Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men globally. CRC arises from one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Genetic instability is usually caused by aneuploidy and loss of heterozygosity. Mutations in the tumor suppressor or cell cycle genes may also lead to cellular transformation. Similarly, epigenetic and/or genetic alterations resulting in impaired cellular pathways, such as DNA repair mechanism, may lead to microsatellite instability and mutator phenotype. Non-coding RNAs, more importantly microRNAs and long non-coding RNAs have also been implicated at various CRC stages. Understanding the specific mechanisms of tumorigenesis and the underlying genetic and epigenetic traits is critical in comprehending the disease phenotype. This paper reviews these mechanisms along with the roles of various non-coding RNAs in CRCs.

Student engagement refers to a broad range of activities where students participate in management, education, research, and community activities within their institutions. It is a mutually beneficial collaborative approach between students and their institutions. This article provides practical advice for the implementation or further development of student engagement at medical, dental, and veterinary schools. The tips provided are based on the experiences of a group of universities recently recognized for best practice in student engagement, and are supported by evidence from the literature. The tips cover overarching themes which include the creation of an institutional culture and formal framework for student engagement, and maximize communication routes between students with peers and faculty. Tips are for specific areas of active student engagement, covering curriculum design and development, peer teaching, governance processes, research activities, peer support programs, and interaction with the local community.

Enzastaurin (LY317615), an acyclic bisindolylmaleimide, is an oral inhibitor of the protein kinase CB isozyme. The objective of this study was to assess the efficacy of enzastaurin in inducing apoptosis in multiple myeloma (MM) cell lines and to investigate possible mechanisms of apoptosis. Cell proliferation assays were done on a variety of MM cell lines with unique characteristics (dexamethasone sensitive, dexamethasone resistant, chemotherapy sensitive, and melphalan resistant). The dexamethasonesensitive MM.1S cell line was used to further assess the effect of enzastaurin in the presence of dexamethasone, insulin-like growth factor-I (IGF-I), interleukin-6, and the pan-specific caspase inhibitor ZVAD-fmk. Enzastaurin increased cell death in all cell lines at clinically significant low micromolar concentrations (1 -3 Mmol/L) after 72 hours of treatment. Dexamethasone and enzastaurin were shown to have an additive effect on MM.1S cell death. Although IGF-I blocked the effect of 1 Mmol/L enzastaurin, IGF-I did not abrogate cell death induced with 3 Mmol/L enzastaurin. Moreover, enzastaurin-induced cell death was not affected by interleukin-6 or ZVAD-fmk. GSK3B phosphorylation, a reliable pharmacodynamic marker for enzastaurin activity, and AKT phosphorylation were both decreased with enzastaurin treatment. These data indicate that enzastaurin induces apoptosis in MM cell lines in a caspase-independent manner and that enzastaurin exerts its antimyeloma effect by inhibiting signaling through the AKT pathway. [Mol Cancer Ther 2006;5(7):1783 -9]

Depression is common in MDR-TB patients, and should be screened for and treated within MDR-TB treatment programmes.

Background. Early onset colorectal carcinoma (CRC) is rare and has been hypothesized to be a biologically and clinically distinct entity personifying aggressive disease and worse survival. Methods. Data for 131 patients was collected by retrospective chart review. Cox proportional hazard model was used to compute prevalence ratios and 95% confidence intervals. Results. Early onset sporadic CRC accounted for 32% of all CRC treated in the specified time period. The mean age was 33.3 ± 7.9 years and the male to female ratio was 2 : 1. Colon and rectal cancers accounted for 55% and 45% of patients, respectively. 96% of rectal carcinoma patients received appropriate therapy as opposed to 65% of colon cancers. On multivariable analysis, appropriate reception of therapy (PR 4.99; 95% CI, 1.21–20.6) and signet ring morphology (PR 2.40; 95% CI, 1.33–4.32) were significantly associated with rectal cancers as opposed to colon cancer. Kaplan-Meier analysis revealed a trend towards inferior survival for rectal carcinoma 2 years after diagnosis. Conclusion.A high prevalence of early onset CRC was noted in the study. A trend towards inferior survival was seen in patients with rectal cancer. This finding raises the possibility of rectal carcinoma being an aggressive subset of young CRC.

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BackgroundHonesty and integrity are key attributes of an ethically competent physician. However, academic misconduct, which includes but is not limited to plagiarism, cheating, and falsifying documentation, is common in medical colleges across the world. The purpose of this study is to describe differences in the self-reported attitudes and behaviours of medical students regarding academic misconduct depending on gender, year of study and type of medical institution in Pakistan.MethodsA cross sectional study was conducted with medical students from one private and one public sector medical college. A pre-coded questionnaire about attitudes and behaviours regarding plagiarism, lying, cheating and falsifying documentation was completed anonymously by the students.ResultsA total of 465 medical students filled the questionnaire. 53% of private medical college students reported that they recognize copying an assignment verbatim and listing sources as references as wrong compared to 35% of public medical college students. 26% of private medical college students self-report this behaviour as compared to 42% of public medical college students. 22% of private versus 15% of public medical college students and 21% of students in clinical years compared to 17% in basic science years admit to submitting a fake medical certificate to justify an absence. 87% of students at a private medical college believe that cheating in an examination is wrong as compared to 66% of public medical college students and 24% self-report this behaviour in the former group as compared to 41% in the latter. 63% of clinical year students identify cheating as wrong compared to 89% of their junior colleagues. 71% of male versus 84% of female respondents believe that cheating is wrong and 42% of males compared to 23% of females admit to cheating.ConclusionsThere are significant differences in medical students’ attitudes and behaviours towards plagiarism, lying, cheating and stealing by gender, seniority status and type of institution. The ability to identify acts of academic misconduct does not deter students from engaging in the behaviour themselves, as evidenced by self-reporting.

In total, 513 medical students (66% female) participated. Their mean age was 21 ± 1.6 years. Three hundred seventy-five students (73%) reported having visited a doctor at least once in the past 6 months. Fifty students (9.9%) admitted to having addictions. The overall prevalence of significant hypochondriacal concerns was 11.9% (61 students). The presence of addiction was associated with a greater likelihood of developing significant health-related anxiety (odds ratio = 3.82, p = .003), 95% confidence interval [1.51, 7.11]. Age, gender, medical school, year of medical school, and visits to the doctor in the previous 6 months were not associated with greater likelihood of developing significant health-related anxiety. Second-year medical students experienced a significantly greater degree of worry (MSD-Distress scale) than 5th-year students (M score = 12.6 ± 4.6 vs. 10.7 ± 4.4, p = .04). Insights: The prevalence of substantial hypochondriacal concerns in medical students in Pakistan was low in comparison to similar studies published in literature. Student health physicians should be aware of the true prevalence of hypochondriacal concerns and behavior and not dismiss legitimate complaints. Educational sessions to counteract this phenomenon can be incorporated into the curriculum of undergraduate medicine. By defining heightened awareness of symptoms as a normal process, different coping techniques can be discussed to help medical students reduce their level of stress.