Suppressor of cytokine signaling 6 (SOCS6) promotes mitochondrial fission via regulating DRP1 translocation.

Mitochondria are highly motile organelles that constantly undergo fission and fusion. Impairment of mitochondrial dynamics is associated with mitochondrial dysfunction and is frequently linked to the pathogenesis of neurodegenerative diseases and cancer. We have previously shown that biallelic inactivation of the suppressor of cytokine signaling 6 (SOCS6) gene is a frequent event in human gastric cancer. In this study, we recapitulated the event of SOCS6 loss using a Lentivirus-based knockdown approach, and demonstrated the linkage between SOCS6 depletion and the suppression of programmed cell death. SOCS6 promotes intrinsic apoptosis, with increased Bax conformational change, mitochondrial targeting, and oligomerization. Most importantly, SOCS6 is targeted to mitochondria and induces mitochondrial fragmentation mediated through an increase in DRP1 fission activity. Here, we show that SOCS6 forms complex with DRP1 and the mitochondrial phosphatase PGAM5, attenuates DRP1 phosphorylation, and promotes DRP1 mitochondrial translocation. Based on mutation analyses, SOCS6-mediated apoptosis is tightly coupled to its ability to induce mitochondrial fission. This study demonstrates an important role for SOCS6 in modulating mitochondrial dynamics and apoptosis.

Evaluation of the safety and bioactivity of purified and semi-purified glucoraphanin.

The anti-carcinogenic effects of broccoli have been attributed to sulforaphane, the hydrolysis product of glucoraphanin (GRP). Here we determined if purified GRP, in the absence of the plant-derived hydrolyzing enzyme myrosinase, could affect pulmonary and hepatic ethoxyresorufin O-deethylase (EROD) and/or NAD(P)H-quinone oxidoreductase 1 (NQO1) activity. Male F344 rats were administered semi-synthetic, semi-purified or purified GRP (240 mg/kg: 550 micromol/kg rat daily for 4 days) by gavage. Hepatic and pulmonary NQO1 activity increased ( approximately 20%), but not EROD. Varying doses of semi-purified GRP (30, 60, or 120 mg/kg rat daily for 4 days) again caused no change in EROD activity, although a dose-dependent increase in NQO1 was seen. Urinary excretion of mercapturic acids showed no difference between preparations, and recovery increased with decreasing dose. Histopathologic examination revealed no abnormal tissues other than cecum, where inflammation was dose dependent; mild at 120 mg/kg and severe at 240 mg/kg, a greatly supra-physiological dose. We conclude that GRP 30-60 mg/kg p.o. is safe and effectively enhances NQO1 in all tissues evaluated.

Improvement of practice performance in urological surgery via clinical pathway implementation.

The purpose of this study was to compare performance measurements to evaluate the effects of clinical pathway implementation on improving practice performances in urology. Since April 1997, a total of 18 clinical pathways have been created in the urology department. Of these clinical pathways, six were implemented for endoscopic surgery, and four and eight were for minor and major surgery, respectively. Eight prominent performance measurements, which were identified as representative indicators of the practice performances, were selected in endoscopic surgery, five in minor surgery, and 11 in major surgery. Between April 1997 and March 1999, 2,883 consecutive patients, who underwent endoscopic surgery, minor surgery, and major surgery, were evaluated herein. The treatment results for patients in the first and second years of clinical pathway implementation were compared to those from the year preceding the implementation. In endoscopic surgery, five of the eight performance measurements improved significantly in the first year of implementation. Notably, three of the five improved performances continued to improve in the second year. Similarly, in minor surgery, four of the five performance measurements improved significantly following 2 years. Finally, in major urological surgery, six of the 11 performance measurements also improved significantly after 1 year; four of which continued to improve during the second year. Therefore, we conclude that patient care, which is based on the implementation of clinical pathways, can improve practice performances and facilitate medical care.

Does the use of clinical paths improve the efficiency and quality of care under the case payment system for inguinal herniorrhaphy or transurethral prostatectomy?

BACKGROUND: We evaluated the effects of implementing clinical paths for both inguinal herniorrhaphy (IH) and transurethral prostatectomy (TURP) on the efficiency and quality of medical care under the case payment system. METHODS: Patients undergoing IH or TURP were treated using the guidelines for clinical paths under the case payment system (CPUCP). The results of treatment after implementation of CPUCP were compared with results for patients treated before implementation of CPUCP. We also compared results using eight quality indicators both before and after implementation of CPUCP. RESULTS: The post-CPUCP length of hospital stay decreased significantly in patients who underwent either IH (p < 0.001) or TURP (p = 0.008). The post-CPUCP total admission charges decreased (p = 0.001) by 7.5% in the IH group alone. Two quality indicators in the IH group and three quality indicators in the TURP group were significantly improved after implementation of CPUCP. The percentage of patients who completed treatment without deviation as recommended by the guidelines for CPUCP was about 60% in the IH group and about 70% in the TURP group. CONCLUSION: The results of this study indicate that the implementation of clinical paths under the case payment system for patients undergoing inguinal herniorrhaphy or transurethral prostatectomy can improve the efficiency and quality of medical care.

The implementation of clinical paths for six common urological procedures, and an analysis of variances.

OBJECTIVE: To evaluate the outcomes of treatment after implementing clinical paths for six common urological procedures, and analyse the variances from these paths. PATIENTS AND METHODS: The study comprised 1006 consecutive patients treated according to the recommendations of the clinical path for six common urological procedures; the results of treatment were compared with those from 1006 patients treated by the same physicians before implementing the clinical paths. Total admission charges were divided into five categories, i.e. operation and anaesthesia, laboratory, radiology, pharmacy and other. The differences in these five categories before and after implementation were determined; the variance data were also tracked and analysed. Five quality indicators were monitored during implementation and compared with the data before implementation. RESULTS: The mean length of hospital stay (LOS) and admission charges were significantly lower (P=0.03 and P<0.01) after implementation. The charges for laboratory, radiology, pharmacy and other were significantly decreased after the use of clinical paths. The common variations from the clinical paths were patient-related variance (33%) and discharge variance (26%). Variances affecting the LOS only or the admission charge only were more common than those affecting neither the LOS nor admission charges (both P<0.01), or both (both P<0.01). After implementation, the results of the five quality indicators were significantly improved and the number of patients with surgical complications was significantly reduced (P<0. 01), but the mortality and readmission rate did not increase. CONCLUSIONS: The implementation of clinical paths for six common urological procedures decreased the LOS, admission charges and surgical complications, and improved the quality of care. During implementation, variances can affect the LOS and/or admission charges.

Effects of implementation of 18 clinical pathways on costs and quality of care among patients undergoing urological surgery.

PURPOSE: We evaluated the effects on the costs and quality of care of implementation of 18 clinical pathways for urological operations. MATERIALS AND METHODS: From April 1997 to March 1998 patients undergoing 1 of 18 urological operations were treated according to clinical pathways. The outcomes in terms of length of hospital stay and admission charges of these patients were compared with those of patients treated between April 1996 and March 1997 before clinical pathways were implemented. We also selected 7 clinically relevant quality indicators to assess the quality of care before and after clinical pathway implementation. RESULTS: Of the 1,784 patients undergoing urological surgery from April 1997 to March 1998, 1,382 (77.5%) were treated according to 1 of the 18 clinical pathways. Before implementation 1,279 of 1,615 patients (79.2%) underwent these procedures. The length of hospital stay decreased from 5.5 to 4.9 days (p < 0.01) and the average hospital admission charges decreased by 12.9% (p < 0.01) after implementation. Five of the quality indicators, including the rate of surgical complications, were significantly improved after pathway implementation. The hospitalization rate was not affected (1.3 before versus 0.8% after implementation, p = 0.18). Variations from the clinical pathways occurred in 543 cases (39.3%) and affected the length of hospital stay only (11.6%) or the admission charge only (12.9%) more often than both (7.8%, p < 0.01) or neither (7.0%, p < 0.01). The most common variances in these patients were patient related (30.8%). CONCLUSIONS: Implementation of multiple clinical pathways in a urology department can improve urological practice by decreasing the length of hospital stay, admission charges and rate of surgical complications, and by improving the quality of care.

Use of a medical decision support system to improve the preoperative diagnosis of prostate cancer with pelvic lymph node metastases.

BACKGROUND: We evaluated the effects of a medical decision support system on the preoperative diagnosis of prostate cancer with pelvic lymph node metastases. METHODS: The preoperative accuracy of staging prostate cancer with pelvic lymph node metastasis by the prostate cancer expert system (PCES) for 43 patients was compared to the accuracy of staging performed by 2 urological attending physicians and 5 residents, to test the validity of the PCES. The effect of PCES consultation on physicians' staging for prostate cancer with pelvic lymph node involvement was evaluated. RESULTS: In the diagnosis of prostate cancer with pelvic lymph node metastasis, PCES was significantly more accurate than the two attending physicians alone (p = 0.042; p = 0.008). All the urological residents' diagnoses were significantly less accurate than those of the PCES. After PCES consultation, all the urological residents increased diagnostic specificity significantly. Most residents usually used PCES for consultation only after the attending physician or department asked for the results. CONCLUSION: Owing to an increased ability for preoperative diagnosis of prostate cancer with pelvic lymph node metastasis, as supported by the PCES, some unnecessary pelvic lymphadenectomies may be avoided.

Myocardial protection during aortocoronary bypass.

The authors analyze the results of 220 applications of internal cold cardioplegia in 136 patients with ischaemic heart disease, treated surgically by aortocoronary bypass. The operation was performed under neuroleptanalgesia and artificial circulation with hypothermia (27.9 +/- 0.2 degrees C) and haemodilution (24.9 +/- 0.3%). On the basis of clinical examination, electron microscopy of the myocardial ultrastructure, and investigation of the myocardial metabolism (contents of glucose, lactate, pyruvate, free fatty acids, catecholamines, and oxygen in arterial and venous blood flowing out of the myocardium), they come to the conclusion that internal cold cardioplegia efficiently protects the myocardium during aortocoronary bypass and secures favourable conditions for the development of anastomoses between coronary arteries and venous shunts.