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Purpose: To comparatively analyze the clinical characteristics of patients with ocular myasthenia gravis (OMG) referred to an ophthalmology clinic, according to anti-acetylcholine receptor antibody (AchR Ab)-seropositivity. Study design: Retrospective Cohort Study. Methods: Medical records of patients with OMG who presented to a tertiary eye care center between 2003 and 2020 were retrospectively reviewed. Demographics, ophthalmologic characteristics, response to medical treatment, presence of autoimmune thyroid disease and thyroid autoantibody were compared between the AchR Ab seropositive and seronegative groups. Results: A total of 130 patients with OMG were identified; among them, 46 patients (35.4%) had autoantibody against acetylcholine receptors. The mean age at symptom onset was 42.4 ± 18.9 years. There were no differences in mean age at symptom onset, gender ratio, and mean follow-up period between patients with seropositive and seronegative OMG. Graves ophthalmopathy was significantly more frequent in seronegative patients (p = 0.04), while thymic disease (p < 0.01) was more frequent in seropositive patients (p < 0.01). Among patients with seropositive OMG, 52.3% showed a good response to medical treatment, while only 31.4% of the seronegative patients were classified as good responders (p = 0.01). Thyroid dysfunction was found in 27.4% patients with OMG and the proportion of thyroid dysfunction was not different according to anti-acetylcholine receptor antibody-seropositivity. Conclusion: Seropositivity to acetylcholine receptor antibody is associated with a better response to medical treatment and lower risk of concomitant autoimmune thyroid disease in patients with OMG. [ABSTRACT FROM AUTHOR]

Transcranial focused ultrasound stimulation (tFUS) is an effective noninvasive treatment modality for brain disorders with high clinical potential. However, the therapeutic effects of ultrasound neuromodulation are not widely explored due to limitations in preclinical systems. The current preclinical studies are head‐fixed, anesthesia‐dependent, and acute, limiting clinical translatability. Here, this work reports a general‐purpose ultrasound neuromodulation system for chronic, closed‐loop preclinical studies in freely behaving rodents. This work uses microelectromechanical systems (MEMS) technology to design and fabricate a small and lightweight transducer capable of artifact‐free stimulation and simultaneous neural recording. Using the general‐purpose system, it can be observed that state‐dependent ultrasound neuromodulation of the prefrontal cortex increases rapid eye movement (REM) sleep and protects spatial working memory to REM sleep deprivation. The system will allow explorative studies in brain disease therapeutics and neuromodulation using ultrasound stimulation for widespread clinical adoption. [ABSTRACT FROM AUTHOR]

Background/aim: Small rectal neuroendocrine tumors (NETs) confined to the submucosa are endoscopically resectable. Because most rectal NETs are submucosal tumors, conventional endoscopic mucosal resection (cEMR) may not result in a complete resection. This study investigated whether modified EMRs, namely endoscopic submucosal resection with ligation (ESMR-L), EMR with precutting (EMR-P), and strip biopsy are superior to cEMR for achieving histologically complete resection (HCR) of rectal NETs. Methods: Medical records of 215 patients who were treated with endoscopic resections for rectal NETs between January 2011 and July 2019 were retrospectively enrolled. Of the patients, 110, 33, 29, and 43 underwent cEMR, ESMR-L, EMR-P, and strip biopsy, respectively. For each method, HCR and en bloc resection rates, procedure times, and complication rates were measured. Results: HCR was achieved with cEMR, EMR-P, ESMR-L, and strip biopsies for 74.5%, 90.9%, 93.1%, and 90.7% of cases, respectively. The HCR rate for cEMR was inferior to those of the modified EMRs (p = 0.045 for cEMR vs. EMR-P; p = 0.031 for cEMR vs. ESMR-L; p = 0.027 for cEMR vs. strip biopsy). Among the three modified EMRs, there was no significant difference in achieving HCR (p = 1.000). En bloc resection (p = 0.096) and complication rates (p = 0.071) were not significantly different among the four EMR methods, although EMR-P required the longest procedure time (p = 0.000). Conclusions: All three modified EMRs are superior to cEMR and are equally effective for achieving HCR of rectal NETs. [ABSTRACT FROM AUTHOR]

Background: The effect of renal replacement therapy (RRT) on the outcomes of severe acute kidney injury (AKI) after out-of-hospital cardiac arrest (OHCA) is uncertain. This study aimed to evaluate the association of RRT with 6-month mortality in patients with severe AKI treated with targeted temperature management (TTM) after OHCA.Methods: This was a retrospective analysis of a prospectively collected multicentre observational cohort study that included adult OHCA patients treated with TTM across 22 hospitals in South Korea between October 2015 and December 2018. AKI was diagnosed using the Kidney Disease: Improving Global Outcomes criteria. The primary outcome was 6-month mortality and the secondary outcome was cerebral performance category (CPC) at 6 months. Multivariate Cox regression analysis was performed to define the role of RRT in stage 3 AKI.Results: Among 10,426 patients with OHCA, 1373 were treated with TTM. After excluding those who died within 48 h of return of spontaneous circulation (ROSC) and those with pre-arrest chronic kidney disease, our study cohort comprised 1063 patients. AKI developed in 590 (55.5%) patients and 223 (21.0%) had stage 3 AKI. Among them, 115 (51.6%) were treated with RRT. The most common treatment modality among RRT patients was continuous renal replacement therapy (111 [96.5%]), followed by intermittent haemodialysis (4 [3.5%]). The distributions of CPC (1-5) at 6 months for the non-RRT vs. the RRT group were 3/108 (2.8%) vs. 12/115 (10.4%) for CPC 1, 0/108 (0.0%) vs. 1/115 (0.9%) for CPC 2, 1/108 (0.9%) vs. 3/115 (2.6%) for CPC 3, 6/108 (5.6%) vs. 6/115 (5.2%) for CPC 4, and 98/108 (90.7%) vs. 93/115 (80.9%) for CPC 5, respectively (P = 0.01). The RRT group had significantly lower 6-month mortality than the non-RRT group (93/115 [81%] vs. 98/108 [91%], P = 0.04). Multivariate Cox regression analyses showed that RRT was independently associated with a lower risk of death in patients with stage 3 AKI (hazard ratio, 0.569 [95% confidence interval, 0.377-0.857, P = 0.01]).Conclusion: Dialysis interventions were independently associated with a lower risk of death in patients with stage 3 AKI treated with TTM after OHCA. [ABSTRACT FROM AUTHOR]

Purpose: Targeted therapy using phosphatidylinositol 3-kinase (PI3K) inhibitors is used to treat cancer such as lymphoma. In animal studies, its use raised concern about alteration of glucose metabolism. To date, clinical data are inconclusive; therefore, we investigated the incidence and clinical manifestations of diabetes in cancer patients treated with PI3K inhibitors.Methods: In a retrospective review of diabetes-free patients with advanced solid tumors treated with PI3K inhibitor, we performed Cox regression to identify independent predictors for the development of diabetes.Results: Of 38 patients (mean age: 54.5 years, 23.7% female) having a mean duration of follow-up of 238.5 days who initiated PI3K inhibitors, 55.3% developed diabetes during treatment (mean 29.1 days); among these, 28.6% experienced remission of diabetes after discontinuing PI3K inhibitors (mean 72.1 days). Patients with incident diabetes had higher anti-hypertensive medication use, higher HbA1c levels and fasting glucose at baseline, and longer duration of PI3K inhibitor use (P = 0.024, P = 0.005, P = 0.008, and P = 0.023, respectively). Previous steroid use and lower baseline HbA1c level were significantly associated with development of diabetes (HR = 8.41, 95% CI 1.89-37.33; HR = 2.16, 95% CI 1.09-4.25, respectively). Patients whose diabetes remitted after discontinuing PI3K inhibitors were younger (P = 0.035) and had lower fasting glucose levels during PI3K inhibitor treatment (P = 0.001) compared to those non-remitters.Conclusions: Previous steroid use and lower baseline HbA1c level may be important predictors for developing diabetes in patients with advanced solid tumors treated with PI3K inhibitors, warranting close observation and careful intervention. [ABSTRACT FROM AUTHOR]

We surveyed the variation in perfluorinated compound (PFC) concentrations entering urban wastewater treatment plants and then designed an optimal PFCs treatment method based on a pilot test. The PFCs influent concentration was found to be affected by the types of industries and operating rate. The concentration of PFCs in the wastewater treatment effluent was slightly lower than that of the influent. Thus, PFCs had not been adequately removed by the existing biological treatments. The pilot test results showed that about 10% of PFCs was removed by coagulation and precipitation, and the ozone and chlorine test showed that few, if any, PFCs were removed regardless of the oxidant dose. The activated carbon adsorption test showed that the removal significantly increased with empty bed contact time, with about a 60% removal in five minutes and over 90% removal in over 15 minutes. Therefore, a more stable and higher PFCs removal would result from continuous oxidation processes, such as ozone and adsorption processes involving activated carbon, rather than a single biological treatment. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate whether the augmentation of CaP into the femoral head around the lag screw results in superior clinical and radiological outcomes of treatment of unstable trochanteric fractures using an intramedullary (IM) implant. Fifty-six consecutive patients with unstable trochanteric fractures who had been surgically treated with IM devices between 2014 and 2016 were prospectively reviewed and randomly divided into two groups based on the use of CaP degradable cements: 28 patients were assigned to the CaP group, while the other 28 patients were assigned to the control group (no use of CaP). Clinical evaluations and radiological analyses were conducted during a minimum of 2-year follow-up. No significant differences in the mean visual analogue scale for the hip pain scores and modified Harris Hip Scores were found between the CaP group and the controls at postoperative 2 months and 2 years. However, earlier walker ambulation was possible in the CaP group (10 ± 9 days) compared to the control group (13 ± 12 days) (P = 0.02). In radiological analysis, the CaP group showed significantly lower difference between tip-apex distance measured immediately after surgery and that measured at one-year follow-up compared to the control group (P = 0.012). No screw cut-out occurred in the CaP group, while one patient in the control group was reoperated for screw cut-out. The CaP augmentation into the femoral head around lag screw can reduce lag screw penetration, prevent screw cut-out beyond the femoral head, and facilitate early ambulation in elderly patients with unstable trochanteric fractures. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress occurs due to the excessive generation of cellular reactive oxygen species and antioxidant system dysfunction. The thioredoxin (TXN) system and TXN-domain-containing protein (TXNDC) family form networks maintaining the cellular reducing environment. Recently, the importance of these genes in the tumor environment has been emphasized.Aim: To investigate the clinical significance of TXNs and TXNDC family members in HCC.Methods: Genomic data from 367 hepatocellular carcinoma (HCC) patients who underwent hepatic resections were analyzed to determine genetic alterations in mRNA and protein levels between patients and healthy controls. In addition, functional enrichment and survival analyses were performed.Results: HCC patients were shown to have enhanced expression of TXN, TXNRD1, and TXNDC7/9/14 mRNA and protein compared with controls. In accordance with the survival analyses, strong associations were found that patients with TXN, TXNRD1, and TXNDC1/7/9 alterations were proven to have poor prognosis in overall survival. Moreover, gene set enrichment analysis and network analyses revealed that positive correlations were found in mRNA expression of TXN, TXNRD1, and TXNDC7/9 genes with upregulation of the tumor-promoting genes, specifically mTORC1, E2F targets, and Myc targets. On the other hand, elevated expressions of TXNIP and TXNDC11 genes were correlated with suppression of the above tumor-promoting genes.Conclusions: TXN system and TXNDC family gene panel obtained from the resected tissue of the HCC patients could be used to predict survival prognosis of HCC, and these genes could be considered as potential therapeutic targets for improving HCC survival. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical and radiological outcomes and chondral lesion change using individualized surgery for recurrent patellar dislocation.Methods: A total of 31 knees with recurrent patellar dislocation underwent surgery depending on individual pathologic abnormalities. Pathologic abnormalities including medial laxity, lateral tightness, increased tibial tuberosity (TT)-to-trochlear groove distance (>20 mm), and patella alta (Caton-Deschamps ratio >1.2) were evaluated in each patient. The abnormalities were corrected through medial patellofemoral ligament reconstruction, TT distalization, TT anteromedialization, and lateral retinacula release. The mean follow-up period was 33 months.Results: There was one recurrent case (3.2%), requiring additional surgery. The mean Kujala scores were significantly (P = 0.002) improved from 75.8 (SD 12.4) to 84.6 (SD 13.1). Tegner scores were significantly improved from 3.7 (range 1-9) to 5.4 (range 2-9) (P < 0.001), as were and visual analogue scale pain scores from 4.7 (SD 2.5) to 2.6 (SD 2.2) (P = 0.001). Caton-Deschamps ratio was significantly decreased from 1.1 (SD 0.2) to 0.9 (SD 0.1) (P < 0.001), regardless of TT distalization. Chondral lesions of the patella and trochlear groove were improved or maintained in 57.1 and 71.4% of patients, respectively.Conclusion: Individualized surgery in recurrent patellar dislocation was effective and safe with a low recurrence rate. However, the possibility of unintended patella baja, which might be related to post-operative anterior knee pain, should be considered.Level Of Evidence: IV. [ABSTRACT FROM AUTHOR]

Introduction: Sodium glucose co-transporter 2 (SGLT2) inhibitors, such as dapagliflozin, have demonstrated favorable effects in patients with type 2 diabetes (T2D). However, there are limited reports in the literature regarding the glucose-lowering effects of SGLT2 inhibitors in actual clinical settings.Methods: The post-marketing surveillance data from a longitudinal prospective study of 2007 patients with T2D who were prescribed dapagliflozin (10 mg/day) were analyzed (ClinicalTrials.gov, NCT02252224).Results: After 12 weeks of dapagliflozin treatment, glycated hemoglobin (HbA1c) and body mass index were significantly decreased (P < 0.001) from 8.1 ± 1.3% to 7.5 ± 1.2% and from 28.1 ± 4.4 to 27.6 ± 4.2 kg/m2, respectively. Both body weight and HbA1c were reduced in 67.7% of patients, and HbA1c was lowered in 75.1%. Younger age, male sex, shorter diabetes duration, higher baseline HbA1c and estimated glomerular filtration rate (eGFR), and having dapagliflozin as add-on therapy were associated with stronger HbA1c reductions after dapagliflozin use (all P < 0.05). Moreover, subgroup analysis of eGFR of subjects with renal hyperfiltration (eGFR ≥ 120 ml/min/1.73 m2) showed the largest reduction in glucose level (% change, − 9.5; 95% CI − 6.8 to − 12.3 for HbA1c; P < 0.001). Multivariable logistic regression analysis showed that recent T2D diagnosis and higher HbA1c at baseline in patients who received an add-on regimen of dapagliflozin were statistically significantly associated with a dapagliflozin response (all P < 0.05).Conclusions: Dapagliflozin provides benefits for glycemic control and body weight. Patients in a relatively early stage of the course of diabetes with renal hyperfiltration might be more suitable for and gain maximal benefit from dapagliflozin treatment.Trial Registration: ClinicalTrials.gov identifier, NCT02252224.Funding: AstraZeneca. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported increased levels of phosphate after cardiac arrest. Given the relationship between phosphate level and the severity of ischaemic injury reported in previous studies, higher phosphate levels may be associated with worse outcomes. We investigated the prognostic value of phosphate level after the restoration of spontaneous circulation (ROSC) in adult cardiac arrest patients.Methods: This study was a retrospective observational study including adult cardiac arrest survivors treated at the Chonnam National University Hospital between January 2014 and June 2017. From medical records, data regarding clinical characteristics, outcome at hospital discharge, and laboratory parameters including phosphate levels after ROSC were collected. The primary outcome was poor outcome at hospital discharge, defined as Cerebral Performance Categories 3-5.Results: Of the 674 included patients, 465 had poor outcome at hospital discharge. Serum phosphate level was significantly higher in patients with poor outcome than in those with good outcome (p < 0.001). Phosphate level was correlated with time to ROSC (r = 0.350, p < 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of 0.805 (95% confidence interval [CI], 0.777-0.838) for phosphate level. In multivariate analysis, a higher phosphate level was independently associated with poor outcome at hospital discharge (odds ratio, 1.432; 95% CI, 1.245-1.626; p < 0.001).Conclusions: A higher phosphate level after ROSC was independently associated with poor outcome at hospital discharge in adult cardiac arrest patients. However, given its modest prognostic performance, phosphate level should be used in combination with other prognostic indicators. [ABSTRACT FROM AUTHOR]

Objective: To obtain fundamental information for the standardization of herbal medicine in Korea.Methods: We analyzed the herbal medicine prescription data of patients at the Pusan National University Korean Medicine Hospital from March 2010 to February 2013. We used the Dongui-Bogam (Dong Yi Bao Jian) to classify prescribed herbal medicines.Results: The study revealed that the most frequently prescribed herbal medicine was 'Liuwei Dihuang Pill (LWDHP, 六味地黄丸)' which was used for invigorating 'Shen (Kidndy)-yin'. 'LWDHP' was most frequently prescribed to male patients aged 50-59, 60-69, 70-79 and 80-89 years, and 'Xionggui Tiaoxue Decoction (XGTXD, 芎归调血饮)' was most frequently prescribed to female patients aged 30-39 and 40-49 years. According to the International Classification of Diseases (ICD) codes, 'Diseases of the musculoskeletal system and connective tissue' showed the highest prevalence. 'LWDHP' and 'XGTXD' was the most frequently prescribed in categories 5 and 3, respectively. Based on the percentage of prescriptions for each sex, 'Ziyin Jianghuo Decoction (滋阴降火汤)' was prescribed to mainly male patients, and 'XGTXD' with 'Guima Geban Decoction (桂麻各半汤)' were prescribed to mainly female patients.Conclusion: This study analysis successfully determined the frequency of a variety of herbal medicines, and many restorative herbal medicines were identified and frequently administered. [ABSTRACT FROM AUTHOR]

Unrecognized endobronchial intubation frequently occurs after emergency intubation. However, no study has evaluated the effect of one-lung ventilation on end-tidal carbon dioxide (ETCO2) during cardiopulmonary resuscitation (CPR). We compared the hemodynamic parameters, blood gases, and ETCO2 during one-lung ventilation with those during conventional two-lung ventilation in a pig model of CPR, to determine the effect of the former on ETCO2. A randomized crossover study was conducted in 12 pigs intubated with double-lumen endobronchial tube to achieve lung separation. During CPR, the animals underwent three 5-min ventilation trials based on a randomized crossover design: left-lung, right-lung, or two-lung ventilation. Arterial blood gases were measured at the end of each ventilation trial. Ventilation was provided using the same tidal volume throughout the ventilation trials. Comparison using generalized linear mixed model revealed no significant group effects with respect to aortic pressure, coronary perfusion pressure, and carotid blood flow; however, significant group effect in terms of ETCO2 was found (P < 0.001). In the post hoc analyses, ETCO2 was lower during the right-lung ventilation than during the two-lung (P = 0.006) or left-lung ventilation (P < 0.001). However, no difference in ETCO2 was detected between the left-lung and two-lung ventilations. The partial pressure of arterial carbon dioxide (PaCO2), partial pressure of arterial oxygen (PaO2), and oxygen saturation (SaO2) differed among the three types of ventilation (P = 0.003, P = 0.001, and P = 0.001, respectively). The post hoc analyses revealed a higher PaCO2, lower PaO2, and lower SaO2 during right-lung ventilation than during two-lung or left-lung ventilation. However, the levels of these blood gases did not differ between the left-lung and two-lung ventilations. In a pig model of CPR, ETCO2 was significantly lower during right-lung ventilation than during two-lung ventilation. However, interestingly, ETCO2 during left-lung ventilation was comparable to that during two-lung ventilation. [ABSTRACT FROM AUTHOR]

Introduction: This 32-week, open-label, randomized, parallel-group, multinational trial aimed to compare the efficacy and safety of stepwise insulin intensification of biphasic insulin aspart 30 (BIAsp 30) relative to stepwise intensification of a basal–bolus regimen in insulin-naïve adults with type 2 diabetes (T2D) who continued pretrial treatment with metformin and sulfonylurea.Methods: Adults with T2D were randomized into one of two treatment arms for 32 weeks: (1) BIAsp 30 once daily (OD), with the possibility of stepwise treatment intensification up to BIAsp 30 three times daily (TID); (2) insulin glargine OD, with the possibility of stepwise treatment intensification with insulin aspart up to TID. The primary endpoint was change from baseline in HbA1c after 32 weeks.Results: After 32 weeks, the estimated mean change in HbA1c from baseline was statistically significantly lower in the BIAsp 30 arm (− 1.18%) versus basal–bolus (− 1.36%) [estimated treatment difference 0.18%; 95% confidence interval (95% CI) 0.01; 0.36; p < 0.05]. The proportion of patients with HbA1c below 7.0% was statistically significantly lower with BIAsp 30 (42.9%) compared with basal–bolus (56.9%) (odds ratio 0.58; 95% CI 0.37; 0.89; p = 0.01). The overall rate of severe or blood glucose (BG)-confirmed hypoglycemic events was numerically lower for BIAsp 30 compared with basal–bolus, and a statistically significantly lower rate in nocturnal severe or BG-confirmed hypoglycemia in the BIAsp 30 arm relative to basal–bolus was observed: estimated rate ratio 0.32 (95% CI 0.13; 0.79), p = 0.0131. The proportion of patients with adverse events was similar in both treatment arms.Conclusion: Insulin intensification with BIAsp 30 and basal–bolus showed an improvement in glycemic control; the change in HbA1c was statistically significantly lower for BIAsp 30 compared to basal–bolus. Basal–bolus treatment was accompanied by a numerically, and statistically significantly, higher rate of overall and nocturnal severe or BG-confirmed hypoglycemia, respectively, compared with BIAsp 30.Funding: Novo Nordisk A/S.Trial Registration: ClinicalTrials.gov identifier, NCT02453685. [ABSTRACT FROM AUTHOR]

The self-assembly of β-amyloid (Aβ) peptides into highly stable plaques is a major hallmark of Alzheimer's disease. Here, we report visible light-driven dissociation of β-sheet-rich Aβ aggregates into small, nontoxic fragments using ruthenium (II) complex {[Ru(bpy) 3 ] 2+ } that functions as a highly sensitive, biocompatible, photoresponsive anti-Aβ agent. According to our multiple analyses using thioflavin T, bicinchoninic acid, dynamic light scattering, atomic force microscopy, circular dichroism, and Fourier transform infrared spectroscopy, [Ru(bpy) 3 ] 2+ successfully disassembled Aβ aggregates by destabilizing the β-sheet secondary structure under illumination of white light-emitting diode light. We validated that photoexcited [Ru(bpy) 3 ] 2+ causes oxidative damages of Aβ peptides, resulting in the dissociation of Aβ aggregates. The efficacy of [Ru(bpy) 3 ] 2+ is attributed to reactive oxygen species, such as singlet oxygen, generated from [Ru(bpy) 3 ] 2+ that absorbed photon energy in the visible range. Furthermore, photoexcited [Ru(bpy) 3 ] 2+ strongly inhibited the self-assembly of Aβ monomers even at concentrations as low as 1 nM and reduced the cytotoxicity of Aβ aggregates. Statement of Significance Alzheimer’s disease is the most common progressive neurodegenerative disease, affecting more than 13% of the population over age 65. Over the last decades, researchers have focused on understanding the mechanism of amyloid formation, the hallmark of various amyloid diseases including Alzheimer’s and Parkinson’s. In this paper, we successfully demonstrate the dissociation of β-Amyloid (Aβ) aggregates into small, less-amyloidic fragments by photoexcited [Ru(bpy) 3 ] 2+ through destabilization of β-sheet secondary structure. We validated the light-triggered dissociation of amyloid structure using multiple analytical tools. Furthermore, we confirmed that photoexcited [Ru(bpy) 3 ] 2+ reduces cytotoxicity of Aβ aggregates. Our work should open a new horizon in the study of Alzheimer's amyloid aggregation by showing the potential of photoexcited dye molecules as an alternative therapeutic strategy for treating Alzheimer’s disease in future. [ABSTRACT FROM AUTHOR]

Purpose: Cough on anesthetic emergence should be prevented considering its dangerous complications. Target-controlled infusion (TCI) of remifentanil can reduce emergence cough effectively, and sex-related differences in effect-site concentration (Ce) of remifentanil have been evaluated in young patients. In this study, we determined the Ce of remifentanil for preventing emergence cough following extubation in male and female elderly patients and evaluated the sex-related difference. Patients and methods: Twenty-three male and 22 female elderly patients aged between 60 and 75 years were enrolled. Anesthesia was maintained with sevoflurane and remifentanil TCI. The Ce of remifentanil for preventing emergence cough was determined for each sex using isotonic regression method with a bootstrapping approach, following Dixon's up-and-down method. Results: The Ce of remifentanil for preventing emergence cough in 50% (EC50) and 95% (EC95) of the population was significantly lower in females than in males. Isotonic regression revealed the EC50 (83% confidence interval [Cl]) of remifentanil was 1.67 (1.55-1.83) ng/mL in females and 2.60 (2.29-2.91) ng/mL in males. The EC95 (95% Cl) of remifentanil was 2.30 (2.02-2.62) ng/mL in females and 3.41 (3.27-3.58) ng/mL in males. Dixon's up-and-down method indicated that the mean EC50 in females was lower than in males (1.56±0.26 ng/mL vs 2.56±0.37 ng/mL, P<0.001). Conclusion: The remifentanil requirement for preventing emergence cough was lower in female than in male elderly patients, indicative of sex-related differences in Ce of remifentanil. Sex should be considered when using remifentanil TCl for preventing emergence cough in elderly patients. [ABSTRACT FROM AUTHOR]

Background: Hydroxychloroquine (HCQ) retinopathy can accompany other retinal complications such as cystoid macular edema (CME), which leads to central visual loss. We report a case of CME with HCQ retinopathy that improved with the use of oral acetazolamide, and discussed the possible mechanisms of CME in HCQ retinopathy using multimodal imaging modalities.Case Presentation: A 62-year-old patient with systemic lupus erythematosus (SLE) and HCQ retinopathy developed bilateral CME with visual decline. Fluorescein angiography (FA) showed fluorescein leakage in the macular and midperipheral area. After treatment with oral acetazolamide (250 mg/day) for one month, CME was completely resolved, best corrected visual acuity (BCVA) improved from 20/50 to 20/25, and FA examination showed decreased dye leakage in the macular and midperipheral areas.Conclusions: In cases of vision loss in HCQ retinopathy, it is important to consider not only progression of maculopathy, but also development of CME, which can be effectively treated with oral acetazolamide. [ABSTRACT FROM AUTHOR]

Background: Obesity is a public health concern in many countries due to its increasing prevalence. Euiiyin-tang is an herbal medicine formula often used as a clinical treatment for obesity. It acts to eliminate humidity and purify the blood, the causes of obesity identified by the theoretical framework of Korean medicine. The purpose of this study is to evaluate the efficacy and safety of Euiiyin-tang in treating obesity.Methods/design: This study is a randomised, double-blinded and placebo-controlled, multicentre trial. It has two parallel arms: the Euiiyin-tang group and the placebo group. A total of 160 obese adult women will be enrolled in the trial. The participants will be randomly divided at a 1:1 ratio at visit 2 (baseline). The participants will be administered Euiiyin-tang or placebo for 12 weeks. The primary endpoint is the change in weight occurring between baseline and post-treatment. The secondary outcomes include average weight reduction, changes in body fat, waist and hip circumferences, body mass index, and lipid profile, and the results of questionnaires such as the Korean version of Obesity-related Quality of Life, the Korean version of Eating Attitudes Test, the Social Readjustment Rating Scale, and the Stress Reaction Inventory.Discussion: The present study will provide research methodologies for evaluating the efficacy and safety of Euiiyin-tang in patients with obesity. In addition, it will provide evidence of correlation between obesity and Sasang constitutional medicine.Trial Registration: ClinicalTrials.gov, NCT01724099 . Registered on 2 November 2012. [ABSTRACT FROM AUTHOR]

Aim Of the Study: Previous studies on the relationship between age and outcomes after cardiac arrest were performed in settings where the majority of patients died after the withdrawal of life support (WLS). We examined the association between age and outcomes of comatose cardiac arrest survivors in a setting where WLS was not performed.Methods: This single-centre retrospective observational study included adult comatose cardiac arrest survivors treated with targeted temperature management. In Korea, WLS is not permitted unless the patient is pronounced brain-dead. The primary outcome was poor neurologic outcome at hospital discharge, defined as Cerebral Performance Categories scores of 3-5. The secondary outcomes were in-hospital and six-month mortalities.Results: A total of 534 patients were analysed. In multivariate analysis, age was not associated with in-hospital mortality (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.99-1.02), but it was independently associated with neurologic outcome at hospital discharge (OR, 1.03; 95% CI, 1.02-1.05) and six-month mortality (OR, 1.05; 95% CI, 1.03-1.07). When age was categorised into 10-year intervals, age groups less than 61-70 years had significantly lower OR for poor neurologic outcome compared with the reference group (61-70 years), while the OR for poor neurologic outcome in age groups greater than 70 years did not differ from that in the reference group.Conclusion: In a setting where WLS is not performed, we found that age was not associated with in-hospital mortality but was independently associated with neurologic outcome at hospital discharge and six-month mortality. [ABSTRACT FROM AUTHOR]

Aim Of the Study: Studies examining associations between time to target temperature and outcomes in cardiac arrest patients who underwent targeted temperature management (TTM) have shown inconsistent results. We examined these associations separately for time from restoration of spontaneous circulation to TTM initiation (pre-induction time) and time from TTM initiation to target temperature (induction time). Furthermore, we examined whether critical time thresholds exist if there is an association.Methods: This was a single-centre retrospective observational study including adult cardiac arrest patients treated with TTM from 2008 to 2015. We tested the associations of pre-induction time and induction time with outcomes at hospital discharge using multivariate logistic regression analysis. We then performed additional multivariate analyses, each with the significant timing variable at different binary cutoffs.Results: A total of 515 patients were analysed. At hospital discharge, 357 patients (69.3%) were alive, of whom 161 (31.3%) had a favourable neurologic outcome. In multivariate analysis, a shorter pre-induction time was independently associated with a favourable neurologic outcome (odds ratio [OR], 1.110; 95% confidence interval [CI], 1.025-1.202), whereas the induction time was not (OR, 0.954; 95% CI, 0.852-1.067). We found two pre-induction time thresholds (120 and 360min) that were associated with neurologic outcome.Conclusion: We found that a shorter pre-induction time was independently associated with a favorable neurologic outcome at hospital discharge, whereas induction time was not. We also found two time thresholds at 120 and 360min, after which initiation of cooling was associated with a worse neurologic outcome. [ABSTRACT FROM AUTHOR]

Background: There has been no large-scale trial comparing endovascular treatment (add-on EVT) after intravenous tissue plasminogen activator (IV tPA) and IV tPA alone in acute ischemic stroke (AIS) caused by internal carotid artery occlusion (ICAO). We aimed at investigating the effectiveness and safety of add-on EVT after IV tPA in AIS patients with ICAO. Methods: Between March 2010 and March 2013, 3,689 consecutive ischemic stroke patients who were hospitalized within 4.5 h of onset were identified using a prospective stroke registry at 11 centers in Korea. Among them, patients with persistent ICAO after receiving IV tPA and whose 3-month modified Rankin Scale (mRS) was available were finally enrolled. A propensity score analysis with inverse-probability of treatment weighting was used to eliminate baseline imbalances between those receiving add-on EVT and IV tPA alone. Results: Among 264 patients enrolled in this study (mean age 71.4; male 56.4%; median National Institute of Health Stroke Scale score 15), 117 (44.3%) received add-on EVT. The add-on EVT group had a higher frequency of favorable outcome on the mRS ≤ 2 (35.0 vs. 18.4%; adjusted OR (aOR) 2.79; 95% CI 1.66-4.67) and lower mortality (17.9 vs. 35.4%; aOR 0.24; 95% CI 0.13-0.42) at 3 months, when compared to the IV tPA-alone group. Add-on EVT did not significantly increase the risk of symptomatic hemorrhage (5.1 vs. 4.1%; aOR 1.01; 95% CI 0.37-2.70). The rate of successful recanalization (thrombolysis in cerebral infarction grade ≥ 2b) in the add-on EVT group was 69.2%. Conclusions: Compared to an IV tPA alone, add-on EVT can improve clinical outcomes in patients with symptomatic ICAO within 4.5 h of onset without a significant increase of symptomatic hemorrhage. [ABSTRACT FROM AUTHOR]

Spleen tyrosine kinase ( SYK) is a cytosolic nonreceptor protein tyrosine kinase that mediates key signal transduction pathways following the activation of immune cell receptors. SYK regulates cellular events induced by the B-cell receptor and Fc receptors with high intrinsic activity. Furthermore, SYK has been regarded as an attractive target for the treatment of autoimmune diseases and cancers. Here, we report the crystal structures of SYK in complex with seven newly developed inhibitors (G206, G207, O178, O194, O259, O272, and O282) to provide structural insights into which substituents of the inhibitors and binding regions of SYK are essential for lead compound optimization. Our kinase inhibitors exhibited high inhibitory activities against SYK, with half-maximal inhibitory concentrations ( IC50) of approximately 0.7-33 n m, but they showed dissimilar inhibitory activities against KDR, RET, JAK2, JAK3, and FLT3. Among the seven SYK inhibitors, O272 and O282 exhibited highly specific inhibitions against SYK, whereas O194 exhibited strong inhibition of both SYK and FLT3. Three inhibitors (G206, G207, and O178) more efficiently inhibited FLT3 while still substantially inhibiting SYK activity. The binding mode analysis suggested that a highly selective SYK inhibitor can be developed by optimizing the functional groups that facilitate direct interactions with Asn499. Database The atomic coordinates and structure factors for human SYK are in the Protein Data Bank under accession codes (inhibitor-free form), (G206), (G207), (O178), (O194), (O259), (O272), and (O282). [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is the most common allergic inflammatory skin disease. The activation of innate immunity by house dust mite (Dermatophagoides farinae extract, DFE) allergen plays an important role in the pathogenesis of AD. We previously showed the inhibitory effect of an extract of Amomum xanthioides on allergic diseases, and isolated 1,2,4,5-tetramethoxybenzene (TMB) as a major active component. In this study, we investigated whether TMB relieves DFE-induced allergic inflammation symptoms. Methods: We established a DFE-induced allergic inflammation model in BALB/c mice by repeated skin exposure to DFE. To define the underlying mechanisms of action, we used a tu-mor necrosis factor-a and interferon-?-activated human keratinocytes (HaCaT cell line) and mouse keratinocytes (3PC cell line) cell line model. Results: Oral administration of TMB suppressed allergic inflammation symptoms, such as histopathological analysis and ear thickness, in addition to serum IgE, DFE-specific IgE and IgG2a levels. TMB decreased the serum histamine levels and tissue infiltration of inflammatory cells, including mast cells and eosinophils. TMB also inhibited CD4+IFN-γ+, CD4+IL-4+, and CD4+IL-17A+ lymphocyte expansion in the draining lymph nodes and expression of the Th2 cytokines in the ear tissue. TMB significantly inhibited the expression of cytokines and chemokines by the downregulation of the mitogen-activated protein kinases and nuclear factor of activated cytoplasmic T cells in HaCaT cells. Conclusions: TMB improved DFE-induced allergic inflammation by suppressing the production of proinflammatory cytokines and chemokines. Our results suggest that TMB might be a potential therapeutic agent for AD. [ABSTRACT FROM AUTHOR]

Aim Of the Study: We evaluated the influence of post-rewarming temperature management (PRTM) on post-rewarming fever development and determined the association between the temperature in the immediate post-targeted temperature management (TTM) period and outcomes.Methods: This retrospective observational study included consecutive adult cardiac arrest survivors treated with TTM from January 2008 to December 2013. Beginning in August 2010, our institution implemented a PRTM protocol involving continued use of temperature management device to maintain normothermia during the first 24h after rewarming. The outcomes were in-hospital mortality and neurologic outcome at discharge. We evaluated the effect on clinical outcomes of post-rewarming fever defined at a temperature over 38 °C within 48 h after rewarming.Results: Of 277 included patients, 55.2% underwent PRTM. The incidence of post-rewarming fever did not differ between the PRTM and no-PRTM groups (odds ratio [OR] 0.963, confidence interval [CI] 0.519, 1.787). Post-rewarming fever was associated with decreased in-hospital mortality (OR 0.243, CI 0.110, 0.534) and decreased rate of unfavorable neurologic outcome (OR 0.312, CI 0.182, 0.534). During 48 h following rewarming, mean temperature was 36.5 °C (36.2-36.8 °C), and peak temperature was 37.5 °C (36.8-38.1 °C). On multivariate analyses, lower mean temperature was associated with increased in-hospital mortality (OR 0.099, CI 0.037, 0.262) and unfavorable neurologic outcome (OR 0.071, CI 0.026, 0.193).Conclusion: It appeared that PRTM did not prevent post-rewarming fever development. Post-rewarming fever was associated with favorable outcomes while lower body temperature after rewarming was associated with unfavorable outcomes. Our results require further confirmation by larger prospective studies. [ABSTRACT FROM AUTHOR]

Objective Cilostazol, a phosphodiesterase 3, has been widely used in patients with arterial disease and is known to have additional beneficial effects on dyslipidemia. However, the effect of cilostazol on hepatic steatosis has not been fully elucidated. We investigated the effect of cilostazol on hepatic ABCA1 expression and hepatic steatosis in diet-induced obesity mice model. Methods Hepatic ABCA1 expression and lipid accumulation were analyzed in HepG2 cell lines treated with cilostazol. Male C57BL/6 mice were randomly divided into three groups: (1) fed normal chow diet with vehicle; (2) fed high-fat diet (HFD) with vehicle; (3) fed HFD with cilostazol. Cilostazol (30 mg/kg) was orally administered once daily for 9 weeks. Results Cilostazol significantly enhanced ABCA1 expression and restored ABCA1 expression reduced by palmitate in HepG2 cells. Cilostazol treatment ameliorated lipid accumulation induced by palmitate, and this effect was diminished when ABCA1 or LRP1 was silenced by small interference RNA. After silencing of LRP1, ABCA1 expression was decreased in HepG2 cells. Cilostazol significantly enhanced hepatic ABCA1 expression and decreased hepatic fat in HFD-fed mice. Hepatic expression of cleaved caspase-3 and PARP1 was also decreased in HFD-fed mice treated with cilostazol. Conclusions Cilostazol ameliorated hepatic steatosis and increased ABCA1 expression in the hepatocytes. Enhancing ABCA1 expression with cilostazol represents a potential therapeutic avenue for treatment of hepatic steatosis. [ABSTRACT FROM AUTHOR]

The article focuses on a research on 1,3,4-Thiadiazol-2-amine derivatives as urotensin-II receptor (UT) antagonists. It states that urotensin-II (U-II) is the most potent of all vasoconstrictors which involved in the regulation of cardiovascular functions. It mentions that replacement of the phenylurea group with aminobenzyl group was expected to provide an interaction with U-II receptor and synthesis is carried out of biological evaluation and structure-activity relationship (SAR) study.

The clear cell/lipid-rich change has been described in neuroendocine tumors in several organs, but rarely observed in the appendix. In this study, we describe the morphologic, immunohistochemical features of incidentally discovered appendiceal carcinoids entirely represented by clear cells in a 22-year-old man and a 52-year-old woman. Ultrastructual examination demonstrated abundant lipid droplets and dense core granules. The mechanism leading to lipid accumulation in the cytoplasm has not been discovered, but degenerative processes following recurrent inflammatory change might be considered. This uncommon variant of appendiceal classic carcinoid tumors may bear a superficial resemblance to goblet carcinoid and/or appendiceal metastases from clear cell carcinoma. Awareness of clear cell carcinoid of the appendix will prevent incorrect diagnosis and unnecessary aggressive management. [ABSTRACT FROM AUTHOR]

Platelet-rich fibrin (PRF) is nowadays often used in various fields, but no removal torque studies have yet been done to evaluate the effects of the platelet-rich fibrin on the bone integration at the initial healing period. An experimental study have been performed in rabbits to evaluate whether the complete PRF clots can accelerate the bone integration of implants at the initial healing period after creating bone defects in tibias. The effec t of the complete PRF clots on bone integration was studied in two rabbit groups, 4-week group (group A) and 6-week group (group B) after preparing bony defects. Artificial bony defects were prepared in the tibias of rabbits. The complete PRF clots was applied to the defects in the experimental group, whereas the defects were unfilled in the control group. Four weeks later, machined implants were installed into the rabbit tibias (group A). Six weeks after installation, the removal torque from nine rabbits was measured to examine the bone healing effect of PRF. In another rabbits (group B), 6 weeks after preparing bony defects, installation was performed, and another 6 weeks after installation, the removal torque from nine rabbits was measured. The authors found a positive significant effect of the complete PRF clots on bone integration (higher bone density) in group A installed at 4 weeks after preparing bony defects ( p = 0.008; t-test), but not in group B installed at 6 weeks after preparing bony defects ( p = 0.677). [ABSTRACT FROM AUTHOR]

Anti-inflammatory effects of glycosaminoglycan (GAG) derived from cricket (Gryllus bimaculatus, Gb) were investigated in a complete Freund’s adjuvant (CFA)-treated chronic arthritic rat model. This GAG produced a significant anti-edema effect as evidenced by inhibition of C-reactive protein (CRP) and rheumatoid factor, and interfered with atherogenesis by reducing proinflammatory cytokine levels of (1) vascular endothelial growth factor (VEGF) production in human umbilical vein endothelial cells (HUVEC), (2) interleukin-6, (3) prostaglandin E2-stimulated lipopolysaccharide in RAW 264.7 cells, and (4) tumor necrosis factor (TNF)-α production in normal splenocytes, in a dose-dependent manner. This GAG was also found to induce nitric oxide (NO) production in HUVEC cells and elevated endothelial nitric oxide synthase (eNOS) activity levels. Histological findings demonstrated the fifth lumbar vertebrae (LV) dorsal root ganglion, which was linked to the paw treated with Gb GAG, was repaired against CFA-induced cartilage destruction. Further, combined indomethacin (5 mg/kg)–Gb GAG (10 mg/kg) inhibited more effectively CFA-induced paw edema at 3 h and 2 or 3 d after treatment to levels comparable to only the anti-inflammatory drug indomethacin. Ultraviolet (UV)-irritated skin inflammation also downregulated nuclear factor κB (NFκB) activity in transfected HaCaT cells. Data suggest that the anti-inflammatory effects of GAG obtained from cricket (Gb) may be useful for treatment of inflammatory diseases including chronic arthritis. [ABSTRACT FROM PUBLISHER]

Aloe has been used in versatile herbal medications and nutraceuticals throughout history. Aloe is widely considered to be generally safe for humans and used globally. The effectiveness and pharmacological properties of aloe are dependent upon when the plant is collected. However, little is known about the toxicology of whole-body aloe collected within less than 1 yr. Based upon widespread exposure to aloe, it is important to determine a daily intake level of this chemical to ensure its safety for humans. To determine the no-observed-adverse-effect level (NOAEL) of baby aloe powder (BAP) for clinical application, Sprague-Dawley (SD) rats were treated orally for 4 wk with 4 different concentrations: 0, 0.125, 0.5, and 2 g/kg body weight (bw). In this study, no significant or dose-dependent toxicological effects of BAP were observed in biochemical or hematological parameters, urinalysis, clinical signs, body weight, and food and water consumption. There were changes in some biomarkers in certain treated groups compared to controls; however, all values were within their reference ranges and not dose-dependent. Based on these results, the NOAEL of BAP was estimated to be greater than 2 g/kg bw in male and 2 g/kg bw in female SD rats. Collectively, these data suggest that BAP used in this study did not produce any marked subacute toxic effects up to a maximum concentration of 2 g/kg bw, and thus use in nutraceuticals and in pharmaceutical and cosmetic applications at a concentration of >2 g/kg is warranted. [ABSTRACT FROM PUBLISHER]

Purpose: [F]Flumazenil, which has the advantage of a longer half-life than [C]flumazenil, is well known for determining of the central benzodiazepine receptor concentrations. However, [F]flumazenil has not been widely used because fluctuating and relatively low yields render automatic production insufficient for routine and multicenter clinical trials. Here, we describe the results of a 2.5-year production study of [F]flumazenil using an iodonium tosylate precursor, which allowed us to overcome the limitations of low and fluctuating radiochemical yields. Procedures: We developed a clinically applicable production system by modifying a commercial synthesizer for the reliable and reproducible production of [F]flumazenil for routine clinical studies. [F]Flumazenil was prepared at 150 °C for 5 min in the presence of 4-methylphenyl-mazenil iodonium tosylate (4 mg), a radical scavenger (TEMPO, 1 mg), and [F]KF/kryptofix 2.2.2 complex in N, N-dimethylformamide (1 ml). In the purification step, the final mixture was pretreated using different cartridges before performing high-performance liquid chromatography (HPLC) separation. Finally, we measured the radiochemical yield and performed quality-control assays on 94 batches. Results: After carrying out additional purification before HPLC separation using a C18 plus Sep-Pak cartridge, the radiochemical yield of [F]flumazenil increased from 34.4 ± 9.7 % (without the pretreatment, n = 24) to 53.4 ± 9.0 % ( n = 94), and the lifetime of the semi-preparative column was five times that of the column without the C18 plus Sep-Pak cartridge. The mean-specific activity of [F]flumazenil was 572 ± 116 GBq/μmol at the end of synthesis, and the radiochemical purity was more than 99 %, as determined by analytical HPLC and radio-TLC. [F]Flumazenil prepared using this method satisfied all quality-control test standards and was highly stable for up to 6 h after preparation. Conclusions: The results of the 2.5-year production study using an iodonium tosylate precursor indicate that [F]flumazenil has commercial and routine clinical applicability. [ABSTRACT FROM AUTHOR]

Amiodarone, bi-iodinated benzofuran derivative, is one of the most frequently prescribed and efficacious antiarrhythmic drugs. Despite its low incidence, amiodarone-induced pulmonary toxicity is of great concern and the leading cause of discontinuation. Autophagy is an essential homeostatic process that mediates continuous recycling of intracellular materials when nutrients are scarce. It either leads to a survival advantage or initiates death processes in cells under stress. In the present study, we investigated the role of autophagy in amiodarone-induced pulmonary toxicity. Amiodarone treatment–induced autophagy in H460 human lung epithelial cells and BEAS-2B normal human bronchial epithelial cells was demonstrated by increased LC3-II conversion, Atg7 upregulation, and autophagosome formation. Autophagic flux, as determined by the lysosomal inhibitor bafilomycin A1, was also increased following amiodarone treatment. To determine the role of autophagy in amiodarone toxicity, amiodarone-induced cell death was evaluated in the presence of 3-methyladenine or by knocking down the autophagy-related genes Atg7. Inhibition of autophagy decreased cellular viability and significantly increased apoptosis. Intratracheal instillation of amiodarone in rats increased the number of inflammatory cells recovered from bronchoalveolar lavage fluid, and periodic acid-Schiff-positive staining in bronchiolar epithelial cells. However, induction of autophagy by rapamycin treatment inhibited amiodarone-induced pulmonary toxicity. In conclusion, amiodarone treatment induced autophagy, which is involved in protection against cell death and pulmonary toxicity. [ABSTRACT FROM PUBLISHER]

Glycogen synthase kinase-3β (GSK-3β) plays an important role in the regulation of apoptosis. To investigate its involvement in acquired cadmium (Cd) resistance, Cd-resistant cells (RH460) were established from H460 lung carcinoma cells. Cd resistance led to interruption of apoptosis and autophagy, as determined by an apoptotic sub-G1 population, procaspase-3 clevage, and LC3-II induction. Cd-induced autophagy preceded apoptosis as determined by 3-methyladenine or zVAD and time-course experiments after Cd treatment. Despite β-catenin accumulation, phospho(p)-Ser/Tyr GSK-3α/β increased in the nucleus until 12h after treatment and then p-Ser partly translocated to the cytoplasm. The GSK-3 inhibitor lithium augmented Cd-induced p-Ser GSK-3α/β, which accumulated in the nucleus and cytoplasm, and increased autophagy. SB216763 inhibited p-Ser/p-Tyr GSK-3α/β and subsequent autophagy. GSK-3β knockdown decreased Cd-induced autophagy. Cd exposure to RH460 cells overexpressed with pcDNA-GSK-3β-HA strongly phosphorylated Ser9/Tyr216 residues and decreased LC3-II. Constitutively active pcDNA-GSK-3β(S9A)-HA overexpression phosphorylated Tyr216 and decreased LC3-II, suggesting that p-Tyr inhibits autophagy. PI3K inhibitors decreased Cd-induced p-Ser GSK-3αβ and LC3-II, whereas a Ser/Thr phosphatase inhibitor, okadaic acid, hyperphosphorylated Ser residues, which accumulated in the nucleus and cytosol, and enhanced LC3-II. The general tyrosine kinase inhibitor genistein suppressed Cd-induced p-Tyr/p-Ser GSK-3α/β and LC3-II. Mouse lung tissues respond to long-term Cd exposure increased p-Tyr, downregulated LC3-II, and accumulated full-length Bax and procaspase-3. Taken together, this study shows that acquired Cd resistance is regulated by GSK-3β phosphorylation state, but not activation state, and intracellular localization of p-Ser GSK-3 regulates Cd-induced autophagy and apoptosis. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? As most urologist known, obesity significantly lowers serum PSA levels. So there is some concern about delayed diagnosis of prostate cancer in obese men., In the present study, we found that the accuracy level of PSA for detecting prostate cancer was not significantly different between different obesity levels. A well-designed study adjusting for several factors, e.g. diet, exercise, medication and comorbidity, which may possibly compensate for the associated effects on PSA levels, is needed for confirmation of the present findings., Objective To investigate prostate-specific antigen ( PSA) accuracy in detecting prostate cancer according to body mass index ( BMI) in Asian men with a PSA level of <30 ng/mL using contemporary multicore (≥12) prostate biopsy., Patients and Methods We reviewed the records of 3471 patients, whose initial PSA levels were <30 ng/mL, who underwent multicore (≥12) transrectal ultrasound-guided prostate biopsy between January 2004 and May 2011., BMI was categorised as performed previously for the Asian population: <23, 23-24.9, 25-29.9, and ≥30 kg/m2. PSA accuracy for detecting prostate cancer in each BMI group was assessed based on the receiver operating characteristics-derived area under the curve., Results The mean age and median PSA level were inversely associated with BMI; the median PSA level in each BMI category was 7.84, 7.75, 7.33 and 5.79 ng/mL, respectively ( P < 0.001)., In all, prostate cancer was detected from biopsy in 1102 (31.7%) patients., The PSA accuracy for predicting prostate cancer in all patients was estimated to be 0.607, and PSA accuracies in each BMI category were 0.638, 0.572, 0.613 and 0.544, respectively; there was no significant difference among the groups in terms of PSA accuracy., Conclusions The accuracy of PSA in predicting prostate cancer did not change regardless of BMI category in Asian men., However, as patients with higher BMIs had lower PSA levels than those with lower BMIs, it can therefore be suggested that the PSA threshold should be lower in obese men to discriminate between prostate cancer and benign conditions in the real clinical situation. [ABSTRACT FROM AUTHOR]

A case is reported of unexplained unilateral thigh muscle atrophy and frequent falling with poor response to conventional conservative treatments in a patient with bipolar disorder who self-selected acupuncture treatment as a last resort. The patient experienced gradual improvements in lower extremity weakness and fewer falls during the 8-month treatment. No adverse event or aggravation of the bipolar disorder was observed. These outcomes suggest that acupuncture may be a feasible adjunct for reducing falling and restoring postural balances in patients with bipolar disorder. [ABSTRACT FROM AUTHOR]

Advanced malignant melanoma remains a challenging cancer. Over the past year, there have been 3 agents approved for treatment of melanoma by Food and Drug Administration. These include pegylated interferon alpha- 2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for treatment of unresectable or metastatic melanoma. This review will also update on the development of novel agents, including tyrosine kinase inhibitors and adoptive cellular therapy. [ABSTRACT FROM AUTHOR]

Abstract: Pathological angiogenesis is the most common cause of blindness at all ages including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Despite advances in therapy, retinopathy of prematurity remains the most sight-threatening vaso-proliferative retinopathy in children. Herein, we demonstrated that rosmarinic acid has an anti-angiogenic activity to retinal neovascularization in a mouse model of retinopathy of prematurity, which is related to cell cycle arrest with increase of p21WAF1. Rosmarinic acid significantly inhibited the proliferation of retinal endothelial cells in a dose-dependent manner, and inhibited in vitro angiogenesis of tube formation. Interestingly, the anti-proliferative activity of rosmarinic acid on retinal endothelial cells was related to G2/M phase cell cycle arrest in a dose-dependent manner. With treatment of rosmarinic acid, retinal endothelial cells in G2/M phase increased whereas those in G0/G1 and S phases decreased, which was accompanied by increase of p21WAF1 expression in a dose-dependent manner. Moreover, rosmarinic acid effectively suppressed retinal neovascularization in a mouse model of retinopathy of prematurity, and showed no retinal toxicity. These data suggest rosmarinic acid could be a potent inhibitor of retinal neovascularization and may be applied in the treatment of other vasoproliferative retinopathies. [Copyright &y& Elsevier]

Abstract: Aim of the study: Rehmannia glutinosa, the steamed root of the Scrophulariaceae family, has been widely used in Asian countries for the treatment of renal diseases. In this study, we evaluated the renoprotective effect of aqueous extract of Rehmannia glutinosa in progressive renal failure. Materials and methods: The effects of Rehmannia glutinosa on renal function, 24-h proteinuria, and the expression of angiotensin II, angiotensin II type 1 (AT1) receptor, TGF-β1, and type IV collagen in renal cortex were analyzed in progressive renal failure rats induced by 5/6 nephrectomy. Results: Rehmannia glutinosa reduced the serum creatinine level, 24-h urinary protein excretion, and glomerulosclerosis, and it also inhibited the expression of angiotensin II, AT1 receptor, TGF-β1 and type IV collagen in the renal cortex. Conclusions: These results suggest that the renoprotective effect of Rehmannia glutinosa might be mediated by suppressing the expression of angiotensin II and AT1 receptor and by regulating TGF-β1 and type IV collagen expression. [Copyright &y& Elsevier]

Objective: Primary Budd-Chiari syndrome (BCS) is a rare form of hepatic venous outflow obstruction at the suprahepatic inferior vena cava (IVC), the hepatic veins, or both. We assessed our 4-year experience in the management of BCS to evaluate the results of our methods of care. Methods: We conducted a retrospective review of a nonrandomized clinical trial conducted in three teaching hospitals. Among 28 primary BCS patients, 9 remained in medical treatment only, and 19 who failed to respond to medical treatment received additional endovascular (n = 17) or surgical therapy (n = 2). Nine underwent IVC balloon angioplasty alone, 6 had angioplasty plus stents, and 2 had transjugular intrahepatic portosystemic shunts (TIPS) for hepatic vein lesions. One patient had a mesoatrial bypass; another had liver transplantation. Immediate response to the therapy was assessed with angiography and ultrasonography based on anatomic and/or hemodynamic correction or reduction of the lesion. Subsequent assessment of portal hypertension status was made with periodic clinical and laboratory evaluation (eg, ultrasonography, liver biopsy). Results: Twenty-six patients had had IVC stenosis or occlusion by focal or segmental lesion. Two patients had hepatic vein outlet obstruction. There was no evidence of coagulopathy as the pathogenesis; all were related to membranous obstruction of the vena cava. Excellent immediate response to the endovascular therapy and subsequent relief of portal hypertension were achieved in 14 patients. Four patients had restenosis or progression of the residual lesion within 2 years; three responded to repeated stenting. Primary patency was 76.5%, and primary assisted patency was 94.1%. Two patients with TIPS and two with surgical therapy maintained excellent results. The medical treatment remained effective only in a limited group of 6 (21.4%) of the 28 patients. Conclusions: In BCS, both endovascular and surgical interventions provide excellent results and potentially halt liver parenchymal deterioration caused by portal hypertension. Liver transplantation remains the ultimate solution for advanced liver failure. [Copyright &y& Elsevier]

The article presents a case study of a 23-year-old male patient who was admitted due to aggravated psychotic symptoms, auditory hallucination and paranoid delusions. The patient was diagnosed with schizophrenia after mental status examination and was given risperidone six milligrams (mg) and increased to 8 mg, which improved his condition.The authors suggest the efficay of resperidone augmentation with amisulpride even without antipsychotics discontinuation or replacement of other neuroleptics.

Integrin αvβ3 is a molecular marker for the estimation of tumor angiogenesis and is an imaging target for radiolabeled Arg-Gly-Asp (RGD) peptides. In this study, the authors investigated the clinical efficacy and safety of a novel radiolabeled RGD peptide, 99mTc-IDA-D-[c(RGDfK)]2, for the imaging of integrin αvβ3 expression, as a measure of tumor angiogenesis in lung cancers and brain tumors. Five patients with lung cancers and seven with brain tumors underwent 99mTc-IDA-D-[c(RGDfK)]2 single-photon emission computed tomography (SPECT) imaging. Tumors were also assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Uptake of the radiotracer was expressed as the tumor-to-normal uptake ratio (TNR). All the lung cancers and brain tumors were well visualized on 99mTc-IDA-D-[c(RGDfK)]2 SPECT. TNR for 99mTc-IDA-D-[c(RGDfK)]2 was significantly higher than that for 18F-FDG in brain tumors (6.4 ± 4.1 vs. 0.9 ± 0.4). Proliferation index of brain tumors showed a significant positive correlation with TNR for 99mTc-IDA-D-[c(RGDfK)]2 and 18F-FDG. No laboratory and clinical adverse events were reported after 99mTc-IDA-D-[c(RGDfK)]2 injection. Their results suggest that 99mTc-IDA-D-[c(RGDfK)]2 is an efficacious and safe radiotracer for imaging integrin αvβ3 expression with potential application to monitoring the clinical efficacy of antiangiogenic agents in malignant tumors. In addition, this is the first clinical application of radiolabeled RGD peptides for SPECT imaging of brain tumors. [ABSTRACT FROM AUTHOR]

Abstract: Previous scientific research has elucidated the correlation between changes in levels of the DNA base excision repair protein, apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1), and ischemic neuronal DNA damage. However, to date, no studies have addressed the question of whether treatment involving this protein''s repair function may prevent ischemic neuron death in vivo. Therefore, we aimed to investigate whether treatment with APE peptide is sufficient to prevent neuron death after ischemia/reperfusion (I/R) in mice. Mice were subjected to intraluminal suture occlusion of the middle cerebral artery for 1h followed by reperfusion. Post-ischemic treatment with the peptide containing only the APE repair functional domain was introduced intracerebroventricularly. Endonuclease activity assay and immunohistochemistry were performed. Assays of apurinic/apyrimidinic (AP) sites, single-strand DNA breaks, caspase-3 activity, and cell death were examined and quantified. We found that post-ischemic administration of the APE peptide up to 4h after reperfusion significantly inhibited the induction of cell death and subsequent infarct volume, measured 24h after I/R. [Copyright &y& Elsevier]

Acetaminophen (APAP)-induced liver injury (AILI) is initiated by the generation of a reactive metabolite and ultimately leads to hepatocyte necrosis. Necrotic cells secrete damage-associated molecular patterns that activate hepatic nonparenchymal cells and induce an inflammatory response. Fetuin-A is a hepatokine with reported involvement in low-grade inflammation in many diseases, due to acting as an endogenous ligand for TLR4. However, little is known about the role of fetuin-A in AILI. In this study, we showed that fetuin-A is involved in the aggravation of hepatotoxicity during the initial phase of AILI progression. Treatment with APAP increased the expression and serum levels of fetuin-A in mice. Fetuin-A upregulated transcription of pro-inflammatory cytokines and chemokines through activation of TLR4 and also increased monocyte infiltration into the liver, leading to necroinflammatory reactions in AILI. However, these reactions were attenuated with the silencing of fetuin-A using adenoviral shRNA. As a result, mice with silenced fetuin-A exhibited less centrilobular necrosis and liver injury compared to controls in response to APAP. In conclusion, our results suggest that fetuin-A is an important hepatokine that mediates the hepatotoxicity of APAP through production of chemokines and thus regulates the infiltration of monocytes into the liver, a critical event in the inflammatory response during the initial phase of AILI. Our results indicate that a strategy based on the antagonism of fetuin-A may be a novel therapeutic approach to the treatment of acetaminophen-induced acute liver failure. [ABSTRACT FROM AUTHOR]

Due to the emergence of multidrug-resistant and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis , new antituberculosis drugs are urgently required to improve the efficacy of current tuberculosis (TB) treatment. To achieve this goal, ca. 1000 chemical compounds were screened for potential antimycobacterial activity, among which methyl 5-(2-diethylaminoethoxy)-7,12-dioxo-7,12 dihydrodinaphtho[1,2- b ;2′,3′- d ]furan-6-carboxylate (DNF-3) showed strong activity against all of the tested drug-susceptible and -resistant M. tuberculosis strains, with 50% minimum inhibitory concentrations (MIC 50 values) of 0.02–0.39 µg/mL both in culture broth and within murine RAW 264.7 macrophage cells. When DNF-3 was used in combination with rifampicin or streptomycin, it exhibited direct synergy against XDR-TB and an additive effect against M. tuberculosis H37Rv. DNF-3 displayed a long post-antibiotic effect (PAE) that was comparable with rifampicin but was superior to isoniazid, streptomycin and ethambutol. Importantly, DNF-3 showed no cytotoxicity to any cell line tested, with a selectivity index (SI) of >32. DNF-3 was also active against 27 nontuberculous mycobacteria (NTM) strains, Staphylococcus spp. and Streptococcus spp. Taken together, these results indicate that DNF-3 is a promising new candidate drug for treating TB. Further studies are warranted to establish the in vivo effect and therapeutic potential of DNF-3. [ABSTRACT FROM AUTHOR]

Background: From the viewpoint of cardiac pump theory, the area of the left ventricle (LV) subjected to compression increases as the LV lies closer to the sternum, possibly resulting in higher blood flow in patients with LV closer to the sternum. However, no study has evaluated LV position during cardiac arrest or its relationship with haemodynamic parameters during cardiopulmonary resuscitation (CPR). The objectives of this study were to determine whether the position of the LV relative to the anterior-posterior axis representing the direction of chest compression shifts during cardiac arrest and to examine the relationship between LV position and haemodynamic parameters during CPR.Methods: Subcostal view echocardiograms were obtained from 15 pigs with the transducer parallel to the long axis of the sternum before inducing ventricular fibrillation (VF) and during cardiac arrest. Computed tomography was performed in three pigs to objectively observe LV position during cardiac arrest. LV position parameters including the shortest distance between the anterior-posterior axis and the mid-point of the LV chamber (DAP-MidLV), the shortest distance between the anterior-posterior axis and the LV apex (DAP-Apex), and the area fraction of the LV located on the right side of the anterior-posterior axis (LVARight/LVATotal) were measured.Results: DAP-MidLV, DAP-Apex, and LVARight/LVATotal decreased progressively during untreated VF and basic life support (BLS), and then increased during advanced cardiovascular life support (ACLS). A repeated measures analysis of variance revealed significant time effects for these parameters. During BLS, the end-tidal carbon dioxide and systolic right atrial pressure were significantly correlated with the LV position parameters. During ACLS, systolic arterial pressure and systolic right atrial pressure were significantly correlated with DAP-MidLV and DAP-Apex.Conclusions: Left ventricular position changed significantly during cardiac arrest compared to the pre-arrest baseline. LV position during CPR had significant correlations with haemodynamic parameters. [ABSTRACT FROM AUTHOR]

Objective: Methotrexate is an alternative treatment for tubal pregnancy. However, despite initial treatment, ∼15% of women eventually require surgery. This study aimed to identify the risk factors for medical treatment failure in tubal pregnancy and apply them to a risk prediction model.Study Design: This single-center retrospective cohort study included 123 participants initially treated medically for tubal pregnancy between January 2006 and December 2015. Logistic regression analysis was used to construct a risk prediction model (visually presented as a nomogram) for medical treatment failure. Model performance was assessed using discrimination and calibration. The medical treatment failure rate was 36.6%. The prediction model integrated the presence of a gestational sac, ectopic mass size, and follow-up β-human chorionic gonadotropin levels above cut-off values on days 4 and 7. The model used the following cut-off values: increased β-human chorionic gonadotropin levels by 1028.6 mIU/mL, 1.0457-fold higher than baseline level on day 4; and increased β-human chorionic gonadotropin levels by 1233 mIU/mL, 1.3025-fold higher than baseline level on day 7.Results: The corresponding areas under the receiver-operating characteristic curves were 0.8135 (95% confidence interval, 0.733-0.893) for the day 4 model and 0.8600 for the day 7 model (95% confidence interval, 0.788-0.932). Comparison of the day 4 and 7 models revealed no significant difference in their predictive abilities (P = 0.4318).Conclusions: This model identified a substantial proportion of the participants who experienced medical treatment failure for tubal pregnancy. It was visualized as a nomogram, facilitating clinical application. [ABSTRACT FROM AUTHOR]