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Stevens R.G.,onn Health Center
Chronobiology International | Year: 2016

Electric light is one of the signature inventions of human beings. A problem, however, is that electric light can confuse our endogenous circadian rhythmicity. It has now become apparent that circadian biology is fundamental to the functioning and adaptation of almost all life forms. In the modern world, everyone is exposed to electric light during the day and night, and thereby can experience some level of circadian disruption. Perhaps as a canary in the coal mine, study of people whose work hours include nighttime (shift workers) is beginning to yield insights on the adverse health effects of circadian disruption from electric light. © 2016 Taylor & Francis

Glucksman A.,onn Health Center | Naut E.,St Francis Hospital and Medical Center
Connecticut Medicine | Year: 2016

A 43-year-old male with a history of bioprosthetic aortic valve replacement and tricuspid valve annuloplasty presented with vertigo and was found to have an acute infarct in the left superior cerebellum, as well as a left-middle cerebral artery mycotic aneurysm. Blood cultures grew Cardiobacterium hominis and bioprosthetic aortic valve vegetation was found on transthoracic echocardiogram.

Bodakhe S.,National Institute of Pharmaceutical Education and Research | Verma S.,National Institute of Pharmaceutical Education and Research | Verma S.,onn Health Center | Garkhal K.,National Institute of Pharmaceutical Education and Research | And 3 more authors.
Nanomedicine | Year: 2013

Aim: An injectable, photocrosslinkable nanocomposite was prepared using a fumarate derivative of poly(glycerol sebacate) and nanohydroxyapatite. Materials & methods: Polymers with varying physical and mechanical properties were synthesized. Furthermore, nanocomposites were developed using a homogenization process by combining nanohydroxyapatite within poly(glycerol sebacate) matrix via photocrosslinking and evaluated both in vitro and in vivo. Results & discussion: The nanocomposites were injectable, highly bioactive and biocompatible. Addition of nanohydroxyapatite led to enhanced mechanical properties with an ultimate strength of 8 MPa. The optimized nanocomposite showed good in vitro cell attachment, proliferation and differentiation of rat bone marrow-derived mesenchymal stem cells. The in vivo evaluation in a rat calvarial bone defect model showed significantly high alkaline phosphatase activity and bone regeneration. Conclusion: This injectable, biocompatible and bioactive in situ hardening composite graft was found to be suitable for load-bearing bone regeneration applications using minimally invasive surgery. © 2013 Future Medicine Ltd.

Parpart S.,U.S. National Cancer Institute | Parpart S.,Georgetown University | Roessler S.,U.S. National Cancer Institute | Roessler S.,University of Heidelberg | And 12 more authors.
Hepatology | Year: 2014

Globally, hepatocellular carcinoma (HCC) accounts for 70%-85% of primary liver cancers and ranks as the second leading cause of male cancer death. Serum alpha-fetoprotein (AFP), normally highly expressed in the liver only during fetal development, is reactivated in 60% of HCC tumors and associated with poor patient outcome. We hypothesize that AFP+ and AFP- tumors differ biologically. Multivariable analysis in 237 HCC cases demonstrates that AFP level predicts poor survival independent of tumor stage (P<0.043). Using microarray-based global microRNA (miRNA) profiling, we found that miRNA-29 (miR-29) family members were the most significantly (P<0.001) down-regulated miRNAs in AFP+ tumors. Consistent with miR-29's role in targeting DNA methyltransferase 3A (DNMT3A), a key enzyme regulating DNA methylation, we found a significant inverse correlation (P<0.001) between miR-29 and DNMT3A gene expression, suggesting that they might be functionally antagonistic. Moreover, global DNA methylation profiling reveals that AFP+ and AFP- HCC tumors have distinct global DNA methylation patterns and that increased DNA methylation is associated with AFP+ HCC. Experimentally, we found that AFP expression in AFP- HCC cells induces cell proliferation, migration, and invasion. Overexpression of AFP, or conditioned media from AFP+ cells, inhibits miR-29a expression and induces DNMT3A expression in AFP- HCC cells. AFP also inhibited transcription of the miR-29a/b-1 locus, and this effect is mediated through c-MYC binding to the transcript of miR-29a/b-1. Furthermore, AFP expression promotes tumor growth of AFP- HCC cells in nude mice. Conclusion: Tumor biology differs considerably between AFP+ HCC and AFP- HCC; AFP is a functional antagonist of miR-29, which may contribute to global epigenetic alterations and poor prognosis in HCC. © 2014 by the American Association for the Study of Liver Diseases.

Stevens R.G.,onn Health Center | Cologne J.B.,Radiation Effects Research Foundation | Nakachi K.,Radiation Effects Research Foundation | Grant E.J.,Radiation Effects Research Foundation | Neriishi K.,Radiation Effects Research Foundation
Cancer Science | Year: 2011

Iron can be a potent pro-oxidant and, on this basis, elevated body iron may increase the risk of cancer. Although epidemiological evidence is mixed, there is overall support for this possibility. In addition, because of this same oxidative capacity, body iron levels may alter radiation sensitivity. In the present study, a nested case-control study of breast cancer was conducted in Japanese atomic bomb survivors. Stored serum samples from the Adult Health Study cohort were assayed for ferritin levels and joint statistical analyses were conducted of ferritin and radiation dose on the risk of breast cancer. Serum ferritin is the best feasible indicator of body iron levels in otherwise healthy people. A total of 107 cases and 212 controls were available for analysis. The relative risk (RR) of breast cancer for a 1 log unit increase in ferritin was 1.4 (95% confidence interval 1.1-1.8). This translates to an RR of 1.64 comparing high and low values of the interquartile range among controls (58 and 13.2ng/mL, respectively). The results support the hypothesis that elevated body iron stores increase the risk of breast cancer. However, the study was inconclusive regarding the question of whether body iron alters radiation-induced breast cancer risk. © 2011 Japanese Cancer Association.

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