Arsia Jamali

Protein Kinase D1 mediates anchorage-dependent and independent growth of tumor cells via the zinc-finger transcription factor Snail1

Background: The protein kinase D (PKD) family is involved in the control of cell motility and proliferation. Results: PKD1 controls growth of cancer cells through phosphorylation of Snail1 at Ser-11. Conclusion: Only PKD1, but not PKD2, mediates isoform-specific control of pancreatic cancer cell proliferation through Snail1. Significance: We demonstrate for the first time isoform-specific control of pancreatic cancer growth by a single phosphorylation of a substrate. We here identify protein kinase D1 (PKD1) as a major regulator of anchorage-dependent and -independent growth of cancer cells controlled via the transcription factor Snail1. Using FRET, we demonstrate that PKD1, but not PKD2, efficiently interacts with Snail1 in nuclei. PKD1 phosphorylates Snail1 at Ser-11. There was no change in the nucleocytoplasmic distribution of Snail1 using wild type Snail1 and Ser-11 phosphosite mutants in different tumor cells. Regardless of its phosphorylation status or following co-expression of constitutively active PKD, Snail1 was predominantly localized to cell nuclei. We also identify a novel mechanism of PKD1-mediated regulation of Snail1 transcriptional activity in tumor cells. The interaction of the co-repressors histone deacetylases 1 and 2 as well as lysyl oxidase-like protein 3 with Snail1 was impaired when Snail1 was not phosphorylated at Ser-11, which led to reduced Snail1-associated histone deacetylase activity. Additionally, lysyl oxidase-like protein 3 expression was up-regulated by ectopic PKD1 expression, implying a synergistic regulation of Snail1-driven transcription. Ectopic expression of PKD1 also up-regulated proliferation markers such as Cyclin D1 and Ajuba. Accordingly, Snail1 and its phosphorylation at Ser-11 were required and sufficient to control PKD1-mediated anchorage-independent growth and anchorage-dependent proliferation of different tumor cells. In conclusion, our data show that PKD1 is crucial to support growth of tumor cells via Snail1.

Medical students' health‐related quality of life: roles of social and behavioural factors

The long and demanding course of medical education may be accompanied by distress with serious consequences. This study was conducted to assess the multidimensional health‐related quality of life (HR‐QoL) in medical students in different stages of medical education and its associations with behavioural and social factors.

Association of the pre-internship objective structured clinical examination in final year medical students with comprehensive written examinations

Aim The purpose of this study is to evaluate the association of the pre-internship Objective Structured Clinical Examination (OSCE) in final year medical students with comprehensive written examinations. Subjects and material All medical students of October 2004 admission who took part in the October 2010 National Comprehensive Pre-internship Examination (NCPE) and pre-internship OSCE were included in the study (n=130). OSCE and NCPE scores and medical grade point average (GPA) were collected. Results GPA was highly correlated with NCPE (r=0.76 and P<0.001) and moderately with OSCE (r=0.68 and P<0.001). Similarly a moderate correlation was observed between NCPE and OSCE scores(r=0.6 and P<0.001).Linear stepwise regression shows r 2 of a model applying GPA as predictor of OSCE score is 0.46 (β = 0.68 and P<0.001), while addition of gender to the model increases r 2 to 0.59 (β = 0.61 and 0.36, for GPA and male gender, respectively and P<0.001). Logistic forward regression models shows male gender and GPA are the only dependent predictors of high score in OSCE. OR of GPA and male gender for high OSCE score are 4.89 (95% CI = 2.37–10.06) and 6.95 (95% CI = 2.00–24.21), respectively (P<0.001). Discussion Our findings indicate OSCE and examination which mainly evaluate knowledge, judged by GPA and NCPE are moderately to highly correlated. Our results illustrate the interwoven nature of knowledge and clinical skills. In other words, certain level of knowledge is crucial for appropriate clinical performance. Our findings suggest neither OSCE nor written forms of assessments can replace each other. They are complimentary and should also be combined by other evaluations to cover all attributes of clinical competence efficiently.

The Value of Visfatin in the Prediction of Metabolic Syndrome: A Multi-Factorial Analysis

We describe the adipokine concentration in patients with metabolic syndrome, stressing the role of visfatin. A cross-sectional single center study on 70 patients with metabolic syndrome plus 76 controls was performed. Patients with metabolic syndrome had higher visfatin levels compared to controls, following adjustments for age, sex, waist/hip circumference, systolic, and diastolic blood pressure, fasting plasma glucose (FPG), HbA1c, body mass index, and homeostasis model assessment of insulin resistance (HOMA-IR) [(5.39 ± 0.29 vs. 3.88 ± 0.32); F(1, 129) = 10.8, P < 0.01]. A logistic regression analysis revealed that circulating visfatin levels and HbA1c were the top variables for predicating metabolic syndrome. In patients with metabolic syndrome, visfatin did not correlate with any of the measured variables, with the single exception of adiponectin; in patients without metabolic syndrome, circulating visfatin levels were significantly associated with FPG, HbA1c, insulin, HOMA-IR, HDL, and triglyceride. These findings may contribute to our current knowledge about visfatin in metabolic syndrome.

Metabolic syndrome is linked to a mild elevation in liver aminotransferases in diabetic patients with undetectable non-alcoholic fatty liver disease by ultrasound

BackgroundDespite ongoing findings on the relationship between elevated levels of alanine and aspartate aminotransferases (ALT and AST) and metabolic syndrome (MetS), this association in diabetic patients without a known cause for liver enzymes elevation other than diabetes, per se, remains unclear. In this study, we aimed to assess the relationship between circulating liver enzymes and MetS in a relatively large sample of patients with diabetes.MethodsA total of 670 diabetic patients, without known causes of hepatocellular injury, were enrolled. Patients with ultrasonographic signs of fatty liver disease were not included. Fasting blood samples were obtained and biochemical characteristics were measured. MetS was defined according to the international diabetes federation criteria.ResultsSerum ALT and AST were significantly higher in patients with MetS (p < 0.001). High waist circumference and low HDL-cholesterol were significantly associated with elevated ALT (OR = 2.56 and 2.0, respectively) and AST (OR = 2.23 and 2.21, respectively). ALT and AST were significantly associated with MetS (OR = 2.17 and 2.31, respectively). These associations remained significant after multiple adjustments for age, sex, BMI, diabetes duration, HbA1c and medications. There was a significant (p < 0.01) positive association between the number of the MetS features and the level of ALT or AST.ConclusionIn diabetic patients without ultrasonographic evidence of fatty liver, elevated aminotransferases are independently associated with MetS. Despite negative ultrasound results in diabetic patients with MetS, the serum level of liver aminotransferases may be elevated and should be more thoroughly monitored.

Intravitreal Injection of a Rho‐Kinase Inhibitor (Fasudil) for Recent‐Onset Nonarteritic Anterior Ischemic Optic Neuropathy

This study evaluated the effects of intravitreal injection of fasudil (IVF), a Rho‐kinase inhibitor, in cases of recent‐onset nonarteritic anterior ischemic optic neuropathy (NAION). In this interventional case series, 13 eyes of 13 patients diagnosed with NAION within 14 days of onset were included. The affected eyes received a 0.025 mg/0.05 mL IVF. Functional and structural outcomes were assessed 1 and 3 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measured, with mean deviation (MD) index of the VF test and peripapillary retinal nerve fiber layer thickness as secondary measures. There was a statistically significant improvement in the patients’ BCVA 1 and 3 months following IVF; BCVA improved from 1.69 ± 0.55 logMAR at baseline to 0.98 ± 0.47 and 0.93 ± 0.51 logMAR at 1 and 3 months, respectively (P = .004). The change in BCVA was not significant between month 1 and month 3 (P = .22). Peripapillary retinal nerve fiber layer thickness decreased from 173.5 ± 29.28 µm in the baseline evaluation to 85.8 ± 8.8 µm at 1 month, and 62.9 ± 5.97 µm at 3 months (P = .003). MD values changed from 24.60 ± 3.80 to 21.0 ± 6.10 and 20.5 ± 6.50 at 1 and 3 months, respectively (P = .007 and .005, respectively). This pilot study suggests that IVF may be an effective treatment for patients with recent‐onset NAION. Larger studies are required to establish the therapeutic role of fasudil for NAION.

Attitude towards plagiarism among Iranian medical students

In recent years, scientific misconduct has received significant attention within the scientific community. Plagiarism is the most frequent type of scientific misconduct and is defined as ‘unauthorised appropriation of anothers work, ideas, methods, results or words without acknowledging the source and original author’.1 2 …

Rapid research education for medical science students

1184 www.thelancet.com Vol 381 April 6, 2013 protocol by the research council of the university, students do the research under the supervision of SSRC instructors (senior undergraduate students) and faculty members. Currently, SSRC is running RREs in cancer, radiology, medical education, and osteoporosis. Some RREs have shown promising results: students from the ophthalmology RRE presented four oral presentations at the 28th Congress of the European Society of Cataract and Refractive Surgeons in Paris, France, on Sept 4–8, 2010. RREs thus provide the opportunity for students to learn research by actually doing it.

Students' concerns about the pre-internship objective structured clinical examination in medical education

Background: Despite several studies on implementation, reliability and validity of the Objective Structured Clinical Examination (OSCE), the perceptions of examinees toward this evaluation tool remain unclear. The aim of the current study was to assess students′ perceptions of the OSCE. Methods: All students in their final year of studies, who participated in the pre-internship OSCE in September 2010, were included in the study. A 16-item questionnaire was designed to assess: Characteristics of respondents; organization, content and structure of the OSCE; and perceptions of validity, reliability and rating of the OSCE with respect to other assessment methods. Questionnaires were administered immediately after all students had finished the OSCE and before leaving the examination venue. Results: Response rate was 86.2%, with 77% of the students indicating the OSCE as a useful learning experience. A majority of the students (62%) agreed that a wide range of clinical skills was covered in this exam. However, 66% had concerns about the wide coverage of knowledge assessed. A total of 81% of students did not prefer the OSCE to multiple choice question exams and 88% found the OSCE intimidating and more stressful than other forms of assessment. Discussion: Our study demonstrates that although the majority of students believe in the reliability and validity of the OSCE, they have concerns about it and report poor acceptance of the OSCE. Further studies are necessary to assess the important concerns of the students and the effectiveness of interventions in improving the acceptability of the OSCE.