Search

Background: Minimally invasive scoliosis surgery (MISS) is currently introduced on novel technique for surgical treatment of adolescent idiopathic scoliosis (AIS). This study is aimed to evaluate the efficacy of facet fusion in MISS compared to posterior fusion in conventional open scoliosis surgery (COSS) and compare facet fusion rates based on three bone graft substitutes in MISS for adolescent idiopathic scoliosis (AIS). Methods: Eighty six AIS patients who underwent scoliosis surgery were divided into two groups: the COSS group and the MISS group. COSS was performed through posterior fusion with allograft. MISS was applied via facet fusion with three bone graft substitutes. The MISS group was further divided into three subgroups based on graft substitute: Group A (allograft), Group B (demineralized bone matrix [DBM]), and group C (demineralized cancellous bone chips). Fusion rate was measured using conventional radiographs to visualize loss of correction > 10°, presence of lysis around implants, breaks in fusion mass, and abnormal mobility of the fused segment. Results: The fusion rates showed no significant difference in COSS and MISS groups (p = 0.070). In the MISS group, the fusion rates were 85, 100, and 100% in groups A, B, and C, respectively, with no significant difference (p = 0.221). There were no statistical differences between groups A, B, and C in terms of correction rate, fusion rate, and SRS-22 scores (p > 0.05). Conclusions: The facet fusion in MISS showed comparable to posterior fusion in COSS with regard to radiological and clinical outcomes. Furthermore, the type of graft substitute among allograft, DBM, and demineralized cancellous bone chips did not affect facet fusion rate or clinical outcomes in MISS. Therefore, MISS showed comparable fusion rate (with no influences on the type of graft substitute) and clinical outcomes to those of COSS in the surgical treatment of AIS. [ABSTRACT FROM AUTHOR]

Background: Gas forming infection of the spine is a consequence of vertebral osteomyelitis, necrotizing fasciitis, or a gas-forming epidural abscess, which is very rare and fatal conditions. This is the rare case of necrotizing fasciitis that rapidly progressed from the lumbar area to upper thoracic area.Case Presentation: A 58-year-old male complained of lower back pain with fever and chills. The patient had a history of uncontrolled diabetes mellitus without diabetic medication over the previous 3 months, and he had received several local injections around the lumbar area. Laboratory data revealed white blood cell count of 19,710 /mm3, erythrocyte sedimentation of 40 mm/h, and C-reactive protein of 30.7 mg/L. Radiological findings revealed a small amount of air bubbles in the paraspinal area and lumbar epidural spaces. The patient refused emergency surgery and was discharged from the hospital. The patient re-visited the emergency department two days after discharge complaining of more severe back pain with persistent fever, and his vital signs had deteriorated, with low blood pressure and tachycardia. K. pneumoniae was isolated in cultures from ultrasound-guided aspirates and peripheral blood. The follow-up radiographs revealed aggressive dissemination of innumerable air bubbles from the lumbar area to the T5 level. The patient underwent emergent decompressive laminectomy and debridement of infected paravertebral fascia and musculature. Despite intensive care for deteriorated vital signs and his back wound, the patient died on postoperative day 3 due to multi-organ failure.Conclusions: Necrotizing fasciitis involving the spine is a very rare disease with life-threatening conditions, rapid progression, and a high mortality rate. Therefore, prompt surgical treatment with a high index of suspicion is imperative to prevent potentially fatal conditions in similar extremely rare cases. [ABSTRACT FROM AUTHOR]

Background: The associations between various kinds of parental support and children and adolescents' physical activity (PA) are inconclusive. This study aimed 1) to examine the associations between various kinds of parental support and children and adolescents' moderate-to-vigorous physical activity (MVPA), and 2) to examine gender and age differences in the association between each specific kind of parental support and MVPA.Methods: Using a multi-stage stratified and random cluster sampling method, 711 schools in Shanghai were selected (data were collected from October 2014 to February 2015). In total, 61,429 school-aged children (6-18 years old, 50.7% boys) and their parents were included. Self-reported questionnaires were used to measure sociodemographic characteristics, MVPA and various kinds of parental support, including parental encouragement (PAEN), parental involvement (PAIV), parental financial support (PAFS) and, parental modeling (PAMD). Descriptive statistics and Chi-square were used to report the level of MVPA and its difference across various kinds of parental support by gender groups. The logistic regression analysis was used to examine the associations between parental support and MVPA with odds ratios (ORs) and 95% confidence intervals (CIs).Results: Overall, 19.4% of children and adolescents accumulated MVPA at least 60 min/day. Boys were more physically active than girls (21.4% > 17.4%, p <  0.001). According to the observation of OR estimates, girls may be more susceptible to the influences from various kinds of parental support than boys (OR = 1.59, 1.61, 1.27 and 1.63, 95% CI: 1.19-1.73 among girls, and OR = 1.48, 1.60, 1.21, and 1.60, 95% CI: 1.14-1.69 among boys for PAEN, PAIV, PAFS and PAMD respectively). PAMD is the only one supportive kind that was positively associated with MVPA in both genders across all grades (OR = 1.29-2.98, 95% CI: 1.09-4.08 among boys; OR = 1.27-2.64, 95% CI: 1.10-4.10 among girls).Conclusions: Less than one fifth of children and adolescents accumulated 60 min MVPA per day. Various kinds of parental support have important effects on children and adolescents' MVPA, which varied by gender and grades. PAMD, in particular, should be emphasized more than PAEN, PAIV and PAFS in family-based interventions aiming at increasing PA in the future. [ABSTRACT FROM AUTHOR]

Background: Toremifene (TOR) is a selective oestrogen receptor modulator (SERM) and has comparable efficacy to that of tamoxifen (TAM) in breast cancer patients. Herein, we compared the safety of TOR to that of TAM in the adjuvant treatment of premenopausal breast cancer.Methods: This was a prospective randomized and open-label clinical study. Premenopausal patients with hormonal receptor (HR)-positive early breast cancer were randomly assigned (1:1) to receive TOR) or TAM treatment. The follow-up period was 1 year. The primary end point was the incidence of ovarian cysts, and secondary end points were the incidence of endometrial thickening, changes in female hormones, the incidence of fatty liver, changes in the modified Kupperman index (mKMI) and changes in quality of life.Results: There were 92 patients in the final analysis. The incidences of ovarian cysts were 42.6% in the TOR group and 51.1% in the TAM group (p = 0.441). Forty-one patients (87.2%) in the TOR group and 36 patients (80.0%) in the TAM group experienced endometrial thickening (p = 0.348). The proportions of patients with fatty liver were 31.9% in the TOR group and 26.7% in the TAM group (p = 0.581). No significant differences in the mKMI or quality of life were observed between the two groups.Conclusions: TOR and TAM have similar side effects on the female genital system and quality of life in premenopausal early breast cancer patients.Trial Registration: ClinicalTrials.gov NCT02344940. Registered 26 January 2015 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: For patients with varicose veins, the goal is to relieve pain and swelling, reduce the severity of edema, improve skin changes, and heal ulcers associated with venous disease. Compression therapy is the cornerstone of their management. Several studies have shown that wearing an elastic bandage for the first 24 h and then a compression stocking for a week can effectively reduce the pain after thermal ablation. However, in clinical practice, patient compliance with this treatment could be better, considering difficulties in pulling up and removing the compression stocking, tightness, and skin irritation because these must be worn for a prolonged period. A potential solution to battling these barriers is short-term compression therapy. Besides, the effect and necessity of wearing compression stockings after thermal ablation have been questioned. Based on current clinical experience and limited evidence, although some scholars have suggested that compression therapy may be an unnecessary adjunctive therapy after thermal ablation, there is still a great deal of uncertainty in the absence of compression therapy after thermal ablation compared to compression therapy. Therefore, we advocate further research to evaluate the clinical effect of short-term postoperative compression therapy. Furthermore, well-designed randomized controlled trials are needed. Methods: A prospective, multicenter, non-inferiority randomized controlled trial is designed to evaluate the non-inferiority of target vein occlusion rate at 3 months. Three hundred and sixty patients will be randomly assigned in a 1:1 ratio to one of the following treatments: (A) 3 M™ Coban™ elastic bandage for 48 h or (B) 3 M™ Coban™ elastic bandage for the first 24 h and then a class II compression full-length stocking (23–32 mm Hg) for 1 week. The two groups will be compared on several variables, including target vein occlusion rate at 3 months (primary outcome indicator), pain, quality of life, clinical severity of varicose veins, postoperative complications, time to return to regular work, and compliance. Discussion: Suppose the effect of the 3 M™ Coban™ elastic bandage for 48 h proves to be non-inferior to long-term compression therapy. In that case, this short-term treatment may contribute to a future update of clinical guidelines for compression therapy after thermal ablation of varicose veins, resulting in higher patient compliance and better postoperative quality of life. Trial registration: Clinical Trials . Registered on May 2023. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the prevalence, correlates, comorbidities, and suicidal tendencies of problematic game use in a nationally representative sample of Korean adults. Methods: Of the 6022 subjects who participated in the 2011 Korean Epidemiologic Catchment Area study and completed the Composite International Diagnostic Interview 2.1, 1397 game users were evaluated for problematic game use using 9-item DSM-5 proposed criteria for Internet gaming disorder. Respondents who responded "yes" to fve or more of the nine DSM-5 criteria were considered as problematic game users and the reminders were considered as normal game users. Results: 4.0% (56/1397) of game users were classified as a problematic game user. Problematic game users were more likely to be in younger age group and live in urban area compared with normal game user. Problematic game use was positively associated with several psychiatric disorders including nicotine use disorder, depressive disorder, and anxiety disorder, but not associated with alcohol use disorder and obsessive-compulsive disorder, after adjusting for age, sex, and residential area. Problematic game use was significantly and positively associated with suicide plans, after controlling for psychiatric disorders as well as socio-demographic factors. Conclusion: Problematic game use is relatively prevalent in Korean adult population and highly comorbid with other psychiatric disorders and suicidality. Therefore, preventive strategy for problematic game use is needed for game users who were more likely to be addicted such as young adults in urban area, and mental health screening and appropriate treatment are needed for individuals with problematic game use. [ABSTRACT FROM AUTHOR]

Background Major depressive disorder (MDD) is strongly associated with an impaired quality of life (QoL), which is itself affected by various factors. Symptom-oriented ratings poorly reflect the impact of disease on the QoL and level of functioning of the mental health of subjects. The purpose of this study was to assess health-related QoL (HRQoL) using preference-based measures in outpatients with MDD with regard to their remission achievement and clinical factors affecting the HRQoL. Methods This was a cross-sectional observational study. We recruited 811 patients with MDD from 14 psychiatric outpatient clinics in Korea. They were divided into three groups as follows: a new visit group (n = 287), a remitted group (n = 235), and a non-remitted group (n = 289). The 17-item Hamilton Depression Rating Scale was used to assign patients to the remitted or non-remitted group. The general HRQoL was assessed with the EuroQol 5D (EQ-5D), using both the EQ-5D index score and the EuroQol Visual Analog Scale (EQ-VAS). The disease-specific HRQoL was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Results The non-remitted group showed a significant impairment of HRQoL in view of the subscales of EQ-5D index scores, EQ-VAS, and Q-LES-Q-SF. The EQ-5D index score in the remitted group was 0.77 ± 0.10, while it was 0.57 ± 0.23 in the non-remitted group and 0.58 ± 0.24 in the new visit group (p < 0.0001). The EQ-VAS scores for the remitted and non-remitted groups were 72.5 ± 16.6 and 50.9 ± 20.3, respectively (p < 0.0001). Likewise, patients with remission had the Q-LES-Q-SF total score of 46.5 ± 8.8, whereas those with non-remission reported 36.7 ± 7.7 (p < 0.0001). The symptom severity measured by the Depression and Somatic Symptoms Scale was significantly correlated with the HRQoL. Furthermore, patients with severe somatic symptoms showed a significantly lower EQ-5D index score (0.54 ± 0.24) than those with mild/moderate somatic symptoms (0.75 ± 0.12; p = 0.002). Conclusion Non-remitted MDD patients, especially those with more severe somatic symptoms, show a distinct impairment of HRQoL and more clinical symptoms, suggesting the importance of achieving remission in the treatment of MDD. [ABSTRACT FROM AUTHOR]

Background The aims of this study were to determine the utilization of mental health services (MHSs) by adults with a depressive mood and to identify the influencing sociodemographic factors, using a nationwide representative Korean sample. Methods The study included 2735 subjects, aged 19 years or older, who had experienced a depressive mood continuously for over 2 weeks within the previous year, using the data from KNHANES IV (Fourth Korea National Health and Nutrition Examination Survey), which was performed between 2007 and 2009, and involved a nationally representative sample of the Korean community population who were visited at home. A multivariate logistic regression analysis was used to estimate the adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for the use of MHSs, which was defined as using healthcare institutions, consulting services, and inpatient or outpatient treatments due to mental health problems. Results MHSs had been used by 9.6% of the subjects with a depressive mood. The use of the MHSs was significantly associated with age, education level, and employment status, after adjusting for sociodemographic and health-related factors. Specifically, the OR for the nonuse of MHSs by the elderly (>65 years) relative to subjects aged 19-34 years was 2.55 (95% CI = 1.13-5.76), subjects with a lower education level were less likely to use MHSs compared to those with a higher education level (7-9 years, OR = 2.35, 95% CI = 1.19-4.64; 10-12 years, OR = 1.66, 95% CI = 1.07-2.56; ≥13 years, reference), and the OR of unemployed relative to employed was 0.47 (95% CI = 0.32-0.67). Conclusions Among Korean adults with a depressive mood, the elderly, those with a lower education level, and the employed are less likely to use MHSs. These findings suggest that mental health policies should be made based on the characteristics of the population in order to reduce untreated patients with depression. Greater resources and attention to identifying and treating depression in older, less educated, and employed adults are warranted. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders that cause people difficulties in social interaction and communication. Identifying ASD patients based on resting-state functional magnetic resonance imaging (rs-fMRI) data is a promising diagnostic tool, but challenging due to the complex and unclear etiology of autism. And it is difficult to effectively identify ASD patients with a single data source (single task). Therefore, to address this challenge, we propose a novel multi-task learning framework for ASD identification based on rs-fMRI data, which can leverage useful information from multiple related tasks to improve the generalization performance of the model. Meanwhile, we adopt an attention mechanism to extract ASD-related features from each rs-fMRI dataset, which can enhance the feature representation and interpretability of the model. The results show that our method outperforms state-of-the-art methods in terms of accuracy, sensitivity and specificity. This work provides a new perspective and solution for ASD identification based on rs-fMRI data using multi-task learning. It also demonstrates the potential and value of machine learning for advancing neuroscience research and clinical practice. [ABSTRACT FROM AUTHOR]

Background: Para-aortic lymph node (PALN) metastases from primary pelvic malignancies are often treated with resection, but recurrence is common. We report toxicity and oncologic outcomes for patients with PALN metastases from gastrointestinal and gynecologic malignancies treated with resection and intraoperative electron radiotherapy (IORT). Methods: We retrospectively identified patients with recurrent PALN metastases who underwent resection with IORT. All patients were included in the local recurrence (LR) and toxicity analyses. Only patients with primary colorectal tumors were included in the survival analysis. Results: There were 26 patients with a median follow up of 10.4 months. The rate of para-aortic local control (LC) was 77% (20/26 patients) and the rate of any cancer recurrence was 58% (15/26 patients). Median time from surgery and IORT to any recurrence was 7 months. The LR rate for those with positive/close margins was 58% (7/12 patients) versus 7% (1/14 patients) for those with negative margins (p = 0.009). 15% (4/26 patients) developed surgical wound and/or infectious complications, 8% (2/26 patients) developed lower extremity edema, 8% (2/26 patients) experienced diarrhea, and 19% (5/26 patients) developed an acute kidney injury. There were no reported nerve injuries, bowel perforations, or bowel obstructions. For patients with primary colorectal tumors (n = 19), the median survival (OS) was 23 months. Conclusions: We report favorable LC and acceptable toxicity for patients receiving surgical resection and IORT for a population that has historically poor outcomes. Our data show disease control rates similar to literature comparisons for patients with strong risk factors for LR, such as positive/close margins. [ABSTRACT FROM AUTHOR]

Background: The myocardial wall of the left ventricle is a complex, multilayered structure and is not homogenous. The aim of this study was to determine longitudinal strain (LS) in the three myocardial layers in normal pregnant women according to gestation proceedings. Methods: The advanced two-dimensional speckle tracking echocardiography (2D STE) was performed on 62 women during each pregnancy trimester and 6 to 9 weeks after delivery, while 30 age-matched, healthy, nonpregnant women served as controls. LS on endocardial, mid-myocardial and epicardial layers at 18 cardiac segments were measured. Results: As gestation proceeded, all of layer-specific LS and global LS progressively decreased, which subsequently recovered postpartum (P < 0.05), and the LS gradient between inner and outer myocardium became greater, which reached its maximum in the late pregnancy. Peak systolic LS was the highest at endocardium and the lowest at epicardium, while the highest at the apical level and the lowest at the base (P < 0.05). In the early pregnancy and postpartum, LS at basal level was homogenous, meanwhile layer-specific LS showed significant differences at mid-ventricular and apical level throughout the progress of normal pregnancy (P < 0.05). Conclusions: Using 2D STE, three-layer assessment of LS can be performed in pregnant women and shall give us new insights into the quantitative analysis of global and regional LV function during pregnancy. Future studies on the detection of pregnancy related heart disease would require these parameters as reference values for each time point of a normal pregnancy. [ABSTRACT FROM AUTHOR]

Background: Pseudoviruses (PsVs) that encapsidate a reporter plasmid DNA have been used as surrogates for native human papillomavirus (HPV), whose continuous production is technically difficult. HPV PsVs have been designed to form capsids made up of the major capsid protein L1 and the minor capsid proteins L2. HPV PsVs have been produced in 293TT cells transfected with plasmid expressing L1 and L2 protein and plasmid containing the reporter gene. Several studies have suggested that naturally occurring HPV virions contain cellular histones, and histones have also been identified in mature HPV PsVs. However, the effect of the histones on the properties of the PsVs has not been investigated. Using heparin chromatography, we separated mature HPV type 16 PsVs into three fractions (I, II, and III) according to their heparin-binding affinities. Results: The amounts of cellular histone and cellular nucleotides per PsV were found to increase in the order fraction I, II and III. It appeared that PsVs in fraction I contains just small amount of cellular histone in Western blot analysis. The proportions of the three fractions in PsV preparations were 83.4, 7.5, and 9.1 % for fraction I, II, and III PsVs, respectively. In the electron microscope PsVs in fraction I appeared to have a more condensed structure than those in fractions II and III. Under the electron microscope fraction II and III PsVs appeared to be covered by substantial amounts of cellular histone while there was no visible histone covering PsVs of fraction I. Also the levels of reporter gene expression in infections of fraction II and III PsVs to 293TT cells were significantly lower than those in infections of fraction I PsV, and fraction II and III particles had significantly reduced immunogenicity. Conclusions: Our findings suggest that the involvement of large amounts of cellular histones during PsV formation interferes with the structural integrity of the PsVs and affects their immunogenicity. The fraction I particle therefore has the most suitable characteristics for use as an HPV PsV. [ABSTRACT FROM AUTHOR]

Background: The literature has shown depression to be associated with an increased risk of dementia. In addition, hormone therapy can be a responsive treatment option for a certain type of depression. In this study, we examined the association between hormone therapy, including lifetime oral contraceptive (OC) use, and hormone replacement therapy (HRT) after menopause with the occurrence of dementia among female patients with depression. Methods: The South Korean national claims data from January 1, 2005, to December 31, 2018, was used. Female subjects aged 40 years or older with depression were included in the analyses. Information on hormone therapy was identified from health examination data and followed up for the occurrence of dementia during the average follow-up period of 7.72 years. Results: Among 209,588 subjects, 23,555 were diagnosed with Alzheimer's disease (AD) and 3023 with vascular dementia (VD). Lifetime OC usage was associated with a decreased risk of AD (OC use for < 1 year: HR, 0.92 [95% CI, 0.88–0.97]; OC use for ≥ 1 year: HR, 0.89 [95% CI, 0.84–0.94]), and HRT after menopause was associated with a decreased risk of AD (HRT for < 2 years: HR, 0.84 [95% CI, 0.79–0.89]; HRT for 2–5 years: HR, 0.80 [95% CI, 0.74–0.88]; and HRT for ≥ 5 years : HR, 0.78 [95% CI, 0.71–0.85]) and VD (HRT < 2 years: HR, 0.82 [95% CI, 0.71–0.96]; HRT for 2–5 years: HR, 0.81 [95% CI, 0.64–1.02]; and HRT for ≥ 5 years: HR, 0.61 [95% CI, 0.47–0.79]). Conclusions: In this nationwide cohort study, lifetime OC use was associated with a decreased risk of AD, and HRT after menopause was associated with a decreased risk of AD and VD among female patients with depression. However, further studies are needed to establish causality. [ABSTRACT FROM AUTHOR]

Background: In selected patients with bladder cancer, partial cystectomy is an alternative treatment for bladder preservation with fair oncologic result. During partial cystectomy, tumor margin demarcation is difficult. Various methods were adopted, however, there is no standard for tumor margin demarcation. We aimed to introduce and provide our experience with holmium laser-assisted method with ten patients.Methods: From March 2016 and February 2019, patients who want partial cystectomy for bladder cancer were enrolled in this study. Inclusion criteria were stage T2 or T3 disease and tumor location restricted within the dome, and lateral, posterior side of the bladder were included. Transurethral holmium laser-assisted mucosal incision was made and deepened until perivesical fat. Minimal Safety margin for 5-10 mm were spared, and tumor removal was done laparoscopically.Results: Ten patients underwent holmium laser-assisted laparoscopic partial cystectomy. All procedures were done without complication. The tumor locations were laterally in seven patients, dome in two patients, and posterior wall in one patient. Pathologic examination of surgical margin showed no cancer cell involvement in all cases. There were no recurrences or metastases for 12 months follow up.Conclusions: Holmium laser-assisted laparoscopic partial cystectomy is effective and safe technique in carefully selected patients. To achieve precise and appropriate surgical margin during the laparoscopic partial cystectomy, holmium laser resection provides feasible and safe method that assists in bladder incision with minimal ureteral orifice involvement.Trial Registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to assess the economic benefit of achieving remission among outpatients with major depressive disorder (MDD) who are currently employed in Korea. Methods Cross-sectional observational study. A total of 337 outpatients with MDD with paid jobs were recruited from 14 psychiatric clinics in Korea and were then divided into three groups as follows: new visit group (n = 128), remitted group (n = 100) and non-remitted group (n = 109). The 17-item Hamilton Depression Rating Scale (HAM-D) was used to decide whether a patient should be assigned to the remitted or non-remitted group. Direct medical and nonmedical costs were measured via interview with the subjects. The World Health Organization Health and Work Performance Questionnaire (HPQ) were applied in order to measure the lost productive time (LPT) and related productivity costs. Results The three groups did not show a significant difference in direct medical cost. However, the difference between the remitted group and non-remitted group was statistically significant (25.49 ± 52.99 vs. 44.79 ± 126.55, χ2 = X²12.99, p = 0.0015). The remitted group demonstrated a significant improvement in productivity (particularly presenteeism) when compared with the new visit group (Z = -3.29, p = 0.001). Although the non-remitted group received treatment at psychiatric clinics similar to the remitted group, it lost 33 more working hours per month, which is compatible to $332 per month. Conclusion These results suggest the economic importance of achieving remission in treating depression. [ABSTRACT FROM AUTHOR]

Background: Recent studies have confirmed that combined surgery and anti-TNF therapy could improve outcomes in patients with perianal fistulising Crohn's disease (PFCD). However, the optimal timing for infliximab infusion after surgical intervention is uncertain. We aimed to determine the long-term efficacy of early initiation of infliximab following surgery among PFCD patients.Methods: We performed a retrospective cohort study of PFCD patients who received combined infliximab and surgical treatment between 2010 and 2018 at a tertiary referral hospital. Patients were grouped according to the time interval between surgery and infliximab infusion, with < 6 weeks into early infliximab induction group and > 6 weeks into delayed infliximab induction group. The primary outcome was to compare surgical re-intervention between early and delayed infliximab induction groups. The secondary outcomes were fistula healing and predictors associated with these outcomes of early infliximab induction approach.Results: One hundred and seventeen patients were included (73 in early infliximab induction, 44 in delayed infliximab induction). The median interval between surgery and infliximab initiation was 9.0 (IQR 5.5-17.0) days in early infliximab induction group and 188.0 (IQR 102.25-455.75) days in delayed infliximab induction group. After followed-up for a median of 36 months, 61.6% of patients in early infliximab induction group and 65.9% in delayed infliximab induction group attained fistula healing (p = 0.643). The cumulative re-intervention rate was 23%, 32%, 34% in early infliximab induction group and 16%, 25%, 25% in delayed infliximab induction group, at 1, 2, and 3 years respectively (p = 0.235). Presence of abscess at baseline (HR = 5.283; 95% CI, 1.61-17.335; p = 0.006) and infliximab maintenance therapy > 3 infusions (HR = 3.691; 95% CI, 1.233-11.051; p = 0.02) were associated with re-intervention in early infliximab induction group. Presence of abscess at baseline also negatively influenced fistula healing (HR = 3.429, 95% CI, 1.216-9.668; p = 0.02).Conclusion: Although no clear benefit was shown compared with delayed infliximab induction group, early initiation of infliximab after surgery could achieve promising results for PFCD patients. Before infliximab infusion, durable drainage is required for patients with concomitant abscess or prolonged infliximab maintenance therapy. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light chain (NFL) level has been suggested as a blood-based biomarker for neurodegeneration in dementia. However, the association between baseline NFL levels and cognitive stage transition or cortical thickness is unclear. This study aimed to investigate whether baseline NFL levels are associated with cognitive stage transition or cortical thickness in mild cognitive impairment (MCI) and cognitively unimpaired (CU) participants. Methods: This study analyzed data on participants from the independent validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE-V) study. Among the participants of KBASE-V study, 53 MCI and 146 CU participants who were followed up for ≥ 2 years and had data on the serum NFL levels were eligible for inclusion in this study. Participants were classified into three groups according to baseline serum NFL levels of low, middle, or high. Results: The Kaplan–Meier analysis showed association between the serum NFL tertiles and risk of cognitive stage transition in MCI (P = 0.002) and CU (P = 0.028) participants, analyzed separately. The same is true upon analysis of MCI and CU participants together (P < 0.001). In MCI participants, the highest serum NFL tertile and amyloid-beta positivity were independent predictors for cognitive stage transition after adjusting for covariates. For CU participants, only amyloid-beta positivity was identified to be an independent predictor. Conclusion: The study shows that higher serum NFL tertile levels correlate with increased risk of cognitive stage transition in both MCI and CU participants. Serum NFL levels were negatively correlated with the mean cortical thickness of the whole-brain and specific brain regions. [ABSTRACT FROM AUTHOR]

Background: Interspinous devices have been introduced as alternatives to decompression or fusion in surgery for degenerative lumbar diseases. This study aimed to investigate 15-year survivorship and risk factors for reoperation of a Device for Intervertebral Assisted Motion (DIAM) in surgery for 1-level lumbar disc herniation (LDH).Methods: A total of 94 patients (54 men and 40 women) underwent discectomy and DIAM implantation for 1-level LDH, with a mean follow-up of 12.9 years (range, 6.3-15.3 years). The mean age was 46.2 years (range, 21-65 years). Sixty-two patients underwent DIAM implantation for L4-5, 27 for L5-6, and 5 for L3-4. Reoperations due to any reason associated with DIAM implantation level or adjacent levels were defined as failure and used as the end point of determining survivorship.Results: During the 15-year follow-up, 8 patients (4 men and 4 women) underwent reoperation due to recurrence of LDH at the DIAM implantation level, a reoperation rate of 8.5%. The mean time to reoperation was 6.5 years (range, 0.8-13.9 years). Kaplan-Meier analysis showed a cumulative survival rate of the DIAM implantation of 97% at 5 years, 93% at 10 years, and 92% at 15 years after surgery; the cumulative reoperation rate of the DIAM implantation was 3% at 5 years, 7% at 10 years, and 8% at 15 years after surgery. Mean survival time was predicted to be 14.5 years (95% CI, 13.97-15.07). The log-rank test and Cox proportional hazard model showed that age, sex, and location did not significantly affect the reoperation rate of DIAM implantation.Conclusions: Our results showed that DIAM implantation significantly decreased reoperation rate for LDH in the 15-year survivorship analysis. We suggest that DIAM implantation could be considered a useful intermediate step procedure for LDH surgery. To the best of our knowledge, this is the longest follow-up study in which surgical outcomes of interspinous device surgery were reported. [ABSTRACT FROM AUTHOR]

Background: The leading causes of death among the elderly with cognitive impairment are unknown. This study aims to estimate the suicide and accidental death rates on the basis of a clinical case registry of patients diagnosed with cognitive impairment. Methods: The target sample consisted of 10,169 patients diagnosed with dementia or mild cognitive impairment (MCI), who were evaluated at the Clinical Research Center for Dementia of Korea (CREDOS) from January 2005 to December 2013. Information about whether the patients had died from suicide or in any kind of accident by December 31, 2016, was obtained from the database of the National Statistical Office (NSO). The standardized mortality ratio (SMR) and Cox-regression analysis were performed for evaluating the risk of suicide and accidental death as identified by the ICD-10. Results: The average of the Clinical Dementia Rating Scale (CDR) score (0.68 vs 0.93) was lower, and the age at the time of study registration (71.42 vs 75.68 years) was younger in the suicidal death group, as compared to the accidental death group. The overall SMR for accidental death in cognitively impaired patients (1.44, 95% CI 1.22–1.71) was significantly higher than the general population. Later onset (1.43, 95% CI 1.20–1.71) and older age (2.21, 95% CI 1.04–4.68) increased the risk of accidental death in cognitively impaired patients. According to the dementia subtypes, the SMR for accidental death was higher in both Alzheimer's disease (1.72, 95% CI 1.36–2.14) and vascular dementia (2.14, 95% CI 1.27–3.38). Additionally, the SMR for accidental death showed an increasing tendency as the CDR score increased (mild 1.80, 95% CI 1.32–2.42, moderate 1.86, 95% CI 1.07–3.03, severe 3.32, 95% CI 1.08–7.76). Unemployment increased the risks of both suicide (3.71, 95% CI 1.54–8.95) and accidental death (2.09, 95% CI 1.20–3.63). Conclusions: Among people with cognitive impairment, the risk of death by suicide did not increase, whereas that of accidental death increased significantly. Preventive strategies for premature mortality in those with cognitive impairment should be implemented from the early stages and should include careful evaluation of the individual risk factors for each type of death. [ABSTRACT FROM AUTHOR]

Background The transcriptome complexity in an organism can be achieved by alternative splicing of precursor messenger RNAs. It has been revealed that alternations in mRNA splicing play an important role in a number of diseases including human cancers. Methods In this study, we exploited whole transcriptome sequencing data from five lung adenocarcinoma tissues and their matched normal tissues to interrogate intron retention, a less studied alternative splicing form which has profound structural and functional consequence by modifying open reading frame or inserting premature stop codons. Results Abundant intron retention events were found in both tumor and normal tissues, and 2,340 and 1,422 genes only contain tumor-specific retentions and normal-specific retentions, respectively. Combined with gene expression analysis, we showed that genes with tumorspecific retentions tend to be over-expressed in tumors, and the abundance of intron retention within genes is negatively related with gene expression, indicating the action of nonsense mediated decay. Further functional analysis demonstrated that genes with tumor-specific retentions include known lung cancer driver genes and are found enriched in pathways important in carcinogenesis. Conclusions We hypothesize that intron retentions and consequent nonsense mediated decay may collectively counteract the over-expression of genes promoting cancer development. Identification of genes with tumor-specific retentions may also help develop targeted therapies. [ABSTRACT FROM AUTHOR]

Background: The accumulation of somatic mutations in genes and molecular pathways is a major factor in the evolution of oral squamous cell carcinoma (OSCC), which sparks studies to identify somatic mutations with clinical potentials. Recently, massively parallel sequencing technique has started to revolutionize biomedical studies, due to the rapid increase in its throughput and drop in cost. Hence sequencing of whole transcriptome (RNA-Seq) becomes a superior approach in cancer studies, which enables the detection of somatic mutations and accurate measurement of gene expression simultaneously. Methods: We used RNA-Seq data from tumor and matched normal samples to investigate somatic mutation spectrum in OSCC. Results: By applying a sophisticated bioinformatic pipeline, we interrogated two tumor samples and their matched normal tissues and identified 70,472 tumor somatic mutations in protein-coding regions. We further identified 515 significantly mutated genes (SMGs) and 156 tumor-specific disruptive genes (TDGs), with six genes in both sets, including ANKRA2, GTF2H5, STOML1, NUP37, PPP1R26, and TAF1L. Pathway analysis suggested that SMGs were enriched in cell adhesion pathways, which are frequently indicated in tumor development. We also found that SMGs tend to be differentially expressed between tumors and normal tissues, implying a regulatory role of accumulation of genetic aberrations in these genes. Conclusions: Our finding of known tumor genes proves of the utility of RNA-Seq in mutation screening, and functional analysis of genes detected here would help understand the molecular mechanism of OSCC. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer's disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population. Methods: One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI], and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs. Results: In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10−8). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74–0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain. Conclusion: The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations. [ABSTRACT FROM AUTHOR]

Background: The 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2-) early breast cancer patients. Age would influence the interaction between RS and chemotherapy effect. The current study aimed to determine RS thresholds which were predictive of chemotherapy benefit in young and old women, respectively.Methods: Patients diagnosed with pN0-1, ER+/HER2- breast cancer between 2009 and 2016 were retrospectively reviewed. Propensity score matching was performed according to chemotherapy usage. After stratifying patients with different cutoffs of age, the RS threshold indicating chemotherapy benefit in each age strata were determined by cox proportional hazard models.Results: A total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS thresholds suggesting chemotherapy benefit varied with age. For patients ≤55 years, chemotherapy benefit was observed in those having RS > 25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) of 97.0 and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS: 95.3% vs. 94.6%). For patients > 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS > 36 (P = 0.014, 4-year IDFS: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS: 92.3% vs. 95.8%).Conclusions: Old patients need higher RS thresholds to demonstrate the chemotherapy benefit. Further efforts are warranted to investigate the association between age and predictive RS thresholds. [ABSTRACT FROM AUTHOR]

Background: The fibula is only indirectly involved in the composition of the human knee joint and has therefore been neglected in the research on knee osteoarthritis. Nonuniform settlement of the proximal tibia plateau is clinically defined as when the height of the medial tibial plateau is lower than that of the lateral side in medial compartment knee osteoarthritis (KOA). The non-uniform settlement of the proximal tibia plateau may be caused by fibular support on the lateral side. Orthopedic surgeons practice partial fibulectomy based on the clinical manifestation of nonuniform settlement, and this technique has been shown to reduce pain and improve function in patients with medial compartment KOA. However, this hypothesis of the mechanism of nonuniform settlement lacks an anatomical basis. Methods: The P45 polyester plastination technique was used to prepare sections of the proximal tibiofibular joint to investigate the distribution of the bone trabeculae in the region of the lateral tibial plateau. Results: There was uneven distribution of trabeculae in the lateral condyle of the tibia and the head and neck of the fibula. The fibula and the posterolateral cortex of the shaft of the tibia united to form an arch beam via the tibiofibular joint. Many thick, dense trabeculae were present in a longitudinal direction above the tibiofibular arch. Conclusions: The fibula supports the lateral tibial plateau, and the trabeculae were concentrated above the tibiofibular arch. [ABSTRACT FROM AUTHOR]

Background: Endometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions. Methods: In this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™), and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database. Results: In total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein. Conclusions: The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Background: The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition. Methods: We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer's disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1–9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group. Results: Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7–9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1–3 or 4–6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex. Conclusions: When predicting cognitive decline of patients with focal Aß deposition, the patients' cognitive level, extent, and location of the focal involvement are important. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability in diverse ethnic groups are necessary for their use in clinics and clinical trials. With lack of cutoffs from fully automated immunoassay platforms in diverse races, the aim of this study is to evaluate the clinical utility of CSF AD biomarkers from the Lumipulse fully automated immunoassay based on β-amyloid (Aβ) positron emission tomography (PET) status comparing with these from two manual immunoassays, in Koreans. Methods: Among 331 Korean participants enrolled from a prospective, 3-year longitudinal observational study of the validation cohort of Korean Brain Aging Study for the Early Diagnosis and Prediction of AD, 139 (29 CN, 58 SCD, 29 MCI, and 23 AD) provided CSF and 271 underwent baseline amyloid PET (n = 128 with overlapping CSF and Aβ-PET, and 143 without CSFs). Three annual cognitive and neuropsychiatric function tests were conducted. Aβ42, Aβ40, total-tau, and phosphorylated-tau181 were measured by Lumipulse fully automated immunoassay and two manual immunoassays (INNO-BIA AlzBio3, INNOTEST). Clinical utility of CSF biomarker cutoffs, based on 128 participants with Aβ-PET, was evaluated. Results: Cognitive and neuropsychological scores differed significantly among the groups, with descending performance among CN>SCD>MCI>AD. Biomarker levels among immunoassays were strongly intercorrelated. We determined the Aβ-PET status in a subgroup without CSF (n = 143), and then when we applied CSF biomarker cutoffs determined based on the Aβ-PET status, the CSF biomarkers (cutoffs of 642.1 pg/mL for Aβ42, 0.060 for Aβ42/Aβ40, 0.315 for t-tau/Aβ42, and 0.051 for p-tau/Aβ42, respectively) showed good agreement with Aβ-PET (overall AUC ranges of 0.840–0.898). Use of the Aβ-PET-based CSF cutoffs showed excellent diagnostic discrimination between AD and CN (Aβ42, Aβ42/Aβ40, t-tau/Aβ42, and p-tau/Aβ42) with overall AUC ranges of 0.876–0.952. During follow-up, participants with AD-like CSF signature determined by Aβ-PET-based cutoffs from Lumipulse showed rapid progression of cognitive decline in 139 subjects, after adjustment for potential confounders, compared with those with a normal CSF signature. Conclusion: CSF AD biomarkers measured by different immunoassay platforms show strong intercorrelated agreement with Aβ-PET in Koreans. The Korean-specific Aβ-PET-based CSF biomarker cutoffs measured by the Lumipulse assay strongly predicts progression of cognitive decline. The clinical utility of CSF biomarkers from fully-automated immunoassay platforms should be evaluated in larger, more diverse cohorts. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by gradual memory loss and neuropsychiatric symptoms. We have previously demonstrated that the 2-({3-[2-(1-cyclohexene-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111), the inhibitor of CHI3L1, has the inhibitory effect on memory impairment in Αβ infusion mouse model and on LPS-induced neuroinflammation in the murine BV-2 microglia and primary cultured astrocyte.Methods: In the present study, we investigated the inhibitory effect of K284-6111 on memory dysfunction and neuroinflammation in Tg2576 transgenic mice, and a more detailed correlation of CHI3L1 and AD. To investigate the effects of K284-6111 on memory dysfunction, we administered K284-6111 (3 mg/kg, p.o.) daily for 4 weeks to Tg2576 mice, followed by behavioral tests of water maze test, probe test, and passive avoidance test.Results: Administration of K284-6111 alleviated memory impairment in Tg2576 mice and had the effect of reducing the accumulation of Aβ and neuroinflammatory responses in the mouse brain. K284-6111 treatment also selectively inactivated ERK and NF-κB pathways, which were activated when CHI3L1 was overexpressed, in the mouse brain and in BV-2 cells. Web-based gene network analysis and our results of gene expression level in BV-2 cells showed that CHI3L1 is closely correlated with PTX3. Our result revealed that knockdown of PTX3 has an inhibitory effect on the production of inflammatory proteins and cytokines, and on the phosphorylation of ERK and IκBα.Conclusion: These results suggest that K284-6111 could improve memory dysfunction by alleviating neuroinflammation through inhibiting CHI3L1 enhancing ERK-dependent PTX3 pathway. [ABSTRACT FROM AUTHOR]

Background: Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder of unknown etiology, but is closely associated with damage to dopaminergic neurons. MSA progression is rapid. Hence, long-term drug treatments do not have any therapeutic benefits. We assessed the inhibitory effect of mesenchymal stem cells (MSCs) on double-toxin-induced dopaminergic neurodegenerative MSA. Results: Behavioral disorder was significantly improved and neurodegeneration was prevented following MSC transplantation. Proteomics revealed lower expression of polyamine modulating factor-binding protein 1 (PMFBP1) and higher expression of 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMGCL), but these changes were reversed after MSC transplantation. In the in vitro study, the 6-OHDA-induced effects were reversed following co-culture with MSC. However, PMFBP1 knockdown inhibited the recovery effect due to the MSCs. Furthermore, HMGCL expression was decreased following co-culture with MSCs, but treatment with recombinant HMGCL protein inhibited the recovery effects due to MSCs. Conclusions: These data indicate that MSCs protected against neuronal loss in MSA by reducing polyamine- and cholesterol-induced neural damage. [ABSTRACT FROM AUTHOR]

Background: Chitinase 3 like 1 protein (Chi3L1) is expressed in several cancers, and a few evidences suggest that the secreted Chi3L1 contributes to tumor development. However, the molecular mechanisms of intracellular Chi3L1 are unknown in the lung tumor development. Methods: In the present study, we generated Chi3L1 knockout mice (Chi3L1KO(−/−)) using CRISPR/Cas9 system to investigate the role of Chi3L1 on lung tumorigenesis. Results: We established lung metastasis induced by i.v. injections of B16F10 in Chi3L1KO(−/−). The lung tumor nodules were significantly reduced in Chi3L1KO(−/−) and protein levels of p53, p21, BAX, and cleaved-caspase 3 were significantly increased in Chi3L1KO(−/−), while protein levels of cyclin E1, CDK2, and phsphorylation of STAT3 were decreased in Chi3L1KO(−/−). Allograft mice inoculated with B16F10 also suppressed tumor growth and increased p53 and its target proteins including p21 and BAX. In addition, knockdown of Chi3L1 in lung cancer cells inhibited lung cancer cell growth and upregulated p53 expression with p21 and BAX, and a decrease in phosphorylation of STAT3. Furthermore, we found that intracellular Chi3L1 physically interacted and colocalized with p53 to inhibit its protein stability and transcriptional activity for target genes related with cell cycle arrest and apoptosis. In lung tumor patient, we clinically found that Chi3L1 expression was upregulated with a decrease in p53 expression, as well as we validated that intracellular Chi3L1 was colocalized, reversely expressed, and physically interacted with p53, which results in suppression of the expression and function of p53 in lung tumor patient. Conclusions: Our studies suggest that intracellular Chi3L1 plays a critical role in the lung tumorigenesis by regulating its novel target protein, p53 in both an in vitro and in vivo system. [ABSTRACT FROM AUTHOR]

Background: To evaluate the maximal sectional area (SA) of the rectus capitis posterior minor (RCPmi) muscle and its potential correlation with to be named ligament (TBNL) in the suboccipital area using 3D MR imaging.Methods: A total of 365 subjects underwent sagittal 3D T2WI MR imaging of the RCPmi and TBNL. Among them, 45 subjects were excluded due to a particular clinical history or poor image quality. Finally, 320 subjects met the inclusion criteria, including 138 men and 182 women. The 624 RCPmi muscles were classified into positive and negative groups according to their attachment to the TBNL. Two experienced radiologists manually measured the maximum SA of the RCPmi muscle on the parasagittal image with a 30° deviation from the median sagittal plane. The correlations between the SA and the subject's age, height, BMI, gender, handedness, and age-related disc degeneration were tested by Spearman analysis. The SA differences between different groups were compared using independent samples t-test.Results: A total of 123 RCPmi-TBNL attachments were identified in the positive group, while 501 RCPmi muscles were identified in the negative group. The SA of the 624 RCPmi muscles was 62.71 ± 28.72 mm2 and was poorly correlated with the subject's age, BMI, or handedness, with no correlation with age-related disc degeneration. A fair correlation was found between the SA and the body height in the whole group, and poor correlation in each male/female group. The SA of the RCPmi muscle in males was significantly bigger than that in women ([75.54 ± 29.17] vs. [52.74 ± 24.07] mm2). The SA of RCPmi muscle in the positive group was significantly smaller than that in the negative group ([55.95 ± 26.76] mm2 vs. [64.37 ± 28.97] mm2).Conclusions: Our results revealed a significantly smaller SA of the RCPmi in subjects with RCPmi-TBNL attachment. Besides, a larger SA of the RCPmi was correlated with the male gender. These findings suggest that the SA of the RCPmi ought to be interpreted with care for each patient since there could be considerable variations. [ABSTRACT FROM AUTHOR]

Background: Although amyloid PET of typical Alzheimer's disease (AD) shows diffuse ß-amyloid (Aß) deposition, some patients show focal deposition. The clinical significance of this focal Aß is not well understood. We examined the clinical significance of focal Aß deposition in terms of cognition as well as Aß and tau cerebrospinal fluid (CSF) levels. We further evaluated the order of Aß accumulation by visual assessment. Methods: We included 310 subjects (125 cognitively unimpaired, 125 mild cognitive impairment, and 60 AD dementia) from 9 referral centers. All patients underwent neuropsychological tests and 18F-flutemetamol (FMM) PET. Seventy-seven patients underwent CSF analysis. Each FMM scan was visually assessed in 10 regions (frontal, precuneus and posterior cingulate, lateral temporal, parietal, and striatum of each hemisphere) and was classified into three groups: No-FMM, Focal-FMM (FMM uptake in 1–9 regions), and Diffuse-FMM (FMM uptake in all 10 regions). Results: 53/310 (17.1%) subjects were classified as Focal-FMM. The cognitive level of the Focal-FMM group was better than that of Diffuse-FMM group and worse than that of No-FMM group. Among the Focal-FMM group, those who had FMM uptake to a larger extent or in the striatum had worse cognitive levels. Compared to the Diffuse-FMM group, the Focal-FMM group had a less AD-like CSF profile (increased Aß42 and decreased t-tau, t-tau/Aß42). Among the Focal-FMM group, Aß deposition was most frequently observed in the frontal (62.3%) and least frequently observed in the striatum (43.4%) and temporal (39.6%) regions. Conclusions: We suggest that focal Aß deposition is an intermediate stage between no Aß and diffuse Aß deposition. Furthermore, among patients with focal Aß deposition, those who have Aß to a larger extent and striatal involvement show clinical features close to diffuse Aß deposition. Further longitudinal studies are needed to evaluate the disease progression of patients with focal Aß deposition. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) play a significant role in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the effects of exosomal miR-133b derived from MSCs on glioma cell behaviors. Methods: Microarray-based analysis identified the differentially expressed genes (DEGs) in glioma. The expression patterns of EZH2 and miR-133b along with interaction between them were clarified in glioma. The expression of miR-133b and EZH2 in glioma cells was altered to examine their functions on cell activities. Furthermore, glioma cells were co-cultured with MSC-derived exosomes treated with miR-133b mimic or inhibitor, and EZH2-over-expressing vectors or shRNA against EZH2 to characterize their effect on proliferation, invasion, and migration of glioma cells in vitro. In vivo assays were also performed to validate the in vitro findings. Results: miR-133b was downregulated while EZH2 was upregulated in glioma tissues and cells. miR-133b was found to target and negatively regulate EZH2 expression. Moreover, EZH2 silencing resulted in inhibited glioma cell proliferation, invasion, and migration. Additionally, MSC-derived exosomes containing miR-133b repressed glioma cell proliferation, invasion, and migration by inhibiting EZH2 and the Wnt/β-catenin signaling pathway. Furthermore, in vivo experiments confirmed the tumor-suppressive effects of MSC-derived exosomal miR-133b on glioma development. Conclusion: Collectively, the obtained results suggested that MSC-derived exosomes carrying miR-133b could attenuate glioma development via disrupting the Wnt/β-catenin signaling pathway by inhibiting EZH2, which provides a potential treatment biomarker for glioma. [ABSTRACT FROM AUTHOR]

Background: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer.Methods: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes.Results: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively).Conclusions: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence for the prevalence of the co-existence of physical activity (PA) and sedentary behavior (SED), and its correlates among children and adolescents. This study has two aims: 1) to investigate the prevalence of PA and SED, and their co-existence, and 2) to examine the associations between PA or SED, or both with gender and age among children and adolescents in Shanghai, China.Methods: Using a cross-sectional study design (conducted from September to December 2014), 50,090 children and adolescents (10-18 years old, 50.4% boys) were included in this study. A self-reporting questionnaire was used to measure participants' sociodemographic characteristics, PA, and SED. Descriptive statistics were used to describe sample characteristics, the prevalence of PA and SED, and their co-existence. A Generalized Linear Model was conducted to explore the associations between the prevalence of PA and SED, and their co-existence with gender and age separately.Results: Of the children and adolescents studied, only 18.4% met the guidelines for PA, 25.5% met the guidelines for SED, and 5.7% met the guidelines for both. Boys were more physically active (aOR = 1.43, 95% CI: 1.36-1.50), and girls were less sedentary (aOR = 1.29, 95%CI: 1.24-1.34). The prevalence of PA, SED, or both all declined as age increased (p < 0.001). Stratified analysis by gender revealed greater declining trends of meeting the PA or SED guidelines, or both in girls (all p < 0.005).Conclusion: Very few children and adolescents showed active lifestyles, and this was significantly related to age. Effective interventions aiming to promote PA and concurrently to limited SED among children and adolescents should be implemented as early as possible. [ABSTRACT FROM AUTHOR]

Background: Uridine (Urd), which has been reported as a major component of RNA, plays an important role in various biological process including neuroprotection, biochemical modulation and glycolysis, although its role in constipation has yet to be established. Therefore, in this study, we investigated the laxative effects of Urd on chronic constipation.Methods: The constipation phenotypes and their related mechanisms were investigated in the transverse colons of SD rats with loperamide (Lop)-induced constipation after treatment with 100 mg/kg of Urd.Results: The number, weight and water contents of stools were significantly higher in the Lop + Urd treated group than the Lop + Vehicle treated group, while food intake and water consumption of the same group were maintained at a constant level. The thickness of the mucosa layer, muscle and flat luminal surface, as well as the number of goblet cells, paneth cells and lipid droplets were enhanced in the Lop + Urd treated group. Furthermore, the expression of the muscarinic acetylcholine receptors M2 and M3 (mAChR M2 and M3) at the transcriptional and translational level was recovered in the Lop + Urd treated group, while some markers such as Gα and inositol triphosphate (IP3) in their downstream signaling pathway were completely recovered by Urd treatment. Moreover, the ability for mucin secretion and the expression of membrane water channel (aquaporine 8, AQP8) were increased significantly in the Lop + Urd treated group compared with Lop + Vehicle treated group. Finally, the activity of Urd was confirmed in primary smooth muscle of rat intestine cells (pRISMC) based on Gα expression and IP3 concentration.Conclusions: The results of the present study provide the first strong evidence that Urd can be considered an important candidate for improving chronic constipation induced by Lop treatment in animal models. [ABSTRACT FROM AUTHOR]

Background East Asian countries have high suicide rates. However, little is known about clinical and sociodemographic factors associated with suicidality in Asian populations. The aim of this study was to evaluate the factors associated with suicidality in patients with major depressive disorder (MDD) from six Asian countries. Methods The study cohort consisted of 547 outpatients with MDD. Patients presented to study sites in China (n = 114), South Korea (n = 101), Malaysia (n = 90), Singapore (n = 40), Thailand (n = 103), and Taiwan (n = 99). All patients completed the Mini-International Neuropsychiatric Interview (MINI), the Montgomery-Asberg Depression Rating Scale (MADRS), the Global Severity Index(SCL-90R), the Fatigue Severity Scale, the 36-item short-form health survey, the Sheehan Disability Scale, and the Multidimensional Scale of Perceived Social Support (MSPSS). Patients were classified as showing high suicidality if they scored ≥6 on the MINI suicidality module. Multivariate logistic regression analysis was used to examine sociodemographic and clinical factors related to high suicidality. Results One hundred and twenty-five patients were classed as high suicidality. Unemployed status (adjusted odds ratio [OR] 2.43, p < 0.01), MADRS score (adjusted OR 1.08), p < 0.001, and GSI (SCL-90R) score (adjusted OR 1.06, p < 0.01) were positively related to high suicidality. Hindu (adjusted OR 0.09, p < 0.05) or Muslim (adjusted OR 0.21, p < 0.001) religion and MSPSS score (adjusted OR 0.82, p < 0.05) were protective against high suicidality. Conclusions A variety of sociodemographic and clinical factors were associated with high suicidality in Asian patients with MDD. These factors may facilitate the identification of MDD patients at risk of suicide. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is known to be more prevalent in spontaneous abortions than in elective terminations of pregnancy. More recently, placental infection with HPV was shown to be associated with spontaneous preterm delivery. However, no study has evaluated the prevalence of HPV infection in pregnant Korean females and its association with adverse pregnancy outcomes.Methods: We conducted a cross-sectional study of 311 females who gave birth at Korea University Medical Center. Our sample included 45 preterm deliveries, 50 cases of premature rupture of the membranes (PROM), 21 preeclampsia cases, and 8 gestational diabetes mellitus (GDM) patients. We used the Hybrid Capture II system to detect high-risk (HR)-HPV infection at six weeks postpartum.Results: The prevalence of HR-HPV infection was 14.1%. Women with HR-HPV infection had a higher incidence of PROM than those without HR-HPV. HR-HPV infection was associated with an increased risk of PROM (OR, 2.380; 95% CI, 1.103-5.134). The prevalence of preterm delivery, preeclampsia, or GDM was not different between the two groups.Conclusions: We observed a high prevalence of HR-HPV infection in pregnant women. Moreover, HR-HPV infection was associated with a risk of PROM at term. Further studies are needed to evaluate mechanisms by which HR-HPV infection induces PROM. [ABSTRACT FROM AUTHOR]

Background: Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. Method: In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. Results: In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry. Conclusion: After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can be enhanced by IL-2 as an adjuvant. Cellular immune responses may play an important role in HSI against influenza virus [ABSTRACT FROM AUTHOR]

Background: Proteomics may help us better understand the changes of multiple proteins involved in oncogenesis and progression of prostate cancer(PCa) and identify more diagnostic and prognostic biomarkers. The aim of this study was to screen biomarkers of PCa by the proteomics analysis using isobaric tags for relative and absolute quantification(iTRAQ). Methods: The patients undergoing prostate biopsies were classified into 3 groups according to pathological results: benign prostate hyperplasia (BPH, n = 20), PCa(n = 20) and BPH with local prostatic intraepithelial neoplasm (PIN, n = 10). Then, all the specimens from these patients were analyzed by iTRAQ and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS). The Gene Ontology(GO) function and the transcription regulation networks of the differentially expressed were analyzed by MetaCore software. Western blotting and Immunohistochemical staining were used to analyze the interesting proteins. Result: A total of 760 proteins were identified from 13787 distinct peptides, including two common proteins that enjoy clinical application: prostate specific antigen (PSA) and prostatic acid phosphatase(PAP). Proteins that expressed differentially between PCa and BPH group were further analyzed. Compared with BPH, 20 proteins were significantly differentially up-regulated (>1.5-fold) while 26 were significantly down-regulated in PCa(<0.66-fold). In term of GO database, the differentially expressed proteins were divided into 3 categories: cellular component(CC), molecular function (MF) and biological process(BP). The top 5 transcription regulation networks of the differentially expressed proteins were initiated through activation of SP1, p53, YY1, androgen receptor(AR) and c-Myc The overexpression of periostin in PCa was verified by western blotting and immunohistochemical staining. Conclusion: Our study indicates that the iTRAQ technology is a new strategy for global proteomics analysis of the tissues of PCa. A significant up-regulation of periostin in PCa compared to BPH may provide clues for not only a promising biomarker for the prognosis of PCa but also a potential target for therapeutical intervention. [ABSTRACT FROM AUTHOR]

It is known that estrogen can protect neurons from excitotoxicity. Since isoflavones possess estrogen-like activity, it is of interest to determine whether isoflavones can also protect neurons from glutamate-induced neuronal injury. Morphological observation and lactate dehydrogenase (LDH) release assay were used to estimate the cellular damage. It is surprising that, contrary to estrogen, isoflavones, specifically genistein and daidzein, are toxic to primary neuronal culture at high concentration. Treatment of neurons with 50 μM genistein and daidzein for 24 h increased LDH release by 90% and 67%, respectively, indicating a significant cellular damage. Under the same conditions, estrogen such as 17 β-estradiol did not show any effect on primary culture of brain cells. At 100 μM, both genistein and daidzein increased LDH release by 2.6- and 3-fold, respectively with a 30-min incubation. Furthermore, both genistein and daidzein at 50 μM increased the intracellular calcium level, [Ca2+]i, significantly. To determine their mode of action, genistein and daidzein were tested on glutamate and GABAA receptor binding. Both genistein and daidzein were found to have little effect on glutamate receptor binding, while the binding of [3H]muscimol to GABAA receptors was markedly inhibited. However, 17 β-estradiol did not affect GABAA receptor binding suggesting that the toxic effect of genistein and daidzein could be due to their inhibition of the GABAA receptor resulting in further enhancement of excitation by glutamate and leading to cellular damage. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation and accumulation of β-amyloid (Aβ) play a significant role in the onset and progression of Alzheimer's disease (AD). Our previous study demonstrated that signal transducer and activator of transcription-3 (STAT3) plays a major role in neuroinflammation and amyloidogenesis. Methods: In the present study, we investigated the inhibitory effect of bee venom phospholipase A2 (bvPLA2) on memory deficiency in Tg2576 mice, which demonstrate genetic characteristics of AD and the mechanism of its action at the cellular and animal level. For in vivo study, we examined the effect of bvPLA2 on improving memory by conducting several behavioral tests with the administration of bvPLA2 (1 mg/kg) to Tg2576 mice. For in vitro study, we examined the effect of bvPLA2 on amyloidogenesis and neuroinflammation by treating bvPLA2 on LPS-activated BV2 cells. Results: We found that bvPLA2 alleviated memory impairment in Tg2576 mice, as demonstrated in the behavioral tests assessing memory. In the bvPLA2-treated group, Aβ, amyloid precursor protein (APP), and β-secretase 1 (BACE1) levels and β-secretase activity were significantly decreased. Expression of pro-inflammatory cytokines and inflammation-related proteins decreased in the brain of bvPLA2-treated group, whereas anti-inflammatory cytokines increased. In addition, bvPLA2 reduced STAT3 phosphorylation in the brains of the bvPLA2-treated group. At the cellular level, bvPLA2 inhibits production of nitric oxide, pro-inflammatory cytokines, and inflammation-related proteins including p-STAT3. Additionally, bvPLA2 inhibits the production of Aβ in cultured BV-2 cells. Results from the docking experiment, pull-down assay, and the luciferase assay show that bvPLA2 directly binds STAT3 and, thus, regulates gene expression levels. Moreover, when the STAT3 inhibitor and bvPLA2 were administered together, the anti-amyloidogenic and anti-inflammatory effects were further enhanced than when they were administered alone. Conclusion: These results suggest that bvPLA2 could restore memory by inhibiting the accumulation of Aβ and inflammatory responses via blockage of STAT3 activity. [ABSTRACT FROM AUTHOR]

Background: Alcohol abuse and alcoholism lead to alcohol liver disease such as alcoholic fatty liver. Parkin is a component of the multiprotein E3 ubiquitin ligase complex and is associated with hepatic lipid accumulation. However, the role of parkin in ethanol-induced liver disease has not been reported. Here, we tested the effect of parkin on ethanol-induced fatty liver in parkin knockout (KO) mice with chronic ethanol feeding. Methods: Male wild type (WT) and parkin KO mice (10–12 weeks old, n = 10) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 10 days. Liver histological, biochemical, and gene-expression studies were performed. Results: Parkin KO mice exhibited lower hepatosteatosis after ethanol consumption. Because several studies reported that β-catenin is a critical factor in ethanol metabolism and protects against alcohol-induced hepatosteatosis, we investigated whether parkin changes β-catenin accumulation in the liver of ethanol-fed mice. Our results show that β-catenin was greatly accumulated in the livers of ethanol-fed parkin KO mice compared to ethanol-fed WT mice, and that parkin binds to β-catenin and promotes its degradation it by ubiquitination. Moreover, the β-catenin inhibitor IWR-1 abrogated the attenuation of ethanol-induced hepatic lipid accumulation by parkin deficiency in the livers of parkin KO mice and parkin siRNA-transfected human hepatic cell line. Conclusions: Parkin deficiency prevents ethanol-induced hepatic lipid accumulation through promotion of β-catenin signaling by failure of β-catenin degradation. [ABSTRACT FROM AUTHOR]

Background: Tumor-associated macrophages can promote breast cancer metastasis by secreting cytokines and growth factors. Interleukin (IL)-32θ, a newly identified IL-32 isoform, was previously shown to down-regulate various proinflammatory factors of macrophages. Here, we report the presence of IL-32θ in breast cancer tissues and evaluate its effects on macrophage-regulated breast cancer metastasis. Methods: RT-qPCR was used to analyze the mRNA expression of IL-32θ, Chemokine (C-C motif) ligand 18 (CCL18) in breast cancer tissues. In vitro cell-based experiments using IL-32θ-expressing MDA-MB-231 cells were conducted to examine the effects of IL-32θ on metastasis and its molecular signaling. In vivo xenograft, immunohistochemistry, and optical imaging models were generated to support in vitro and clinical findings. Results: The clinical data displayed opposite expression patterns of CCL18 and IL-32θ mRNA in macrophage-infiltrated breast tumor tissues compared with those in the other tissues tested. In MDA-MB-231 cells, IL-32θ overexpression attenuated migration, invasion, tumor-promoting factors, and increased epithelial markers levels upon treatment with conditioned media from THP-1-derived macrophages. Additionally, IL-32θ expression in a xenograft model led to a remarkable decrease in tumor size and macrophage-stimulated tumor promotion. This inhibition was mediated through a direct interaction with protein kinase C-δ (PKCδ), subsequently eliminating the downstream factors STAT3 and NF-κB. Blocking CCL18 during co-culture of macrophages and breast cancer cells reduced the levels of breast cancer progression-related factors and PKCδ downstream signaling suggesting CCL18 as the main macrophage-secreted factors triggering the signaling pathway inhibited by IL-32θ. Conclusions: Our findings demonstrate a novel role of IL-32θ as an intracellular modulator to suppress macrophage-promoted breast cancer progression by targeting CCL18-dependent signaling. [ABSTRACT FROM AUTHOR]

Background: Interleukin-32 (IL-32) has been associated with various diseases. Previous studies have shown that IL-32 inhibited the development of several tumors. However, the role of IL-32γ, an isotype of IL-32, in skin carcinogenesis remains unknown. Methods: We compared 7,12-Dimethylbenz[a]anthracene/12-O-Tetradecanoylphorbol-13-acetate (DMBA/TPA)-induced skin carcinogenesis in wild type (WT) and IL-32γ-overexpressing mice to evaluate the role of IL-32γ. We also analyzed cancer stemness and NF-κB signaling in skin cancer cell lines with or without IL-32γ expression by western blotting, quantitative real-time PCR and immunohistochemistry analysis. Results: Carcinogen-induced tumor incidence in IL-32γ mice was significantly reduced in comparison to that in WT mice. Infiltration of inflammatory cells and the expression levels of pro-inflammatory mediators were decreased in the skin tumor tissues of IL-32γ mice compared with WT mice. Using a genome-wide association study analysis, we found that IL-32 was associated with integrin αV (ITGAV) and tissue inhibitor of metalloproteinase-1 (TIMP-1), which are critical factor for skin carcinogenesis. Reduced expression of ITGAV and TIMP-1 were identified in DMBA/TPA-induced skin tissues of IL-32γ mice compared to that in WT mice. NF-κB activity was also reduced in DMBA/TPA-induced skin tissues of IL-32γ mice. IL-32γ decreased cancer cell sphere formation and expression of stem cell markers, and increased chemotherapy-induced cancer cell death. IL-32γ also downregulated expression of ITGAV and TIMP-1, accompanied with the inhibition of NF-κB activity. In addition, IL-32γ expression with NF-κB inhibitor treatment further reduced skin inflammation, epidermal hyperplasia, and cancer cell sphere formation and downregulated expression levels of ITGAV and TIMP-1. Conclusions: These findings indicated that IL-32γ suppressed skin carcinogenesis through the inhibition of both stemness and the inflammatory tumor microenvironment by the downregulation of TIMP-1 and ITGAV via inactivation of NF-κB signaling. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease, which is pathologically characterized by an excessive accumulation of amyloid beta (Aβ) fibrils, is a degenerative brain disease and the most common cause of dementia. In a previous study, it was reported that an increased level of CHI3L1 in plasma was found in AD patients. We investigated the inhibitory effect of 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111), an inhibitor of chitinase 3 like 1 (CHI3L1), on memory impairment in Aβ1-42-infused mice, and microglial BV-2 cells and astrocytes.Methods: We examined whether K284-6111 (3 mg/kg given orally for 4 weeks) prevents amyloidogenesis and memory loss in Aβ1-42-induced AD mice model. After intracerebroventrical (ICV) infusion of Aβ1-42 for 14 days, the cognitive function was assessed by the Morris water maze test and passive avoidance test. K284-6111 treatment was found to reduce Aβ1-42-induced memory loss.Results: A memory recovery effect was found to be associated with the reduction of Aβ1-42-induced expression of inflammatory proteins (iNOS, COX-2, GFAP, and Iba-1) and the suppression of CHI3L1 expression in the brain. Additionally, K284-6111 reduced Aβ1-42-induced β-secretase activity and Aβ generation. Lipopolysaccharide (LPS)-induced (1 μg/mL) expression of inflammatory (COX-2, iNOS, GFAP, Iba-1) and amyloidogenic proteins (APP, BACE1) were decreased in microglial BV-2 cells and cultured astrocytes by the K284-6111 treatment (0.5, 1, and 2 μM). Moreover, K284-6111 treatment suppressed p50 and p65 translocation into the nucleus, and phosphorylation of IκB in vivo and in vitro.Conclusion: These results suggest that CHI3L1 inhibitor could be an applicable intervention drug in amyloidogenesis and neuroinflammation, thereby preventing memory dysfunction via inhibition of NF-κB. [ABSTRACT FROM AUTHOR]

Background: Past attempted suicide is a strong predictor of future suicide risk, but the risk varies among suicide attempters. Hence, it is important to clarify distinguishing features of lifetime attempters with a high level of current suicide risk for efficient preventive management.Methods: We compared characteristics of suicide attempts and clinical characteristics among high-, moderate-, and low-risk attempters. Among the total of 6022 participants in the Korean Epidemiologic Catchment Area study, 193 reported a suicide attempt in their lifetime, 36 of which had high, 126 moderate, and 30 low levels of current suicide risk (1 incomplete response).Results: High-risk suicide attempters had more past attempts compared with moderate- and low-risk suicide attempters. Suicide attempts were closely linked to a wide range of psychiatric comorbidities regardless of degree of current level of suicide risk, but the relative risk for having at least one mental disorder was the highest in high-risk attempters. Specifically, the relative risks for depressive disorder, anxiety disorders including obsessive-compulsive disorder and post-traumatic stress disorder, and substance use disorders were higher in high-risk attempters, and relative risk for somatoform disorder was higher in low-risk attempters than others.Conclusions: Our findings indicated that special attention is required for suicide attempters with a history of repeated attempts and current mental disorders, particularly anxiety disorders. [ABSTRACT FROM AUTHOR]

Background: Accumulation of beta-amyloid and neuroinflammation trigger Alzheimer's disease. We previously found that lipopolysaccharide (LPS) caused neuroinflammation with concomitant accumulation of beta-amyloid peptides leading to memory loss. A variety of anti-inflammatory compounds inhibiting nuclear factor kappaB (NF-κB) activation have showed efficacy to hinder neuroinflammation and amyloidogenesis. We also found that bee venom (BV) inhibits NF-κB.Methods: A mouse model of LPS-induced memory loss used administration of BV (0.8 and 1.6 μg/kg/day, i.p.) to ICR mice for 7 days before injection of LPS (2.5 mg/kg/day, i.p.). Memory loss was assessed using a Morris water maze test and passive avoidance test. For in vitro study, we treated BV (0.5, 1, and 2 μg/mL) to astrocytes and microglial BV-2 cells with LPS (1 μg/mL).Results: We found that BV inhibited LPS-induced memory loss determined by behavioral tests as well as cell death. BV also inhibited LPS-induced increases in the level of beta-amyloid (Aβ), β-and γ-secretases activities, NF-κB and its DNA-binding activity and expression of APP, and BACE1 and neuroinflammation proteins (COX-2, iNOS, GFAP and IBA-1) in the brain and cultured cells. In addition, pull-down assay and molecular modeling showed that BV binds to NF-κB.Conclusions: BV attenuates LPS-induced amyloidogenesis, neuroinflammation, and therefore memory loss via inhibiting NF-κB signaling pathway. Thus, BV could be useful for treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: ent-Sauchinone is a polyphenolic compound found in plants belonging to the lignan family. ent-Sauchinone has been shown to modulate the expression of inflammatory factors through the nuclear factor-kappa B (NF-κB) signaling pathway. It is well known that neuroinflammation is associated with amyloidogenesis. Thus, in the present study, we investigated whether ent-Sauchinone could have anti-amyloidogenic effects through the inhibition of NF-κB pathways via its anti-inflammatory property.Methods: To investigate the potential effect of ent-Sauchinone on anti-neuroinflammation and anti-amyloidogenesis in in vitro studies, we used microglial BV-2 cells and cultured astrocytes treated with ent-Sauchinone (1, 5, and 10 μM) for 24 hours. For the detection of anti-neuro-inflammatory responses, reative oxygen species (ROS) and Nitric oxide (NO) generation and inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were measured with assay kits and western blotting. β-secretase and β-secretase activities and β-amyloid levels were determined for measuring the anti-amyloidogenic effects of ent-Sauchinone by enzyme assay kits. NF-κB and STAT3 signals were detected with electromobility shift assay (EMSA) to study the related signaling pathways. The binding of ent-Sauchinone to STAT3 was evaluated by a pull-down assay and by a docking model using Autodock VINA software (Hoover's Inc., Texas, United states).Results: ent-Sauchinone (1, 5, and 10 μM) effectively decreased lipopolysaccharide (LPS)-(1 μg/ml) induced inflammatory responses through the reduction of ROS and NO generations and iNOS and COX-2 expressions in cultured astrocytes and microglial BV-2 cells. ent-Sauchinone also inhibited LPS-induced amyloidogenesis through the inhibition of β-secretase and β-secretase activity. NF- κB amyloid and STAT3, critical transcriptional factors regulating not only inflammation but also amyloidogenesis, were also inhibited in a concentration dependent manner by ent-Sauchinone by blocking the phosphorylation of I κB and STAT3 in cultured astrocytes and microglial BV-2 cells. The docking model approach showed that ent-Sauchinone binds to STAT3, and the employment of a STAT3 inhibitor and siRNA reversed ent-Sauchinone-induced inhibition NF-κB activation and Aβ generation.Conclusions: These results indicated that ent-Sauchinone inhibited neuroinflammation and amyloidogenesis through the inhibition of STAT3-mediated NF-κB activity, and thus could be applied in the treatment of neuro-inflammatory diseases, including Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Abundant research suggested that the cancer cells avoid destruction by the immune system through down-regulation or mutation of death receptors. Therefore, it is very important that finding the agents that increase the death receptors of cancer cells. In this study, we demonstrated that the snake venom toxin from Vipera lebetina turanica induce the apoptosis of colon cancer cells through reactive oxygen species (ROS) and c-Jun N-terminal kinases (JNK) dependent death receptor (DR4 and DR5) expression.Methods: We used cell viability assays, DAPI/TUNEL assays, as well as western blot for detection of apoptosis related proteins and DRs to demonstrate that snake venom toxin-induced apoptosis is DR4 and DR5 dependent. We carried out transient siRNA knockdowns of DR4 and DR5 in colon cancer cells.Results: We showed that snake venom toxin inhibited growth of colon cancer cells through induction of apoptosis. We also showed that the expression of DR4 and DR5 was increased by treatment of snake venom toxin. Moreover, knockdown of DR4 or DR5 reversed the effect of snake venom toxin. Snake venom toxin also induced JNK phosphorylation and ROS generation, however, pretreatment of JNK inhibitor and ROS scavenger reversed the inhibitory effect of snake venom toxin on cancer cell proliferation, and reduced the snake venom toxin-induced upregulation of DR4 and DR5 expression.Conclusions: Our results indicated that snake venom toxin could inhibit human colon cancer cell growth, and these effects may be related to ROS and JNK mediated activation of death receptor (DR4 and DR5) signals. [ABSTRACT FROM AUTHOR]