Ketamine-induced ulcerative cystitis and bladder apoptosis involve oxidative stress mediated by mitochondria and the endoplasmic reticulum.

Ketamine abusers develop severe lower urinary tract symptoms. The major aims of the present study were to elucidate ketamine-induced ulcerative cystitis and bladder apoptosis in association with oxidative stress mediated by mitochondria and the endoplasmic reticulum (ER). Sprague-Dawley rats were distributed into three different groups, which received normal saline or ketamine for a period of 14 or 28 days, respectively. Double-labeled immunofluorescence experiments were performed to investigate tight junction proteins for urothelial barrier functions. A TUNEL assay was performed to evaluate the distribution of apoptotic cells. Western blot analysis was carried out to examine the expressions of urothelial tight junction proteins, ER stress markers, and apoptosis-associated proteins. Antioxidant enzymes, including SOD and catalase, were investigated by real-time PCR and immunofluorescence experiments. Ketamine-treated rats were found to display bladder hyperactivity. This bladder dysfunction was accompanied by disruptions of epithelial cadherin- and tight junction-associated proteins as well as increases in the expressions of apoptosis-associated proteins, which displayed features of mitochondria-dependent apoptotic signals and ER stress markers. Meanwhile, expressions of mitochondria respiratory subunit enzymes were significantly increased in ketamine-treated bladders. Conversely, mRNA expressions of the antioxidant enzymes Mn-SOD (SOD2), Cu/Zn-SOD (SOD1), and catalase were decreased after 28 days of ketamine treatment. These results demonstrate that ketamine enhanced the generation of oxidative stress mediated by mitochondria- and ER-dependent pathways and consequently contributed to bladder apoptosis and urothelial lining defects. Such oxidative stress-enhanced bladder cell apoptosis and urothelial barrier defects are potential factors that may play a crucial role in bladder overactivity and ulceration.

Clinical learning environment measurement for medical trainees at transitions: relations with socio-cultural factors and mental distress.

BACKGROUND: Measuring clinical learning environment is crucial for the quality improvement of medical education, especially for medical trainees at transition stages. Medical education in Taiwan is shaped by multiple socio-cultural influences. The aims of this study were to construct an instrument for measuring clinical learning environment in alignment with the local socio-cultural factors and medical training settings, and further investigate the relationship between the quality of the clinical learning environment and the status of mental distress among medical trainees. METHODS: Participants consisted of 189 medical trainees (62 interns, 52 postgraduate year one (PGY1) residents, and 75 senior residents). Instruments included a designed 40-item Clinical Learning Environment Questionnaire (CLENQ) and a five-item Brief Symptoms Rating Scale (BSRS-5) for evaluating mental distress. Constructs of CLENQ were examined using factor analysis. Correlations were calculated between BSRS-5 and CLENQ across the three levels of medical trainees. RESULTS: Factor analysis of CLENQ yielded five factors- I: Teaching (13 items), II: Workload (7 items), III: Relationship pressure (9 items), IV: Organisational support (4 items) and V: Mutual trust (6 items). Intern trainees reported the lower total CLENQ scores in comparison to PGY1 and senior resident trainees. Mental distress using BSRS-5 was negatively correlated with total CLENQ scores and several key factors in all three groups. CONCLUSIONS: Our study using CLENQ has identified five major factors of clinical learning environment that are closely linked with our local socio-cultural factors and medical training settings. Medical trainee's mental distress status was negatively correlated with the quality of CLENQ. These findings have socio-cultural relevance and medical contextual significance and might be applicable to other countries. It warrants further study to investigate the impact of clinical learning environment improvement on the medical trainee's mental distress and performance.

Effects of supraphysiological testosterone treatment and orchiectomy on ischemia/reperfusion-induced bladder dysfunction in male rabbits.

INTRODUCTION: The roles of testosterone and orchiectomy on male bladder subjected to ischemic/reperfusion (I/R) injuries received little attention. To fill this gap, the present study intended to examine testosterone and orchiectomy effects on male rabbits subjected to I/R damages. AIM: To elucidate the effects of testosterone and orchiectomy on contractile response, bladder morphology, interstitial fibrosis, and oxidative stress in male rabbit bladder subjected to I/R surgery. METHODS: Male New Zealand rabbits were distributed into five groups as follows: Group 1 received sham surgical procedure. In group 2, I/R surgery was performed. In group 3, testosterone (100 µg/kg/day) was intramuscularly injected prior to I/R surgery. In group 4, orchiectomy was performed prior to I/R surgery. In group 5, orchiectomy was performed with subsequent testosterone administration, followed by I/R surgery. All the rabbits were euthanized 7 days after I/R. Comparative studies were analyzed to elucidate the effects of testosterone and orchiectomy on bladder dysfunction subjected to I/R injuries. MAIN OUTCOME MEASURES: Bladder contractile function was evaluated. Masson's trichrome staining and immunohistochemical studies were performed to evaluate bladder morphology and intramural nerve terminals. Western blotting was examined to investigate the expressions of fibrosis and oxidative stress markers. RESULTS: I/R surgery significantly decreased bladder contractility in response to various stimulations with and without testosterone treatment. I/R damages decreased bladder nerve density with and without testosterone. The expressions of fibrosis and oxidative stress-related proteins were increased by I/R injuries with or without testosterone treatment. Testosterone depletion significantly decreased the expressions of transforming growth factor-ß and fibronectin expressions after I/R injury. Supraphysiological testosterone treatment after orchiectomy greatly increased the expressions of these fibrosis proteins; however, orchiectomy alone ameliorated I/R injuries. CONCLUSIONS: Testosterone treatment or orchiectomy affected I/R-induced bladder damages in male rabbits. Orchiectomy decreased the level of fibrosis and oxidative stress markers and increased neurofilament densities. Supraphysiological exogenous testosterone administration after orchiectomy further exacerbated such detrimental effects of I/R.

Dual involvements of cyclooxygenase and nitric oxide synthase expressions in ketamine-induced ulcerative cystitis in rat bladder.

AIMS: The aims of the present study were to investigate voiding patterns, tissue constituents and the expressions of cyclooxygenase-2 (COX-2) and nitric oxide synthase (NOS) involved in ketamine-induced ulcerative cystitis in rat urinary bladder. METHODS: Thirty Sprague-Dawley rats were distributed into three groups which received saline or ketamine (25 mg/kg/day) for a period of 14 and 28 days. In each group, cystometry was performed weekly and the concentration of ketamine and its metabolites (norketamine) was assayed. Paraffin-embedded sections were stained with Masson's trichrome stain, and ketamine-induced morphological changes were examined. Western blot analyses were carried out to examine the expressions of COX-2 and different NOS isoforms in bladder tissues. Immunofluorescence study was done to evaluate the expressions of COX-2 and macrophage infiltration (stained with ED-1 macrophage cell surface antigen) within the bladder. RESULTS: Ketamine treatment resulted in bladder hyperactivity and the non-voiding contractions were significantly increased. The urine concentrations of ketamine and norketamine were much higher in ketamine-treated group. Moreover, ulcerated urothelium and mononuclear cell infiltration were noted in ketamine-treated group. These alterations in urodynamic functions and tissue constituents were accompanied by increases in the expression of COX-2. Two NOS isoforms (iNOS and eNOS) were also overexpressed, but no significant change was observed for nNOS. COX-2 positive stained cells were significantly increased. Meanwhile, increased amounts of ED-1 positive stained macrophages were present and most of COX-2 expressed cells were co-stained with ED-1 in the early stage of ketamine treatment. CONCLUSIONS: Ketamine treatment affected bladder tissues by enhancing interstitial fibrosis and accelerating macrophages infiltration. Ketamine also initiated the up-regulations of COX-2 and iNOS and eNOS expressions. These up-regulated enzymes might play an important role in contributing to ketamine-induced alterations in micturition patterns and ulcerative cystitis.

Power of the policy: how the announcement of high-stakes clinical examination altered OSCE implementation at institutional level.

BACKGROUND: The Objective Structured Clinical Examination (OSCE) has been widely applied as a high-stakes examination for assessing physicians' clinical competency. In 1992, OSCE was first introduced in Taiwan, and the authorities announced that passing the OSCE would be a prerequisite for step-2 medical licensure examination in 2013. This study aimed to investigate the impacts of the announced national OSCE policy on implementation of OSCE at the institutional level. Further, the readiness and the recognition of barriers toward a high-stakes examination were explored. METHODS: In 2007 and 2010, the year before and after the announcement of high-stakes OSCE policy in 2008, respectively, questionnaires on the status of OSCE implementation were distributed to all hospitals with active OSCE programs in Taiwan. Information on OSCE facilities, equipment, station length, number of administrations per year, and the recognition of barriers to the success of implementing an OSCE were collected. The missing data were completed by telephone interviews. The OSCE format, administration, and facilities before and after the announcement of the nationwide OSCE policy were compared. RESULTS: The data were collected from 17 hospitals in 2007 and 21 in 2010. Comparing the OSCE formats between 2007 and 2010, the number of stations increased and the station length decreased. The designated space and the equipment for OSCE were also found to have been improved. As for the awareness of OSCE implementation barriers, the hospital representatives concerned mostly about the availability and quality of standardized patients in 2007, as well as space and facilities in 2010. CONCLUSIONS: The results of this study underscored an overall increase in the number of OSCE hospitals and changes in facilities and formats. While recruitment and training of standardized patients were the major concerns before the official disclosure of the policy, space and facilities became the focus of attention after the announcement. The study results highlighted the influence of government policy on different aspects of OSCE implementation in Taiwanese training institutes that showed high level of support as reflected in the improved hardware and the change in OSCE format to serve the summative purpose.

Protective effects of estrogen on ischemia/reperfusion-induced bladder dysfunction in female rabbits.

OBJECTIVE: The present study investigated the effects of ovarian hormone depletion and estrogen administration on ischemia/reperfusion (I/R)-induced bladder damage in female rabbits. METHODS: Female New Zealand white rabbits were divided into five groups. A sham surgical procedure was performed on rabbits in group 1. In group 2, both vesical arteries were clamped for 2 hours and then released (I/R surgical procedure). In group 3, 17ß-estradiol (100 µg/kg/d) was injected intramuscularly before I/R surgical procedure. In group 4, ovariectomies were performed before I/R surgical procedure. Group 5 had ovariectomy, recovered for 2 weeks, and then received 17ß-estradiol for 2 weeks. I/R surgical procedure was performed thereafter. Rabbits were killed 7 days after I/R surgical procedure. Masson's trichrome stain was used, and immunohistochemical experiments were performed to evaluate interstitial fibrosis and intramural nerve changes. Western immunoblots were examined to determine the expressions of markers for inflammation, fibrosis, and oxidative stress. RESULTS: I/R surgical procedure decreased bladder contractile responses by 30% to 50%. Ovarian hormone depletion further reduced bladder contractile function by 45% to 55% compared with the I/R group members that retained their ovaries. Moreover, I/R surgical procedure significantly decreased intramural neurofilament staining by two thirds compared with the control group. Estrogen replacement after ovariectomy significantly increased the density of nerve terminals. In addition, the expression of transforming growth factor-ß and fibronectin increased twofold and fivefold after I/R, respectively. Ovarian hormone depletion further increased the expression of these inflammatory and fibrosis markers. Ovariectomy significantly exacerbated oxidative damage, whereas estrogen replacement diminished oxidative stress to a level approaching that of the control group. CONCLUSIONS: I/R surgical procedure increases oxidative damage, enhances interstitial fibrosis, and results in bladder denervation. Ovarian hormone deficiency exacerbates this I/R-induced bladder damage, whereas estrogen therapy after ovariectomy attenuates this injury. These results reveal estrogen's protective effects on bladders subjected to I/R injury and the potential benefits of estrogen therapy on I/R-induced bladder damage.

Green tea catechins decrease oxidative stress in surgical menopause-induced overactive bladder in a rat model.

UNLABELLED: What's known on the subject? and What does the study add? Ovary hormone deficiency and the age-related changes in post-menopausal women are subjected to a number of urological dysfunctions, including overactive bladder syndrome. Green tea is a popular healthy drink worldwide and its extract catechin has strong anti-inflammatory and antioxidant properties. EGCG, the major type of catechin, is an antioxidant polyphenol flavonoid isolated from green tea. EGCG supplement could prevent ovariectomy-induced bladder dysfunction in a dose-related manner through its anti-oxidant, anti-fibrosis and anti-apoptosis effects. OBJECTIVE: To evaluate whether green tea extract, epigallocatechin gallate (EGCG), could prevent ovariectomy-induced overactive bladder (OAB) and to investigate its antioxidant, anti-apoptotic and anti-fibrosis effects. MATERIALS AND METHODS: In all, 48 female Sprague-Dawley rats were divided into four groups. After bilateral ovariectomy, the first group served as the ovariectomy control, the second group received EGCG 1 µM/kg daily i.p. injection after ovariectomy surgery, and the third group received EGCG 10 µM/kg daily i.p. injection. The fourth group was taken as the sham without ovariectomy surgery. The rats were killed after 6 months after ovariectomy surgery. Cystometrograms were performed for the measure of bladder overactivity. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was used to evaluate apoptotic cells. Western immunoblots were performed to determine the expressions of inflammatory markers, apoptosis-associated proteins and oxidative stress markers. RESULTS: Long-term ovariectomy significantly increased non-voiding contractions and decreased bladder compliance. Treatment with EGCG significantly increased bladder compliance and diminished non-voiding contractions. Ovariectomy significantly increased apoptotic cells and enhanced interstitial fibrosis in bladders. The expression of caspase-3 significantly increased, while that of Bcl-2 notably decreased after ovariectomy. Inflammatory and fibrosis markers, TGF-ß, fibronectin and type I collagen expressions were significantly increased after 6 months of ovariectomy surgery. Treatment with EGCG significantly decreased TGF-ß and type I collagen expressions. Oxidative stress markers, nitrotyrosine and protein carbonylation levels were significantly increased in the ovariectomy group. EGCG could attenuate this oxidative damage in dose-dependent fashion. CONCLUSIONS: Ovariectomy increased oxidative damage, enhanced voiding frequency and decreased bladder compliance. EGCG could restore ovariectomy-induced bladder dysfunction in a dose-dependent fashion through antioxidant, anti-fibrosis and anti-apoptosis effects.

Neuroprotection of green tea catechins on surgical menopause-induced overactive bladder in a rat model.

OBJECTIVE: A rat model of ovariectomy-induced voiding dysfunction has been established, which mimicked the urge incontinence in postmenopausal women. Previous studies have identified strong anti-inflammatory/antioxidant properties of green tea and its associated polyphenols. The aim of this study was to evaluate whether the green tea extract, epigallocatechin gallate (EGCG), could prevent an ovariectomy-induced overactive bladder. METHODS: The study included 48 female Sprague-Dawley rats, which were divided into four groups. After bilateral ovariectomy during the following 6-month period, 12 rats received an intraperitoneal injection of saline, 24 rats received either a low-dose (1 µM kg(-1) d(-1)) or a high-dose (10 µM kg(-1) d(-1)) EGCG intraperitoneal injection. The sham group consisted of twelve rats that were not ovariectomized. In vivo isovolumetric cystometrograms were performed in all groups before the animals were euthanized. The immunofluorescence study used neurofilament stains to evaluate intramural nerve damage. Western immunoblots and real-time polymerase chain reaction were performed to determine M2 and M3 muscarinic cholinergic receptors (MChRs) at both protein and messenger RNA (mRNA) expressions. RESULTS: Long-term ovariectomy significantly increased non-voiding contractions, whereas treatment with EGCG significantly attenuated the frequency of non-voiding contractions. Ovariectomy significantly decreased the numbers of neurofilament and increased M2 and M3 MChR protein and mRNA expressions. Treatment with EGCG restored the amount of neurofilament staining and decreased M2 and M3 MChR protein and mRNA overexpressions. CONCLUSIONS: This study confirmed that ovary hormone deficiency induced overactive bladder dysfunction via intramural nerve damage and muscarinic receptor overexpression. EGCG prevented ovariectomy-induced bladder dysfunction through neuroprotective effects in a dose-dependent fashion.

Protein kinase C inhibitor prevents renal apoptotic and fibrotic changes in response to partial ureteric obstruction.

UNLABELLED: What's known on the subject? and What does the study add? Protein kinase C inhibitor (PKCI) can decrease glomerular and tubular cell apoptosis and mitosis and attenuate collagen accumulation and fibronectin expression in a PUUO rat model. Although the role of PKC has been well studied in diabetic nephropathy, there is no report on its role in obstructive nephropathy. This investigation evaluated the processes that were associated with the activation of PKCα and PKCß pathways and showed that PKCI played an important role in the protection of renal function during ureteric obstruction. OBJECTIVES: • To investigate the expression of the protein kinase C (PKC) pathway after partial unilateral ureteric obstruction (PUUO). • To evaluate the therapeutic potential of a PKC inhibitor (PKCI) in obstructive nephropathy. MATERIALS AND METHODS: • Thirty-six rats were divided into three groups. One sham-operated group served as the control. The other two groups received PUUO surgery, after which one group received no treatment and the other group was treated with PKCI, chelerythrine. • The severity of hydronephrosis and renal morphology were assessed: tubular and glomerularcell apoptosis, mitosis and interstitial fibrosis were examined using immunohistochemistry. • Western immunoblots were performed to determine fibronectin, transforming growth factor-ß (TGF-ß), and PKC isoform levels. RESULTS: • Two weeks after PUUO surgery, hydronephrosis progressively developed. Tubular-interstitial fibrosis, collagen deposition and fibronectin expression were increased. • PUUO also activated the expression of PKCα and PKCß and the translocation of PKCs from cell cytosol to cell membranes. • Treatment with PKCI significantly decreased PKCα and PKCß expression and translocation in the renal cortex. • Treatment with PKCI also reduced the severity of hydronephrosis, decreased both glomerular and tubular cell apoptosis and mitosis, and attenuated the collagen and fibronectin accumulation in renal interstitium. CONCLUSIONS: • Renal tubular apoptosis and interstitial fibrosis after obstructive nephropathy are associated with PKCα and PKCß activation. • The PKCI, chelerythrine, is capable of decreasing PKC expression and translocation in the renal cortex, suggesting that this inhibitor may have therapeutic potential in the protection of renal function in the first few weeks after PUUO surgery.

Ebf2 marks early cortical neurogenesis and regulates the generation of cajal-retzius neurons in the developing cerebral cortex.

Mammalian cortical neurogenesis occurs on a precise time schedule during development. The earliest born neurons form the preplate and later separate into layer 1, which includes Cajal-Retzius (C-R) neurons, and the subplate. The preplate and its derivatives play a critical role in regulating subsequent neuron migration and cortical lamination. Using an early B cell factor 2 (Ebf2)-enhanced green fluorescent protein (EGFP) transgenic mouse line, we show that Ebf2-EGFP is expressed in the preplate and persists in C-R neurons, allowing us to follow the development of these early born neurons. Therefore, Ebf2 is a genetic marker for preplate neurons from the earliest stage of their differentiation and C-R cells after the preplate is split. Additionally, we examined the function of Ebf2 in the development of C-R neurons using both lentiviral-mediated knock-down overexpression approaches to perturb Ebf2 expression. Our data show that Ebf2 overexpression increases the generation of early born neurons including C-R cells, while Ebf2 knock-down decreases it, without affecting the generation of other layer-specific neurons in vitro. These results indicate that Ebf2 is important for early cortical neurogenesis and regulates the generation of C-R neurons in the developing cerebral cortex.

The effect of L-arginine on bladder dysfunction following ovariectomy in a rabbit model.

INTRODUCTION AND HYPOTHESIS: The present study was designed to investigate the effect of nitric oxide precursor, L: -arginine, on bladder function following ovariectomy. METHODS: Twenty-eight New Zealand white female rabbits were separated into seven groups. Groups 1 to 6 underwent ovariectomy surgery. Among them, groups 1 and 2 received ovariectomy without treating with L-arginine. Groups 3, 4, 5, and 6 were given high L-arginine diet and were sacrificed 1, 3, 7, and 14 days after ovariectomy, respectively. Group 7 served as the control group. The effects of L: -arginine on the contractility of bladder tissues were determined in response to various stimulations. In addition, L-arginine effects on the expression of Rho kinase (ROK), protein kinase C potentiated inhibitor (CPI-17), caldesmon (CaD), and calponin (CaP) were studied by immunoblotting. RESULTS: Ovariectomy significantly decreases contractile response to all forms of stimulation. Feeding rabbits L: -arginine significantly increases contractile response at 1 day following ovariectomy, but the response decreases to the control level by 14 days. Ovariectomy increases the expressions of both isoforms of CaD, CaP, and CPI-17; L-arginine treatment induces ROK underexpression, while CaP is overexpressed in the early few days of ovariectomy but returns to the control level at 2 weeks after ovariectomy. CONCLUSIONS: Ovariectomy appreciably reduced bladder contractility. Treatment with L-arginine reversed the ovariectomy-induced bladder dysfunction. Decreased bladder contractile response was observed in the early days following ovariectomy.

The experience of an objective, structured clinical examination at Kaohsiung Medical University.

The objective, structured clinical examination (OSCE) is a method to assess clinical competency based on objective testing, through direct observation in a formal setting. The Kaohsiung Medical University (KMU) has pioneered OSCEs in Taiwan. In KMU, three groups of examinees---medical students in years 3 and 4, medical students in years 5 and 6, and medical students in year 7---were assessed using different OSCEs. Each OSCE was set up using the following five steps: (1) create cases; (2) decide on the items or clinical skills to be evaluated; (3) train standardized patients; (4) run the OSCE and (5) review videos to improve the curriculum. We expect that KMU will become the premier OSCE center in Taiwan.

Evaluation of the effectiveness of postgraduate general medicine training by objective structured clinical examination---pilot study and reflection on the experiences of Kaohsiung Medical University Hospital.

Objective structured clinical examination (OSCE) is an effective assessment method to evaluate medical students' clinical competencies performance. Postgraduate year 1 (PGY1) residents have been initiated in a general medicine training program in Taiwan since 2003. However, little is known about the learning effectiveness of trainees from this program. This pilot study aimed to evaluate the clinical core competencies of PGY1 residents using OSCE, and to reflect on the strengths and weaknesses of this pilot assessment project. OSCE was conducted for five PGY1 examinees (4 men, 1 woman) with five stations covering core themes, including history taking, physical examination, clinical procedure of airway intubation, clinical reasoning, and communication skills for informing bad news. Itemized checklists and five-point Likert scale global ratings were used for evaluating performance. The results showed that the performance of our PGY1 residents on history taking was significantly better after about 2 months of postgraduate training on general internal medicine. Self-evaluation on performance by examinees revealed significantly lower global ratings on post-course OSCE (4.14 +/- 0.80 vs. 3.68 +/- 0.66; p < 0.02). Surveys from tutors and standardized patients (SPs) completed at pre- and post-course OSCEs showed consistently favorable responses on the purposes, content, process, and environment of this assessment (4.0 +/- 0.17 vs. 4.0 +/- 0.12, nonsignificant). However, a survey of the examinees completed at pre- and post-course OSCEs showed relatively unfavorable responses to the same aspects, and to tutors and SPs (4.1 +/- 0.09 vs. 3.7 +/- 0.18; p < 0.05). Qualitative information revealed that tutors and SPs remarked that PGY1 residents' medical knowledge performance was satisfactory but their clinical reasoning performance, communication skills (giving bad news) and self-confidence were unsatisfactory. In conclusion, this pilot study has demonstrated that OSCE is a rational and feasible assessment method for evaluating the effectiveness of our PGY general medicine training program. The quantitative data and qualitative information provide a foundation to improve the quality of the program design and evaluation in implementing postgraduate general medicine training.

Setting pass scores for clinical skills assessment.

In a clinical skills assessment, the decision to pass or fail an examinee should be based on the test content or on the examinees' performance. The process of deciding a pass score is known as setting a standard of the examination. This requires a properly selected panel of expert judges and a suitable standard setting method, which best fits the purpose of the examination. Six standard setting methods that are often used in clinical skills assessment are described to provide an overview of the standard setting process.

Correlations between academic achievement and anxiety and depression in medical students experiencing integrated curriculum reform.

This study aimed to examine the correlations between academic achievement and levels of anxiety and depression in medical students who were experiencing curriculum reform. The differences in academic achievement and the directions of correlations between academic achievement and anxiety and depression among the medical students with different levels of anxiety and depression were also examined. Grade 1 students from graduate-entry program and grade 3 students from undergraduate-entry program in their first semester of the new curriculum were recruited to complete the Zung's Anxiety and Depression Scale twice to examine their levels of anxiety and depression. Their academic achievement ratings in the four blocks of the first semester of the new curriculum were collected. The results indicated that no significant correlation was found between academic achievement and global anxiety and depression. However, by dividing the medical students into low, moderate and high level anxiety or depression groups, those who had poorer academic achievement in the first learning block were more likely to have higher levels of depression in the first psychologic assessment. Among the medical students who were in the high anxiety level group in the first psychologic assessment, those who had more severe anxiety had poorer academic achievement in the fourth learning block. Among the medical students who were in the low anxiety level group in the second psychologic assessment, those who had more severe anxiety had better academic achievement in the fourth learning block. Among the medical students who were in the moderate anxiety level group in the second psychologic assessment, those who had more severe anxiety had poorer academic achievement in the second learning block. Among the medical students who were in the high depression level group in the second psychologic assessment, those who had more severe depression had poorer academic achievement in the fourth learning block. The results of this study indicate that there are both positive and negative correlations between academic achievement and anxiety and depression in medical students, regarding differing levels of severity of anxiety or depression. The results could represent a reference for teachers on the planning of teaching and assessment programs.

Implementation of an OSCE at Kaohsiung Medical University.

The Objective Structured Clinical Examination (OSCE), a tool to objectively and fairly assess medical students' clinical competences, has become widely used in medical education worldwide. However, most medical schools in Taiwan have just begun to adopt this assessment method. In 2003, Kaohsiung Medical University (KMU) established the first standardized patient (SP) program in Taiwan and applied SPs with an OSCE. This study reports the process of the implementation of an OSCE at KMU, which includes collecting information, visiting leading clinical skills centers, consulting medical educators from other countries, holding international conferences, establishing an OSCE committee, writing cases, training SPs, administrating the OSCE, and receiving feedback from medical students. Most students were satisfied with the assessment and appreciated the learning experience. Based on the experience in 2003, the OSCE committee decided to incorporate the OSCE into the medical curriculum as a measure to assess medical students' clinical competences. In addition to assessing medical students' clinical competence, the OSCE can also be applied to other professional health education, such as dentistry, nursing, and pharmacy. We are currently sharing our experience with other colleges at KMU.

Assessing core clinical competencies required of medical graduates in Taiwan.

Medical students are assumed to be competent to provide basic patient care independently on graduation. However, there is a gap between what students are expected to learn and what they have actually learned. This may be due to the lack of clearly defined learning objectives, well-organized curriculum, and properly administered assessment. In an attempt to tackle this problem, we conducted a three-step study. Firstly, we identified the core clinical competencies required of medical graduates in Taiwan. Secondly, we incorporated these clinical competencies into a new medical curriculum. Finally, we identified the most appropriate assessment methods for each clinical competency. In 2004, a set of minimally required clinical competencies for medical undergraduates in Taiwan was developed, which included 92 clinical skills, four communication skills, and seven kinds of attitudes. In order to prepare 3rd and 4th year medical students at Kaohsiung Medical University (KMU) for later clinical work, the medical curriculum committee integrated the teaching and assessment of the core clinical skills identified previously into relevant organ-system blocks of the new curriculum. To identify appropriate assessment methods for each clinical skill, a structured questionnaire of assessment methods based on the Toolbox of Assessment Methods (Accreditation Council for Graduate Medical Education) and The Scottish Doctor (Scottish Deans' Medical Curriculum Group) was developed and distributed to 40 senior clinical faculty members at KMU. Simulations and Models, Standardized Patient Examination (SP), and Objective Structured Clinical Examination (OSCE) were suggested to be most suitable to assess two-thirds of the core clinical skills. These assessment methods are commonly used in American and European medical schools. We believe that the implementation of the new curriculum at KMU accompanied by the use of Simulations and Models, SP, OSCE, and other teaching and assessment methods will help 3rd and 4th year students to prepare better for clinical practice in clerkships.

Radiation-induced modulation of the microglial population in the normal and injured mature spinal cord.

Recent attempts by other investigators to enhance repair processes in the spinal cord have involved the administration of X rays to spinal cord injury sites. Although some functional improvement has been reported, the underlying cellular changes within the irradiated spinal cords are not clear. Studies initiated recently in this laboratory examined the potential of X rays to modulate nonneuronal cell populations associated with an injury site in adult mammalian spinal cords. These studies revealed a unique and previously unreported radiosensitivity of the microglial cell population. Administration of X radiation to a unilateral dorsal lesion cavity in the cervical spinal cord revealed a significant decrease (approximately half) in numbers of microglia associated with the cavity. Even more unexpected were the significant decreases in microglial cells observed on the nonlesioned side of the spinal cord or in sham-operated spinal cords in irradiated rats. In contrast to reports of others, densitometric quantification of GFAP immunoreactive cells and processes indicated no differences in the astrocytic reactions associated with the lesion cavities between nonirradiated and irradiated groups in our studies. The demonstration that exposure of a spinal cord injury site to radiation modifies the responses of certain components of the glial environment to injury may offer a noninvasive approach for direct treatment of that site. Studies are in progress to determine if this altered glial environment enhances the extension of regrowing axons from a peripheral nerve graft across the interface with the irradiated lesion cavity and into the spinal cord parenchyma.