Application of Brownian motion theory to the analysis of membrane channel ionic trajectories calculated by molecular dynamics

This paper shows how Brownian motion theory can be used to analyze features of individual ion trajectories in channels as calculated by molecular dynamics, and that its use permits more precise determinations of diffusion coefficients than would otherwise be possible. We also show how a consideration of trajectories of single particles can distinguish between effects due to the magnitude of the diffusion coefficient and effects due to barriers and wells in the potential profile, effects which can not be distinguished by consideration of average fluxes

Genetic counseling of patients with ovarian carcinoma:acceptance, timing, and psychological wellbeing

The new Dutch guidelines on hereditary and familial ovarian carcinoma recommend genetic testing of all patients with epithelial ovarian cancer (EOC). With this study, we aimed to obtain insight into (1) the acceptance and timing of the offer of genetic counseling in women with EOC, (2) reasons for accepting or declining genetic counseling, and (3) psychological differences between women who did and did not have genetic counseling. A multicenter questionnaire survey was performed in patients with EOC in four Dutch oncology centers. The questionnaire addressed whether, how, and when genetic counseling was offered, women's arguments to accept or decline genetic counseling, and included the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). A total of 67 women completed the questionnaire, of which 43 had genetic counseling. Despite a wide variability in the timing of the offer of genetic counseling, 89% of the women were satisfied with the timing. No significant differences were found between the CWS and HADS scores for the timing of the offer of genetic counseling and whether or not women had genetic counseling. Taking the small sample size into account, the results tentatively suggest that genetic counseling may have limited impact on the psychosocial wellbeing of women with EOC. Therefore, we assume that implementation of the new guidelines offering genetic counseling to all patients with EOC will not cause considerable additional burden to these patients

Polygenic Risk Scores for Genetic Counseling in Psychiatry: Lessons Learned from other Fields of Medicine

Polygenic risk scores (PRS) may aid in the identification of individuals at-risk for psychiatric disorders, treatment optimization, and increase in prognostic accuracy. PRS may also add significant value to genetic counseling. Thus far, integration of PRSs in genetic counseling sessions remains problematic because of uncertainties in risk prediction and other concerns. Here, we review the current utility of PRSs in the context of clinical psychiatry. By comprehensively appraising the literature in other fields of medicine including breast cancer, Alzheimer's Disease, and cardiovascular disease, we outline several lessons learned that could be applied to future studies and may thus benefit the incorporation of PRS in psychiatric genetic counseling. These include integrating PRS with environmental factors (e.g. lifestyle), setting up large-scale studies, and applying reproducible methods allowing for cross-validation between cohorts. We conclude that psychiatry may benefit from experiences in these fields. PRS may in future have a role in genetic counseling in clinical psychiatric practice, by advancing prevention strategies and treatment decision-making, thus promoting quality of life for (potentially) affected individuals

Модификации арефлюксного холедохоеюноанастомоза с восстановлением пассажа желчи в двенадцатиперстную кишку

Разработаны модификации формирования холедохоеюноанастомоза, способствующие восстановлению желчетока с пассажем желчи в двенадцатиперстную кишку, что предупреждает развитие в ней пептической язвы. Предложена специальная методика мобилизации отключенного по Ру сегмента тощей кишки, обеспечивающая его полноценную моторику.Modifications of forming choledochoanastomosis promoting restoration of bile passage to the duodenum, which prevented development of peptic ulcer, were worked out. A special technique for mobilization of the switched off segment of the jejunum according to Roux promoting an adequate motility was suggested

Lack of genotype-phenotype correlation in basal cell nevus syndrome:A Dutch multicenter retrospective cohort study

Contains fulltext : 225468.pdf (Publisher’s version ) (Closed access

Surgical Oncologists and Nurses in Breast Cancer Care are Ready to Provide Pre-Test Genetic Counseling

Background: Pre-test genetic counseling for patients with breast cancer is increasingly being provided by nongenetic healthcare professionals. We evaluated the attitudes, knowledge, and self-efficacy of surgeons, oncologists, and nurses regarding mainstream genetic testing and the feasibility to incorporate pre-test genetic counseling into routine care. Methods: We offered an online training to healthcare professionals from 13 hospitals and implemented a mainstream genetic testing pathway in 11/13 (85%) hospitals. Questionnaires were sent before (T0) and 6 months after (T1) completing the training. Those who did not complete the training received a questionnaire to assess their motivations. Results: In 11 hospitals, 80 (65%) healthcare professionals completed the training, of whom 70 (88%) completed both questionnaires. The attitudes, (perceived) knowledge and self-efficacy of healthcare professionals were high both at baseline and 6 months after completing the training. After 6 months, their perceived knowledge about the advantages and disadvantages of a genetic test and implications for family members had significantly improved (p = 0.012 and p = 0.021, respectively). For the majority (89%), the time investment for pre-test genetic counseling was less than 15 min per patient and as expected or better. Healthcare professionals considered the total time investment feasible to incorporate mainstream genetic testing into their daily practice. The main barrier to complete the training was lack of time. The online training was considered useful, with a rating of 8/10. Conclusion: Surgical oncologists and nurses in breast cancer care feel well-equipped and motivated to provide pre-test genetic counseling after completion of an online training module

Barriers to genetic testing in clinical psychiatry and ways to overcome them: from clinicians’ attitudes to sociocultural differences between patients across the globe

Genetic testing has evolved rapidly over recent years and new developments have the potential to provide insights that could improve the ability to diagnose, treat, and prevent diseases. Information obtained through genetic testing has proven useful in other specialties, such as cardiology and oncology. Nonetheless, a range of barriers impedes techniques, such as whole-exome or whole-genome sequencing, pharmacogenomics, and polygenic risk scoring, from being implemented in psychiatric practice. These barriers may be procedural (e.g., limitations in extrapolating results to the individual level), economic (e.g., perceived relatively elevated costs precluding insurance coverage), or related to clinicians’ knowledge, attitudes, and practices (e.g., perceived unfavorable cost-effectiveness, insufficient understanding of probability statistics, and concerns regarding genetic counseling). Additionally, several ethical concerns may arise (e.g., increased stigma and discrimination through exclusion from health insurance). Here, we provide an overview of potential barriers for the implementation of genetic testing in psychiatry, as well as an in-depth discussion of strategies to address these challenges

Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer susceptibility

Background In approximately 10% of all gastric cancer (GC) cases, a heritable cause is suspected. A subset of these cases have a causative germline CDH1 mutation; however, in most cases the cause remains unknown. Our objective was to assess to what extent these remaining cases may be explained by germline mutations in the novel candidate GC predisposing genes CTNNA1, MAP3K6 or MYD88. Methods We sequenced a large cohort of unexplained young and/or familial patients with GC (n=286) without a CDH1germline mutation for germline variants affecting CTNNA1, MAP3K6 and MYD88 using a targeted next-generation sequencing approach based on single-molecule molecular inversion probes. Results Predicted deleterious germline variants were not encountered in MYD88, but recurrently observed in CTNNA1 (n=2) and MAP3K6 (n=3) in our cohort of patients with GC. In contrast to deleterious variants in CTNNA1, deleterious variants in MAP3K6 also occur frequently in the general population. Conclusions Based on our results MAP3K6 should no longer be considered a GC predisposition gene, whereas deleterious CTNNA1 variants are confirmed as an infrequent cause of GC susceptibility. Biallelic MYD88 germline mutations are at most a very rare cause of GC susceptibility as no additional cases were identified.This study was funded by KWF Kankerbestrijding (grant number KUN2013-5876, RSvdP)

Design and Feasibility of an Intervention to Support Cancer Genetic Counselees in Informing their At-Risk Relatives

Cancer genetic counselees receive individualized information regarding heightened risks and medical recommendations which is also relevant for their at-risk relatives. Unfortunately, counselees often insufficiently inform these relatives. We designed an intervention aimed at improving counselees' knowledge regarding which at-risk relatives to inform and what information to disclose, their motivation to disclose, and their self-efficacy. The intervention, offered by telephone by trained psychosocial workers, is based on the principles of Motivational Interviewing. Phase 1 of the intervention covers agenda setting, exploration, and evaluation, and phase 2 includes information provision, enhancing motivation and self-efficacy, and brainstorming for solutions to disseminate information within the family. Fidelity and acceptability of the intervention were assessed using recordings of intervention sessions and by counselee self-report. A total of 144 counselees participated. Psychosocial workers (n = 5) delivered the intervention largely as intended. Counselees highly appreciated the content of the intervention and the psychosocial workers who delivered the intervention. In the sessions, psychosocial workers provided additional and/or corrective information, and brainstorming for solutions was performed in 70 %. These results indicate that this intervention is feasible and warrants testing in clinical practice. For this, a randomized controlled trial is currently in progress to test the intervention's efficacy