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Sung Y.-S.,NY | Zhang L.,NY | Chen C.-L.,NY | Huang S.-C.,Chang Gung University | Antonescu C.R.,NY
Genes Chromosomes and Cancer | Year: 2016

Ossifying fibromyxoid tumor (OFMT) is an uncommon mesenchymal neoplasm of uncertain differentiation and intermediate malignant potential. Recurrent gene fusions involving either PHF1 or BCOR have been found in 85% of OFMT, including typical and malignant examples. As a subset of OFMT still lack known genetic abnormalities, we identified two OFMTs negative for PHF1 and BCOR rearrangements, which were subjected to transcriptome analysis for fusion discovery. The RNA sequencing found a novel CREBBP-BCORL1 fusion candidate in an axillary mass of a 51 year-old male and a KDM2A-WWTR1 in a thigh mass of a 36 year-old male. The gene fusions were validated by RT-PCR and FISH in the index cases and then screened by FISH on 4 additional OFMTs lacking known fusions. An identical CREBBP-BCORL1 fusion was found in an elbow tumor from a 30 year-old male. Both OFMTs with CREBBP-BCORL1 fusions had areas of typical OFMT morphology, exhibiting uniform round to epithelioid cells arranged in cords or nesting pattern in a fibromyxoid stroma. The OFMT with KDM2A-WWTR1 fusion involved dermis and superficial subcutis, being composed of ovoid cells in a fibromyxoid background with hyalinized giant rosettes. The S100 immunoreactivity ranged from very focal to absent. Similar to other known fusion genes in OFMT, BCORL1, CREBBP and KDM2A are also involved in histone modification. In summary, we expand the spectrum of molecular abnormalities in OFMT with 2 novel fusions, CREBBP-BCORL1 and KDM2A-WWTR1, further implicating the epigenetic deregulation as the leading pathogenetic mechanism in OFMT. © 2016 Wiley Periodicals, Inc.

Bichoupan K.,NY | Martel-Laferriere V.,NY | Ng M.,NY | Schonfeld E.A.,NY | And 11 more authors.
Hepatology | Year: 2014

In registration trials, triple therapy with telaprevir (TVR), pegylated interferon (Peg-IFN), and ribavirin (RBV) achieved sustained virological response (SVR) rates between 64% and 75%, but the clinical effectiveness and economic burdens of this treatment in real-world practice remain to be determined. Records of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical Center (May-December 2011) were reviewed. Direct medical costs for pretreatment, on-treatment, and post-treatment care were calculated using data from Medicare reimbursement databases, RED Book, and the Healthcare Cost and Utilization Project database. Costs are presented in 2012 U.S. dollars. SVR (undetectable hepatitis C virus [HCV] RNA 24 weeks after the end of treatment) was determined on an intention-to-treat basis. Cost per SVR was calculated by dividing the median cost by the SVR rate. Median age of the 147 patients was 56 years (interquartile range [IQR]=51-61), 68% were male, 19% were black, 11% had human immunodeficiency virus/HCV coinfection, 36% had advanced fibrosis/cirrhosis (FIB-4 scores ≥3.25), and 44% achieved an SVR. The total cost of care was $11.56 million. Median cost of care was $83,721 per patient (IQR=$66,652-$98,102). The median cost per SVR was $189,338 (IQR=$150,735-$221,860). Total costs were TVR (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees (2%), and laboratory tests (1%). Conclusions: TVR and Peg-IFN accounted for 85% of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world study, were major contributors to the high cost per SVR. © 2014 by the American Association for the Study of Liver Diseases.

Humberg L.,U.S. Department of Agriculture | Lowney M.,U.S. Department of Agriculture | Simon R.,NY | Calvanese N.,Central Park Conservancy
Emerging Infectious Diseases | Year: 2012

In 2009, an outbreak of raccoon rabies in Central Park in New York City, New York, USA, infected 133 raccoons. Five persons and 2 dogs were exposed but did not become infected. A trap-vaccinate-release program vaccinated ≈500 raccoons and contributed to the end of the epizootic.

Dominguez-Bello M.G.,University of Puerto Rico at San Juan | Blaser M.J.,NY | Blaser M.J.,New York Harbor Veterans Affairs Medical Center | Blaser M.J.,New York University | And 3 more authors.
Gastroenterology | Year: 2011

Little was known about the development of the gastrointestinal (GI) tract microbiota, until recently, because of difficulties in obtaining sufficient sequence information from enough people or time points. Now, with decreased costs of DNA sequencing and improved bioinformatic tools, we can compare GI tract bacterial communities among individuals, of all ages from infancy to adulthood. Some key recent findings are that the initial bacterial community, even in the GI tract, depends strongly on delivery mode; that the process of early development of the microbiota is highly unstable and idiosyncratic; that the microbiota differs considerably among children from different countries; and that older adults have substantially different GI tract communities than younger adults, indicating that the GI tract microbiota can change throughout life. We relate these observations to different models of evolution including the evolution of senescence and suggest that probiotics be selected based on patient age. Studies of the microbiota in older people might tell us which probiotics could increase longevity. Drug metabolism varies among individuals with different microbial communities, so age- and region-specific clinical trials are required to ensure safety and efficacy. © 2011 AGA Institute.

Jones J.A.,NY | Collins S.M.,NY | Vernacchio V.R.,NY | Lachance D.M.,NY | Koffas M.A.G.,Rensselaer Polytechnic Institute
Biotechnology Progress | Year: 2015

Flavonoids are a growing class of bioactive natural products with distinct and interesting bioactivity both in vitro and in vivo. The extraction of flavonoids from plant sources is limited by their low natural abundance and commonly results in a mixture of products that are difficult to separate. However, due to recent advances, the microbial production of plant natural products has developed as a promising alternative for flavonoid production. Through optimization of media, induction temperature, induction point, and substrate delay time, we demonstrate the highest conversion of naringenin to eriodictyol (62.7 ± 2.7 mg/L) to date, using the native E. coli hydroxylase complex, HpaBC. We also show the first evidence of in vivo HpaBC activity towards the monohydroxylated flavan-3-ol afzelechin with catechin product titers of 34.7 ± 1.5 mg/L. This work confirms the wide applicability of HpaBC towards realizing efficient de novo production of various orthohydroxylated flavonoids and flavonoid derived products in E. coli. © 2015 American Institute of Chemical Engineers.

Smith H.C.,NY | Smith H.C.,Cancer Center Rochester | Smith H.C.,Rochester BioVenture Center | Bennett R.P.,NY | And 4 more authors.
Seminars in Cell and Developmental Biology | Year: 2012

APOBEC1 is a cytidine deaminase that edits messenger RNAs and was the first enzyme in the APOBEC family to be functionally characterized. Under appropriate conditions APOBEC1 also deaminates deoxycytidine in single-stranded DNA (ssDNA). The other ten members of the APOBEC family have not been fully characterized however several have deoxycytidine deaminase activity on ssDNAs. Despite the nucleic acid substrate preferences of different APOBEC proteins, a common feature appears to be their intrinsic ability to bind to RNA as well as to ssDNA. RNA binding to APOBEC proteins together with protein-protein interactions, post-translation modifications and subcellular localization serve as biological modulators controlling the DNA mutagenic activity of these potentially genotoxic proteins. © 2011 Elsevier Ltd.

Lewis A.,NYU Langone Medical Center | Weaver J.,NY | Caplan A.,NYU Langone Medical Center
American Journal of Transplantation | Year: 2016

We sought to evaluate whether television and cinematic coverage of brain death is educational or misleading. We identified 24 accessible productions that addressed brain death using the archives of the Paley Center for Media (160 000 titles) and the Internet Movie Database (3.7 million titles). Productions were reviewed by two board-certified neurologists. Although 19 characters were pronounced brain dead, no productions demonstrated a complete examination to assess for brain death (6 included an assessment for coma, 9 included an evaluation of at least 1 brainstem reflex, but none included an assessment of every brainstem reflex, and 2 included an apnea test). Subjectively, both authors believed only a small fraction of productions (13% A.L., 13% J.W.) provided the public a complete and accurate understanding of brain death. Organ donation was addressed in 17 productions (71%), but both reviewers felt that the discussions about organ donation were professional in a paucity of productions (9% for A.L., 27% for J.W.). Because television and movies serve as a key source for public education, the quality of productions that feature brain death must be improved. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Israelow B.,NY | Narbus C.M.,NY | Sourisseau M.,NY | Evans M.J.,NY
Hepatology | Year: 2014

Hepatitis C virus (HCV) exposure leads to persistent life-long infections characterized by chronic inflammation often developing into cirrhosis and hepatocellular carcinoma. The mechanism by which HCV remains in the liver while inducing an inflammatory and antiviral response remains unclear. Though the innate immune response to HCV in patients seems to be quite active, HCV has been shown in cell culture to employ a diverse array of innate immune antagonists, which suggests that current model systems to study interactions between HCV and the innate immune system are not representative of what happens in vivo. We recently showed that hepatoma-derived HepG2 cells support the entire HCV life cycle if the liver-specific microRNA, miR-122, is expressed along with the entry factor, CD81 (termed HepG2-HFL cells). We found that there was a striking difference in these cells' ability to sustain HCV infection and spread when compared with Huh-7 and Huh-7.5 cells. Additionally, HepG2-HFL cells exhibited a more robust antiviral response when challenged with other RNA viruses and viral mimetics than Huh-7 and Huh-7.5 cells. HCV infection elicited a potent interferon-lambda (IFN-λ), IFN-stimulated gene, and cytokine response in HepG2-HFL cells, but not in Huh-7 cells, suggesting that HepG2-HFL cells more faithfully recapitulate the innate immune response to HCV infection in vivo. Using this model, we found that blocking the retinoic acid-inducible gene I (RIG-I)-like receptor pathway or the IFN-λ-signaling pathway promoted HCV infection and spread in HepG2-HFL cells. Conclusion: HepG2-HFL cells represent a new system to study the interaction between HCV and the innate immune system, solidifying the importance of IFN-λ in hepatic response to HCV infection and revealing non-redundant roles of RIG-I and melanoma differentiation-associated protein 5 in HCV recognition and repression of infection. © 2014 by the American Association for the Study of Liver Diseases.

Ndila C.,Kenya Medical Research Institute | Bauni E.,Kenya Medical Research Institute | Nyirongo V.,NY | Mochamah G.,Kenya Medical Research Institute | And 8 more authors.
BMC Medicine | Year: 2014

Background: Sickle cell disease (SCD) is common in many parts of sub-Saharan Africa (SSA), where it is associated with high early mortality. In the absence of newborn screening, most deaths among children with SCD go unrecognized and unrecorded. As a result, SCD does not receive the attention it deserves as a leading cause of death among children in SSA. In the current study, we explored the potential utility of verbal autopsy (VA) as a tool for attributing underlying cause of death (COD) in children to SCD.Methods: We used the 2007 WHO Sample Vital Registration with Verbal Autopsy (SAVVY) VA tool to determine COD among child residents of the Kilifi Health and Demographic Surveillance System (KHDSS), Kenya, who died between January 2008 and April 2011. VAs were coded both by physician review (physician coded verbal autopsy, PCVA) using COD categories based on the WHO International Classification of Diseases 10th Edition (ICD-10) and by using the InterVA-4 probabilistic model after extracting data according to the 2012 WHO VA standard. Both of these methods were validated against one of two gold standards: hospital ICD-10 physician-assigned COD for children who died in Kilifi District Hospital (KDH) and, where available, laboratory confirmed SCD status for those who died in the community.Results: Overall, 6% and 5% of deaths were attributed to SCD on the basis of PCVA and the InterVA-4 model, respectively. Of the total deaths, 22% occurred in hospital, where the agreement coefficient (AC1) for SCD between PCVA and hospital physician diagnosis was 95.5%, and agreement between InterVA-4 and hospital physician diagnosis was 96.9%. Confirmatory laboratory evidence of SCD status was available for 15% of deaths, in which the AC1 against PCVA was 87.5%.Conclusions: Other recent studies and provisional data from this study, outlining the importance of SCD as a cause of death in children in many parts of the developing world, contributed to the inclusion of specific SCD questions in the 2012 version of the WHO VA instruments, and a specific code for SCD has now been included in the WHO and InterVA-4 COD listings. With these modifications, VA may provide a useful approach to quantifying the contribution of SCD to childhood mortality in rural African communities. Further studies will be needed to evaluate the generalizability of our findings beyond our local context. © 2014 Ndila et al.; licensee BioMed Central Ltd.

Bankole A.,Guttmacher Institute Inc. | Biddlecom A.E.,NY
AIDS Education and Prevention | Year: 2011

This article draws on biomarker data from Demographic and Health Surveys (2003-2007) in 10 sub-Saharan African countries to examine differences in fertility preferences and contraceptive behaviors by HIV status for women and men, taking into account whether or not they probably know their HIV status. The objective is to determine if there are common patterns in the associations between these variables across several countries. Women's and men's fertility preferences and contraceptive behaviors are relatively similar across HIV status and probable knowledge of that status. However, two consistent differences emerge in some of the countries: HIV positive women who probably know their status are less likely to want more children and are more likely to be using male condoms than women who are HIV-negative and probably know it. A similar association is observed for men for condom use but not for limiting childbearing. Other factors unrelated to HIV status seem to be shaping women's and men's unmet demand for contraception and use of methods other than the condom. © 2011 The Guilford Press.

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