Currently there is no neuroprotective or neurorestorative therapy for Parkinson's disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous ...production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration of dopamine neurons and leads to behavioural recovery through CNTF receptor alpha (CNTFRα) on nigral dopamine neurons in both the MPP(+)-lesioned or adeno-associated virus α-synuclein rat models of Parkinson's disease. Western blot and immunohistochemical analysis of human post-mortem substantia nigra from Parkinson's disease suggests that this endogenous neuroprotective system (TRPV1 and CNTF on astrocytes, and CNTFRα on dopamine neurons) might have relevance to human Parkinson's disease. Our results suggest that activation of astrocytic TRPV1 activates endogenous neuroprotective machinery in vivo and that it is a novel therapeutic target for the treatment of Parkinson's disease.
Reducing the number of design changes in vehicle seat development is critical for minimizing both production cost and product lead time. Generally, discrepancies in measured dimensional ...specifications of vehicle-seat prototypes and computer-aided design (CAD) models cause significant quality control issues of the finished products. Although three-dimensional (3D) scanning technology enables the efficient evaluations and inspection processes of vehicle-seat prototypes, many evaluation processes require time-consuming tasks. This paper proposes an automated system for evaluating a geometrical consistency between a 3D scan of a prototype and the original CAD model. In the current study, the existing evaluation processes conducted by seat engineers were examined by survey questionnaires. The survey responses were analyzed to define a standardized evaluation process for the automated system. Various computational algorithms, including a function-based scan-to-CAD registration, standard seat dimension estimation, and template-based reporting algorithms, were developed to evaluate the scan and CAD consistency automatically. The developed system not only reduced over 99 % of the evaluation time (on average, existing method: > 2 hrs per seat and system method: < 5 min per seat) but also increased the repeatability of evaluations. Furthermore, the system can collect dimensions of diverse seat designs, prototypes, and products to construct a database of seat dimensions for benchmarking and design improvement.
Abstract Aims Basal insulin treatment is frequently used in type 2 diabetes, but the successful control of postprandial glucose is challenging. We compared the effect of preferential postprandial ...glucose targeting drugs for postprandial glucose control after optimizing fasting glucose with basal insulin. Methods This study was performed in 58, insulin naïve type 2 diabetes. After fasting glucose was optimized by insulin glargine, nateglinide or acarbose was initiated and then crossed over after second wash out period. 75 g oral glucose tolerance test and 7 point self monitoring blood glucose for 3days at the end of each period was performed. Results Both drugs effectively reduced postprandial glucose levels compared with the insulin glargine monotherapy. No significant differences were found between nateglinide and acarbose in terms of mean glucose level, standard deviation of glucose levels, mean average glucose excursion and average daily risk range. Homeostasis model analysis (HOMA)% β, corrected insulin response and insulin-to-glucose ratio were significantly higher in the responder group compared with the non-responder. There was no episode of severe hypoglycemia. Conclusions Nateglinide and acarbose are equally effective in type 2 diabetes for postprandial glucose excursions during basal insulin treatment. The markers of beta cell function might be used for predicting response. (Clinical trial reg. no. NCT 00437918 , clinicaltrail.gov.)
Background Renal infarction is a rare condition resulting from an acute disruption of renal blood flow, and the cause and outcome of renal infarction are not well established. Study Design Case ...series. Setting & Participants 438 patients with renal infarction in January 1993 to December 2013 at 9 hospitals in Korea were included. Renal infarction was defined by radiologic findings that included single or multiple wedge-shaped parenchymal perfusion defects in the kidney. Predictor Causes of renal infarction included cardiogenic (n = 244 55.7%), renal artery injury (n = 33 7.5%), hypercoagulable (n = 29 6.6%), and idiopathic (n = 132 30.1%) factors. Outcomes We used recurrence, acute kidney injury (AKI; defined as creatinine level increase ≥ 0.3 mg/dL within 48 hours or an increase to 150% of baseline level within 7 days during the sentinel hospitalization), new-onset estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (for >3 months after renal infarction in the absence of a history of decreased eGFR), end-stage renal disease (ESRD; receiving hemodialysis or peritoneal dialysis because of irreversible kidney damage), and mortality as outcome metrics. Results Treatment included urokinase (n = 19), heparin (n = 342), warfarin (n = 330), and antiplatelet agents (n = 157). 5% of patients died during the initial hospitalization. During the median 20.0 (range, 1-223) months of follow-up, 2.8% of patients had recurrent infarction, 20.1% of patients developed AKI, 10.9% of patients developed new-onset eGFR < 60 mL/min/1.73 m2 , and 2.1% of patients progressed to ESRD. Limitations This was a retrospective study; it cannot clearly determine the specific causal mechanism for certain patients or provide information about the causes of mortality. 16 patients were excluded from the prognostic analysis. Conclusions Cardiogenic origins were the most important causes of renal infarction. Despite aggressive treatment, renal infarction can lead to AKI, new-onset eGFR < 60 mL/min/1.73 m2 , ESRD, and death.
The status of neointimal coverage on the drug-eluting stent (DES) struts, which are placed across the side-branch vessels, remains unclear. The degree of neointimal coverage of stent struts crossing ...the side-branch vessel was evaluated according to the different types of DESs. Follow-up optical coherence tomography images at 9.3 months after the index procedure were identified in 51 patients who had undergone DES (sirolimus-eluting stents SESs in 22 patients, paclitaxel-eluting stents PESs in 15, and zotarolimus-eluting stents ZESs in 14) implantation with crossover of the side-branch vessels (size >2.0 mm). The enrolled patients were classified as a covered group if every unapposed strut showed neointimal coverage or an uncovered group if any struts lacked neointimal coverage. The neointimal hyperplasia thickness was also measured. The number of patients in the covered group was 15 (29%), with 36 patients in the uncovered group. Significant differences were found in the proportion of the covered group among the 3 DES types (6 27% of 22 with SESs, 1 7% of 15 with PESs, and 8 57% of 14 with ZESs; p = 0.011). The percentage of neointimal coverage in the overall stent struts was also significantly different among the 3 DES types (65% of 356 struts, 20% of 165 struts, and 83% of 143 struts for the SESs, PESs, and ZESs, respectively; p<0.001). The neointimal hyperplasia thickness in the PES group was significantly smaller than those of the ZES and SES groups (0.02 ± 0.02 mm vs 0.08 ± 0.06 mm and 0.04 ± 0.03 mm, respectively; p = 0.002). In conclusion, different patterns of neointimal coverage of the stent struts crossing the side branch vessels were observed according to the type of DES.
Abstract Objectives The authors aimed to evaluate the role of post-resuscitation electrocardiogram (ECG) in patients showing significant ST-segment changes on the initial ECG and to provide useful ...diagnostic indicators for physicians to determine in which out-of-hospital cardiac arrest (OHCA) patients brain computed tomography (CT) should be performed before emergency coronary angiography. Background The usefulness of immediate brain CT and ECG for all resuscitated patients with nontraumatic OHCA remains controversial. Methods Between January 2010 and December 2014, 1,088 consecutive adult nontraumatic patients with return of spontaneous circulation who visited the emergency department of 3 tertiary care hospitals were enrolled. After excluding 245 patients with obvious extracardiac causes, 200 patients were finally included. Results The patients were categorized into 2 groups: those with ST-segment changes with spontaneous subarachnoid hemorrhage (SAH) (n = 50) and those with OHCA of suspected cardiac origin group (n = 150). The combination of 4 ECG characteristics including narrow QRS (<120 ms), atrial fibrillation, prolonged QTc interval (≥460 ms), and ≥4 ST-segment depressions had a 66.0% sensitivity, 80.0% specificity, 52.4% positive predictive value, and 87.6% negative predictive value for predicting SAH. The area under the receiver-operating characteristic curves in the post-resuscitation ECG findings was 0.816 for SAH. Conclusions SAH was observed in a substantial number of OHCA survivors (25.0%) with significant ST-segment changes on post-resuscitation ECG. Resuscitated patients with narrow QRS complex and any 2 ECG findings of atrial fibrillation, QTc interval prolongation, or ≥4 ST-segment depressions may help identify patients who need brain CT as the next diagnostic work-up.
Abstract Objective Conduction disturbances are common in patients with aortic stenosis (AS). We investigated the incidence, reversibility, and prognosis of conduction disorders requiring permanent ...pacemaker (PPM) implantation in patients with degenerative AS after isolated aortic valve replacement (AVR). Methods This was a retrospective study conducted at a tertiary care center. We evaluated the incidence of conduction disturbances in patients who underwent isolated surgical AVR for AS between January 2005 and May 2015. Relevant clinical information was obtained from the patients’ medical records. Results We reviewed results of 663 patients with pathologically proven degenerative AS bicuspid aortic valve, n=285 (43.0%) who underwent isolated AVR mechanical valve, n=310 (46.8%). Patients’ mean age was 67.1±8.1 years, and 362 were male (54.6%). Immediate postoperative intraventricular conduction disorders occurred in 56 patients (8.4%), and atrioventricular block (AVB) occurred in 68 patients (10.3%). Ten patients with symptomatic second-degree or third- degree AVB underwent PPM implantation within 30 days of AVR. During the mean follow-up period of 1288 ± 1122 days, 64 patients (9.7%) developed irreversible conduction disorders (bundle branch block (BBB), n=24; and first degree AVB, n=42). Of the 10 patients requiring PPM, four remained PPM-dependent during follow-up. Beyond 30 days after AVR, one patient underwent PPM implantation for de novo conduction disturbance 44 months post-operatively. Conclusions After isolated AVR, PPM implantation for conduction disturbance is rare (n = 10/663, 1.5%). Isolated AVR for degenerative AS has a low risk of conduction disturbances during long-term follow-up.
Background The quality of life (QOL) of patients who survive early gastric cancer (EGC) is an area of increasing interest. Objective To compare the QOL and degree of worry of cancer recurrence in EGC ...patients who underwent endoscopic submucosal dissection (ESD) or surgery. Design Cross-sectional study. Settings A tertiary referral center. Patients A total of 565 patients with EGC who received ESD or surgery. Intervention Questionnaires. Main Outcome Measurements QOL was evaluated using the Short-form Health Survey and the European Organization for Research and Treatment of Cancer QOL questionnaires (QLQ-C30 and EORTC-QLQ-STO22). Mood disorders and the worry of cancer recurrence were estimated using the Hospital Anxiety and Depression Scale (HADS) and Worry of Cancer Scale, respectively. Results Questionnaires were completed by 55.7% of the ESD (137/246) and 58.9% of the surgery (188/319) patients. The surgery group had more QOL-related symptomatic and functional problems, including fatigue ( P = .044), nausea/vomiting ( P = .032), appetite loss ( P = .023), diarrhea ( P < .001), pain ( P = .013), reflux symptoms ( P = .005), eating restrictions ( P < .001), anxiety ( P = .015), taste impairment ( P = .011), and poor body image ( P < .001). The ESD group had significantly higher worry of cancer recurrence scores after adjusting for covariates, especially when visiting their physicians. The HADS results did not differ between the groups. Limitations Cross-sectional design. Conclusions Endoscopic treatment for EGC provides a better QOL, but stomach preservation might provoke cancer recurrence worries. Endoscopists should address this issue for relieving a patient’s concern of cancer recurrence during follow-up period after ESD. (Clinical trial registration number: WHO ICTRP KCT0000791.)
Summary Recently, it has been reported that SIRT1 and DBC1 may be involved in the development of tumors and predict poor survival in some cancers. However, their exact role is not clear. Therefore, ...we investigated the expression status and clinical significance of DBC1 and SIRT1 expression in breast carcinomas. We evaluated the immunohistochemical expression of DBC1, SIRT1, and p53 using a 3-mm core from 122 patients with breast cancer for tissue microarray. Positive expression of DBC1 and SIRT1 were seen in 71% and 67% of patients, respectively. In the patients with breast cancer, overall, expression of DBC1 and SIRT1 was significantly associated with distant metastatic relapse and shorter relapse-free survival and overall survival by univariate analysis. Tumor stage and DBC1 and SIRT1 expression were also independent prognostic factors by multivariate analysis. Among the patients who had received chemotherapy, DBC1 and SIRT1 expression was significantly associated with distant metastatic relapse and shorter survival by univariate analysis. DBC1 expression was also associated with distant metastatic relapse and shorter survival in patients who had received endocrine therapy, according to univariate and multivariate analysis. In conclusion, this study shows that expression of DBC1 and SIRT1 is a significant prognostic indicator for breast carcinoma patients.
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