Dental pulp pluripotent-like stem cells (DPPSC), a new stem cell population with chromosomal stability and osteogenic capacity for biomaterials evaluation

Background: Biomaterials are widely used to regenerate or substitute bone tissue. In order to evaluate their potential use for clinical applications, these need to be tested and evaluated in vitro with cell culture models. Frequently, immortalized osteoblastic cell lines are used in these studies. However, their uncontrolled proliferation rate, phenotypic changes or aberrations in mitotic processes limits their use in long-term investigations. Recently, we described a new pluripotent-like subpopulation of dental pulp stem cells derived from the third molars (DPPSC) that shows genetic stability and shares some pluripotent characteristics with embryonic stem cells. In this study we aim to describe the use of DPPSC to test biomaterials, since we believe that the biomaterial cues will be more critical in order to enhance the differentiation of pluripotent stem cells. Methods: The capacity of DPPSC to differentiate into osteogenic lineage was compared with human sarcoma osteogenic cell line (SAOS-2). Collagen and titanium were used to assess the cell behavior in commonly used biomaterials. The analyses were performed by flow cytometry, alkaline phosphatase and mineralization stains, RT-PCR, immunohistochemistry, scanning electron microscopy, Western blot and enzymatic activity. Moreover, the genetic stability was evaluated and compared before and after differentiation by short-comparative genomic hybridization (sCGH). Results: DPPSC showed excellent differentiation into osteogenic lineages expressing bone-related markers similar to SAOS-2. When cells were cultured on biomaterials, DPPSC showed higher initial adhesion levels. Nevertheless, their osteogenic differentiation showed similar trend among both cell types. Interestingly, only DPPSC maintained a normal chromosomal dosage before and after differentiation on 2D monolayer and on biomaterials. Conclusions: Taken together, these results promote the use of DPPSC as a new pluripotent-like cell model to evaluate the biocompatibility and the differentiation capacity of biomaterials used in bone regeneration

Polymeric Nanocomposite Structures Based on Functionalized Graphene with Tunable Properties for Nervous Tissue Replacement

Electroconductive scaffolds can be a promising approach to repair conductive tissues when natural healing fails. Recently, nerve tissue engineering constructs have been widely investigated due to the challenges in creating a structure with optimized physiochemical and mechanical properties close to the native tissue. The goal of the current study was to fabricate graphene-containing polycaprolactone/gelatin/polypyrrole (PCL/gelatin/PPy) and polycaprolactone/polyglycerol-sebacate/polypyrrole (PCL/PGS/PPy) with intrinsic electrical properties through an electrospinning process. The effect of graphene on the properties of PCL/gelatin/PPy and PCL/PGS/PPy were investigated. Results demonstrated that graphene incorporation remarkably modulated the physical and mechanical properties of the scaffolds such that the electrical conductivity increased from 0.1 to 3.9 ± 0.3 S m–1 (from 0 to 3 wt % graphene) and toughness was found to be 76 MPa (PCL/gelatin/PPy 3 wt % graphene) and 143.4 MPa (PCL/PGS/PPy 3 wt % graphene). Also, the elastic moduli of the scaffolds with 0, 1, and 2 wt % graphene were reported as 210, 300, and 340 kPa in the PCL/gelatin/PPy system and 72, 85, and 92 kPa for the PCL/PGS/PPy system. A cell viability study demonstrated the noncytotoxic nature of the resultant scaffolds. The sum of the results presented in this study suggests that both PCL/gelatin/PPy/graphene and PCL/PGS/PPy/graphene compositions could be promising biomaterials for a range of conductive tissue replacement or regeneration applications

Air pollution and general practitioner access and utilization: a population-based study in Sarnia, ‘Chemical Valley’

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Health impacts of poor environmental quality have been identified in studies around the world and in Canada. While many of the studies have identified associations between air pollution and mortality or morbidity, few have focused on the role of health care as a potential moderator of impacts. This study assessed the determinants of health care access and utilization in the context of ambient air pollution in Sarnia, Ontario, Canada. Methods: Residents of Sarnia participated in a Community Health Study administered by phone, while several ambient air pollutants including nitrogen dioxide (NO2), sulphur dioxide (SO2) and the volatile organic compounds benzene, toluene, ethylbenzene, mp- and o-xylene (BTEX) were monitored across the city. Land Use Regression models were used to estimate individual exposures to the measured pollutants and logistic regression models were utilized to assess the relative influence of environmental, socioeconomic and health related covariates on general practitioner access and utilization outcomes. Results: The results show that general practitioner use increased with levels of exposure to nitrogen dioxide (NO2- Odds Ratio [OR]: 1.16, p 0.05). Conclusions: This study provides evidence for inequitable health care access and utilization in Sarnia, with particular relevance to its situation as a sentinel high exposure environment. Levels of exposure to pollution appears to influence utilization of health care services, but poor access to primary health care services additionally burden certain groups in Sarnia, Ontario, Canada

Air pollution and general practitioner access and utilization: a population based study in Sarnia, 'Chemical Valley,' Ontario

<p>Abstract</p> <p>Background</p> <p>Health impacts of poor environmental quality have been identified in studies around the world and in Canada. While many of the studies have identified associations between air pollution and mortality or morbidity, few have focused on the role of health care as a potential moderator of impacts. This study assessed the determinants of health care access and utilization in the context of ambient air pollution in Sarnia, Ontario, Canada.</p> <p>Methods</p> <p>Residents of Sarnia participated in a Community Health Study administered by phone, while several ambient air pollutants including nitrogen dioxide (NO₂), sulphur dioxide (SO₂) and the volatile organic compounds benzene, toluene, ethylbenzene, mp- and o-xylene (BTEX) were monitored across the city. Land Use Regression models were used to estimate individual exposures to the measured pollutants and logistic regression models were utilized to assess the relative influence of environmental, socioeconomic and health related covariates on general practitioner access and utilization outcomes.</p> <p>Results</p> <p>The results show that general practitioner use increased with levels of exposure to nitrogen dioxide (NO₂- Odds Ratio [OR]: 1.16, <it>p </it>< 0.05) and sulphur dioxide (SO₂- OR: 1.61, <it>p </it>< 0.05). Low household income was a stronger predictor of having no family doctor in areas exposed to high concentrations of NO₂and SO₂. Respondents without regular care living in high pollution areas were also more likely to report travelling or waiting for care in excess of 20 minutes (OR: 3.28, <it>p </it>< 0.05) than their low exposure counterparts (OR: 1.11, <it>p </it>> 0.05).</p> <p>Conclusions</p> <p>This study provides evidence for inequitable health care access and utilization in Sarnia, with particular relevance to its situation as a sentinel high exposure environment. Levels of exposure to pollution appears to influence utilization of health care services, but poor access to primary health care services additionally burden certain groups in Sarnia, Ontario, Canada.</p

Efficacy and safety of metabolic interventions for the treatment of severe COVID-19: in vitro, observational, and non-randomized open-label interventional study

Background: Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention. Methods: We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples and perform in vitro metabolism-focused drug screen on primary lung epithelial cells infected with different strains of the virus. We perform observational analysis of Israeli patients hospitalized due to COVID-19 and comparative epidemiological analysis from cohorts in Italy and the Veteran's Health Administration in the United States. In addition, we perform a prospective non-randomized interventional open-label study in which 15 patients hospitalized with severe COVID-19 were given 145 mg/day of nanocrystallized fenofibrate added to the standard of care. Results: SARS-CoV-2 infection produced transcriptional changes associated with increased glycolysis and lipid accumulation. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication through a PPARα-dependent mechanism in both alpha and delta variants. Analysis of 3233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective non-randomized interventional open-label study was carried out on 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to patients admitted during the same period. Conclusions: Taken together, our data suggest that pharmacological modulation of PPARα should be strongly considered as a potential therapeutic approach for SARS-CoV-2 infection and emphasizes the need to complete the study of fenofibrate in large randomized controlled clinical trials. Funding: Funding was provided by European Research Council Consolidator Grants OCLD (project no. 681870) and generous gifts from the Nikoh Foundation and the Sam and Rina Frankel Foundation (YN). The interventional study was supported by Abbott (project FENOC0003). Clinical trial number: NCT04661930

Assessing the distribution of volatile organic compounds using land use regression in Sarnia, "Chemical Valley", Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Land use regression (LUR) modelling is proposed as a promising approach to meet some of the challenges of assessing the intra-urban spatial variability of ambient air pollutants in urban and industrial settings. However, most of the LUR models to date have focused on nitrogen oxides and particulate matter. This study aimed at developing LUR models to predict BTEX (benzene, toluene, ethylbenzene, m/p-xylene and o-xylene) concentrations in Sarnia, 'Chemical Valley', Ontario, and model the intra-urban variability of BTEX compounds in the city for a community health study.</p> <p>Method</p> <p>Using Organic Vapour Monitors, pollutants were monitored at 39 locations across the city of Sarnia for 2 weeks in October 2005. LUR models were developed to generate predictor variables that best estimate BTEX concentrations.</p> <p>Results</p> <p>Industrial area, dwelling counts, and highways adequately explained most of the variability of BTEX concentrations (<it>R</it>²: 0.78 – 0.81). Correlations between measured BTEX compounds were high (> 0.75). Although most of the predictor variables (e.g. land use) were similar in all the models, their individual contributions to the models were different.</p> <p>Conclusion</p> <p>Yielding potentially different health effects than nitrogen oxides and particulate matter, modelling other air pollutants is essential for a better understanding of the link between air pollution and health. The LUR models developed in these analyses will be used for estimating outdoor exposure to BTEX for a larger community health study aimed at examining the determinants of health in Sarnia.</p

The prevalence and contextual correlates of non-communicable diseases among inter-provincial migrants and non-migrants in South Africa

BACKGROUND: The socioeconomic conditions of different environments manifest in varying experiences of illnesses. Even as migrants do transit across these different environments for various reasons, including settlement, they are bound to have peculiar experiences of diseases, which could be traced to lifestyle, gender, adaptation, and reactions to specific social, economic, psychological and climatic conditions. Paying attention to such unique scenarios, our study examines the prevalence and contextual correlates of non-communicable diseases among inter-provincial migrants and non-migrants in South Africa. METHODS: Data was from the National Income Dynamics Study (NIDS), waves 5 of 2017, which comprised of 28,055 respondents aged 15–64 years made up of 22,849 inter-provincial non-migrants and 5206 inter-provincial migrants. A composite dependent/outcome variable of non-communicable diseases (NCDs) was generated for the study and data analysis involved descriptive statistics, chi Square analysis and multilevel logistic regression analysis. RESULTS: More migrants (19.81%) than non-migrants (16.69%) reported prevalence of NCDs. With the exception of household size for migrants and smoking for non-migrants, the prevalence of NCDs showed significant differences in all the community, behavioral, and individual variables. The factors in the full model, which significantly increased odds of NCDs among the migrants and the non-migrants, were older populations, the non-Blacks, and those with higher education levels. On the one hand, being married, having a household with 4–6 persons, and being residents of urban areas significantly increased odds of NCDs among the migrant population. While on the other, living in coastal provinces, being a female, and belonging to the category of those who earn more than 10,000 Rands were significantly associated with increased odds of NCDs among the non-migrants. CONCLUSIONS: These findings, therefore, among other things underscore the need for increased education and awareness campaigns, especially among the older populations on the preventive and mitigative strategies for NCDs. In addition, changes in lifestyles with regard to smoking and physical exercises should be more emphasized in specific contextual situations for the migrant and non-migrant populations, as highlighted by the results of this study