Effect of rhBMP-2 applied with a 3D-printed titanium implant on new bone formation in rabbit calvarium

Objective: This study sought to compare the biocompatibility of a three-dimensional (3D)-printed titanium implant with a conventional machined titanium product, as well as the effect of such implant applied with recombinant human Bone Morphogenetic Protein Type 2 (rhBMP-2) for guided bone regeneration. Methodology: Disk-shaped titanium specimens fabricated either by the conventional machining technique or by the 3D-printing technique were compared by MC3T3-E1 cells cytotoxicity assay. New bone formation was evaluated using a rapid prototype titanium cap applied to the calvaria of 10 rabbits, which were divided into two groups: one including an atelopeptide collagen plug on one side of the cap (group I) and the other including a plug with rhBMP-2 on the other side (group II). At six and 12 weeks after euthanasia, rabbits calvaria underwent morphometric analysis through radiological and histological examination. Results: Through the cytotoxicity assay, we identified a significantly higher number of MC3T3-E1 cells in the 3D-printed specimen when compared to the machined specimen after 48 hours of culture. Moreover, morphometric analysis indicated significantly greater bone formation at week 12 on the side where rhBMP-2 was applied when evaluating the upper portion immediately below the ca p. Conclusion: The results suggest that 3D-printed titanium implant applied with rhBMP-2 enables new bone formation

Enhanced DET-Based Fault Signature Analysis for Reliable Diagnosis of Single and Multiple-Combined Bearing Defects

To early identify cylindrical roller bearing failures, this paper proposes a comprehensive bearing fault diagnosis method, which consists of spectral kurtosis analysis for finding the most informative subband signal well representing abnormal symptoms about the bearing failures, fault signature calculation using this subband signal, enhanced distance evaluation technique- (EDET-) based fault signature analysis that outputs the most discriminative fault features for accurate diagnosis, and identification of various single and multiple-combined cylindrical roller bearing defects using the simplified fuzzy adaptive resonance map (SFAM). The proposed comprehensive bearing fault diagnosis methodology is effective for accurate bearing fault diagnosis, yielding an average classification accuracy of 90.35%. In this paper, the proposed EDET specifically addresses shortcomings in the conventional distance evaluation technique (DET) by accurately estimating the sensitivity of each fault signature for each class. To verify the efficacy of the EDET-based fault signature analysis for accurate diagnosis, a diagnostic performance comparison is carried between the proposed EDET and the conventional DET in terms of average classification accuracy. In fact, the proposed EDET achieves up to 106.85% performance improvement over the conventional DET in average classification accuracy

Design and synthesis of multigrain nanocrystals via geometric misfit strain.

The impact of topological defects associated with grain boundaries (GB defects) on the electrical, optical, magnetic, mechanical and chemical properties of nanocrystalline materials1,2 is well known. However, elucidating this influence experimentally is difficult because grains typically exhibit a large range of sizes, shapes and random relative orientations3-5. Here we demonstrate that precise control of the heteroepitaxy of colloidal polyhedral nanocrystals enables ordered grain growth and can thereby produce material samples with uniform GB defects. We illustrate our approach with a multigrain nanocrystal comprising a Co3O4 nanocube core that carries a Mn3O4 shell on each facet. The individual shells are symmetry-related interconnected grains6, and the large geometric misfit between adjacent tetragonal Mn3O4 grains results in tilt boundaries at the sharp edges of the Co3O4 nanocube core that join via disclinations. We identify four design principles that govern the production of these highly ordered multigrain nanostructures. First, the shape of the substrate nanocrystal must guide the crystallographic orientation of the overgrowth phase7. Second, the size of the substrate must be smaller than the characteristic distance between the dislocations. Third, the incompatible symmetry between the overgrowth phase and the substrate increases the geometric misfit strain between the grains. Fourth, for GB formation under near-equilibrium conditions, the surface energy of the shell needs to be balanced by the increasing elastic energy through ligand passivation8-10. With these principles, we can produce a range of multigrain nanocrystals containing distinct GB defects

Mortality risk and causes of death in patients with non-cystic fibrosis bronchiectasis

Background All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis. Methods Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. Among the patients without bronchiectasis, a control group was selected after applying additional exclusion criteria. We compared the mortality risk and causes of death between the bronchiectasis and control groups without lung disease. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status. Results Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were included. The all-cause mortality rate in the bronchiectasis group was 1608.8 per 100,000 person-years (95% confidence interval (CI), 1531.5–1690.0), which was higher than that in the control group (133.5 per 100,000 person-years; 95% CI, 124.1–143.8; P < 0.001). The bronchiectasis group had higher all-cause (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.09–1.47), respiratory (aHR, 3.49; 95% CI, 2.21–5.51), and lung cancer-related (aHR, 3.48; 95% CI, 2.33–5.22) mortality risks than the control group. In subgroup analysis, patients with airflow limitation and ever smokers showed higher all-cause mortality risk among bronchiectasis patients. Therefore, we observed significant interrelation between bronchiectasis and smoking, concerning the risks of all-cause mortality (P for multiplicative interaction, 0.030, RERI, 0.432; 95% CI, 0.097–0.769) and lung cancer-related mortality (RERI, 8.68; 95% CI, 1.631–15.736). Conclusion Individuals with bronchiectasis had a higher risk of all-cause, respiratory, and lung cancer-related mortality compared to control group. The risk of all-cause mortality was more prominent in those with airflow limitation and in ever smokers

Risk of all-cause and cause-specific mortality associated with immune-mediated inflammatory diseases in Korea

ObjectiveImmune-mediated inflammatory disease (IMID) is associated with an increased risk of mortality. It is unclear whether the higher mortality is attributable to the IMIDs themselves or to the higher prevalence of comorbidities in IMIDs. We aimed to investigate whether IMIDs per se confer a higher risk of mortality.MethodsFrom the Korean National Health Insurance Service-National Sample Cohort database, this population-based cohort study included 25,736 patients newly diagnosed with IMIDs between January 2007 and December 2017, and 128,680 individuals without IMIDs who were matched for age, sex, income, hypertension, type 2 diabetes, dyslipidemia, and the Charlson comorbidity index. All individuals were retrospectively observed through December 31, 2019. The outcomes included all-cause and cause-specific mortalities. Adjustments for age, sex, and comorbidities were performed using multivariable Cox proportional hazard regression analyses, and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the outcomes were estimated.ResultsThe adjusted risk of all-cause mortality was significantly lower in patients with IMIDs than that in those without (aHR, 0.890; 95% CI, 0.841–0.942). Regarding cause-specific mortality, cancer-specific (aHR, 0.788; 95% CI, 0.712–0.872) and cardiovascular disease-specific (aHR, 0.798; 95% CI, 0.701–0.908) mortalities were the two causes of death that showed significantly lower risks in patients with IMIDs. A similar trend was observed when organ based IMIDs were analyzed separately (i.e., gut, joint, and skin IMIDs).ConclusionAfter adjusting for comorbidities, IMIDs were associated with a lower risk of all-cause mortality compared to those without IMIDs. This was attributable to the lower risks of cancer-and cardiovascular disease-specific mortalities

Characteristics and outcomes of endoscopically resected colorectal cancers that arose from sessile serrated adenomas and traditional serrated adenomas

Background/AimsThe efficacy and safety of endoscopic resection of colorectal cancer derived from sessile serrated adenomas or traditional serrated adenomas are still unknown. The aims of this study were to verify the characteristics and outcomes of endoscopically resected early colorectal cancers developed from serrated polyps.MethodsAmong patients who received endoscopic resection of early colorectal cancers from 2008 to 2011, cancers with documented pre-existing lesions were included. They were classified as adenoma, sessile serrated adenoma, or traditional serrated adenoma according to the baseline lesions. Clinical characteristics, pathologic diagnosis, and outcomes were reviewed.ResultsOverall, 208 colorectal cancers detected from 198 patients were included: 198 with adenoma, five with sessile serrated adenoma, and five with traditional serrated adenoma. The sessile serrated adenoma group had a higher prevalence of high-grade dysplasia (40.0% vs. 25.8%, P<0.001) than the adenoma group. During follow-up, local recurrence did not occur after endoscopic resection of early colorectal cancers developed from serrated polyps. In contrast, two cases of metachronous recurrence were detected within a short follow-up period.ConclusionsCautious observation and early endoscopic resection are recommended when colorectal cancer from serrated polyp is suspected. Colorectal cancers from serrated polyp can be treated successfully with endoscopy

Association of immune-mediated inflammatory diseases with depression and anxiety in patients with type 2 diabetes: A nationwide population-based study

ObjectivePatients with type 2 diabetes (T2DM) are at a high risk of developing depression and anxiety. To better stratify the risk, we aimed to assess whether the presence of immune-mediated inflammatory diseases (IMIDs) confers a higher risk of depression and anxiety in these patients.MethodsPatients with T2DM without prior depression or anxiety who underwent national health examination between 2009 and 2012 (n = 1,612,705) were enrolled from the nationwide health check-up data from Korean National Health Insurance Service. The outcome events were incident depression and anxiety, defined as International Classification of Diseases, 10th Revision codes F32–F33 and F40–F41, respectively. Multivariable Cox proportional hazard regression analyses were conducted to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) according to the existence of IMIDs.ResultsOver an average follow-up time of 6.4 years, existence of gut IMIDs was associated with a higher risk of depression (aHR: 1.28 [95% CI: 1.08–1.53]) and anxiety (1.22 [1.06–1.42]). Existence of joint IMIDs was associated with a higher risk of depression (1.34 [1.31–1.37]) and anxiety (1.31 [1.29–1.34]). Existence of skin IMID was associated with a higher risk of depression (1.18 [1.14–1.23]) and anxiety (1.13 [1.09–1.16]). The effect sizes of IMIDs on depression and anxiety were larger in those with ≥ 2 IMIDs (1.42 [1.19–1.69] and 1.49 [1.29–1.72], respectively) than in those with one IMID (1.30 [1.27–1.32] and 1.26 [1.24–1.28], respectively).ConclusionIn patients with T2DM, presence of IMIDs was associated with a higher risk of depression and anxiety. More stringent attention and screening for anxiety and depression should be encouraged in patients with T2DM and comorbid IMIDs due to clinical implications of psychological distress on patient-reported outcomes and prognosis

Clinical features and outcomes in spontaneous intramural small bowel hematoma: cohort study and literature review

Background/Aims Spontaneous intramural small bowel hematoma (SISBH) is an extremely rare complication of anticoagulant or antiplatelet therapy. We assessed the clinical characteristics and outcomes of patients with SISBH according to the anatomical location of the hematoma. Methods From January 2003 to February 2016, medical records for all patients hospitalized for SISBH at 2 tertiary referral hospitals were retrospectively reviewed. The primary outcome was requirement for surgery. Results A total of 37 patients were enrolled. The mean age was 74.1 years. Among them, 33 patients (89.2%) were taking anticoagulant and/or antiplatelet agents. Duodenal intramural hematoma was detected in 4 patients (10.8%), jejunal in 16 (43.2%), and ileal in 17 (45.9%). Compared to jejunal and ileal involvement, duodenal intramural hematoma was significantly associated with high Charlson comorbidity index and low levels of white blood cells, hemoglobin, and platelets in the blood. SISBH in the duodenum was related to thrombocytopenia in 3 patients following systemic chemotherapy for malignancy. All patients with SISBH showed clinical improvement with conservative therapy. Mean length of hospital stay was 9.35 days. Independent predictors of a hospital stay of more than 7 days were body weight less than 60 kg (odds ratio [OR], 12.213; 95% confidence interval [CI], 1.755–84.998; P=0.011) and a history of cerebrovascular accidents (OR, 6.667; 95% CI, 1.121–39.650; P=0.037). Conclusions Compared to jejunal and ileal involvement, thrombocytopenia may result in spontaneous duodenal intramural hematoma among patients who are treated with systemic chemotherapy for malignancies. Patients with SISBH have excellent clinical outcomes with conservative therapy regardless of the anatomical location of the hematoma

Risk of acute exacerbations in chronic obstructive pulmonary disease associated with biomass smoke compared with tobacco smoke

Background Risk of exacerbations in chronic obstructive pulmonary disease (COPD) associated with biomass smoke has not been well addressed, although biomass smoke is similar in composition to tobacco smoke. Methods To investigate whether the risk of exacerbations in COPD associated with biomass smoke differs from that in COPD associated with tobacco smoke, we recruited patients with COPD from two Korean multicenter prospective cohorts. In a multiple linear regression model, the standardized regression coefficient (β) of biomass smoke exposure ≥25 years was most similar to that (β′) of tobacco smoke exposure ≥10 pack-years (β = − 0.13 and β′ = − 0.14). We grouped patients with COPD into four categories based on the above cut-offs: Less Tobacco-Less Biomass, Less Tobacco-More Biomass, More Tobacco-Less Biomass, and More Tobacco-More Biomass. The main outcome was the incidence of moderate or severe exacerbations. Results Among 1033 patients with COPD, 107 were included in Less Tobacco-Less Biomass (mean age: 67 years, men: 67%), 40 in Less Tobacco-More Biomass (mean age: 70 years, men: 35%), 631 in More Tobacco-Less Biomass (mean age: 68 years, men: 98%), and 255 in More Tobacco-More Biomass (mean age: 69 years, men: 97%). The incidence rates of exacerbations were not significantly different between Less Tobacco-More Biomass and More Tobacco-Less Biomass (adjusted incidence rate ratio, 1.03; 95% confidence interval, 0.56–1.89; P = 0.921). No interaction between sex and tobacco and biomass smoke was observed. When propensity score matching with available covariates including age and sex was applied, a similar result was observed. Conclusions Patients with COPD associated with biomass smoke and those with COPD associated with tobacco smoke had a similar risk of exacerbations. This suggests that patients with COPD associated with biomass smoke should be treated actively.None declared

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc