Patient and provider factors associated with the noninitiation of tamoxifen for young women at high-risk for the development of breast cancer

We sought to identify factors associated with disparities in tamoxifen utilization among young patients at high- risk for developing breast cancer. We identified 67 premenopausal, high- risk women age 35- 45, without surgical prophylaxis, who did not initiate tamoxifen. Factors associated with noninitiation were examined. About 37% of patients had no documented provider- based discussion regarding initiation. Type of high- risk diagnosis was the only factor associated with a provider- based discussion (P = .03). For patients offered tamoxifen, primary reasons for noninitiation were perceived minimal benefit (66.7%), fertility concerns (16.7%), and concerns about side effects (7.1%). Implementation of comprehensive educational strategies regarding the benefits of tamoxifen should be facilitated to improve initiation among young high- risk patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154627/1/tbj13528_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154627/2/tbj13528.pd

Patient and provider factors associated with the noninitiation of tamoxifen for young women at high-risk for the development of breast cancer

We sought to identify factors associated with disparities in tamoxifen utilization among young patients at high- risk for developing breast cancer. We identified 67 premenopausal, high- risk women age 35- 45, without surgical prophylaxis, who did not initiate tamoxifen. Factors associated with noninitiation were examined. About 37% of patients had no documented provider- based discussion regarding initiation. Type of high- risk diagnosis was the only factor associated with a provider- based discussion (P = .03). For patients offered tamoxifen, primary reasons for noninitiation were perceived minimal benefit (66.7%), fertility concerns (16.7%), and concerns about side effects (7.1%). Implementation of comprehensive educational strategies regarding the benefits of tamoxifen should be facilitated to improve initiation among young high- risk patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154627/1/tbj13528_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154627/2/tbj13528.pd

Screening and management of viral hepatitis and hepatocellular carcinoma in Mongolia: results from a survey of Mongolian physicians from all major provinces of Mongolia

published_or_final_versio

O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

n/

Fetal Brain mTOR Signaling Activation in Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is characterized by developmental malformations of the cerebral cortex known as tubers, comprised of cells that exhibit enhanced mammalian target of rapamycin (mTOR) signaling. To date, there are no reports of mTORC1 and mTORC2 activation in fetal tubers or in neural progenitor cells lacking Tsc2. We demonstrate mTORC1 activation by immunohistochemical detection of substrates phospho-p70S6K1 (T389) and phospho-S6 (S235/236), and mTORC2 activation by substrates phospho-PKCα (S657), phospho-Akt (Ser473), and phospho-SGK1 (S422) in fetal tubers. Then, we show that Tsc2 shRNA knockdown (KD) in mouse neural progenitor cells (mNPCs) in vitro results in enhanced mTORC1 (phospho-S6, phospho-4E-BP1) and mTORC2 (phospho-Akt and phospho-NDRG1) signaling, as well as a doubling of cell size that is rescued by rapamycin, an mTORC1 inhibitor. Tsc2 KD in vivo in the fetal mouse brain by in utero electroporation causes disorganized cortical lamination and increased cell volume that is prevented with rapamycin. We demonstrate for the first time that mTORC1 and mTORC2 signaling is activated in fetal tubers and in mNPCs following Tsc2 KD. These results suggest that inhibition of mTOR pathway signaling during embryogenesis could prevent abnormal brain development in TS

Gene therapy rescues cone function in congenital achromatopsia

The successful restoration of visual function with recombinant adeno-associated virus (rAAV)-mediated gene replacement therapy in animals and humans with an inherited disease of the retinal pigment epithelium has ushered in a new era of retinal therapeutics. For many retinal disorders, however, targeting of therapeutic vectors to mutant rods and/or cones will be required. In this study, the primary cone photoreceptor disorder achromatopsia served as the ideal translational model to develop gene therapy directed to cone photoreceptors. We demonstrate that rAAV-mediated gene replacement therapy with different forms of the human red cone opsin promoter led to the restoration of cone function and day vision in two canine models of CNGB3 achromatopsia, a neuronal channelopathy that is the most common form of achromatopsia in man. The robustness and stability of the observed treatment effect was mutation independent, but promoter and age dependent. Subretinal administration of rAAV5–hCNGB3 with a long version of the red cone opsin promoter in younger animals led to a stable therapeutic effect for at least 33 months. Our results hold promise for future clinical trials of cone-directed gene therapy in achromatopsia and other cone-specific disorders