Addressing ethical challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT).

BACKGROUND: The conduct of international collaborative genomics research raises distinct ethical challenges that require special consideration, especially if conducted in settings that are research-naïve or resource-limited. Although there is considerable literature on these issues, there is a dearth of literature chronicling approaches taken to address these issues in the field. Additionally no previous ethical guidelines have been developed to support similar research in Trinidad and Tobago. METHODS: A literature review was undertaken to identify strategies used to address common ethical issues relevant to human genetics and genomics research in research-naïve or resource-limited settings. Strategies identified were combined with novel approaches to develop a culturally appropriate, multifaceted strategy to address potential challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT). RESULTS: Regarding the protection of study participants, we report a decision to exclude children as participants; the use of a Community Engagement and Sensitization Strategy to increase the genetic literacy of the target population; the involvement of local expertise to ensure cultural sensitivity and to address potential comprehension barriers in informed consent; and an audit of the informed consent process to ensure valid consent. Concerning the regulation of the research, we report on ethics approvals from relevant authorities; a Materials Transfer Agreement to guide sample ownership and export; and a Sample Governance Committee to oversee data use and data access. Finally regarding the protection of the interests of scientists from the host country, we report on capacity building efforts to ensure that local scientists have access to data collected through the project and appropriate recognition of their contributions in future publications. CONCLUSION: This paper outlines an ethical framework for the conduct of population-based genetics and genomics research in Trinidad and Tobago; highlights common issues arising in the field and strategies to address these

Mechanical behaviour and rupture of normal and pathological human ascending aortic wall

The mechanical properties of aortic wall, both healthy and pathological, are needed in order to develop and improve diagnostic and interventional criteria, and for the development of mechanical models to assess arterial integrity. This study focuses on the mechanical behaviour and rupture conditions of the human ascending aorta and its relationship with age and pathologies. Fresh ascending aortic specimens harvested from 23 healthy donors, 12 patients with bicuspid aortic valve (BAV) and 14 with aneurysm were tensile-tested in vitro under physiological conditions. Tensile strength, stretch at failure and elbow stress were measured. The obtained results showed that age causes a major reduction in the mechanical parameters of healthy ascending aortic tissue, and that no significant differences are found between the mechanical strength of aneurysmal or BAV aortic specimens and the corresponding age-matched control group. The physiological level of the stress in the circumferential direction was also computed to assess the physiological operation range of healthy and diseased ascending aortas. The mean physiological wall stress acting on pathologic aortas was found to be far from rupture, with factors of safety (defined as the ratio of tensile strength to the mean wall stress) larger than six. In contrast, the physiological operation of pathologic vessels lays in the stiff part of the response curve, losing part of its function of damping the pressure waves from the heart

Mistletoe lectin is not the only cytotoxic component in fermented preparations of Viscum album from white fir (Abies pectinata)

<p>Abstract</p> <p>Background</p> <p>Preparations of mistletoe (<it>Viscum album</it>) are the form of cancer treatment that is most frequently used in the complementary medicine. Previous work has shown that these preparations are able to exert cytotoxic effects on carcinoma cells, the extent of which might be influenced by the host tree species and by the content of mistletoe lectin.</p> <p>Methods</p> <p>Using colorimetric assays, we have now compared the cytotoxic effects of <it>Viscum album </it>preparations (VAPs) obtained from mistletoe growing on oak (<it>Quercus robur </it>and <it>Q. petraea</it>, VAP-Qu), apple tree (<it>Malus domestica</it>,, VAP-M), pine (<it>Pinus sylvestris</it>, VAP-P) or white fir (<it>Abies pectinata</it>, VAP-A), on the <it>in vitro </it>growth of breast and bladder carcinoma cell lines. While MFM-223, KPL-1, MCF-7 and HCC-1937 were the breast carcinoma cell lines chosen, the panel of tested bladder carcinoma cells comprised the T-24, TCC-SUP, UM-UC-3 and J-82 cell lines.</p> <p>Results</p> <p>Each of the VAPs inhibited cell growth, but the extent of this inhibition differed with the preparation and with the cell line. The concentrations of VAP-Qu, VAP-M and VAP-A which led to a 50 % reduction of cell growth (IC₅₀) varied between 0.6 and 0.03 mg/ml. Higher concentrations of VAP-P were required to obtain a comparable effect. Purified mistletoe lectin I (MLI) led to an inhibition of breast carcinoma cell growth at concentrations lower than those of VAPs, but the sensitivity towards purified MLI did not parallel that towards VAPs. Bladder carcinoma cells were in most cases more sensitive to VAPs treatment than breast carcinoma cells. The total mistletoe lectin content was very high in VAP-Qu (54 ng/mg extract), intermediate in VAP-M (25 ng/mg extract), and very low in VAP-P (1.3 ng/mg extract) and in VAP-A (1 ng/mg extract). As to be expected from the low content of mistletoe lectin, VAP-P led to relatively weak cytotoxic effects. Most remarkably, however, the lectin-poor VAP-A revealed a cytotoxic effect comparable to, or even stronger than, that of the lectin-rich VAP-Qu, on all tested bladder and breast carcinoma cell lines.</p> <p>Conclusion</p> <p>The results suggest the existence of cytotoxic components other than mistletoe lectin in VAP-A and reveal an unexpected potential of this preparation for the treatment of breast and bladder cancer.</p

Implementing shared decision-making in nutrition clinical practice: A theory-based approach and feasibility study

<p>Abstract</p> <p>Background</p> <p>There are a growing number of dietary treatment options to choose from for the management of many chronic diseases. Shared decision making represents a promising approach to improve the quality of the decision making process needed for dietary choices that are informed by the best evidence and value-based. However, there are no studies reporting on theory-based approaches that foster the implementation of shared decision making in health professions allied to medicine. The objectives of this study are to explore the integration of shared decision making within real nutritional consultations, and to design questionnaires to assess dieticians' intention to adopt two specific behaviors related to shared decision making using the Theory of Planned Behavior.</p> <p>Methods</p> <p>Forty dieticians will audiotape one clinical encounter to explore the presence of shared decision making within the consultation. They will also participate to one of five to six focus groups that aim to identify the salient beliefs underlying the determinants of their intention to present evidence-based dietary treatment options to their patients, and clarify the values related to dietary choices that are important to their patients. These salient beliefs will be used to elaborate the items of two questionnaires. The internal consistency of theoretical constructs and the temporal stability of their measurement will be checked using the test-retest method by asking 35 dieticians to complete the questionnaire twice within a two-week interval.</p> <p>Discussion</p> <p>The proposed research project will be the first study to: provide preliminary data about the adoption of shared decision making by dieticians and theirs patients; elicit dieticians' salient beliefs regarding the intention to adopt shared decision making behaviors, report on the development of a specific questionnaire; explore dieticians' views on the implementation of shared decision making; and compare their views regarding the implementation of shared decision making in different clinical settings.</p> <p>It is anticipated that the results generated by the proposed research project will significantly contribute to the emergence of shared decision making in nutrition through a theory-based approach.</p

Intraaortic Balloon Pump Counterpulsation and Cerebral Autoregulation: an observational study

The use of Intra-aortic counterpulsation is a well established supportive therapy for patients in cardiac failure or after cardiac surgery. Blood pressure variations induced by counterpulsation are transmitted to the cerebral arteries, challenging cerebral autoregulatory mechanisms in order to maintain a stable cerebral blood flow. This study aims to assess the effects on cerebral autoregulation and variability of cerebral blood flow due to intra-aortic balloon pump and inflation ratio weaning

CpG site degeneration triggered by the loss of functional constraint created a highly polymorphic macaque drug-metabolizing gene, CYP1A2

<p>Abstract</p> <p>Background</p> <p>Elucidating the pattern of evolutionary changes in drug-metabolizing genes is an important subject not only for evolutionary but for biomedical research. We investigated the pattern of divergence and polymorphisms of macaque <it>CYP1A1 </it>and <it>CYP1A2 </it>genes, which are major drug-metabolizing genes in humans. In humans, <it>CYP1A2 </it>is specifically expressed in livers while <it>CYP1A1 </it>has a wider gene expression pattern in extrahepatic tissues. In contrast, macaque <it>CYP1A2 </it>is expressed at a much lower level than <it>CYP1A1 </it>in livers. Interestingly, a previous study has shown that <it>Macaca fascicularis CYP1A2 </it>harbored unusually high genetic diversity within species. Genomic regions showing high genetic diversity within species is occasionally interpreted as a result of balancing selection, where natural selection maintains highly diverged alleles with different functions. Nevertheless many other forces could create such signatures.</p> <p>Results</p> <p>We found that the <it>CYP1A1/2 </it>gene copy number and orientation has been highly conserved among mammalian genomes. The signature of gene conversion between <it>CYP1A1 </it>and <it>CYP1A2 </it>was detected, but the last gene conversion event in the simian primate lineage occurred before the <it>Catarrhini-Platyrrhini </it>divergence. The high genetic diversity of macaque <it>CYP1A2 </it>therefore cannot be explained by gene conversion between <it>CYP1A1 </it>and <it>CYP1A2</it>. By surveying <it>CYP1A2 </it>polymorphisms in total 91 <it>M. fascicularis </it>and <it>M. mulatta</it>, we found several null alleles segregating in these species, indicating functional constraint on <it>CYP1A2 </it>in macaques may have weakened after the divergence between humans and macaques. We propose that the high genetic diversity in macaque <it>CYP1A2 </it>is partly due to the degeneration of CpG sites, which had been maintained at a high level by purifying selection, and the rapid degeneration process was initiated by the loss of functional constraint on macaque <it>CYP1A2</it>.</p> <p>Conclusions</p> <p>Our findings show that the highly polymorphic <it>CYP1A2 </it>gene in macaques has not been created by balancing selection but by the burst of CpG site degeneration after loss of functional constraint. Because the functional importance of <it>CYP1A1/2 </it>genes is different between humans and macaques, we have to be cautious in extrapolating a drug-testing data using substrates metabolized by <it>CYP1A </it>genes from macaques to humans, despite of their somewhat overlapping substrate specificity.</p

Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines

Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. Previous analyses have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. The genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours’ biology have not yet been established. In this study, genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data from primary tumours to address this question. Genome methylation was analysed using the Illumina infinium HumanMethylome450 bead chip system and gene expression was analysed using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Regulation by methylation was confirmed by demethylation using 5-aza-2-deoxycytidine and reverse transcription–quantitative PCR. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested played a role in their silencing in yolk sac tumour cells and many of these genes were also differentially expressed in primary tumours. Genes silenced by methylation in the various GCT cell lines were identified. Several pluripotency-associated genes were identified as a major functional group of silenced genes

Validation of the western ontario rotator cuff index in patients with arthroscopic rotator cuff repair: A study protocol

<p>Abstract</p> <p>Background</p> <p>Arthroscopic rotator cuff repair is described as being a successful procedure. These results are often derived from clinical general shoulder examinations, which are then classified as 'excellent', 'good', 'fair' or 'poor'. However, the cut-off points for these classifications vary and sometimes modified scores are used.</p> <p>Arthroscopic rotator cuff repair is performed to improve quality of life. Therefore, disease specific health-related quality of life patient-administered questionnaires are needed. The WORC is a quality of life questionnaire designed for patients with disorders of the rotator cuff. The score is validated for rotator cuff disease, but not for rotator cuff repair specifically.</p> <p>The aim of this study is to investigate reliability, validity and responsiveness of WORC in patients undergoing arthroscopic rotator cuff repair.</p> <p>Methods/Design</p> <p>An approved translation of the WORC into Dutch is used. In this prospective study three groups of patients are used: 1. Arthroscopic rotator cuff repair; 2. Disorders of the rotator cuff without rupture; 3. Shoulder instability.</p> <p>The WORC, SF-36 and the Constant Score are obtained twice before therapy is started to measure reliability and validity. Responsiveness is tested by obtaining the same tests after therapy.</p

The 2018 Lake Louise Acute Mountain Sickness Score.

Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bärtsch, Andrew M. Luks, Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus Committee. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol 19:1-4, 2018.- The Lake Louise Acute Mountain Sickness (AMS) scoring system has been a useful research tool since first published in 1991. Recent studies have shown that disturbed sleep at altitude, one of the five symptoms scored for AMS, is more likely due to altitude hypoxia per se, and is not closely related to AMS. To address this issue, and also to evaluate the Lake Louise AMS score in light of decades of experience, experts in high altitude research undertook to revise the score. We here present an international consensus statement resulting from online discussions and meetings at the International Society of Mountain Medicine World Congress in Bolzano, Italy, in May 2014 and at the International Hypoxia Symposium in Lake Louise, Canada, in February 2015. The consensus group has revised the score to eliminate disturbed sleep as a questionnaire item, and has updated instructions for use of the score