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Background: The objective of this study was to identify growth parameters that can affect mortality of cerebral palsy (CP). Method: This was a birth cohort study based on the National Health Screening Program for Infants and Children database along with the National Health Insurance Service, which were linked using a personal identifier number. The birth cohort consisted of 2 191 956 subjects, representing 93.5% of live births from 2007–2011, with maximal 10-year follow-up (range, 5–10 years) until October 2016. Subjects with CP were identified. Growth parameters in terms of birth weight, underweight (weight-for-age below the 3rd percentile), rate of body weight gain were collected, along with all-cause mortality after the age of 1 year. Result: Prevalence of CP was 2.0 per 1000 live births (95% CI, 1.94–2.06). All-cause mortality after the age of 1 year was 0.09 deaths/1000 person-years (95% CI, 0.08–0.09) in the general population (GP) and 2.85 deaths/1000 person-years (95% CI, 2.32–3.50) in subjects with CP during the follow-up. Therefore, the incidence rate ratio for all-cause mortality was 32.15 (95% CI, 25.72–39.76) in subjects with CP compared to GP. Presence of underweight was significantly associated with higher mortality in both subjects with CP and GP, where the adjusted hazard ratio of death was 2.60 (95% CI, 1.93–3.50) at the age of 18–24 months, 3.12 at 30–36 months, 4.37 at 42–48 months, 5.12 at 54–60 months, and 4.17 at 66–71 months. Birth weight did not affect mortality in both subjects with CP and GP after the age of 1 year (p > 0.05). Conclusion: While subjects with CP shows higher mortality, underweight is an important growth parameter that affects all-cause mortality of both subjects with CP and GP. This study urges increased awareness that subjects with CP who are underweight require special care. [ABSTRACT FROM AUTHOR]

Background/Aims: Diverticulosis and colorectal neoplasia share epidemiological trends and risk factors which are common in Western countries and incidences increase with age. However, the data on an association between diverticulosis and colorectal neoplasia are conflicting. Thus, we performed a meta-analysis to evaluate whether diverticulosis is associated with colorectal neoplasia. Methods: A systematic literature search of PubMed, EMBASE, Cochrane Library, Web of Science, and SCOPUS was conducted to identify studies that investigated the association between diverticulosis and advanced colorectal neoplasia (advanced adenoma, colorectal cancer), adenomas, or polyps. The demographic characteristics of patients, including age, gender, indication for colonoscopy, confounding factors, and outcomes of colorectal neoplasia were assessed. Results: We identified 29 cross-sectional studies (N = 450,953) that investigated the association between diverticulosis and colorectal neoplasia. The meta-analysis found that diverticulosis was not associated with advanced colorectal neoplasia (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.63–1.50). Although there was a positive correlation between diverticulosis and adenomas (OR 1.47, 95% CI 1.18–1.84) and diverticulosis and polyps (OR 1.95, 95% CI 1.15–3.31), diverticulosis did not increase the risk of adenomas (OR 1.34, 95% CI 0.87–2.06) in patients who underwent screening colonoscopy. Moreover, all the increased risk of colorectal neoplasia in patients with diverticulosis was observed in published studies only, and not in unpublished ones. Conclusions: This meta-analysis demonstrated that diverticulosis is not associated with an increased risk of advanced colorectal neoplasia. Although diverticulosis was associated with a higher risk of polyps and adenomas, the risk was not increased in screening populations. Moreover, the increased risk of colorectal neoplasia in patients with diverticulosis was observed only in published studies and not in unpublished ones. [ABSTRACT FROM AUTHOR]

Perioperative anemia frequently occurs in patients undergoing orthopedic surgery. We aimed to evaluate the efficacy of perioperative intravenous iron therapy (IVIT) on transfusion and recovery profiles during orthopedic surgery. We searched PubMed, Embase, Cochrane, and Google Scholar for eligible clinical trials (randomized controlled trials, RCTs; case-control studies, CCSs) in comparing IVIT and no iron therapy, up to September 2018. Primary outcomes were the effects of IVIT on the proportion of patients transfused and units of red blood cells (RBCs) transfused perioperatively. Secondary outcomes were the effects of IVIT on recovery profiles, such as length of hospital stay (LOS), post-operative infection, and mortality. Subgroup analysis was performed based on iron dose (low: ≤ 300 mg, high: > 400 mg), IVIT period (pre-operative, post-operative, perioperative), and study design. We identified 12 clinical trials (4 RCTs with 616 patients and 8 CCSs with 1,253 patients). IVIT significantly reduced the proportion of patients transfused by 31% (RR, 0.69; P = 0.0002), and units of RBCs transfused by 0.34 units/person (MD, −0.34; P = 0.0007). For subgroup analysis by iron dose, low- or high-dose IVIT significantly reduced the proportion of patients transfused (RR, 0.73, P = 0.005; RR, 0.68, P = 0.008), and RBC units transfused (MD, −0.47, P < 0.0001; MD, −0.28, P = 0.04). For subgroup analysis by period, IVIT administered post-operatively significantly reduced the proportion of patients transfused (post-operative: RR, 0.60, P = 0.002; pre-operative: RR, 0.74, P = 0.06) and RBC units transfused (post-operative: MD, −0.44, P <0.00001; pre-operative: MD, −0.29, P = 0.06). For subgroup analysis by study design, IVIT decreased the proportion of patients transfused and RBC units transfused in the group of CCSs, but IVIT in the group of RCTs did not. IVIT significantly shortened LOS by 1.6 days (P = 0.0006) and reduced post-operative infections by 33% (P = 0.01). IVIT did not change mortality. Perioperative IVIT during orthopedic surgery, especially post-operatively, appears to reduce the proportion of patients transfused and units of RBCs transfused, with shorter LOS and decreased infection rate, but no change in mortality rate. These were only found in CCSs and not in RCTs due to the relatively small number of RCTs with low to high risk of bias. [ABSTRACT FROM AUTHOR]

Introduction: The prognostic relevance of gender is undetermined in patients with small-cell lung cancer (SCLC). Therefore, we investigated whether gender is a prognostic factor in a SCLC cohort after controlling for confounding factors. Materials and methods: Fifteen prognostic factors were classified into four groups (patient, stage migration, tumor, and treatment). The prognostic relevance of gender was evaluated using propensity score matching, Cox proportional hazards regression, and stepwise fashion adjustments. Results: Of 591 patients with SCLC, 88 were women (14.9%). Women were more likely than men to have no history of smoking (48.9% vs. 2.0%, P < 0.001) and limited disease (48.9% vs. 37.8%, P = 0.050). Women had less progressive disease in M stage than men (52.3% vs. 62.8%, P = 0.031). Women had better survival than men in the entire cohort (median survival times [MSTs] and 95% confidence intervals [CIs]: 9.7 months and 7.8–11.6 for women, 8.0 months and 7.0–8.9 for men, log-rank P = 0.034) and in the matched cohort (MSTs and 95% CIs: 8.8 months and 5.8–11.8 for women, 5.9 months and 4.5–7.4 for men, log-rank P = 0.013). Female gender was a prognostic factor predicting better survival, even after stepwise and full adjustment with all prognostic variables (adjusted hazard ratios and 95% CIs: 0.51 and 0.34–0.77, P = 0.001 for entire cohort, 0.42 and 0.24–0.75, P = 0.003 for matched cohort). Conclusions: Our results confirmed that gender is an independent prognostic factor in patients with SCLC. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus is a rapidly growing life-threatening mycobacterium with multiple drug-resistance mechanisms. However, there is no official regimen for M. abscessus therapy. In this study, we screened the Pathogen Box, which contains 400 drug-like molecules active against neglected diseases, to identify active molecules targeting Mycobacterium abscessus using resazurin live/dead assays. In this screening assay, the Z-factor was 0.7, as an indicator of the statistical confidence of the assay. A cut-off of 80% growth inhibition in the screening resulted in the identification of four different compounds at a single concentration (20 μM). Dose-response curves identified three different hit candidates, i.e., MMV688508, MMV688844, and MMV688845, which generated good inhibitory curves. All hit candidates were expected to have different molecular targets. Among them, MMV688844 showed the best minimum inhibitory concentration value for not only wild-type M. abscessus but also for nine different R and S morphotype clinical isolates. Thus, we found that MMV688844, identified from the Pathogen Box screen, may be a promising candidate in the M. abscessus drug discovery pipeline. [ABSTRACT FROM AUTHOR]

Numerous peripheral tissues possess self-sustaining daily biologic rhythms that are regulated at the molecular level by clock genes such as PER1, PER2, CLOCK, and BMAL1. Physiological function of nasal mucosa exhibits rhythmic variability to a day-night environmental cycle. Nevertheless, little is known of the expression and distribution pattern of clock genes in nasal mucosa. The present study investigates the expression level and distribution pattern of PER1, PER2, CLOCK, and BMAL1 genes in nasal mucosa of healthy controls, allergic rhinitis patients, and normal rats. In human and rat nasal mucosa, the levels of these genes are asymmetrically expressed in nasal mucosa derived from right and left cavities in normal controls, allergic patients, and rat. In human nasal mucosa, the expression levels of these genes were higher in the decongested side than the congested mucosa. In rat nasal mucosa, these clock genes are expressed in a rhythmic circadian manner under the regular light/dark cycles. The expression levels of MUC5AC, a key mucin genes produced in superficial epithelium, are higher in decongested side than that congested side in human nasal mucosa. In rat nasal mucosa, MUC5AC levels showed a circadian rhythm which was associated with different expression levels in nasal mucosa derived from the right and left nasal cavities. Taken together with these results, the present study shows that the clock genes such as PER1, PER2, CLOCK, and BMAL1 are present in human and rat nasal mucosa, and suggest that these clock genes may control the pathophysiological function of nasal mucosa as circadian oscillators and affect the maintenance of the nasal cycle. [ABSTRACT FROM AUTHOR]

Objective: This study aims to analyze the published literatures on the effect of less radical fertility-preserving procedures, such as conization or simple trachelectomy, on oncological outcomes in IA1 cervical cancer patients with lymphovascular space invasion (LVSI) through a systematic-review. Methods: The EMBASE and MEDLINE databases and Cochrane Library were searched for published studies reporting the oncological outcomes of conization/simple trachelectomy in these patients, through April 2017. The endpoints were recurrence and mortality rates. Data were presented as per the Meta-analysis Of Observational Studies in Epidemiology checklist. Practice guidelines were generated via the Grading of Recommendation, Assessment, Development and Evaluation system. Results: From 6,755 records, 94 full-texts articles were reviewed for eligibility, and five studies were included in this systematic review. All included studies were nonrandomized studies: two case-control studies comparing conization (n = 14) with hysterectomy (n = 24), and the other three were interrupted time series including conization (n = 20) and simple vaginal trachelectomy (n = 59). During the median follow-up duration of 43 months, no recurrence was reported in both conization and simple trachelectomy groups in IA1 patients with LVSI. From three studies reporting the fertility outcomes, the rates of pregnancy, live birth, preterm delivery, and second-trimester miscarriage were 73% (35/48), 64% (32/50), 10% (5/48), and 6% (3/48), respectively. Conclusion: Results suggest that simple trachelectomy or conization could be performed for IA1 cervical cancer patients with LVSI who want to preserve fertility, although these results are only based on a small number of nonrandomized studies (recommendation grade 2 = weak; evidence level D = very low). Further randomized trials with long-term study period are needed to address this issue. [ABSTRACT FROM AUTHOR]

Background: Advances in bronchoscopy and CT-guided lung biopsy have improved the evaluation of small pulmonary lesions (PLs), leading to an increase in preoperative histological diagnosis. We aimed to evaluate the efficacy and safety of transbronchial lung biopsy using radial endobronchial ultrasound and virtual bronchoscopic navigation (TBLB-rEBUS&VBN) and CT-guided transthoracic needle biopsy (CT-TNB) for tissue diagnosis of small PLs. Methods: A systematic search was performed in five electronic databases, including MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, Web of Science, and Scopus, for relevant studies in May 2016; the selected articles were assessed using meta-analysis. The articles were limited to those published after 2000 that studied small PLs ≤ 3 cm in diameter. Results: From 7345 records, 9 articles on the bronchoscopic (BR) approach and 15 articles on the percutaneous (PC) approach were selected. The pooled diagnostic yield was 75% (95% confidence interval [CI], 69–80) using the BR approach and 93% (95% CI, 90–96) using the PC approach. For PLs ≤ 2 cm, the PC approach (pooled diagnostic yield: 92%, 95% CI: 88–95) was superior to the BR approach (66%, 95% CI: 55–76). However, for PLs > 2 cm but ≤ 3 cm, the diagnostic yield using the BR approach was improved to 81% (95% CI, 75–85). Complications of pneumothorax and hemorrhage were rare with the BR approach but common with the PC approach. Conclusions: CT-TNB was superior to TBLB-rEBUS&VBN for the evaluation of small PLs. However, for lesions greater than 2 cm, the BR approach may be considered considering its diagnostic yield of over 80% and the low risk of procedure-related complications. [ABSTRACT FROM AUTHOR]

Background: Beta-blockers are first-line therapy in patients with congenital long-QT syndrome (LQTS). Objective: This study sought to determine the differences in effectiveness of beta-blockers on risk reduction according to LQTS genotype. Methods: We searched MEDLINE, EMBASE, and CENTRAL databases to investigate the use of beta-blockers (atenolol, nadolol, propranolol, and metoprolol) in patients with LQTS. Hazard ratio (HR) and relative risk (RR) were extracted or calculated from studies reporting cardiac events (syncope, aborted cardiac arrest (ACA), or sudden cardiac death (SCD)). Results: Among 2,113 articles searched, 10 studies (7 registry-based cohort studies (Cohort) and 3 interrupted time series studies (ITS)) involving 9,727 patients were included. In a meta-analysis using a random-effect model, the use of beta-blocker was associated with significant risk reduction of all cardiac events (HR 0.49, p<0.001 in Cohort; RR 0.39, p<0.001 in ITS) and serious cardiac events (ACA or SCD) (HR 0.47, p<0.001 in Cohort). In both LQT1 and LQT2, the risk was reduced with beta-blocker therapy in Cohort (HR 0.59 in LQT1; HR 0.39 in LQT2) as well as ITS (RR 0.29 in LQT1; RR 0.48 in LQT2). Among the beta-blockers, nadolol showed a significant risk reduction in both LQT1 and LQT2 (HR 0.47 and 0.27, respectively), whereas atenolol and propranolol decreased the risk only in LQT1 (HR 0.36 and 0.46, respectively). Metoprolol showed no significant reduction in either genotype. In LQT3, beta-blocker therapy was not as effective as LQT1 or LQT2; however, it was inconclusive due to data insufficiency. Conclusion: This meta-analysis showed that beta-blockers were effective in reducing risk of cardiac events in patients with LQTS. Among them, nadolol was effective in LQT1 and LQT2, whereas other drugs showed different effectiveness depending on LQT genotype. [ABSTRACT FROM AUTHOR]

The marine diatoms Thalassiosira proschkinae and T. spinulata are relatively small in size; their taxonomic identities have been debated owing to the diverse morphological variations. In the present study, we isolated both morphotypes from Korean coastal waters and examined their fine structures and conducted molecular sequence comparisons. The morphological and molecular analyses showed that T. proschkinae and T. spinulata were certainly distinct, and phenotypic plasticity of valve structure was not noted. Based on the morphological similarity and phylogenetic relationship, we transferred T. proschkinae and T. spinulata to another genus Minidiscus within Thalassiosirales that includes small-sized species and proposed new combination names, Minidiscus proschkinae (Makarova) Park & Lee comb. nov. and Minidiscus spinulatus (Takano) Park & Lee comb. nov., respectively. The genus description of Minidiscus was emended. [ABSTRACT FROM AUTHOR]

Background: Theoretical considerations suggest that leg length increases after opening wedge high tibial osteotomy (HTO) and decreases after closing wedge HTO; however, in vivo studies have yielded conflicting results. This meta-analysis therefore assessed changes in leg length after opening wedge and closing wedge HTO. Methods: All studies comparing pre- and postoperative leg length in patients who underwent opening and/or closing wedge HTO were included. Two reviewers independently recorded data from each study in terms of sample size as well as preoperative and postoperative leg length of open wedge and/or closed wedge HTO groups. Results: Four studies were included in the meta-analysis. Although pooled results showed leg length changes from before to after surgery were –6.93 mm (95% confidence interval [CI]: –17.53 to 3.67 mm; P = 0.20) in opening wedge HTO and 1.97 mm (95% CI: –7.13 to 11.07 mm; P = 0.67) in closing wedge HTO, respectively, these values were statistically not significant. However, the difference in the pooled mean leg length change from before to after surgery between opening wedge and closing wedge HTO was 8 mm, a difference that was significant (95% CI: 6.53 to 9.46 mm; P<0.001). Conclusion: The change in leg length was not statistically significant for either opening or closing wedge HTO. However, leg length change from before to after surgery was 8 mm greater for opening wedge HTO than for closing wedge HTO. [ABSTRACT FROM AUTHOR]

Background: A family history can be a valuable tool in the era of precision medicine. Although a few studies have described an association of family history of lung cancer with EGFR activating mutation, their impact on survival of lung cancer patients is unclear. Methods: The study included consecutive 829 non-small-cell lung cancer patients who received analysis of EGFR mutation in a prospective lung cancer cohort. Family history of lung cancer was obtained by face-to-face interviews at the time of diagnosis. An association of EGFR activating mutation with a family history of lung cancer in first-degree relatives was evaluated with multivariate logistic regression analysis, and its association with survival was estimated with Cox’s proportional hazards model. Results: Seventy five (9.0%) patients had family history of lung cancer. The EGFR mutation was commonly observed in patients with positive family history compared to those with no family history (46.7% v 31.3%, χ2 p = 0.007). The family history was significantly associated with the EGFR mutation (aOR and 95% CI: 2.01 and 1.18–3.60, p = 0.011). Patients with the positive family history survived longer compared to those without (MST, 17.9 v 13.0 months, log-rank p = 0.037). The presence of the EGFR mutation was associated with better survival in patients without the family history (aHR and 95% CI: 0.72 and 0.57–0.90, p = 0.005). However, this prognostic impact was not observed in patients with the positive family history (aHR and 95% CI: 1.01 and 0.50–2.36, p = 0.832). Conclusions: In comparison to patients without the family history, EGFR activating mutation was common, and it did not affect prognosis in patients with positive family history. [ABSTRACT FROM AUTHOR]

In spite of the usefulness of the Ki-67 labeling index (LI) as a prognostic and predictive marker in breast cancer, its clinical application remains limited due to variability in its measurement and the absence of a standard method of interpretation. This study was designed to compare the two methods of assessing Ki-67 LI: the average method vs. the hot spot method and thus to determine which method is more appropriate in predicting prognosis of luminal/HER2-negative breast cancers. Ki-67 LIs were calculated by direct counting of three representative areas of 493 luminal/HER2-negative breast cancers using the two methods. We calculated the differences in the Ki-67 LIs (ΔKi-67) between the two methods and the ratio of the Ki-67 LIs (H/A ratio) of the two methods. In addition, we compared the performance of the Ki-67 LIs obtained by the two methods as prognostic markers. ΔKi-67 ranged from 0.01% to 33.3% and the H/A ratio ranged from 1.0 to 2.6. Based on the receiver operating characteristic curve method, the predictive powers of the KI-67 LI measured by the two methods were similar (Area under curve: hot spot method, 0.711; average method, 0.700). In multivariate analysis, high Ki-67 LI based on either method was an independent poor prognostic factor, along with high T stage and node metastasis. However, in repeated counts, the hot spot method did not consistently classify tumors into high vs. low Ki-67 LI groups. In conclusion, both the average and hot spot method of evaluating Ki-67 LI have good predictive performances for tumor recurrence in luminal/HER2-negative breast cancers. However, we recommend using the average method for the present because of its greater reproducibility. [ABSTRACT FROM AUTHOR]

Background: There is still controversy as to whether initial combination treatment is superior to serial addition of anticholinergics after maintenance or induction of alpha blockers in benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) Objective: The objective of this study was to determine the benefits and safety of initial combination treatment of an alpha blocker with anticholinergic medication in BPH/LUTS through a systematic review and meta-analysis. Methods: We conducted a meta-analysis of improvement in LUTS using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Results: In total, 16 studies were included in our analysis, with a total sample size of 3,548 subjects (2,195 experimental subjects and 1,353 controls). The mean change in total IPSS improvement from baseline in the combination group versus the alpha blocker monotherapy group was -0.03 (95% CI: -0.14–0.08). The pooled overall SMD change of storage IPSS improvement from baseline was -0.28 (95% CI: -0.40 - -0.17). The pooled overall SMD changes of QoL, Qmax, and PVR were -0.29 (95% CI: -0.50 - -0.07), 0.00 (95% CI: -0.08–0.08), and 0.56 (95% CI: 0.23–0.89), respectively. There was no significant difference in the number of acute urinary retention (AUR) events or PVR. Conclusions: Initial combination treatment of an alpha blocker with anticholinergic medication is efficacious for in BPH/ LUTS with improved measures such as storage symptoms and QoL without causing significant deterioration of voiding function. [ABSTRACT FROM AUTHOR]

Objective: We conducted a systematic review and meta-analysis of studies to quantify the association between body mass index (BMI) and the risks of all-cause and cardiovascular mortality in patients with type 2 diabetes. Methods: We included studies assessing the impact of BMI on all-cause and cardiovascular mortality in patients with type 2 diabetes. Data were combined using a random-effects dose-response model. Results: Sixteen cohort studies on all-cause mortality (n = 445,125) and two studies on cardiovascular mortality (n = 92,841) were evaluated in the meta-analysis. A non-linear association was observed between BMI and all-cause mortality among patients with type 2 diabetes. With a BMI nadir of 28–30 kg/m2, the risk of all-cause mortality displayed a U-shaped increase. With a BMI nadir of 29–31 kg/m2, the risk of cardiovascular mortality exhibited a gradual non-linear increase for BMI > 31 kg/m2. Subgroup analyses suggested that study location, diabetes duration, and smoking history may have contributed to heterogeneity among the studies. Conclusions: An obesity paradox exists for patients with type 2 diabetes with respect to all-cause and cardiovascular mortality. Study location, diabetes duration, and smoking history might contribute to heterogeneity among obesity paradox studies of patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

This meta-analysis was designed to compare the incidence of deep vein thrombosis (DVT) and venous thromboembolism (VTE) following total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). All studies directly comparing the post-TKA incidence of DVT and/or VTE in patients with RA and OA were included. For all comparisons, odds ratios and 95% confidence intervals (CI) were calculated for binary outcomes. Six studies were included in the meta-analysis. The pooled data showed that the combined rates of asymptomatic and symptomatic DVT did not differ significantly in the RA and OA groups (1065/222,714 [0.5%] vs. 35,983/6,959,157 [0.5%]; OR 0.77, 95% CI: 0.57 to 1.02; P = 0.07). The combined rates of asymptomatic and symptomatic DVT and pulmonary embolism (PE) after TKA were significantly lower in the RA than in the OA group (1831/225,406 [0.8%] vs. 63,953/7,018,721 [0.9%]; OR 0.76, 95% CI: 0.62 to 0.93; P = 0.008). Conclusiviely, the DVT rates after primary TKA were similar in RA and OA patients. In contrast, the incidence of VTE (DVT plus PE) after primary TKA was lower in RA than in OA patients, despite patients with RA being at theoretically higher risk of thrombi due to chronic inflammation. [ABSTRACT FROM AUTHOR]

The dorsal approach allows better central screw placement along the long axis of the scaphoid compared with the volar approach in managing acute scaphoid fractures. However, it is unclear whether the dorsal approach leads to better clinical outcomes than the volar approach. This meta-analysis compared clinical outcomes, including the incidence of nonunion, postoperative complications, overall functional outcome, postoperative pain, grip strength, and range of wrist motion, between the dorsal and volar percutaneous approaches for the management of acute scaphoid fractures. Seven studies met the criteria for inclusion in the meta-analysis. The proportion of patients who developed nonunion (OR 0.74, 95% CI: 0.21 to 2.54; P = 0.63) and postoperative complications (OR 1.05, 95% CI: 0.45 to 2.44; P = 0.91) did not differ significantly between the dorsal and volar approaches. Both approaches also led to similar results in terms of overall functional outcome (95% CI: -0.39 to 0.22; P = 0.57), postoperative pain (95% CI: -0.52 to 0.46; P = 0.92), grip strength (95% CI: -4.56 to 1.02; P = 0.21), flexion (95% CI: -2.86 to 1.13; P = 0.40), extension (95% CI: -1.17 to 2.67; P = 0.44), and radial deviation (95% CI: -1.94 to 2.58; P = 0.78). However, ulnar deviation (95% CI: -7.48 to 0.05; P = 0.05) was significantly greater with the volar approach. Thus, orthopedic surgeons need to master both the dorsal and volar percutaneous approaches because not all acute scaphoid fractures can be dealt with completely with one approach. [ABSTRACT FROM AUTHOR]

Objectives: The ability of contrast-enhanced MRI to distinguish between malignant and benign ovarian masses is limited. The aim of this meta-analysis is to evaluate the diagnostic performance of diffusion-weighted imaging (DWI) in differentiating malignant from benign ovarian masses. Methods: A comprehensive literature search was performed in several authoritative databases to identify relevant articles. The weighted mean difference (WMD) and corresponding 95% confidence interval (95% CI) were calculated. We also used subgroup analysis to analyze study heterogeneity, and evaluated publication bias. Results: The meta-analysis is based on 21 studies, which reported the findings for 731 malignant and 918 benign ovarian masses. There was no significant difference in apparent diffusion coefficient (ADC) values for DWI between benign and malignant lesions (WMD = 0.22, 95% CI = -0.02–0.47, p = 0.08). Subgroup analysis by benign tumor type revealed higher ADC values (or a trend toward higher values) for cysts, cystadenomas and other benign tumors compared to malignant masses (cyst: WMD = 0.54, 95% CI = -0.05–1.12, p = 0.07; cystadenoma: WMD = 0.73, 95% CI = 0.38–1.07, p < 0.0001; other benign tumor: WMD = 0.16, 95% CI = -0.13–0.46, p = 0.28). On the other hand, lower ADC values (or a trend toward lower values) were observed for endometrioma and teratoma compared to malignant masses (endometrioma: WMD = -0.09, 95% CI = -0.47–0.29, p = 0.64; teratoma: WMD = -0.49, 95% CI = -0.85–0.12, p = 0.009). Subgroup analysis by mass property revealed higher ADC values in cystic tumor types than in solid types for both benign and malignant tumors. Significant study heterogeneity was observed. There was no notable publication bias. Conclusions: Quantitative DWI is not a reliable diagnostic method for differentiation between benign and malignant ovarian masses. This knowledge is essential in avoiding misdiagnosis of ovarian masses. [ABSTRACT FROM AUTHOR]

This meta-analysis was performed to analyze serial changes in thigh muscles, including quadriceps and hamstring muscles, from before to one year after total knee arthroplasty (TKA). All studies sequentially comparing isokinetic quadriceps and hamstring muscle strengths between the TKA side and the contralateral uninjured limb were included in this meta-analysis. Five studies with 7 cohorts were included in this meta-analysis. The mean differences in the strengths of quadriceps and hamstring muscles between the TKA and uninjured sides were greatest three months after surgery (26.8 N∙m, 12.8 N∙m, P<0.001), but were similar to preoperative level at six months (18.4 N∙m, 7.4 N∙m P<0.001) and were maintained for up to one year (15.9 N∙m, 4.1 N∙m P<0.001). The pooled mean differences in changes in quadriceps and hamstring strengths relative to preoperative levels were 9.2 N∙m and 4.9 N∙m, respectively, three months postoperatively (P = 0.041), but were no longer significant after six months and one year. During the year after TKA, quadriceps and hamstring muscle strengths were lowest after 3 months, recovering to preoperative level after six months, but not reaching the muscle strength on the contralateral side. Relative to preoperative levels, the difference in muscle strength between the TKA and contralateral knees was only significant at three months. Because decrease of strength of the quadriceps was significantly greater than decrease in hamstring muscle strength at postoperative three months, early rehabilitation after TKA should focus on recovery of quadriceps muscle strength. [ABSTRACT FROM AUTHOR]

Theoretical compensation after anterior cruciate ligament (ACL) tear could cause quadriceps weakness and hamstring activation, preventing anterior tibial subluxation and affecting the expected hamstring-to-quadriceps ratio. Although quadriceps weakness often occurs after ACL tears, it remains unclear whether hamstring strength and hamstring-to-quadriceps ratio increase in ACL deficient knees. This meta-analysis compared the isokinetic muscle strength of quadriceps and hamstring muscles, and the hamstring-to-quadriceps ratio, of the injured and injured limbs of patients with ACL tears. This meta-analysis included all studies comparing isokinetic thigh muscle strengths and hamstring-to-quadriceps ratio in the injured and uninjured legs of patients with ACL tear, without or before surgery. Thirteen studies were included in the meta-analysis. Quadriceps and hamstring strengths were 22.3 N∙m (95% CI: 15.2 to 29.3 N∙m; P<0.001) and 7.4 N∙m (95% CI: 4.3 to 10.5 N∙m; P<0.001) lower, respectively, on the injured than on the uninjured side. The mean hamstring-to-quadriceps ratio was 4% greater in ACL deficient than in uninjured limbs (95% CI: 1.7% to 6.3%; P<0.001). Conclusively, Decreases were observed in both the quadriceps and hamstring muscles of patients with ACL tear, with the decrease in quadriceps strength being 3-fold greater. These uneven reductions slightly increase the hamstring-to-quadriceps ratio in ACL deficient knees. [ABSTRACT FROM AUTHOR]

Thermoplasma acidophilum is a thermophilic archaeon that uses both non-phosphorylative Entner-Doudoroff (ED) pathway and Embden-Meyerhof-Parnas (EMP) pathway for glucose degradation. While triosephosphate isomerase (TPI), a well-known glycolytic enzyme, is not involved in the ED pathway in T. acidophilum, it has been considered to play an important role in the EMP pathway. Here, we report crystal structures of apo- and glycerol-3-phosphate-bound TPI from T. acidophilum (TaTPI). TaTPI adopts the canonical TIM-barrel fold with eight α-helices and parallel eight β-strands. Although TaTPI shares ~30% sequence identity to other TPIs from thermophilic species that adopt tetrameric conformation for enzymatic activity in their harsh physiological environments, TaTPI exists as a dimer in solution. We confirmed the dimeric conformation of TaTPI by analytical ultracentrifugation and size-exclusion chromatography. Helix 5 as well as helix 4 of thermostable tetrameric TPIs have been known to play crucial roles in oligomerization, forming a hydrophobic interface. However, TaTPI contains unique charged-amino acid residues in the helix 5 and adopts dimer conformation. TaTPI exhibits the apparent Td value of 74.6°C and maintains its overall structure with some changes in the secondary structure contents at extremely acidic conditions (pH 1–2). Based on our structural and biophysical analyses of TaTPI, more compact structure of the protomer with reduced length of loops and certain patches on the surface could account for the robust nature of Thermoplasma acidophilum TPI. [ABSTRACT FROM AUTHOR]

This study investigated the association of employment status with health-related quality of life in adult Koreans, as well as the gender difference in the relationship, using a large, nationally representative sample. Using data from the Korea Health Panel survey, we examined the relationship between quality of life measured by EQ-5D and work status among Korean adults. We also tested whether and how the relationship between quality of life and work status differed by gender. Quality of life among working adults was better than among non-working adults. The gap between the two groups was larger among male than female participants. Further, the gender differential effect was larger in the 41–60-year-old age group than in the 18–40-year-old and 61-or-older groups. Being employed has a positive relation to quality of life among adults. Work status plays a more important role in quality of life for men than for women, especially for the working elderly men than working elderly women. [ABSTRACT FROM AUTHOR]

Despite the growing attention given to Traditional Medicine (TM) worldwide, there is no well-known, publicly available, integrated bio-pharmacological Traditional Korean Medicine (TKM) database for researchers in drug discovery. In this study, we have constructed PharmDB-K, which offers comprehensive information relating to TKM-associated drugs (compound), disease indication, and protein relationships. To explore the underlying molecular interaction of TKM, we integrated fourteen different databases, six Pharmacopoeias, and literature, and established a massive bio-pharmacological network for TKM and experimentally validated some cases predicted from the PharmDB-K analyses. Currently, PharmDB-K contains information about 262 TKMs, 7,815 drugs, 3,721 diseases, 32,373 proteins, and 1,887 side effects. One of the unique sets of information in PharmDB-K includes 400 indicator compounds used for standardization of herbal medicine. Furthermore, we are operating PharmDB-K via phExplorer (a network visualization software) and BioMart (a data federation framework) for convenient search and analysis of the TKM network. Database URL: , . [ABSTRACT FROM AUTHOR]

Background: Although smoking is the most important and modifiable cause of chronic obstructive pulmonary disease (COPD), other risk factors including asthma and tuberculosis (TB) are also associated. It is common for COPD patients to have more than one of these risk factors. The aims of this study were to determine the prevalence of airflow limitation (FEV1/FVC<0.7) according to the risk factors and to investigate their impact and interaction in airflow limitation. Methods: From the Korean National Health and Nutrition Examination Survey between 2008 and 2012, we analyzed participants over 40 years of age by spirometry, chest radiograph and questionnaire about asthma and smoking history. Results: Of 12,631 participants, 1,548 (12.3%) had airflow limitation. The prevalence of airflow limitation in smokers (≥10 pack-year), asthmatics, and those with inactive TB was 23.9%, 32.1%, and 33.6%. The prevalence increased with the number of risk factors: 86.1% had airflow limitation if they had all three risk factors. Impacts of inactive TB and asthma on airflow limitation were equivalent to 47 and 69 pack-years of smoking, respectively. Airflow limitation resulted from lower levels of smoking in those with inactive TB and asthma. A potential interaction between smoking and inactive tuberculosis in the development of airflow limitation was identified (p = 0.054). Conclusions: Asthma and inactive TB lesions increase susceptibility to smoking in the development of airflow limitation. People with these risk factors should be seen as a major target population for anti-smoking campaigns to prevent COPD. [ABSTRACT FROM AUTHOR]

Background and Aims: Heat shock proteins (HSPs) have been regarded as cytoprotectants that protect brain cells during the progression of neurodegenerative diseases and from damage resulting from cerebral ischemia. In this study, we assessed the association between plasma HSP 70/27 levels and cognitive decline. Methods: Among participants in the community-based cohort study of dementia called the Gwangju Dementia and Mild Cognitive Impairment Study, subjects without cognitive impairment at baseline, who then either remained without impairment (non-conversion group), or suffered mild cognitive impairment (MCI) (conversion group) (non-conversion group, N = 36; conversion group, N = 30) were analyzed. Results: After a five to six year follow-up period, comparison of the plasma HSP 70 and HSP 27 levels of the two groups revealed that only the plasma HSP 70 level was associated with a conversion to MCI after adjustments for age, gender, years of education, follow-up duration, APOE e4, hypertension, and diabetes (repeated measure analysis of variance: F = 7.59, p = 0.008). Furthermore, an increase in plasma HSP 70 level was associated with cognitive decline in language and executive function (linear mixed model: Korean Boston Naming Test, -0.426 [-0.781, -0.071], p = 0.019; Controlled Oral Word Association Test, -0.176 [-0.328, -0.023], p = 0.024; Stroop Test, -0.304 [-0.458, -0.150], p<0.001). Conclusions: These findings suggest that the plasma HSP 70 level may be related to cognitive decline in the elderly. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs) have the ability to proliferate and differentiate into neurons and glia. Regulation of NSC fate by small molecules is important for the generation of a certain type of cell. The identification of small molecules that can induce new neurons from NSCs could facilitate regenerative medicine and drug development for neurodegenerative diseases. In this study, we screened natural compounds to identify molecules that are effective on NSC cell fate determination. We found that Kuwanon V (KWV), which was isolated from the mulberry tree (Morus bombycis) root, increased neurogenesis in rat NSCs. In addition, during NSC differentiation, KWV increased cell survival and inhibited cell proliferation as shown by 5-bromo-2-deoxyuridine pulse experiments, Ki67 immunostaining and neurosphere forming assays. Interestingly, KWV enhanced neuronal differentiation and decreased NSC proliferation even in the presence of mitogens such as epidermal growth factor and fibroblast growth factor 2. KWV treatment of NSCs reduced the phosphorylation of extracellular signal-regulated kinase 1/2, increased mRNA expression levels of the cyclin-dependent kinase inhibitor p21, down-regulated Notch/Hairy expression levels and up-regulated microRNA miR-9, miR-29a and miR-181a. Taken together, our data suggest that KWV modulates NSC fate to induce neurogenesis, and it may be considered as a new drug candidate that can regenerate or protect neurons in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The N-end rule states that half-life of protein is determined by their N-terminal amino acid residue. N-terminal glutamine amidohydrolase (Ntaq) converts N-terminal glutamine to glutamate by eliminating the amine group and plays an essential role in the N-end rule pathway for protein degradation. Here, we report the crystal structure of human Ntaq1 bound with the N-terminus of a symmetry-related Ntaq1 molecule at 1.5 Å resolution. The structure reveals a monomeric globular protein with alpha-beta-alpha three-layer sandwich architecture. The catalytic triad located in the active site, Cys-His-Asp, is highly conserved among Ntaq family and transglutaminases from diverse organisms. The N-terminus of a symmetry-related Ntaq1 molecule bound in the substrate binding cleft and the active site suggest possible substrate binding mode of hNtaq1. Based on our crystal structure of hNtaq1 and docking study with all the tripeptides with N-terminal glutamine, we propose how the peptide backbone recognition patch of hNtaq1 forms nonspecific interactions with N-terminal peptides of substrate proteins. Upon binding of a substrate with N-terminal glutamine, active site catalytic triad mediates the deamination of the N-terminal residue to glutamate by a mechanism analogous to that of cysteine proteases. [ABSTRACT FROM AUTHOR]

Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been proposed as one of the Parkinson's disease (PD) related genes, but the possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant UCH-L1 that we called NT-UCH-L1, in mouse brain tissue as well as in NCI-H157 lung cancer and SH-SY5Y neuroblastoma cell lines. In vivo experiments and hydrogen-deuterium exchange (HDX) with tandem mass spectrometry (MS) studies showed that NT-UCH-L1 is readily aggregated and degraded, and has more flexible structure than UCH-L1. Post-translational modifications including monoubiquitination and disulfide crosslinking regulate the stability and cellular localization of NT-UCH-L1, as confirmed by mutational and proteomic studies. Stable expression of NT-UCH-L1 decreases cellular ROS levels and protects cells from H2O2, rotenone and CCCP-induced cell death. NT-UCH-L1-expressing transgenic mice are less susceptible to degeneration of nigrostriatal dopaminergic neurons seen in the MPTP mouse model of PD, in comparison to control animals. These results suggest that NT-UCH-L1 may have the potential to prevent neural damage in diseases like PD. [ABSTRACT FROM AUTHOR]

Repeat proteins have recently attracted much attention as alternative scaffolds to immunoglobulin antibodies due to their unique structural and biophysical features. In particular, repeat proteins show high stability against temperature and chaotic agents. Despite many studies, structural features for the stability of repeat proteins remain poorly understood. Here we present an interesting result from in silico analyses pursuing the factors which affect the stability of repeat proteins. Previously developed repebody structure based on variable lymphocytes receptors (VLRs) which consists of leucine-rich repeat (LRR) modules was used as initial structure for the present study. We constructed extra six repebody structures with varying numbers of repeat modules and those structures were used for molecular dynamics simulations. For the structures, the intramolecular interactions including backbone H-bonds, van der Waals energy, and hydrophobicity were investigated and then the radius of gyration, solvent-accessible surface area, ratio of secondary structure, and hydration free energy were also calculated to find out the relationship between the number of LRR modules and stability of the protein. Our results show that the intramolecular interactions lead to more compact structure and smaller surface area of the repebodies, which are critical for the stability of repeat proteins. The other features were also well compatible with the experimental results. Based on our observations, the repebody-5 was proposed as the best structure from the all repebodies in structure optimization process. The present study successfully demonstrated that our computer-based molecular modeling approach can significantly contribute to the experiment-based protein engineering challenge. [ABSTRACT FROM AUTHOR]

Objective: The Trail Making Test (TMT) has its limitations when applied to Eastern cultures due to its reliance on the alphabet. We looked for an alternative tool that is reliable and distinguishable like the TMT and devised the Trail Making Test Black & White (TMT-B&W) as a new variant. This study identifies the applicability of the TMT-B&W as a useful neuropsychological tool and determines whether the TMT-B&W could play an equivalent role as the TMT. Methods: The TMT-B&W uses numbers encircled by black or white circles as stimuli, instead of using the alphabet. A total of 138 participants were including containing groups of 31 cognitively normal controls (NC), 55 mild cognitive impairment (MCI), and 52 people with Alzheimer’s disease (AD). Along with the TMT-B&W, the TMT and other neuropsychological tests were administered to all subjects. Results: A considerably low dropout rate for TMT B&W demonstrates that all participants were more willingly engaged in the TMT B&W than the TMT. In particular, subjects with cognitive impairments or lower levels of education performed better on the TMT-B&W than the TMT. The difference in time-to-completion of the TMT-B&W was significant according to the level of cognitive impairment. The TMT-B&W revealed a high correlation with the TMT and frontal lobe function test. Conclusion: The TMT-B&W is as reliable and effective as the TMT. It is worth developing a new variant of the TMT. [ABSTRACT FROM AUTHOR]

Recurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes patients. Moderate hypoglycemia is not life-threatening, but if experienced recurrently it may present several clinical complications. Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored. Pyruvate, however, can be metabolized in the absence of cytosolic NAD. We therefore hypothesized that pyruvate may be able to improve the outcome in diabetic rats subjected to insulin-induced R/M hypoglycemia by terminating hypoglycemia with glucose plus pyruvate, as compared with delivering just glucose alone. In an effort to mimic juvenile type 1 diabetes the experiments were conducted in one-month-old young rats that were rendered diabetic by streptozotocin (STZ, 50mg/kg, i.p.) injection. One week after STZ injection, rats were subjected to moderate hypoglycemia by insulin injection (10U/kg, i.p.) without anesthesia for five consecutive days. Pyruvate (500mg/kg) was given by intraperitoneal injection after each R/M hypoglycemia. Three hours after last R/M hypoglycemia, zinc accumulation was evaluated. Three days after R/M hypoglycemia, neuronal death, oxidative stress, microglial activation and GSH concentrations in the cerebral cortex were analyzed. Sparse neuronal death was observed in the cortex. Zinc accumulation, oxidative injury, microglial activation and GSH loss in the cortex after R/M hypoglycemia were all reduced by pyruvate injection. These findings suggest that when delivered alongside glucose, pyruvate may significantly improve the outcome after R/M hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation. [ABSTRACT FROM AUTHOR]

Modulation of the DNA repair pathway is an emerging target for the development of anticancer drugs. DNA interstrand cross-links (ICLs), one of the most severe forms of DNA damage caused by anticancer drugs such as cisplatin and mitomycin C (MMC), activates the Fanconi anemia (FA)/BRCA DNA repair pathway. Inhibition of the FA/BRCA pathway can enhance the cytotoxic effects of ICL-inducing anticancer drugs and can reduce anticancer drug resistance. To find FA/BRCA pathway inhibitory small molecules, we established a cell-based high-content screening method for quantitating the activation of the FA/BRCA pathway by measuring FANCD2 foci on DNA lesions and then applied our method to chemical screening. Using commercial LOPAC1280 chemical library screening, ouabain was identified as a competent FA/BRCA pathway inhibitory compound. Ouabain, a member of the cardiac glycoside family, binds to and inhibits Na+/K+-ATPase and has been used to treat heart disease for many years. We observed that ouabain, as well as other cardiac glycoside family members―digitoxin and digoxin―down-regulated FANCD2 and FANCI mRNA levels, reduced monoubiquitination of FANCD2, inhibited FANCD2 foci formation on DNA lesions, and abrogated cell cycle arrest induced by MMC treatment. These inhibitory activities of ouabain required p38 MAPK and were independent of cellular Ca2+ ion increase or the drug uptake-inhibition effect of ouabain. Furthermore, we found that ouabain potentiated the cytotoxic effects of MMC in tumor cells. Taken together, we identified an additional effect of ouabain as a FA/BRCA pathway-inhibiting chemosensitization compound. The results of this study suggest that ouabain may serve as a chemosensitizer to ICL-inducing anticancer drugs. [ABSTRACT FROM AUTHOR]