Ethical Challenges in Teaching Genetics for Medical Students

Although inclusion of ethics as a study course in medical students’ curricula is a common practice, special approaches in teaching ethics in the context of genetics should be considered. In the realm of genomics, there are several ethically sensitive topics such as diagnosis of genetic diseases, in vitro fertilization, and identification of genetic susceptibility to common diseases. In addition, in communication with the general public, genetic terms should be used with caution. Demonstration of the phenotypes of affected individuals should be regarded as a particular aspect of teaching genetics. In a description of a patient’s phenotype, not only is it necessary to provide scientifically precise characteristics of a patient; voice timbre, facial expression, and body language should also be carefully controlled. Furthermore, in medicine, the theory–practice gap is a problematic aspect, and students often find it difficult to apply knowledge on ethical issues to real situations in clinics. For this purpose, clinical cases are presented during classes and their analysis requires a very respectful attitude on the part of both students and lecturers. For many genetic diseases, evaluation of minor anomalies such as a curved fifth finger, low situated ears, or missing of some teeth is required. Some minor anomalies are found in healthy individuals too, and interpretation of such features must therefore be considered carefully. This article describes our experiences in teaching genetics at Riga Stradinš University, ethical problems faced while teaching genetics, and their solutions.publishersversionPeer reviewe

TWO APPROACHES IN STUDENT ACHIEVEMENTS ASSESSMENT – PRO ET CONTRA

Student achievement depends very much on reliable and valid assessment methods. In this paper assessment of reflecting writing and computer based on - line tests will be discussed. The main challenge in evaluation reflecting writing tests is objectivity. For this purpose test papers were evaluated mutually by different lecturers and grading compared by Pearson`s correlation coefficient. Results showed that strong correlation exists in all compared assessor pairs. In computer based on-line test in Moodle platform evaluation is done by computer programme and grading is announced just after student finishes the test. In purpose to maintain student`s reflective skills clinical case and/or problem were included in computer based tests. These questions were evaluated manually. Two types of assessment – manual and computer based have their advantages and disadvantages. Our conclusion is that different tests and assessment methods should be used for comprehensive and objective evaluation of student`s outcomes

KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission

Renewed global efforts toward malaria eradication have highlighted the need for novel antimalarial agents with activity against multiple stages of the parasite life cycle. We have previously reported the discovery of a novel class of antimalarial compounds in the imidazolopiperazine series that have activity in the prevention and treatment of blood stage infection in a mouse model of malaria. Consistent with the previously reported activity profile of this series, the clinical candidate KAF156 shows blood schizonticidal activity with 50% inhibitory concentrations of 6 to 17.4 nM against P. falciparum drug-sensitive and drug-resistant strains, as well as potent therapeutic activity in a mouse models of malaria with 50, 90, and 99% effective doses of 0.6, 0.9, and 1.4 mg/kg, respectively. When administered prophylactically in a sporozoite challenge mouse model, KAF156 is completely protective as a single oral dose of 10 mg/kg. Finally, KAF156 displays potent Plasmodium transmission blocking activities both in vitro and in vivo. Collectively, our data suggest that KAF156, currently under evaluation in clinical trials, has the potential to treat, prevent, and block the transmission of malaria

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Laminin-binding integrin gene copy number alterations in distinct epithelial-type cancers.

The laminin-binding integrin (LBI) family are cell adhesion molecules that are essential for invasion and metastasis of human epithelial cancers and cell adhesion mediated drug resistance. We investigated whether copy number alteration (CNA) or mutations of a five-gene signature (ITGB4, ITGA3, LAMB3, PLEC, and SYNE3), representing essential genes for LBI adhesion, would correlate with patient outcomes within human epithelial-type tumor data sets currently available in an open access format. We investigated the relative alteration frequency of an LBI signature panel (integrin β4 (ITGB4), integrin α3 (ITGA3), laminin β3 chain (LAMB3), plectin (PLEC), and nesprin 3 (SYNE3)), independent of the epithelial cancer type, within publically available and published data using cBioPortal and Oncomine software. We rank ordered the results using a 20% alteration frequency cut-off and limited the analysis to studies containing at least 100 samples. Kaplan-Meier survival curves were analyzed to determine if alterations in the LBI signature correlated with patient survival. The Oncomine data mining tool was used to compare the heat map expression of the LBI signature without SYNE3 (as this was not included in the Oncomine database) to drug resistance patterns. Twelve different cancer types, representing 5,647 samples, contained at least a 20% alteration frequency of the five-gene LBI signature. The frequency of alteration ranged from 38.3% to 19.8%. Within the LBI signature, PLEC was the most commonly altered followed by LAMB3, ITGB4, ITGA3, and SYNE3 across all twelve cancer types. Within cancer types, there was little overlap of the individual amplified genes from each sample, suggesting different specific amplicons may alter the LBI adhesion structures. Of the twelve cancer types, overall survival was altered by CNA presence in bladder urothelial carcinoma (p=0.0143*) and cervical squamous cell carcinoma and endocervical adenocarcinoma (p=0.0432*). Querying the in vitro drug resistance profiles with the LBI signature demonstrated a positive correlation with cells resistant to inhibitors of HDAC (Vorinostat, Panobinostat) and topoisomerase II (Irinotecan). No correlation was found with the following agents: Bleomycin, Doxorubicin, Methotrexate, Gemcitabine, Docetaxel, Bortezomib, and Shikonen. Our work has identified epithelial-types of human cancer that have significant CNA in our selected five-gene signature, which was based on the essential and genetically-defined functions of the protein product networks (in this case, the LBI axis). CNA of the gene signature not only predicted overall survival in bladder, cervical, and endocervical adenocarcinoma but also response to chemotherapy. This work suggests that future studies designed to optimize the gene signature are warranted.The use of the Tissue Acquisition and Molecular Analysis Support Service (TACMASR) of the UA Cancer Center was essential for this work. Of particular note was the expert technical assistance of Ed Abril. The work was supported in part by CA P30 23074, CA164484 and CA159406.Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Laminin-binding integrin gene copy number alterations in distinct epithelial-type cancers.

The laminin-binding integrin (LBI) family are cell adhesion molecules that are essential for invasion and metastasis of human epithelial cancers and cell adhesion mediated drug resistance. We investigated whether copy number alteration (CNA) or mutations of a five-gene signature (ITGB4, ITGA3, LAMB3, PLEC, and SYNE3), representing essential genes for LBI adhesion, would correlate with patient outcomes within human epithelial-type tumor data sets currently available in an open access format.The use of the Tissue Acquisition and Molecular Analysis Support Service (TACMASR) of the UA Cancer Center was essential for this work. Of particular note was the expert technical assistance of Ed Abril. The work was supported in part by CA P30 23074, CA164484 and CA159406.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]