Dynamic measurements of geographical accessibility considering traffic congestion using open data: a cross-sectional assessment for haemodialysis services in Cali, Colombia.

Background: Many cities with traffic congestion lack accessibility assessments accounting for traffic congestion and equity considerations but have disaggregated georeferenced municipal-level open data on health services, populations, and travel times big data. We convened a multistakeholder intersectoral collaborative group that developed a digital, web-based platform integrating open and big data to derive dynamic spatial-temporal accessibility measurements (DSTAM) for haemodialysis services. We worked with stakeholders and data scientists and considered people's places of residence, service locations, and travel time to the service with the shortest travel time. Additionally, we predicted the impacts of strategically introducing haemodialysis services where they optimise accessibility. Methods: Cross-sectional analyses of DSTAM, accounting for traffic congestion, were conducted using a web-based platform. This platform integrated traffic analysis zones, public census and health services datasets, and Google Distance Matrix API travel-time data. Predictive and prescriptive analytics identified optimal locations for new haemodialysis services and estimated improvements. Primary outcomes included the percentage of residents within a 20-min car drive of a haemodialysis service during peak and free-flow traffic congestion. Secondary outcomes focused on optimal locations to maximise accessibility with new services and potential improvements. Findings were disaggregated by sociodemographic characteristics, providing an equity perspective. The study in Cali, Colombia, used geographic and disaggregated sociodemographic data from the adjusted 2018 Colombian census. Predicted travel times were obtained for two weeks in 2020. Findings: There were substantial traffic variations. Congestion reduced accessibility, especially among marginalised groups. For 6-12 July, free-flow and peak-traffic accessibility rates were 95.2% and 45.0%, respectively. For 23-29 November, free-flow and peak traffic accessibility rates were 89.1% and 69.7%. The locations where new services would optimise accessibility had slight variation and would notably enhance accessibility and health equity. Interpretation: Establishing haemodialysis services in targeted areas has significant potential benefits. By increasing accessibility, it would enhance urban health and equity. Funding: No external or institutional funding was received.

Visualization of transepithelial passage of the immunogenic 33-residue peptide from alpha-2 gliadin in gluten-sensitive macaques.

BACKGROUND: Based on clinical, histopathological and serological similarities to human celiac disease (CD), we recently established the rhesus macaque model of gluten sensitivity. In this study, we further characterized this condition based on presence of anti-tissue transglutaminase 2 (TG2) antibodies, increased intestinal permeability and transepithelial transport of a proteolytically resistant, immunotoxic, 33-residue peptide from alpha(2)-gliadin in the distal duodenum of gluten-sensitive macaques. METHODOLOGY/PRINCIPAL FINDINGS: Six rhesus macaques were selected for study from a pool of 500, including two healthy controls and four gluten-sensitive animals with elevated anti-gliadin or anti-TG2 antibodies as well as history of non-infectious chronic diarrhea. Pediatric endoscope-guided pinch biopsies were collected from each animal's distal duodenum following administration of a gluten-containing diet (GD) and again after remission by gluten-free diet (GFD). Control biopsies always showed normal villous architecture, whereas gluten-sensitive animals on GD exhibited histopathology ranging from mild lymphocytic infiltration to villous atrophy, typical of human CD. Immunofluorescent microscopic analysis of biopsies revealed IgG+ and IgA+ plasma-like cells producing antibodies that colocalized with TG2 in gluten-sensitive macaques only. Following instillation in vivo, the Cy-3-labeled 33-residue gluten peptide colocalized with the brush border protein villin in all animals. In a substantially enteropathic macaque with "leaky" duodenum, the peptide penetrated beneath the epithelium into the lamina propria. CONCLUSIONS/SIGNIFICANCE: The rhesus macaque model of gluten sensitivity not only resembles the histopathology of CD but it also may provide a model for studying intestinal permeability in states of epithelial integrity and disrepair.

A food-grade enzyme preparation with modest gluten detoxification properties.

BACKGROUND AND AIMS: Celiac sprue is a life-long disease characterized by an intestinal inflammatory response to dietary gluten. A gluten-free diet is an effective treatment for most patients, but accidental ingestion of gluten is common, leading to incomplete recovery or relapse. Food-grade proteases capable of detoxifying moderate quantities of dietary gluten could mitigate this problem. METHODS: We evaluated the gluten detoxification properties of two food-grade enzymes, aspergillopepsin (ASP) from Aspergillus niger and dipeptidyl peptidase IV (DPPIV) from Aspergillus oryzae. The ability of each enzyme to hydrolyze gluten was tested against synthetic gluten peptides, a recombinant gluten protein, and simulated gastric digests of whole gluten and whole-wheat bread. Reaction products were analyzed by mass spectrometry, HPLC, ELISA with a monoclonal antibody that recognizes an immunodominant gluten epitope, and a T cell proliferation assay. RESULTS: ASP markedly enhanced gluten digestion relative to pepsin, and cleaved recombinant alpha2-gliadin at multiple sites in a non-specific manner. When used alone, neither ASP nor DPPIV efficiently cleaved synthetic immunotoxic gluten peptides. This lack of specificity for gluten was especially evident in the presence of casein, a competing dietary protein. However, supplementation of ASP with DPPIV enabled detoxification of moderate amounts of gluten in the presence of excess casein and in whole-wheat bread. ASP was also effective at enhancing the gluten-detoxifying efficacy of cysteine endoprotease EP-B2 under simulated gastric conditions. CONCLUSIONS: Clinical studies are warranted to evaluate whether a fixed dose ratio combination of ASP and DPPIV can provide near-term relief for celiac patients suffering from inadvertent gluten exposure. Due to its markedly greater hydrolytic activity against gluten than endogenous pepsin, food-grade ASP may also augment the activity of therapeutically relevant doses of glutenases such as EP-B2 and certain prolyl endopeptidases.

Corrosion behaviour of a beta-titanium alloy.

The beta-titanium alloy, a particular type of titanium, has been investigated as a biomaterial because of its good mechanical performances and its high corrosion resistance and biocompatibility. This work focuses on the corrosion performance of a beta-titanium alloy of composition Ti-11Mo-2V-4Nb-3Al in Hank's physiological solution. Potentiodynamic tests were performed from -0.25 V to 3.5 V; the breakdown potential was not reached. To observe the behaviour of the alloy while submitted to long-term aggressive conditions, 1, 4 and 8 cycles of cyclic polarization were carried out. Results show a high resistance of the alloy to corrosion and a stabilization of the surface after several corrosion cycles. Pitting was not observed and a fast ability of the surface to repassivate was noticed. The surface was characterized by different techniques before and after corrosion testing. Following the corrosion tests, X-ray Photoelectron Spectroscopy (XPS) showed the presence of calcium and phosphorus, an increase of the oxide layer was measured by Auger Electron Spectroscopy (AES), a relatively smooth surface was visualised by Scanning Electron Microscopy (SEM) and contact-angle measurements showed that the surface energy increased.