Should individuals be informed about their salt sensitivity status? First indications of the value of testing for genetic predisposition to low-risk conditions

The present study examined the possible pathways of effect of genetic testing for relatively "low-risk" conditions by exploring positive as well as negative effects of anticipated test results on the intention to restrict salt intake. In a cross-sectional within-subjects design, patients being tested for genetic predispositions to salt sensitivity reported higher overall intentions to restrict their salt intake when anticipating positive test results, confirming the value of genetic testing for low-risk conditions. However, participants in the precontemplation and preparation stages of change reported lower intentions when anticipating negative test results. This result suggests that negative test results have a negative impact on the motivation to perform preventive behavior among those who have not yet considered, and those who are planning to perform, the preventive behavior. Although the results show that, overall, genetic testing for low-risk conditions has a positive impact on the motivation to engage in preventive behavior, one needs to be aware of the potential negative effect of receiving negative test results. Consequently, individuals receiving negative test results should be carefully counseled on the meaning of the results and the consequences for preventive behavior.     

Associations between anticipated reactions to genetic test results and interest in genetic testing: will self-selection reduce the potential for harm?

The proliferation of genetic susceptibility tests for complex diseases away from clinic settings increases the potential for harm. This study assessed whether people are likely to self-select themselves into or out of genetic testing depending on whether they believe they could cope with the results. Associations between anticipated reactions to adverse genetic test results and interest in taking genetic tests for cancer and heart disease were examined in a community sample of English adults (n = 1,024). Interest in genetic testing overall was 78% for cancer risk and 80% for heart disease risk. As predicted, there were differences by anticipated reactions. People who anticipated regret about having taken a genetic test for cancer risk expressed lower interest than those who did not anticipate regret (46% vs. 89%), and people who anticipated being glad to know of increased risk status (i.e., reduced uncertainty) were more interested than those who did not look forward to reduced uncertainty (91% vs. 22%). Patterns were similar for heart disease ("regret" 66% vs. 87%; "reduced uncertainty" 87% vs. 38%). The potential for harm from future genetic susceptibility tests may be less than feared if people who anticipate adverse reactions self-select themselves out of testing. However, given that a significant proportion of people who anticipated adverse reactions also expressed interest in testing, there is still a concern about safety. It remains to be seen whether the same patterns emerge in studies that actually offer genetic tests for common gene variants in community settings.     

“It could just be an additional test couldn't it?” 1 Genetic testing for susceptibility to aggression and violence

Much of the current genetic research into aggressive and violent behavior focuses on young people and might appear to offer the hope of targeted prediction and intervention. In the UK data are collected on children from various agencies and collated to produce “at risk of offending” identities used to justify intervention. Information from behavioral genetic tests could conceivably be included. Regulatory frameworks for collecting, storing and using information from DNA samples differ between the health service and the police particularly in the need for consent and the treatment of children. This paper draws on discussions with professionals involved with “problem” young people to consider their views on the utility of genetic research for tackling violent/aggressive behavior and the impact an identification of genetic susceptibility might have on their clients.     

Animal models of human genetic diseases: do they need to be faithful to be useful?

With the advances in molecular genetics, animal models of human diseases are becoming more numerous and more refined every year. Despite this, one must recognize that they generally do not faithfully and comprehensively mimic the homologous human disease. Faced with these imperfections, some geneticists believe that these models are of little value, while for others, on the contrary, they are important tools. We agree with this second statement, and in this review, we examine the reasons that may explain the observed differences and suggest means to circumvent or even exploit them. Our opinion is that animal models should be regarded more as tools capable of answering specific questions rather than mere replicas, at a smaller scale, of a given human disease. Far from disappointing they are probably called for a promising future.     

Diffusion of genetic testing in oncology: what criteria for regulation?

Does gene testing indicate a switch from an histopathological to a molecular approach of human diseases ? Disease management in oncology is already improved by gene testing, at least for some specific cancers. It is however necessary to distinguish the analysis of genes specific to the tumour which gives clues about the fate of the tumours, from those unique to the patients, which gives clues about the future of the person. For the latter so-called germline mutations, wide scale gene-default screening would put pressure on resource allocation from the health care systems of developed countries. Currently the cost of detecting of 700 genes in the whole French population would exceed the whole health budget of the country for the next 10 years. Even if we can anticipate a dramatic decrease in the unit cost of these genetic tests in the future, their diffusion should not be controlled exclusively by technological and market forces. In this paper, we propose to discuss four main parameters for regulating these genetic tests, using as an archetypal example their application to cancer prevention and treatment: (1) which specific cancer disease is targeted by the test (prevalence, incidence, likelihood of cure with current therapeutics, number of years of life potentially saved...); (2) what are the characteristics of the genes tested and which level of evidence is required about the predictive value of the test; (3) what are the size and characteristics of the population who will be offered the test, and (4) which process and public control are necessary before market approval of the test and reimbursement of related expenditures by health care insurance schemes.     

Can genetic variability for nitrogen metabolism in the developing ear of maize be exploited to improve yield?

Quantitative trait loci (QTLs) for the main steps of nitrogen (N) metabolism in the developing ear of maize (Zea mays L.) and their co-localization with QTLs for kernel yield and putative candidate genes were searched in order to identify chromosomal regions putatively involved in the determination of yield. During the grain-filling period, the changes in physiological traits were monitored in the cob and in the developing kernels, representative of carbon and N metabolism in the developing ear. The correlations between these physiological traits and traits related to yield were examined and localized with the corresponding QTLs on a genetic map. Glycine and serine metabolism in developing kernels and the cognate genes appeared to be of major importance for kernel production. The importance of kernel glutamine synthesis in the determination of yield was also confirmed. The genetic and physiological bases of N metabolism in the developing ear can be studied in an integrated manner by means of a quantitative genetic approach using molecular markers and genomics, and combining agronomic, physiological and correlation studies. Such an approach leads to the identification of possible new regulatory metabolic and developmental networks specific to the ear that may be of major importance for maize productivity.     

How many alleles per locus should be used to estimate genetic distances?

As more microsatellite loci become available for use in genetic surveys of population structure, population geneticists are able to select loci to use in population structure surveys. This study used computer simulations to investigate how the number of alleles at loci affects the precision of estimates of four common genetic distances. This showed that equivalent results could be achieved by examining either a few loci with many alleles or many loci with a few alleles. More specifically, the total number of independent alleles appears to be a good indicator of how precise estimates of genetic distance will be.     

MDSCs might be “Achilles heel” for eradicating CSCs

During tumor initiation and progression, the complicated role of immune cells in the tumor immune microenvironment remains a concern. Myeloid-derived suppressor cells (MDSCs) are a group of immune cells that originate from the bone marrow and have immunosuppressive potency in various diseases, including cancer. In recent years, the key role of cancer stemness has received increasing attention in cancer development and therapy. Several studies have demonstrated the important regulatory relationship between MDSCs and cancer stem cells (CSCs). However, there is still no clear understanding regarding the complex interacting regulation of tumor malignancy, and current research progress is limited. In this review, we summarize the complicated role of MDSCs in the modulation of cancer stemness, evaluate the mechanism of the relationship between CSCs and MDSCs, and discuss potential strategies for eradicating CSCs with respect to MDSCs.     

Do relevant shear forces appear in isokinetic shoulder testing to be implemented in biomechanical models?

Isokinetic dynamometers measure joint torques about a single fixed rotational axis. Previous studies yet suggested that muscles produce both tangential and radial forces during a movement, so that the contact forces exerted to perform this movement are multidirectional. Then, isokinetic dynamometers might neglect the torque components about the two other Euclidean space axes. Our objective was to experimentally quantify the shear forces impact on the overall shoulder torque, by comparing the dynamometer torque to the torque computed from the contact forces at the hand and elbow. Ten healthy women performed isokinetic maximal internal/external concentric/eccentric shoulder rotation movements. The hand and elbow contact forces were measured using two six-axis force sensors. The main finding is that the contact forces at the hand were not purely tangential to the direction of the movement (effectiveness indexes from 0.26 ± 0.25 to 0.54 ± 0.20), such that the resulting shoulder torque computed from the two force sensors was three-dimensional. Therefore, the flexion and abduction components of the shoulder torque measured by the isokinetic dynamometer were significantly underestimated (up to 94.9%). These findings suggest that musculoskeletal models parameters should not be estimated without accounting for the torques about the three space axes.