T-maze learning, spontaneous activity and food intake recovery following systemic administration of the noradrenaline neurotoxin, DSP4

Following systemic administration of the noradrenaline (NA) neurotoxin, DSP4 (50 mg/kg), rats were found to be retarded in the rate at which they acquired the "right-turn" running response in a modified T-maze choice situation, as measured by the total number of errors per session and median latency to reach the goal box. Desipramine (DMI, 20 mg/kg), injected 30 min before DSP4 blocked the acquisition retardation. DSP4 was found to have a short-lasting effect upon spontaneous motor activity, while food and water intake recovery was complete within 7 days of the injection. Both the NA-accumulation data and endogenous NA concentrations indicated profound NA, but not 5-hydroxytryptamine (5-HT) and dopamine (DA), depletions in the cortex, hippocampus and cerebellum. These data seem to confirm the role of the locus coeruleus-noradrenaline (LC-NA) system in an instrumental learning situation.     

伤科洗方熏洗治疗软组织损伤的临床研究

目的：为了验证伤科洗方的最佳熏洗组合，改进伤科洗方剂型，探讨伤科洗方治疗软组织损伤的部分作用机理。方法：以本院门诊和住院软组织损伤病例120例被随机均分为6组，其中4个试验组(A组：熏洗时间30分 酒 浓缩剂；B组：熏洗时间30分 醋 散剂；C组：熏洗时间60分 酒 散剂；D组：熏洗时间60分 醋 浓缩剂。)和1个空白对照组(E组0．9％生理盐水)，1个最佳熏洗组合组(F组：由试验组得出)；试验组采用3因素2水平正交设计，分别进行熏洗治疗，每日1次，每连续7天为1个疗程，治疗后分别观察症状和体征，6—酮—前列腺素F1a和血栓素B2的变化。结果：最佳熏洗组合：熏洗时间60分 酒 浓缩剂，浓缩剂优于散剂；结论：伤科洗方治疗软组织损伤有临床效果。     

儿科重症监护病房中影响机械通气成功的相关因素

目的 探讨儿科重症监护病房(PICU)中影响机械通气成功的相关因素。方法 将lll例行机械通气的危重病儿分成治疗成功组与失败组，对其相关因素进行回顾性分析。结果两组患儿在上机前危重病例评分、是否伴有心跳呼吸骤停和(或)休克及并发多系统器官功能衰竭(MODS)等方面差异有权显著意义(P＜0．001)；超过48h的机械通气患儿是否继发呼吸机相关肺炎(VAP)亦有显著意义(P＜0.05)。结论 PICU中影响机械通气成功率的因素主要是原发病的性质及严重程度，并与MODS与VAP有密切关系。     

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.     

MYC amplification and polysomy 8 in chondrosarcoma: array comparative genomic hybridization, fluorescent in situ hybridization, and association with outcome.

PURPOSE: To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion. Materials and METHODS: Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation. RESULTS: Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance. CONCLUSION: MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.     

ROLE OF INTERMEDIARY BIOMARKERS IN DETERMINING THE ANTICANCER EFFICACY OF MARINE COMPOUNDS

In the present study, two of the probable an umor marine compounds, manzamine A and sarcophine, were screened using benzo[a]pyrene (BP)-derived DNA adduct formation in MCF-7 cells as intermediary biomarker. Briefly, MCF-7 cells were treated with the compounds for 24 h followed by treatment with BP (0.5 μM). After 24h incubation, cellular DNA was isolated and analyzed for BP-derived DNA adducts by ³²P-postlabeling technique. Manzamine A and sarcophine increased the BP-DNA adducts by 2 to 4-folds. Further, manzamine A (50 μM) substantially down regulated the expression of p53 while sarcophine (50 μM) slightly induced the level of p21. The residual DNA repair ability was almost completely abolished by manzamine A while sarcophine was ineffective. Based on our preliminary results, these compounds may be classified as potential genotoxic.     

Modifiable Factors to Decrease the Cost of Robotic-Assisted Procedures

In 2000, the US Food and Drug Administration approved the da Vinci Surgical System® for use in the United States. Since that time, the number of surgical robotic systems throughout the United States has continued to grow. The costs for using the system include the initial purchase ($1 million to $2.3 million) plus annual maintenance fees ($100,000 to $150,000) and the cost of limited-use or disposable instruments. Increasing the number of procedures that are performed using the robotic system can decrease the per-procedure costs. Two modifiable factors that contribute to increasing the annual caseload are increasing the number of surgeons capable of using the system and having a properly educated perioperative nursing team. An educated surgical team decreases turnover time, facilitates proper flow of each surgical procedure, and is able to actively and passively solve intraoperative problems.     

The effect of near‐peer tutoring on medical students' performance in anatomical and physiological sciences

Healthcare professional schools across the world are implementing near‐peer tutoring (NPT) programs owing to numerous benefits to both tutors and tutees. This study determined whether higher attendance at NPT sessions led to improvements in course grades for high and low performing students. Fourth‐year medical students used the USMLE Step 1 question format to tutor first‐year medical students during the second half of the Structure and Function (SF) module, i.e., SF2. Attendance was recorded and students were accordingly divided into three groups: high, moderate, and low‐no attendance. Students’ performances in SF1 and SF2 were compared using Student's t‐test. Differences among the three groups were analyzed using ANOVA and Scheffé post hoc test (P< 0.05). Students who earned 70–79% (C) in SF1 were further examined on the basis of their attendance rate and performance in SF2. Those who attended three or more sessions completed a survey evaluating the NPT program. Course grades were significantly higher in SF2 than SF1 for all students, regardless of attendance rate. However, students who received a C grade in SF1 and had high or moderate attendance improved significantly in their SF2 course grade. Most students agreed that the NPT program was valuable and they evaluated the tutors highly. They also agreed that NPT prepared them for course exams and Step 1, but did not reduce anxiety and stress about Step 1. The positive effect of the NPT program resulted in its expansion to include all first‐year modules. Clin. Anat. 30:922–928, 2017. © 2017 Wiley Periodicals, Inc.