Hyperbaric oxygen inhibits the HMGB1/RAGE signaling pathway by upregulating Mir-107 expression in human osteoarthritic chondrocytes.

OBJECTIVE: MicroRNA (miRNA)107 expression is downregulated but high mobility group box 1 (HMGB-1), Toll-like receptors (TLRs), and receptor for advanced glycation end products (RAGE) are upregulated in osteoarthritic (OA) cartilage. We investigated mir-107/HMGB-1 signaling in OA after hyperbaric oxygen (HBO) treatment. DESIGN: MiR-107 mimic was transfected and the HMGB-1 was analyzed in OA chondrocytes. MiRNA targets were identified using bioinformatics and a luciferase reporter assay. After HBO treatment, the mRNA or protein levels of HMGB-1, RAGE, TLR2, TLR4, and inducible nitric oxide (NO) synthase (iNOS) and phosphorylation of mitogen-activated protein kinase (MAPK) were evaluated. The secreted HMGB-1 and matrix metalloproteases (MMPs) levels were quantified. Finally, we detected the HMGB-1 and iNOS expression in rabbit cartilage defects. RESULTS: Overexpression of miR-107 suppressed HMGB-1 expression in OA chondrocytes. The 3'UTR of HMGB-1 mRNA contained a 'seed-matched-sequence' for miR-107. MiR-107 was induced by HBO and a marked suppression of HMGB-1 was observed simultaneously in OA chondrocytes. Knockdown of miR-107 upregulated HMGB-1 expression in hyperoxic cells. HBO downregulated the mRNA and protein expression of HMGB-1, RAGE, TLR2, TLR4, and iNOS, and the secretion of HMGB-1. HBO decreased the nuclear translocation of nuclear factor (NF)-κB, downregulated the phosphorylation of MAPK, and significantly decreased the secretion of MMPs. Morphological and immunohistochemical observation demonstrated that HBO markedly enhanced cartilage repair and the area stained positive for HMGB-1 and iNOS tended to be lower in the HBO group. CONCLUSIONS: HBO inhibits HMGB-1/RAGE signaling related pathways by upregulating miR-107 expression in human OA chondrocytes.

Effect of benign prostatic hyperplasia on the development of spine, hip, and wrist fractures.

Benign prostatic hyperplasia is one of the most common diseases in the elderly male population. The urinary tract symptoms may increase the risk of falls and fractures. The results indicated that patients with benign prostatic hyperplasia could increase the risk of vertebral compression fractures in both the thoracic and lumbar spine and also hip fractures, but did not increase the risk of wrist fracture. INTRODUCTION: The relationship between benign prostatic hyperplasia and the development of fall-related fractures, especially vertebral compression fractures, has been seldom mentioned in the literature. This study aimed to evaluate the risk of developing vertebral compression fracture, hip fracture, and wrist fracture in patients with benign prostatic hyperplasia. METHODS: This study obtained claims data retrospectively from the National Health Insurance Research Database of Taiwan and identified 48,114 patients who were diagnosed as having benign prostatic hyperplasia. Subjects of the control cohort were individually matched at a ratio of 4:1 with those in the benign prostatic hyperplasia cohort according to age and the index day. Comorbidities were classified as those existing before the index day and included a previous fracture history, osteoporosis, myocardial infarction, congestive heart failure, diabetes mellitus, hypertension, cerebrovascular accident, etc. The end of the follow-up period of the analyses was the day when the patient developed new vertebral compression fractures, hip fractures, or wrist fractures, terminated enrollment from the National Health Insurance, or died or until the end of 2012. The study used the Cox proportion hazard model to determine the hazard ratio for developing new hip fractures. RESULTS: Patients with benign prostatic hyperplasia were significantly more likely than those in the control cohort to develop new vertebral compression fractures in the thoracic spine (0.43% vs. 0.40%, adjusted hazard ratio 3.03, confidence interval 2.12-4.31) and lumbar spine (1.26% vs. 1.23%, adjusted hazard ratio 4.12, confidence interval 3.39-5.01), and hip fracture (1.47% vs. 2.09%, adjusted hazard ratio 1.22, confidence interval 1.10-1.36), but does not increase the risk of wrist fracture (0.61% vs. 0.67%, adjusted hazard ratio 1.07, confidence interval 0.85-1.34). CONCLUSIONS: Patients with benign prostatic hyperplasia exhibited an increased risk of developing vertebral compression fractures in both the thoracic and lumbar spine and also hip fractures, but did not increase the risk of wrist fracture. However, more research is needed to confirm this trend in the clinical setting.

The potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy: A preliminary assessment.

BACKGROUND AND OBJECTIVE: The response to nonsurgical periodontal treatment varied among patients. This study assessed the potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy. MATERIAL AND METHODS: This study recruited 34 participants with severe chronic periodontitis (the test group) and 20 participants without periodontal destruction in any teeth (the control group) from September 6, 2013 to August 25, 2017. Participants in the test group received nonsurgical periodontal therapy and were further divided into 2 subgroups of 17 low responders and 17 high responders, based on probing depth reduction. Clinical periodontal parameters were recorded, and saliva samples were harvested before and after nonsurgical periodontal therapy. Salivary biomarkers, including interleukin (IL)-1beta (IL-1ß), IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, platelet-derived growth factor-BB, vascular endothelial growth factor, MMP-8, MMP-9, C-reactive protein, and lactoferrin were analyzed. RESULTS: Compared with participants in the control group, participants in the test group had significantly greater periodontal pocket depth, clinical attachment level, and salivary IL-1ß and MMP-8 levels, and all of these parameters were significantly reduced after nonsurgical periodontal therapy. The pretreatment levels of IL-1ß, MMP-8, and lactoferrin were significantly higher in participants of the high-responder subgroup than participants of the low-responder subgroup.Based on the analysis from a dichotomous table, MMP-8 and lactoferrin showed odds ratios of 5.76, with 71% sensitivity and 71% specificity, and statistical significance (P = .02) for discriminating between the high- and low-responder subgroups. CONCLUSION: Salivary IL-1ß and MMP-8 might be useful for diagnosing periodontitis and monitoring the recovery of periodontitis following nonsurgical periodontal therapy. MMP-8 and lactoferrin showed potential for predicting the sensitivity to the treatment.

Pharyngeal airway changes following maxillary expansion or protraction: A meta-analysis.

The aim of this meta-analysis was to investigate the changes in airway dimensions after rapid maxillary expansion (RME) and facemask (FM) protraction. Using PubMed, Medline, ScienceDirect and Web of Science, only controlled clinical trials, published up to November 2016, with RME and/or FM as keywords that had ≥6 months follow-up period were included in this meta-analysis. The changes in pharyngeal airway dimension in both two-dimensional and three-dimensional images were included in the analysis. Nine studies met the criteria. There are statically significant changes in upper airway and nasal passage airway in the intervention groups as compared to the control groups, assessed in two-dimensional and three-dimensional images. However , in the lower airway and the airway below the palatal plane, no statistically significant changes are seen in 2D and 3D images. RME/FM treatments might increase the upper airway space in children and young adolescents. However, more RCTs and long-term cohort studies are needed to further clarify the effects on pharyngeal airway changes.

Association between thyroid dysfunction and dysglycaemia: a prospective cohort study.

AIMS: To compare the incidence of hyperglycaemia among participants with low, elevated and normal serum thyroid-stimulating hormone concentration, as well as the incidence of abnormal thyroid function test results among participants with normal blood glucose and those with hyperglycaemia. METHODS: In a prospective study, a cohort of 72 003 participants with normal, low and elevated serum thyroid-stimulating hormone concentration were followed from the study beginning to the first report of diabetes and prediabetes. A proportional hazards regression model was used to calculate the hazard ratios and 95% CIs for each outcome, adjusting for age, sex, education level, smoking, alcohol consumption and obesity. Analyses for the association between dysglycaemia and incident abnormal thyroid function test were also conducted. RESULTS: During a median 2.6 year follow-up, the incident rates for dysglycaemia, particularly prediabetes, were substantially higher in participants with elevated thyroid-stimulating hormone concentrations at baseline, while the rates for participants with normal and low thyroid-stimulating hormone were similar. After controlling for risk factors, participants with elevated thyroid-stimulating hormone retained a 15% increase in risk of prediabetes (adjusted hazard ratio 1.15, 95% CI 1.04-1.26), but were not at greater risk of diabetes (adjusted hazard ratio 0.96, 95% CI 0.64-1.44). By contrast, participants with normal and low thyroid-stimulating hormone concentrations had similar dysglycaemia risks. Participants with diabetes and prediabetes were not at greater risks of developing abnormal thyroid function test results when compared with participants with euglycaemia. CONCLUSIONS: People with elevated serum thyroid-stimulating hormone concentration are at greater risk of developing prediabetes. Whether this includes a greater risk of developing frank diabetes may require an extended period of follow-up to clarify.

Root coverage by coronally advanced flap with connective tissue graft and/or enamel matrix derivative: a meta-analysis.

BACKGROUND AND OBJECTIVE: Previous systematic reviews have reported that the use of a coronally advanced flap (CAF) combined with a connective tissue graft (CTG) or enamel matrix derivative (EMD) is more likely to achieve complete root coverage (CRC) than other modalities. However, the details of periodontal parameters and comparisons among a variety of combinations of CAF with CTG and/or EMD are left to be investigated. This study aimed to analyze the differences in periodontal parameters between these treatment modalities. MATERIAL AND METHODS: A literature search was performed using the Cochrane library and MEDLINE (PubMed) for studies focused on the treatment of gingival recession (Miller Class I, II and III) with CAF alone or combined with CTG, EMD or both up to December 2011. Randomized controlled clinical trials with a follow-up duration ≥ 6 mo were included. The outcome analysis included changes in periodontal probing depth (PPD), clinical attachment level, recession depth (RED) and keratinized tissue width (KTW). RESULTS: Thirteen randomized controlled clinical trials, including 529 Miller Class I-III defects from 321 patients were included. For an increase in KTW, CAF + CTG significantly improved more than CAF alone. CAF + EMD also gained more KTW than CAF alone. EMD reduced PPD, however, a significant difference was not found. Furthermore, the effects on changes of RED and clinical attachment level were not identified in the study. CONCLUSION: When combined with CAF, CTG contributed more in the increase of KTW, while EMD seemed helpful for wound healing by its potential in PPD reduction. However, further research is needed to clarify the effects on changes in RED and clinical attachment level.

Risks and predictors of osteoporosis in patients with inflammatory bowel diseases in an Asian population: a nationwide population-based cohort study.

BACKGROUND: We investigated the inflammatory bowel disease (IBD) specific predictors of osteoporosis and pathological fracture by analysing the Taiwan National Health Insurance Research Database. METHODS: Totally, we enrolled 3141 IBD patients and 12,564 age- and sex-matched controls. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of osteoporosis and pathological fracture in both cohorts. RESULTS: Inflammatory bowel disease patients had significantly higher comorbidity-adjusted rates of osteoporosis and pathological fracture compared with controls [adjusted hazard ratio (aHR), 1.31; 95% CI, 1.09-1.60, p = 0.004]. Further analysis indicated that women (aHR, 1.36; 95% CI, 1.09-1.70, p = 0.008), middle-aged patients (aHR, 1.74; 95% CI, 1.25-2.41, p = 0.001), patients with Crohn's disease (aHR, 1.33; 95% CI, 1.09-1.64, p = 0.006) and patients without comorbidities (aHR, 1.81; 95% CI, 1.23-2.67, p = 0.003) exhibited excessive risks of osteoporosis. Moreover, patients requiring hospitalisation for IBD exhibited the highest risk of developing osteoporosis (aHR, 4.46; 95% CI, 2.74-7.27, p < 0.001) and pathological fracture (aHR, 17.1; 95% CI, 5.78-50.9, p < 0.001). CONCLUSIONS: Patients with IBD, particularly women, middle-aged patients and patients without comorbidities, are associated with a long-term risk of osteoporosis. The risks of osteoporosis and pathological fracture were highest in patients requiring hospitalisation for IBD.

Comparison of treatment effects of guided tissue regeneration on infrabony lesions between animal and human studies: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: For ethical reasons it is becoming increasingly more difficult to obtain, from clinical studies, histological data on infrabony defects treated with guided tissue regeneration (GTR) techniques. The aim of this systematic review was to find the value of extrapolating animal data on treatment of periodontal infrabony lesions, using GTR only or GTR + bone grafts, to human clinical results. MATERIAL AND METHODS: Searches of the PubMed and Cochrane databases were combined with hand searching of articles published from 1 January 1969 to 1 August 2012. The search included any type of barrier membrane, with or without grafted materials, used to treat periodontal infrabony lesions. All studies with histological or re-entry methodology outcome parameters that evaluated bone-filling and/or new-cementum-formation ratios from a defect depth were collected. When comparing animal and human outcomes, a meta-analysis was used to evaluate the bone-filling ratio, but only a descriptive analysis of the histological studies was performed. RESULTS: In total, 22 studies were selected for the meta-analysis. In the GTR + bone graft groups the weighted-average bone-filling ratios were 52% (95% CI: 18-85%) in animals and 57% (95% CI: 30-83%) in humans, which were not statistically significantly different (p = 0.825). Similar results were found in the GTR-only groups, in which the weighted-average bone-filling ratios were 54% (95% CI: 37-72%) in animals and 59% (95% CI: 42-77%) in humans (p = 0.703). New-cementum formation of GTR only and GTR + bone grafts showed comparable ratio outcomes, and both were superior to the control group in animals only (p = 0.042). CONCLUSION: Although quality assessments differed between animal and human studies, our analysis indicated that animal models and human results showed similar bone-filling ratios in infrabony defects treated with GTR only or with GTR + bone grafting.

Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta-analysis.

AIM: Most guidelines recommend metformin as first-line therapy in patients with type 2 diabetes. However, the choice of a second-line drug lacks consistent consensus. We aimed to assess available information of antidiabetic drugs added to metformin on the change in glycated haemoglobin A1c (A1C), risk of hypoglycaemia and change in body weight. METHODS: PubMed and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) written in English through December 2011. We analysed direct and indirect comparisons of different treatments using Bayesian network meta-analysis. RESULTS: Thirty-nine RCTs involving 17 860 individuals were included. Glucagon-like peptide-1 (GLP-1) analogues resulted in greater decrease in A1C compared with sulfonylureas, glinides, thiazolidinediones, α-glucosidase inhibitors and DPP-4 inhibitors [-0.20% (95% CI -0.34 to -0.04%), -0.31% (95% CI -0.61 to -0.02%), -0.20% (95% CI -0.38 to -0.00), -0.36% (95% CI -0.64 to -0.07%), -0.32% (95% CI -0.47 to -0.17%), respectively] and was comparable with basal insulin and biphasic insulin. A1C decrease was greater for sulfonylureas compared with DPP-4 inhibitors [-0.12% (-0.23 to -0.03%)], and for biphasic insulin compared with glinides (-0.36%; 95% CI -0.82 to -0.11%). Compared with placebo, the risk of hypoglycaemia was increased in the sulfonylureas, glinides, basal insulin and biphasic insulin. Weight increase was seen with sulfonylureas, glinides, thiazolidinediones, basal insulin and biphasic insulin, and weight loss was seen with α-glucosidase inhibitors and GLP-1 analogues. CONCLUSIONS: Biphasic insulin, GLP-1 analogues and basal insulin were ranked the top three drugs in terms of A1C reduction. GLP-1 analogues did not increase the risk of hypoglycaemia and resulted in a significant decrease in body weight. Most oral antidiabetic drugs had similar effects on A1C, but some agents had a lower risk of hypoglycaemia and body weight gain.

Effect of Flap Design for Enamel Matrix Derivative Application in Intraosseous Defects.

OBJECTIVE: To systematically review the literature addressing the focused question: What is the effectiveness of different surgical and nonsurgical procedures combined with enamel matrix derivative (EMD) on clinical, radiographic, and patient-centered outcomes in intraosseous defects? METHODS: Electronic (Medline, Scopus, and Cochrane databases) and hand literature searches were performed for studies including at least 1 treatment arm where EMD had been applied according to 1 of the following procedures: modified Widman flap; papilla preservation variants (PPVs), including papilla preservation technique, modified papilla preservation technique, and simplified papilla preservation technique; minimally invasive variants, including minimally invasive surgical approach and minimally invasive surgical technique; single-flap variants (SFVs), including single-flap approach and modified minimally invasive surgical technique; or nonsurgical application (flapless approach). Data from 42 selected articles were used to perform a network meta-analysis, and a hierarchy of surgical and nonsurgical applications of EMD was built separately for EMD and EMD + graft based on 6- to 12-mo clinical and radiographic outcomes. RESULTS: Among surgical approaches, EMD was associated with best regenerative outcomes when applied through SFVs, with a mean clinical attachment level gain of 3.93 mm and a reduction in the intrabony component of the defect of 3.35 mm. For EMD + graft, limited differences in regenerative outcomes were observed among surgical procedures. PPVs were associated with the highest residual probing depth for EMD (4.08 mm) and EMD + graft (4.32 mm). CONCLUSIONS: In the treatment of periodontal intraosseous defects, 1) SFVs appear to optimize the regenerative outcomes of EMD; 2) substantial regenerative outcomes can be obtained with SFVs and conservative double flaps (i.e., PPVs and minimally invasive variants) when EMD is combined with a graft; and 3) residual probing depth was higher following PPVs for EMD and EMD + graft. KNOWLEDGE TRANSFER STATEMENT: The results of the present systematic review and meta-analysis can be used by clinicians to identify the most effective surgical or nonsurgical procedure to treat an intraosseous defect with EMD or EMD + graft. The main findings indicate that when EMD application is indicated, surgical access based on a single flap seems the most appropriate to optimize clinical outcomes. The application of EMD + graft can be effectively combined with single flaps and conservative double flaps.

Risk of Myocardial Infarction and Ischemic Stroke after Dental Treatments.

The association between invasive dental treatments (IDTs) and a short-term risk of myocardial infarction (MI) and ischemic stroke (IS) remains controversial. Bacterial dissemination from the oral cavity and systemic inflammation linked to IDT can induce a state of acute vascular dysfunction. The aim of study is to investigate the relation of IDTs to MI and IS by using case-only study designs to analyze data from a large Taiwanese cohort. A nationwide population-based study was undertaken by using the case-crossover and self-controlled case series design to analyze the Taiwanese National Health Care Claim database. Conditional logistic regression model and conditional Poisson regression model were used to estimate the risks of MI/IS. In addition, we used burn patients as negative controls to explore the potential effect of residual confounding. In total, 123,819 MI patients and 327,179 IS patients in the case-crossover design and 117,655 MI patients and 298,757 IS patients were included in the self-controlled case series design. Results from both study designs showed that the risk of MI within the first 24 wk after IDT was not significantly different from or close to unity except for a modest risk during the first week for patients without other comorbidities (odds ratios [95% confidence intervals] of 1.31 [1.08-1.58] and 1.15 [1.01-1.31] for 3 d and 7 d, respectively). We also observed no association between IDTs and IS, or the risk ratio was close to unity. IDTs did not appear to be associated with a transient risk of MI and IS in the Taiwanese population, with consistent findings from both case-only study designs. However, we cannot exclude that dental infections and diseases may yield a long-term risk of MI and IS.

Prevention of Postdental Procedure Bacteremia: A Network Meta-analysis.

Postdental procedure bacteremia is common and troublesome. The comparative efficacy of multiple prophylactic interventions is unclear. We compared the efficacy of interventions for the prevention of postdental procedure bacteremia. We conducted a review of ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to December 4, 2018. Randomized controlled trials that evaluated prophylactic interventions for the prevention of postdental procedure bacteremia were eligible. The primary outcome was the incidence of postdental procedure bacteremia. A total of 24 trials were included with 2,147 participants. Our network meta-analysis demonstrated that intravenous administration of 1,000/200 mg of amoxicillin/clavulanate provided the least incidence of postdental procedure bacteremia among all the prophylactic interventions (odds ratio = 0.03, 95% CI = 0.00 to 0.63) as compared with the placebo/controls. Oral 3 g of amoxicillin had the least incidence of postdental procedure bacteremia among all oral or topical forms of prophylactic interventions (odds ratio = 0.10, 95% CI = 0.02 to 0.44) as compared with the placebo/controls. No serious adverse events, such as anaphylactic shock, mortality, and the development of antibiotic-resistant bacteria, were reported. None of the included subjects were of high risk of infectious endocarditis. Our network meta-analysis demonstrates that intravenous amoxicillin/clavulanate and oral amoxicillin might be the best prophylactic interventions in preventing postdental procedure bacteremia among all the oral/topical forms of interventions for the overall populations.

Does Classification of Composites for Network Meta-analyses Lead to Erroneous Conclusions?

OBJECTIVES: Composites can be classified differently, according to manufacturer information, filler particle size, resin-monomer base, or viscosity, for example. Using clinical trial data, network meta-analyses aim to rank different composite material classes. Dentists then use these ranks to decide whether to use specific materials. Alternatively, annual failure rates (AFRs) of materials can be assessed, not requiring any classification for synthesis. It is unclear whether different classification systems lead to different rankings of the same material (ie, erroneous conclusions). We aimed to evaluate the agreement of material rankings between different classification systems. METHODS: A systematic review was performed via MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. Randomized controlled trials published from 2005-2015 that investigated composite restorations placed in load-bearing cavitated lesions in permanent teeth were included. Network meta-analyses were performed to rank combinations of composite classes (according to manufacturer, filler particle size, resin-monomers, viscosity) and adhesives. Material combinations were additionally ranked using AFRs. RESULTS: A total of 42 studies (6088 restorations, 2325 patients) were included. The ranking of most material class combinations showed significant agreement between classifications ( R2 ranged between 0.03 and 0.56). Comparing material combinations using AFRs had low precision and agreement with other systems. AFRs were significantly correlated with follow-up periods of trials. CONCLUSION: There was high agreement between rankings of identical materials in different classification systems. Such rankings thus allow cautious deductions as to the performance of a specific material. Syntheses based on AFRs might lead to erroneous results because AFRs are determined by follow-up periods and have low precision.

Chopart amputation with tibiotalocalcaneal arthrodesis and free flap reconstruction for severe foot crush injury.

AIMS: This study reports the outcomes of a technique of soft-tissue coverage and Chopart amputation for severe crush injuries of the forefoot. PATIENTS AND METHODS: Between January 2012 to December 2016, 12 patients (nine male; three female, mean age 38.58 years; 26 to 55) with severe foot crush injury underwent treatment in our institute. All patients were followed-up for at least one year. Their medical records, imaging, visual analogue scale score, walking ability, complications, and functional outcomes one year postoperatively based on the American Orthopedic Foot and Ankle Society (AOFAS) and 36-Item Short-Form Health Survey (SF-36) scores were reviewed. RESULTS: The mean length of follow-up was 18.6 months (13 to 28). Two patients had a local infection, flap necrosis was seen in one patient, and one patient experienced a skin graft wound healing delay. Of the 12 patients, one had persistent infection and eventually required below-knee amputation, but pain-free walking was achieved in all the other patients. The mean one-year postoperative AOFAS and SF-36 scores were 75.6 (68 to 80) and 82 (74 to 88), respectively. CONCLUSION: Although our sample size was small, we believe that this treatment method may be a valuable alternative for treating severe foot crush injuries. Cite this article: Bone Joint J 2018;100-B:1359-63.

What is the effect of adjusting for more than one measure of current body size on the relation between birthweight and blood pressure?

The statistical validity of the negative associations observed between birthweight and disease in later life has recently been questioned, because these associations might be due, in part, to inappropriate adjustment for current body size, creating a statistical artefact known as the 'reversal paradox'. The aim of this study was to explore the effect of adjusting for more than one measure of current body size on the association between birthweight and disease in later life using simulations and meta-analyses of empirical studies. The simulations examined the relation between birthweight and adult systolic blood pressure before and after adjusting for one, two or three measures of current body size by including current weight and subsequently adding body mass index and height in successive analytical models. Meta-analyses were then performed to compare the effect sizes observed among empirical studies reporting associations between birthweight and blood pressure before and after adjusting for one or two measures of current body size. The meta-analyses confirmed the results of the simulations - both showed that associations between birthweight and blood pressure tend to become increasingly negative following adjustment for current body size, and that this effect is enhanced after adjusting for additional measures of current body size.

Long term follow-up results of dorsal root entry zone lesions for intractable pain after brachial plexus avulsion injuries.

Brachial plexus avulsion injury is one of the major complications after traffic, especially motorcycle accidents and machine injuries. Intractable pain and paralysis of the affected limbs are the major neurological deficits. During the past 18 years, we have encountered and treated more than 500 cases with brachial plexus avulsion injuries. Dorsal root entry zone lesions (DREZ) made by thermocoagulation were performed for intractable pain in 60 cases. Forty cases were under regular follow-up for 5-18 years. In early postoperative stage, the pain relief rate was excellent or good in 32 cases (80%). The pain relief rate dropped to 60% in 5 year follow-up period and only 9 cases (50%) had excellent or good result in 10 year follow-up. Reconstructive procedures were performed in almost all patients in the last 10 years. Dorsal root entry zone lesion is an effective procedure for pain control after brachial plexus avulsion injuries.

Effect of Industry Sponsorship on Dental Restorative Trials.

Industry sponsorship was found to potentially introduce bias into clinical trials. We assessed the effects of industry sponsorship on the design, comparator choice, and findings of randomized controlled trials on dental restorative materials. A systematic review was performed via MEDLINE, CENTRAL, and EMBASE. Randomized trials on dental restorative and adhesive materials published 2005 to 2015 were included. The design of sponsored and nonsponsored trials was compared statistically (risk of bias, treatment indication, setting, transferability, sample size). Comparator choice and network geometry of sponsored and nonsponsored trials were assessed via network analysis. Material performance rankings in different trial types were estimated via Bayesian network meta-analysis. Overall, 114 studies were included (15,321 restorations in 5,232 patients). We found 21 and 41 (18% and 36%) trials being clearly or possibly industry sponsored, respectively. Trial design of sponsored and nonsponsored trials did not significantly differ for most assessed items. Sponsored trials evaluated restorations of load-bearing cavities significantly more often than nonsponsored trials, had longer follow-up periods, and showed significantly increased risk of detection bias. Regardless of sponsorship status, comparisons were mainly performed within material classes. The proportion of trials comparing against gold standard restorative or adhesive materials did not differ between trial types. If ranked for performance according to the need to re-treat (best: least re-treatments), most material combinations were ranked similarly in sponsored and nonsponsored trials. The effect of industry sponsorship on dental restorative trials seems limited.

Directly Placed Restorative Materials: Review and Network Meta-analysis.

For restoring cavitated dental lesions, whether carious or not, a large number of material combinations are available. We aimed to systematically review and synthesize data of comparative dental restorative trials. A systematic review was performed. Randomized controlled trials published between 2005 and 2015 were included that compared the survival of ≥2 restorative and/or adhesive materials (i.e., no need for restorative reintervention). Pairwise and Bayesian network meta-analyses were performed, with separate evaluations for cervical cavitated lesions and load-bearing posterior cavitated lesions in permanent and primary teeth. A total of 11,070 restorations (5,330 cervical, 5,740 load bearing) had been placed in 3,633 patients in the included trials. Thirty-six trials investigated restoration of cervical lesions (all in permanent teeth) and 36 of load-bearing lesions (8 in primary and 28 in permanent teeth). Resin-modified glass ionomer cements had the highest chance of survival in cervical cavitated lesions; composites or compomers placed via 2-step self-etch and 3-step etch-and-rinse adhesives were ranked next. Restorations placed with 2-step etch-and-rinse or 1-step self-etch adhesives performed worst. For load-bearing restorations, conventional composites had the highest probability of survival, while siloranes were found least suitable. Ambiguity remains regarding which adhesive strategy to use in load-bearing cavitated lesions. Most studies showed high risk of bias, and several comparisons were prone for publication bias. If prioritized for survival, resin-modified glass ionomer cements might be recommended to restore cervical lesions. For load-bearing ones, conventional or bulk fill composites seem most suitable. The available evidence is quantitatively and qualitatively insufficient for further recommendations, especially with regard to adhesive strategies in posterior load-bearing situations. Moreover, different material classifications might yield different findings on the same materials. Future trials should aim for sufficient power, longer follow-up times, and high internal validity to prove or refute differences between certain material combinations. An agreed material classification for future syntheses is desirable.

Inhibition of nitric oxide can ameliorate apoptosis and modulate matrix protein gene expression in bacteria infected chondrocytes in vitro.

Bacterial infection stimulates nitric oxide (NO) production in chondrocytes. However, the role of NO in chondrocyte apoptosis after infection remains unclear. The purpose of the study was to test if inhibition of NO could ameliorate apoptosis and modulate matrix protein gene expression in bacteria-infected chondrocytes. It was shown that pre-treating chondrocytes with L-NAME (1 mM) significantly decreased the release of NO (from 72 to 14 microM) and the extent of apoptosis (from 52.9% to 18.9%). Pre-treatment with L-NAME also counteracted the bacteria-induced downregulation of Type II collagen (from 26% to 79%) and aggrecan (from 63% to 105%) mRNA levels. Inhibition of NO after the induction of infection could not decrease the extent of apoptosis and modulate matrix protein gene expression. The results of this study support the hypothesis that NO has an important role in bacteria-induced chondrocyte apoptosis. Pre-treatment but not post-treatment could ameliorate the extent of apoptosis and reestablish the cartilage matrix protein gene expression. This study suggests that in addition to NO, other mechanisms may be responsible for the sustained destruction of articular cartilage in the post-infectious arthropathy.