Dental manifestations in adult hypophosphatasia and their correlation with biomarkers.

Hypophosphatasia (HPP) is a genetic condition with broad clinical manifestations caused by alkaline phosphatase (ALP) deficiency. Adults with HPP exhibit a wide spectrum of signs and symptoms. Dental manifestations including premature tooth loss are common. Much of the published literature reporting dental manifestations consists of case reports and series of symptomatic patients, likely biased towards more severe dental manifestations. The objective of this study was to systematically explore the dental manifestations among adults with HPP by conducting a comprehensive dental evaluation. To minimize bias, the study explored dental manifestations in an unselected cohort of adults with HPP. Participants were identified searching electronic health record (EHR) data from a rural health system to discover adults with persistent ALP deficiency. Heterozygotes with pathogenic (P), likely pathogenic (LP), or uncertain variants (VUS) in ALPL and at least one elevated ALP substrate were defined as adults with HPP and underwent genetic, dental, oral radiographic, and biomarker evaluation. Twenty-seven participants completed the study. Premature tooth loss was present in 63% (17/27); 19% (5/27) were missing eight or more teeth. Statistically significant associations were found between premature permanent tooth loss and HPP biomarkers ALP (p = 0.049) and bone-specific ALP (p = 0.006). Serum ALP (ρ = -0.43, p = 0.037) and bone-specific ALP (ρ = -0.57, p = 0.004) were negatively correlated with number of teeth lost prematurely. As noted with tooth loss, periodontal breakdown was associated with bone-specific ALP. An inverse association between periodontal breakdown and bone-specific ALP was observed (p = 0.014). These findings suggest a role for ALP in maintenance of dentition.

Comparison of Mifepristone Followed by Misoprostol with Misoprostol Alone for Treatment of Early Pregnancy Failure: A Randomized Double-Blind Placebo-Controlled Trial.

Objective: To compare the efficacy and safety of mifepristone followed by misoprostol with misoprostol alone in the management of early pregnancy failure (EPF). Study Design: A randomized double-blind placebo-controlled clinical trial. Methods: Ninety-two women with EPF ≤12 weeks were recruited and randomly allocated to receive either mifepristone 200 mg (n = 46) or placebo (n = 46). Forty-eight hours later, patients in both the groups were given 800 µg misoprostol per-vaginum. If no expulsion occurred within 4 h, repeat doses of 400 µg misoprostol were given orally at 3-hourly interval to a maximum of 2 doses in women ≤9 weeks by scan and 4 doses in women >9 weeks by scan. Results: Pre-treatment of misoprostol with mifepristone significantly increased the complete abortion rate (86.7 vs. 57.8%, p = 0.009) and, hence, reduced the need for surgical evacuation (13.3 vs. 42.2%, p = 0.002), induction to expulsion interval (4.74 ± 2.24 vs. 8.03 ± 2.77 h, p = 0.000), mean number of additional doses of misoprostol required (0.68 vs. 1.91, p = 0.000), and side effects. Conclusion: Use of mifepristone prior to misoprostol in EPF significantly improves the efficacy and reduces the side effects of misoprostol alone.

8-Isoprostane in chronic periodontitis and type II diabetes: Exploring the link.

Background. Reactive oxygen species (ROS) are associated with the pathogenesis of inflammatory diseases and have a direct or indirect role in tissue damage constituting oxidative stress. ROS are also involved in impairment of ß-cell function during development of diabetes, which leads to genetic ablation of KATP channels, triggering up-regulation of antioxidant enzymes. Several markers of lipid peroxidation, protein oxidation and DNA damage induced by ROS can be measured. Over the last decade, isoprostanes have been considered as the best markers of lipid peroxidation. The aim of this study was to determine the presence of 8-isoprostane in healthy, chronic periodontitis and chronic periodontitis subjects with type II diabetes and to find the correlation between 8-isoprostane levels among groups and with clinical parameters like gingival index, probing depth and clinical attachment levels. Methods. Ninety subjects were selected and divided into 3 groups: healthy, chronic periodontitis and chronic periodontitis subjects with type II diabetes (n=30 each). Saliva was collected from these subjects after obtaining consent and analyzed for 8-isoprostane levels using ELISA kit. Statistical analysis was performed using Kruskal-Wallis test, Mann-Whitney U test and Spearman's correlation coefficient (P<0.001). Results. Statistically significant difference was found in the levels of 8-isoprostane between healthy, chronic periodontitis and chronic periodontitis subjects with type II diabetes and with all clinical parameters. Conclusion. 8-isoprostane can be considered as a pathophysiological marker to measure oxidative stress in periodontal diseases.

Prevalence of enteric bacterial parasites with respect to anthropogenic factors among commensal rhesus macaques in Dehradun, India.

There has been a recent surge in research on primate infectious disease ecology. Two major areas remain relatively unaddressed to date-the prevalence of enteric bacterial parasites and the role of anthropogenic environmental factors in parasite acquisition in commensally living primate populations. In this preliminary assessment, we address both these gaps by assessing the prevalence, and the role of anthropogenic factors in shaping this prevalence, of three enteric bacterial parasites-E . coli O157:H7, Salmonella sp., Shigella sp.-across populations of rhesus macaques (M. mulatta) that live commensally with humans in Dehradun, northern India. Across 10-week study period, we collected data on (1) human-macaque behavioral interactions, (2) macaque and human demographic and activity scans, and (3) macaque fecal samples from the environment at four different locations in Dehradun. Biochemical tests and morphology-based confirmations clearly established the presence of all three enteric bacterial parasites in rhesus macaques. Overall prevalence ranged from 2 to 5 %, with Shigella sp. being the most prevalent. Regression analyses linking anthropogenic factors to bacterial prevalence showed a positive association between rates of macaques eating human garbage and E. coli O157:H7 (ß = 0.23, p = 0.083), but a negative association with Salmonella sp. (ß = -0.17, p = 0.026). Rather, the prevalence of Salmonella sp. was positively linked to rates of macaque eating provisioned food (ß = 0.0012, p = 0.058). Finally, we found no relationship between anthropogenic factors and the prevalence of Shigella sp. Our findings establish the prevalence of enteric bacterial parasites in commensal populations of primates and suggest that although anthropogenic factors are linked to bacterial prevalence, the nature of the relationships may depend on the socioecological/foraging strategies of macaques and the food sources that facilitate the environmental survival of particular types of enteric bacteria over others.