Role of anatomical sites and correlated risk factors on the survival of orthodontic miniscrew implants:a systematic review and meta-analysis

Abstract Objectives The aim of this review was to systematically evaluate the failure rates of miniscrews related to their specific insertion site and explore the insertion site dependent risk factors contributing to their failure. Search methods An electronic search was conducted in the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Knowledge, Scopus, MEDLINE and PubMed up to October 2017. A comprehensive manual search was also performed. Eligibility criteria Randomised clinical trials and prospective non-randomised studies, reporting a minimum of 20 inserted miniscrews in a specific insertion site and reporting the miniscrews’ failure rate in that insertion site, were included. Data collection and analysis Study selection, data extraction and quality assessment were performed independently by two reviewers. Studies were sub-grouped according to the insertion site, and the failure rates for every individual insertion site were analysed using a random-effects model with corresponding 95% confidence interval. Sensitivity analyses were performed in order to test the robustness of the reported results. Results Overall, 61 studies were included in the quantitative synthesis. Palatal sites had failure rates of 1.3% (95% CI 0.3–6), 4.8% (95% CI 1.6–13.4) and 5.5% (95% CI 2.8–10.7) for the midpalatal, paramedian and parapalatal insertion sites, respectively. The failure rates for the maxillary buccal sites were 9.2% (95% CI 7.4–11.4), 9.7% (95% CI 5.1–17.6) and 16.4% (95% CI 4.9–42.5) for the interradicular miniscrews inserted between maxillary first molars and second premolars and between maxillary canines and lateral incisors, and those inserted in the zygomatic buttress respectively. The failure rates for the mandibular buccal insertion sites were 13.5% (95% CI 7.3–23.6) and 9.9% (95% CI 4.9–19.1) for the interradicular miniscrews inserted between mandibular first molars and second premolars and between mandibular canines and first premolars, respectively. The risk of failure increased when the miniscrews contacted the roots, with a risk ratio of 8.7 (95% CI 5.1–14.7). Conclusions Orthodontic miniscrew implants provide acceptable success rates that vary among the explored insertion sites. Very low to low quality of evidence suggests that miniscrews inserted in midpalatal locations have a failure rate of 1.3% and those inserted in the zygomatic buttress have a failure rate of 16.4%. Moderate quality of evidence indicates that root contact significantly contributes to the failure of interradicular miniscrews placed between the first molars and second premolars. Results should be interpreted with caution due to methodological drawbacks in some of the included studies

Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling

Toll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor (TIR)-domain interactions, which remain structurally elusive. Here we show that MAL TIR domains spontaneously and reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR domains and induce formation of MyD88 assemblies. A 7-Å-resolution cryo-EM structure reveals a stable MAL protofilament consisting of two parallel strands of TIR-domain subunits in a BB-loop-mediated head-to-tail arrangement. Interface residues that are important for the interaction are conserved among different TIR domains. Although large filaments of TLR4, MAL or MyD88 are unlikely to form during cellular signaling, structure-guided mutagenesis, combined with in vivo interaction assays, demonstrated that the MAL interactions defined within the filament represent a template for a conserved mode of TIR-domain interaction involved in both TLR and interleukin-1 receptor signaling

Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behçet's disease

Background/aims: Behçet's disease (BD) is a systemic inflammatory vasculitis of young adults with unknown aetiology, characterised by endothelial dysfunction and occlusion in both deep venous and retinal circulation. Ocular involvement occurs in 70% of cases and is characterised by periphlebitis, periarteritis, vascular occlusion, and thrombosis leading to blindness despite vigorous treatment. Endothelin-1 (ET-1) is a vasoconstricting peptide while nitric oxide (NO) is a relaxing molecule and both are released by endothelium for blood flow regulation. Homocysteinaemia is a newly defined term connected to the increased risk of atherothrombotic and atherosclerotic systemic and retinal vascular occlusive diseases, and its role in the course of BD has not been previously described. The authors aimed to detect serum total homocysteine (tHcy), ET-1, and NO in BD and to assess if tHcy, ET-1, and NO are associated with ocular BD or disease activity. Methods: 43 consecutive patients with ocular (n = 27) or non-ocular (n = 16) BD (36.95 (SD 9.80) years, 22 male, 21 female) satisfying international criteria, and 25 age and sex matched healthy control subjects (37.88 (8.73) years, 13 male, 12 female) without a history of systemic or retinal venous thrombosis were included in this study. Patients were examined by two ophthalmologists with an interest in BD. Serum tHcy, ET-1, and NO concentrations were measured in both groups. Hyperhomocysteinaemia was defined as a tHcy level above the 95th percentile in the control group. Patients were divided into active and inactive period by acute phase reactants including α(1) antitrypsin, α(2) macroglobulin, erythrocyte sedimentation rate, and neutrophil count. Results: The overall mean serum tHcy, ET-1, and NO levels were significantly higher in patients with BD than in control subjects (tHcy = 15.83 (4.44) v 7.96 (2.66) ng/ml, p <0.001; ET-1 = 17.47 (4.33) v 5.74 (2.34) μmol/ml, p <0.001; NO = 37.60 (10.31) v 27.08 (7.76) μmol/l, p <0.001). Serum tHcy, ET-1, and NO levels were significantly higher in active patients than in inactive patients and control subjects. In addition, among patients with ocular BD, the mean tHcy levels were significantly increased and correlated with ET-1 and NO levels when compared with non-ocular disease and control subjects. All acute phase reactant levels were significantly higher in active period than in inactive stage and controls. Conclusions: Elevated tHcy may be responsible for the endothelial damage in BD and may be an additional risk factor for the development of retinal vascular occlusive disease, contributing to the poor visual outcome in these patients. Assessment of tHcy may be important in the investigation and management of patients with BD, especially with ocular disease

Harnessing Knowledge on Very Important Pharmacogenes CYP2C9 and CYP2C19 Variation for Precision Medicine in Resource-Limited Global Conflict Zones

Ankarali, Handan Camdeviren/0000-0002-3613-0523;WOS: 000386220900007PubMed: 27726640Pharmacogenomics harnesses the utility of a patient's genome (n=1) in decisions on which therapeutic drugs and in what amounts should be administered. Often, patients with shared ancestry present with comparable genetic profiles that predict drug response. However, populations are not static, thus, often, population mobility through migration, especially enmasse as is seen for refugees, changes the pharmacogenetic profiles of resultant populations and therefore observed responses to commonly used therapeutic drugs. For example, in the aftermath of the Syrian civil war since 2011, millions have fled their homes to neighboring countries in the Middle East. The growing permanence of refugees and mass migrations is a call to shift our focus in the life sciences community from old models of pharmaceutical innovation. These seismic social changes demand faster decisions for population-to-population bridging, whereby novel drugs developed in or for particular regions/countries can meet with rational regulatory decisions/approval in world regions impacted by migrant/refugee populations whose profiles are dynamic, such as in the Eastern Mediterranean region at present. Thus, it is important to characterize and report on the prevalence of pharmacogenes that affect commonly used medications and predict if population changes may call for attention to particular differences that may impact health of patients. Thus, we report here on four single-nucleotide polymorphism (SNP) variations in CYP2C9 and CYP2C19 genes among Mersin-Turkish healthy volunteers in the Mersin Province in the Eastern Mediterranean region that is currently hosting a vast number of migrant populations from Syria. Both CYP2C9 and CYP2C19 are very important pharmacogene molecular targets. We compare and report here on the observed SNP genetic variation in our sample with data on 12 world populations from dbSNP and discuss the feasibility of forecasting the pharmacokinetics of drugs utilized by migrant communities in Mersin and the Eastern Mediterranean region. This study can serve as a catalyst to invest in research in Syrian populations currently living in the Eastern Mediterranean. The findings have salience for rapid and rational regulatory decision-making for worldwide precision medicine and, specifically, pharmacogenovigilance-guided bridging of pharmacokinetics across world populations in the current era of planetary scale migration

Structure of the Toll/interleukin 1 receptor (TIR) domain of the immunosuppressive Brucella effector BtpA/Btp1/TcpB.

International audienceBtpA/Btp1/TcpB is a virulence factor produced by Brucella species that possesses a Toll interleukin-1 receptor (TIR) domain. Once delivered into the host cell, BtpA interacts with MyD88 to interfere with TLR signalling and modulates microtubule dynamics. Here the crystal structure of the BtpA TIR domain at 3.15 Å is presented. The structure shows a dimeric arrangement of a canonical TIR domain, similar to the Paracoccus denitrificans Tir protein but secured by a unique long N-terminal α-tail that packs against the TIR:TIR dimer. Structure-based mutations and multi-angle light scattering experiments characterized the BtpA dimer conformation in solution. The structure of BtpA will help with studies to understand the mechanisms involved in its interactions with MyD88 and with microtubules