CT imaging methods to differentiate gadolinium, gold, calcium within simulated PMMA and the SPECT to image radioactive 99m Tc distribution. The dual-isotope SPECT imaging of the system was also evaluated by imaging a phantom containing 99m Tc and 123 I. The radiotherapy-related parameters of iodine contrast fraction and virtual non-contrast (VNC) tissue electron density in the Kidney1 inserts of a simulated phantom were decomposed using the Bayesian eigentissue decomposition method for contrast-enhanced CBCT/spectral-CT of the OBI in a single scan. RESULTS: The spatial resolutions of CBCT and SPECT of the OBI were determined to be 15.1 lp/cm at 10% MTF and 4.8-12 mm for radii of rotation of 10-40 cm, respectively. In CBCT image of the contrast phantom, most of the soft-tissue inserts were visible with sufficient spatial structure details. As compared to the CBCT image of gadolinium, the spectral CT image provided higher image contrasts. Calcium, gadolinium, and gold were separated well by using the spectral CT material imaging methods. The reconstructed distribution of 99m Tc agreed with the spatial position within the phantom. The two isotopes were separated from each other in dual-isotope SPECT imaging of the OBI. The iodine fractions and the VNC electron densities were estimated in the iodine-enhanced Kidney1 tissue inserts with reasonable RMS errors. The main procedures of the tri-modal imaging guided online ART workflow were presented with new functional features included. CONCLUSIONS: Using a single photon counting CZT detector panel, an on-board SPECT, spectral CT, and CBCT tri-modal imaging could be realized in Linacs. With the added online molecular/functional imaging obtained from the new OBI for the online ART proposed, the accuracy of radiation treatment delivery could be further improved.

Idiopathic pulmonary fibrosis: current trends in management.

Idiopathic pulmonary fibrosis (IPF) is a chronic scarring illness limited to the lung and characterized by progressive dyspnea, restrictive pulmonary physiology, and radiographic diffuse lung disease. During the past few years, significant progress has been made, particularly in diagnosis: a stricter case definition has been outlined by consensus among international experts. Insights into the pathophysiology have revealed novel areas for therapeutic intervention. These advances have helped clarify many important diagnostic and therapeutic issues in this disease. An effective treatment regimen is yet to be determined. Significant new insights in the natural course and monitoring disease course have provided use of appropriate endpoints to test the safety and efficacy of new treatment regimens. Several multicenter clinical trials are underway and several more are being planned. It is hoped that ongoing molecular genetic studies and results of clinical trials will improve outcome of patients and families affected with this disease in the near future.

Evidence that bone marrow cells do not contribute to the alveolar epithelium.

An ongoing controversy is the role of marrow cells in populating the alveolar epithelium. In this study, we employed flow cytometry and histologic techniques to evaluate this process. Donor bone marrow was harvested from transgenic mice expressing the LacZ or eGFP gene ubiquitously, or under the control of the human surfactant protein (SP)-C promoter, and transplanted into lethally irradiated, neonatal mice. In recipients transplanted with marrow that express eGFP or lacZ ubiquitously, light microscopy revealed cells whose morphology and location were compatible with a type II cell phenotype. Consistent with this, fluorescent microscopy suggested colocalization of eGFP and pro-SP-C proteins in single cells. In mice transplanted with SP-C-eGFP marrow, engraftment was not detectable by histology or flow cytometry. We therefore used deconvolution microscopy to reanalyze histologic sections that were thought to show marrow-derived type II cells. We found that all putative marrow-derived pneumocytes resulted from the overlapping fluorescent signals of an endogenous pro-SP-C+ type II cell and a donor-derived eGFP+ cell. Taken together, our observations underscore the technical difficulties associated with evaluating engraftment in lung, and argue against a contributory role for marrow cells in populating the alveolar epithelium.