Identification of potential non-invasive biomarkers in diastrophic dysplasia.

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by pathogenic variants in the SLC26A2 gene encoding for a cell membrane sulfate/chloride antiporter crucial for sulfate uptake and glycosaminoglycan (GAG) sulfation. Research on a DTD animal model has suggested possible pharmacological treatment approaches. In view of future clinical trials, the identification of non-invasive biomarkers is crucial to assess the efficacy of treatments. Urinary GAG composition has been analyzed in several metabolic disorders including mucopolysaccharidoses. Moreover, the N-terminal fragment of collagen X, known as collagen X marker (CXM), is considered a real-time marker of endochondral ossification and growth velocity and was studied in individuals with achondroplasia and osteogenesis imperfecta. In this work, urinary GAG sulfation and blood CXM levels were investigated as potential biomarkers for individuals affected by DTD. Chondroitin sulfate disaccharide analysis was performed on GAGs isolated from urine by HPLC after GAG digestion with chondroitinase ABC and ACII, while CXM was assessed in dried blood spots. Results from DTD patients were compared with an age-matched control population. Undersulfation of urinary GAGs was observed in DTD patients with some relationship to the clinical severity and underlying SLC26A2 variants. Lower than normal CXM levels were observed in most patients, even if the marker did not show a clear pattern in our small patient cohort because CXM values are highly dependent on age, gender and growth velocity. In summary, both non-invasive biomarkers are promising assays targeting various aspects of the disorder including overall metabolism of sulfated GAGs and endochondral ossification.

Significance of serum Myostatin in hemodialysis patients.

BACKGROUND: Malnutrition and muscle wasting are common in haemodialysis (HD) patients. Their pathogenesis is complex and involves many molecules including Myostatin (Mstn), which acts as a negative regulator of skeletal muscle. The characterisation of Mstn as a biomarker of malnutrition could be useful in the prevention and management of this condition. Previous studies have reported no conclusive results on the actual relationship between serum Mstn and wasting and malnutrition. So, in this study, we evaluated Mstn profile in a cohort of regular HD patients. METHODS: We performed a cross-sectional study, enrolling 37 patients undergoing bicarbonate-HD (BHD) or haemodiafiltration (HDF) at least for six months. 20 sex-matched healthy subjects comprised the control group. Mstn serum levels were evaluated by ELISA before and after HD. We collected clinical and biochemical data, evaluated insulin resistance, body composition, malnutrition [by Malnutrition Inflammation Score (MIS)] and tested muscle function (by hand-grip strength, six-minute walking test and a questionnaire on fatigue). RESULTS: Mstn levels were not significantly different between HD patients and controls (4.7 ± 2.8 vs 4.5 ± 1.3 ng/ml). In addition, while a decrease in Mstn was observed after HD treatment, there were no differences between BHD and HDF. In whole group of HD patients Mstn was positively correlated with muscle mass (r = 0.82, p < 0.001) and inversely correlated with age (r = - 0.63, p < 0.01) and MIS (r = - 0.39, p = 0.01). No correlations were found between Mstn and insulin resistance, such as between Mstn levels and parameters of muscle strength and fatigue. In multivariate analysis, Mstn resulted inversely correlated with fat body content (ß = - 1.055, p = 0.002). CONCLUSIONS: Circulating Mstn is related to muscle mass and nutritional status in HD patients, suggesting that it may have a role in the regulation of skeletal muscle and metabolic processes. However, also considering the lack of difference of serum Mstn between healthy controls and HD patients and the absence of correlations with muscle function tests, our findings do not support the use of circulating Mstn as a biomarker of muscle wasting and malnutrition in HD.

Strategies for Meaningful Engagement between Community-Based Health Researchers and First Nations Participants.

The Baby Teeth Talk Study (BTT) is a partnership-based research project looking at interventions to prevent early childhood caries (ECC) in First Nations populations in Canada. Community-based researchers (CBRs) conducted preventive and behavioral interventions that targeted expectant mothers and their newborns, over a 3-year period. The work of the CBRs requires a great deal of training and skills to administer the interventions. It also requires a broad set of strategies to meaningfully engage participants to make health-promoting changes in their behavior to prevent ECC in their children. After implementing the intervention, BTT CBRs participated in interviews to explore the strategies they employed to engage participants in the prevention of ECC. CBRs perceived two key strategies as essential for meaningful engagement with BTT participants. First, CBRs indicated that their shared experiences through motherhood, First Nations identity, age, and childhood experience provided a positive foundation for dialog with participants that lead to build trust and rapport. Second, supportive interpersonal and culturally based communication skills of the CBR provided further foundation to engage with participants from a strength-based approach. For example, the CBRs knew how to effectively communicate in ways such as being gentle, non-intrusive, and avoiding any perception of judgment when discussing oral health behavior. In First Nations health research, CBRs can provide an essential link in engaging participants and the community for improvements in health. Researchers should carefully consider characteristics such as shared experience and ability to understand cultural communication styles when hiring CBRs in order to build a solid foundation of trust with research participants.

Racism and Oral Health Outcomes among Pregnant Canadian Aboriginal Women.

This study assessed links between racism and oral health outcomes among pregnant Canadian Aboriginal women. Baseline data were analyzed for 541 First Nations (94.6%) and Métis (5.4%) women in an early childhood caries preventive trial conducted in urban and on-reserve communities in Ontario and Manitoba. One-third of participants experienced racism in the past year determined by the Measure of Indigenous Racism Experience. In logistic regressions, outcomes significantly associated with incidents of racism included: wearing dentures, off-reserve dental care, asked to pay for dental services, perceived need for preventive care, flossing more than once daily, having fewer than 21 natural teeth, fear of going to dentist, never received orthodontic treatment and perceived impact of oral conditions on quality of life. In the context of dental care, racism experienced by Aboriginal women can be a barrier to accessing services. Programs and policies should address racism's insidious effects on both mothers' and children's oral health outcomes.

Mesenchymal Stromal Cells Prevent Renal Fibrosis in a Rat Model of Unilateral Ureteral Obstruction by Suppressing the Renin-Angiotensin System via HuR.

We studied Mesenchymal Stromal Cells (MSC) effects in experimental Unilateral Ureteral Obstruction (UUO), a fibrogenic renal disease. Rats were divided in 5 groups: sham, UUO, MSC treated-UUO, ACEi treated-UUO, MSC+ACEi treated- UUO. Data were collected at 1, 7, 21 days. UUO induced monocyte renal infiltration, tubular cell apoptosis, tubular atrophy, interstitial fibrosis and overexpression of TGFß, Renin mRNA (RENmRNA), increase of Renin, Angiotensin II (AII) and aldosterone serum levels. Both lisinopril (ACEi) and MSC treatment prevented monocyte infiltration, reduced tubular cell apoptosis, renal fibrosis and TGFß expression. Combined therapy provided a further suppression of monocyte infiltration and tubular injury. Lisinopril alone caused a rebound activation of Renin-Angiotensin System (RAS), while MSC suppressed RENmRNA and Renin synthesis and induced a decrease of AII and aldosterone serum levels. Furthermore, in in-vitro and in-vivo experiments, MSC inhibit Human antigen R (HuR) trascription, an enhancer of RENmRNA stability by IL10 release. In conclusion, we demonstrate that in UUO MSC prevent fibrosis, by decreasing HuR-dependent RENmRNA stability. Our findings give a clue to understand the molecular mechanism through which MSC may prevent fibrosis in a wide and heterogeneous number of diseases that share RAS activation as common upstream pathogenic mechanism.

Racism and Oral Health Outcomes among Pregnant Canadian Aboriginal Women.

This study assessed links between racism and oral health outcomes among pregnant Canadian Aboriginal women. Baseline data were analyzed for 541 First Nations (94.6%) and Métis (5.4%) women in an early childhood caries preventive trial conducted in urban and on-reserve communities in Ontario and Manitoba. One-third of participants experienced racism in the past year determined by the Measure of Indigenous Racism Experience. In logistic regressions, outcomes significantly associated with incidents of racism included: wearing dentures, off-reserve dental care, asked to pay for dental services, perceived need for preventive care, flossing more than once daily, having fewer than 21 natural teeth, fear of going to dentist, never received orthodontic treatment and perceived impact of oral conditions on quality of life. In the context of dental care, racism experienced by Aboriginal women can be a barrier to accessing services. Programs and policies should address racism's insidious effects on both mothers' and children's oral health outcomes.

Prevalence of dental caries among 7- and 13-year-old First Nations children, District of Manitoulin, Ontario.

PURPOSE: Dental caries is a disease that, although decreasing in the non-Aboriginal child population, remains high for Canadian Aboriginal and Native American children and adolescents. To address dental health issues in First Nations in the District of Manitoulin, Noojmowin Teg Health Centre initiated a multiphase collaborative research project with the department of community dentistry at the University of Toronto. The purpose of this paper was to identify the prevalence of dental caries in children 7 or 13 years of age and to compare these data with published data for the same age groups from other First Nations communities in Canada. METHODS: All children 7 or 13 years of age who were in elementary schools on a reserve in 7 First Nations communities were eligible for a dental health examination as part of the survey. Children attending school off the reserve in 6 of the communities were also eligible. RESULTS: A total of 66 children (56% 7-year-old children, 62% girls) were examined. The mean caries score (deft+ DMFT) for 7-year-old children was 6.2; the mean decayed, extracted, filled permanent teeth (DMFT) score for 13-year-old children was 4.1. Overall, 96% of children had 1 or more past or active carious lesion. CONCLUSION: Results indicate that dental caries is highly prevalent and increasing in severity in this population.

Pacifier use and early childhood caries: an evidence-based study of the literature.

This evidence-based study of the literature investigated the relationship between pacifier use (with and without sweetening and prolonged or short-term) and early childhood caries (ECC). The review was based on evidence from 3 main sources: a search of several electronic bibliographic databases, a review of the references from relevant studies for additional potentially relevant articles and a review of several dental textbooks. A total of 74 articles were reviewed. Of these, 8 were deemed relevant and were critically appraised according to a "causation checklist" of 13 items. The 8 studies assessed were methodologically inconsistent in terms of definitions of ECC, diagnostic criteria for identifying carious lesions, dental examination procedures, interviewing methods, and descriptions of pacifier use. None of the studies achieved a score greater than 6 and hence none was considered to present strong evidence. Six studies did not control for confounding variables, and the conclusions they generated were inconsistent. The evidence from the other 2 studies, which did control for confounding factors, presented slightly stronger evidence, but they indicated no statistical difference in pacifier use between children with and those without ECC; furthermore, the reported odds ratios suggested that pacifier use might have had a mildly protective effect. Overall, the evidence does not suggest a strong or consistent association between pacifier use and ECC.