Goldberg Y.,Hebrew University of Jerusalem |
Porat R.,Hebrew University of Jerusalem |
Kedar I.,Raphael Recanati Genetics Institute |
Shochat C.,Migal Galilee Bio Technology Center |
And 13 more authors.
Familial Cancer | Year: 2010
Mutations in DNA mismatch repair genes underlie lynch syndrome (HNPCC). Lynch syndrome resulting from mutations in MSH6 is considered to be attenuated in comparison to that caused by mutations in MLH1 and MSH2, thus more likely to be under diagnosed. In this study we report of a common mutation in the MSH6 gene in Ashkenazi Jews. Genetic counseling and diagnostic workup for HNPCC was conducted in families who attended the high risk clinic for inherited cancer. We identified the mutation c.3984-3987dup in the MSH6 gene in 19 members of four unrelated Ashkenazi families. This mutation results in truncation of the transcript and in loss of expression of the MSH6 protein in tumors. Tumor spectrum among carriers included colon, endometrial, gastric, ovarian, urinary, and breast cancer. All but one family qualified for the Bethesda guidelines and none fulfilled the Amsterdam Criteria. Members of one family also co-inherited the c.6174delT mutation in the BRCA2 gene. The c.3984-3987dup in the MSH6 gene is a mutation leading to HNPCC among Ashkenazi Jews. This is most probably a founder mutation. In contrast to the c.1906G>C founder mutation in the MSH2 gene, tumors tend to occur later in life, and none of the families qualified for the Amsterdam criteria. c.3984-3987dup is responsible for 1/6 of the mutations identified among Ashkenazi HNPCC families in our cohort. Both mutations: c.3984-3987dup and c.1906G>C account for 61% of HNPCC Ashkenazi families in this cohort. These findings are of great importance for counseling, diagnosis, management and surveillance for Ashkenazi families with Lynch syndrome. ©Springer Science+Business Media B.V. 2009.
Melchert C.,University of Lübeck |
Gez E.,TASMC |
Bohlen G.,University of Lübeck |
Koziol I.,VA Urology Richmond |
And 10 more authors.
Radiotherapy and Oncology | Year: 2013
Purpose: To evaluate dose reduction caused by the implantation of an interstitial inflatable and biodegradable balloon device aiming to achieve lower rectal doses with virtual 3D conformal external beam radiation treatment. Materials and methods: An inflatable balloon device was placed, interstitially and under transrectal ultrasound guidance, into the rectal-prostate interspace prior treatment initiation of 26 patients with localized prostate cancer, who elected to be treated with radiotherapy (3D CRT or IMRT). The pre- and post-implant CT imaging data of twenty two patients were collected (44 images) for the purpose of the 3D conformal virtual planning presented herein. Results: The dorsal prostate-ventral rectal wall separation resulted in an average reduction of the rectal V70% by 55.3% (±16.8%), V80% by 64.0% (±17.7%), V90% by 72.0% (±17.1%), and V100% by 82.3% (±24.1%). In parallel, rectal D2 ml and D0.1 ml were reduced by 15.8% (±11.4%) and 3.9% (±6.4%), respectively. Conclusions: Insertion of the biodegradable balloon into the prostate-rectum interspace is similar to other published invasive procedures. In this virtual dose distribution analysis, the balloon insertion resulted in a remarkable reduction of rectal volume exposed to high radiation doses. This effect has the potential to keep the rectal dose lower especially when higher than usual prostate dose escalation protocols or hypo-fractionated regimes are used. Further prospective clinical investigations on larger cohorts and more conformal radiation techniques will be necessary to define the clinical advantage of the biodegradable interstitial tissue separation device. © 2012 Elsevier Ireland Ltd. All rights reserved.
Goldberg Y.,Hebrew University of Jerusalem |
Kedar I.,Beilinson Hospital |
Kariiv R.,TASMC |
Halpern N.,Hebrew University of Jerusalem |
And 18 more authors.
Familial Cancer | Year: 2014
Lynch Syndrome is caused by mutations in DNA mismatch repair genes. Diagnosis is not always trivial and may be costly. Information regarding incidence, genotype-phenotype correlation, spectrum of mutations and genes involved in specific populations facilitate the diagnostic process and contribute to clinical work-up. To report gene distribution, mutations detected and co-occurrence of related syndromes in a cohort of Ashkenazi Jews in Israel. Patients were identified in dedicated high risk clinics in 3 medical centers in Israel. Diagnostic process followed a multi-step scheme. It included testing for founder mutations, tumor testing, gene sequencing and MLPA. Lynch Syndrome was defined either by positive mutation testing, or by clinical criteria and positive tumor analysis. We report a cohort of 75 Ashkenazi families suspected of Lynch Syndrome. Mutations were identified in 51/75 (68 %) families: 38 in MSH2, 9 in MSH6, and 4 in MLH1. 37/51 (73 %) of these families carried one of the 3 'Ashkenazi' founder mutations in MSH2 or MSH6. Each of the other 14 families carried a private mutation. 3 (6 %) were large deletions. Only 20/51 (39 %) families were Amsterdam Criteria positive; 42 (82 %) were positive for the Bethesda guidelines and 9 (18 %) did not fulfill any Lynch Syndrome criteria. We report C-MMRD and co-occurrence of BRCA and Lynch Syndrome in our cohort. Mutation spectra and gene distribution among Ashkenazi Jews are unique. Three founder Lynch Syndrome mutations are found in 73 % families with known mutations. Among the three, MSH2 and MSH6 are the most common. These features affect the phenotype, the diagnostic process, risk estimation, and genetic counseling. © 2013 Springer Science+Business Media.
News Article | November 1, 2016
A combination of virtual reality and treadmill training may prove effective in preventing dangerous falls associated with aging, Parkinson's disease, mild cognitive impairment or dementia, according to a new Tel Aviv University-Tel Aviv Sourasky Medical Center (TASMC) study published in The Lancet. According to the study's lead authors, Prof. Jeff Hausdorff and Dr. Anat Mirelman, both of TAU's Sackler School of Medicine and TASMC's Center for the Study of Movement, Cognition and Mobility, the intervention combines the physical and cognitive aspects of walking, and could be implemented in gyms, rehabilitation centers and nursing homes to improve walking skills and prevent the falls of older adults and those with movement disorders like Parkinson's disease. "Falls often start a vicious cycle with many negative health consequences," said Dr. Mirelman. "The ability of older people to negotiate obstacles can be impaired because of age-related decline in cognitive abilities like motor planning, divided attention, executive control and judgement. But current interventions typically focus almost exclusively on improving muscle strength, balance and gait. "Our approach helps improve both physical mobility and cognitive aspects that are important for safe walking," Dr. Mirelman continued. "We found that virtual reality plus treadmill training helped to reduce fall frequency and fall risk for at least six months after training -- significantly more than treadmill training alone. This suggests that our use of virtual reality successfully targeted the cognitive aspects of safe ambulation to reduce the risk of falls." The TAU-TASMC team, in collaboration with partners across Europe, collected data from 282 participants at five clinical sites in Belgium, Israel, Italy, the Netherlands and the UK between 2013 and 2015. The participants, all aged 60-90, were able to walk at least five minutes unassisted, were on stable medications and, critically, had reported at least two falls in the six months prior to the start of the study. Nearly half of all participants (130) had Parkinson's disease, and some (43) had mild cognitive impairment. Participants were assigned to treadmill training with virtual reality (146) or treadmill training alone (136). The virtual reality component consisted of a camera that captured the movement of participants' feet and projected it onto a screen in front of the treadmill, so that participants could "see" their feet walking on the screen in real time. The game-like simulation was designed to reduce the risk of falls in older adults by including real life challenges such as avoiding and stepping over obstacles like puddles or hurdles, and navigating pathways. It also provided motivation to the participants, giving them feedback on their performance and scores on the game. While the incident rate of falls was similar in the two groups prior to the intervention, six months after training the rate of falls among those who trained with VR dropped by almost 50%. In contrast, there was no significant reduction in the fall rates among subjects who did not train with the VR. "Interestingly, when we asked people if they enjoyed the treatment program, participants in the virtual reality group reported higher scores on user satisfaction questionnaires and a greater desire to continue to exercise with the 'game,'" said Prof. Hausdorff. "This suggests that the virtual reality not only led to fewer falls, it was also more likely to be used in the long-term. Exercise needs to be fun and effective if it is going to be used continually. "The biggest improvement was seen in participants with Parkinson's disease," Prof. Hausdorff continued. "It was very exciting to see such improvement in the presence of a neurodegenerative disease. Still, we need to conduct further research to verify the results and better understand why the fall rates were so responsive in the people with Parkinson's disease." "Treadmills are widely available, and the additional cost of treadmill training plus virtual reality is only about $4,500. The low cost could permit this approach to be widely used in various settings," said Dr. Mirelman. "Future studies need to examine whether treadmill training plus virtual reality could be used as part of a prevention package to treat fall risk before falls become common and before injuries occur." The research was funded by the European Commission. Tel Aviv University (TAU) is inherently linked to the cultural, scientific and entrepreneurial mecca it represents. It is one of the world's most dynamic research centers and Israel's most distinguished learning environment. Its unique-in-Israel multidisciplinary environment is highly coveted by young researchers and scholars returning to Israel from post-docs and junior faculty positions in the US. American Friends of Tel Aviv University (AFTAU) enthusiastically and industriously pursues the advancement of TAU in the US, raising money, awareness and influence through international alliances that are vital to the future of this already impressive institution.