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Objective: This study aims to determine the efficacy of calcimimetics in improving bone mineral density (BMD) in patients with primary hyperparathyroidism (pHPT) and compare those results to patients undergoing parathyroidectomy. Background: Parathyroidectomy has been shown to improve BMD in pHPT, but calcimimetics have recently been advocated as a medical alternative to parathyroidectomy for pHPT. Materials and Methods: We identified 17 patients that were treated with calcimimetics for pHPT. Seventeen patients with pHPT who underwent parathyroidectomy served as surgical controls. Serum calcium level, parathyroid hormone (PTH) level, and femur and spine BMD T scores were compared before and 1 year after therapy. Results: Both groups were demographically matched. Calcium levels normalized in 70.6% of medically versus 100% of surgically treated patients (P = 0.026). PTH levels normalized in 35% of patients treated with calcimimetics versus 76% of surgical patients (P = 0.036). Femur BMD improved in 18.8% of medically treated patients versus 58.8% of surgical patients (P = 0.032). Spine BMD improved in 70.6% of medically treated patients versus 82.4% of surgical patients (P = 0.69). Further analysis demonstrated that regardless of treatment, normalization of PTH was associated with significant improvement in femur (P = 0.03) and spine BMD (P < 0.001). Normalization of calcium without normalization of PTH did not impact BMD. Conclusions: Parathyroidectomy results in greater normalization of serum calcium and PTH levels and significantly improves cortical BMD compared to calcimimetics. Regardless of treatment, normalization of PTH is associated with significant improvement in spine and femur BMD, suggesting that the superior effects of surgery may be mediated by better control of PTH. © 2012 by Lippincott Williams & Wilkins. Source


Romanel A.,University of Trento | Tandefelt D.G.,Institute of Cancer Research | Conteduca V.,Institute of Cancer Research | Jayaram A.,Institute of Cancer Research | And 22 more authors.
Science Translational Medicine | Year: 2015

Androgen receptor (AR) gene aberrations are rare in prostate cancer before primary hormone treatment but emerge with castration resistance. To determine AR gene status using a minimally invasive assay that could have broad clinical utility, we developed a targeted next-generation sequencing approach amenable to plasma DNA, covering all AR coding bases and genomic regions that are highly informative in prostate cancer. We sequenced 274 plasma samples from 97 castration-resistant prostate cancer patients treated with abiraterone at two institutions. We controlled for normal DNA in patients' circulation and detected a sufficiently high tumor DNA fraction to quantify AR copy number state in 217 samples (80 patients). Detection of AR copy number gain and point mutations in plasma were inversely correlated, supported further by the enrichment of nonsynonymous versus synonymous mutations in AR copy number normal as opposed to AR gain samples. Whereas AR copy number was unchanged from before treatment to progression and no mutant AR alleles showed signal for acquired gain, we observed emergence of T878A or L702H AR amino acid changes in 13% of tumors at progression on abiraterone. Patients with AR gain or T878A or L702H before abiraterone (45%) were 4.9 and 7.8 times less likely to have a ≥50 or ≥90% decline in prostate-specific antigen (PSA), respectively, and had a significantly worse overall [hazard ratio (HR), 7.33; 95% confidence interval (CI), 3.51 to 15.34; P = 1.3 × 10-9) and progression-free (HR, 3.73; 95% CI, 2.17 to 6.41; P = 5.6 × 10-7) survival. Evaluation of plasma AR by next-generation sequencing could identify cancers with primary resistance to abiraterone. Source


Keutgen X.M.,New York Presbyterian Hospital Weill Cornell Medical Center | Filicori F.,New York Presbyterian Hospital Weill Cornell Medical Center | Crowley M.J.,New York Presbyterian Hospital Weill Cornell Medical Center | Wang Y.,Johns Hopkins University | And 8 more authors.
Clinical Cancer Research | Year: 2012

Purpose: Indeterminate thyroid lesions on fine needle aspiration (FNA) harbor malignancy in about 25%of cases. Hemi- or total thyroidectomy has, therefore, been routinely advocated for definitive diagnosis. In this study, we analyzed miRNA expression in indeterminate FNA samples and determined its prognostic effects on final pathologic diagnosis. Experimental Design: A predictive model was derived using 29 ex vivo indeterminate thyroid lesions on FNA to differentiate malignant from benign tumors at a tertiary referral center and validated on an independent set of 72 prospectively collected in vivo FNA samples. Expression levels of miR-222, miR- 328, miR-197, miR-21, miR-181a, and miR-146b were determined using reverse transcriptase PCR. A statistical model was developed using the support vector machine (SVM) approach. Results: A SVM model with four miRNAs (miR-222, miR-328, miR-197, and miR-21) was initially estimated to have 86% predictive accuracy using cross-validation. When applied to the 72 independent in vivo validation samples, performance was actually better than predicted with a sensitivity of 100% and specificity of 86%, for a predictive accuracy of 90% in differentiating malignant from benign indeterminate lesions. When Hurthle cell lesions were excluded, overall accuracy improved to 97% with 100% sensitivity and 95% specificity. Conclusions: This study shows that that the expression of miR-222, miR-328, miR-197, and miR-21 combined in a predictive model is accurate at differentiating malignant from benign indeterminate thyroid lesions on FNA. These findings suggest that FNA miRNA analysis could be a useful adjunct in the management algorithm of patients with thyroid nodules. ©2012 AACR. Source


News Article
Site: http://www.biosciencetechnology.com/rss-feeds/all/rss.xml/all

Scientists have mapped the genome of bedbugs in New York City, then traced fragments of the nefarious pests' DNA through the subway system. In the grubby recesses of hundreds of stations, they discovered surprising genetic diversity among the bloodsucking creatures. The next step is to figure out how the information can be put to good use, such as to develop better insecticides or blood thinners. But these goals will take further medical research. For now, the focus is on two main players in New York life: the subway and bedbugs. Scientists already have found that genetic traces of bedbugs in northern Manhattan are more closely related to those in the island's southern part, while there are bigger variations between the Upper East Side and Upper West Side. Geneticist Christopher Mason, who worked on the project, says the reason for that can be found simply by looking at a subway map: In Manhattan, for instance, subway lines run the length of the island north to south, while there's no subway link through Central Park between the East Side and the West Side. Not that bedbugs are riding the subway, noted George Amato, an evolutionary biologist at the American Museum of Natural History who also worked on bedbug project. He says New York's bedbugs "move around with people, dogs, and people's items - and they probably move most easily the way people move most easily." Amato collaborated with Mason, who works at Weill Cornell Medicine's Institute for Computational Biomedicine. A bedbug colony at the famed museum was used for the genome map. A similar map was assembled by an international research team at 36 institutions, including the University of Cincinnati. The New York team's resulting scientific paper on the subject was published Tuesday in Nature Communications. A second paper on bedbug genetics, from the University of Cincinnati, also appeared Tuesday in the same publication. To learn how the bedbug has evolved and spread, the New York team took DNA sample swabs from 1,400 city locations including subway cars, turnstiles, ticket vending kiosks, and above ground places like parks. Amato said there are many ways small fragments of the critters' DNA, or DNA of a related species, could get into the subway - clinging to the clothes of some of the 6 million daily riders and their belongings, or washed down into the stations. Amato said the first rough bedbug genetic sequence emerged about a year ago, but it took months to refine the model into an accurate genome. "Before this, people were just feeling their way through in the dark; this genome turns the light on for various areas of other research," said Amato. "Our team is now moving on to the genetics of cockroaches and other living fossils."


News Article
Site: http://news.yahoo.com/science/

FILE - In this March 30, 2011, file photo, a bedbug is displayed at the Smithsonian Museum in Washington. Researchers from Weill Cornell and scientists at the American Museum of Natural History have traced the nefarious pest through the New York City subway system and discovered a genetic diversity among the bloodsucking creatures. (AP Photo/Carolyn Kaster, File) More NEW YORK (AP) — Scientists have mapped the genome of bedbugs in New York City, then traced fragments of the nefarious pests' DNA through the subway system. In the grubby recesses of hundreds of stations, they discovered surprising genetic diversity among the bloodsucking creatures. The next step is to figure out how the information can be put to good use, such as to develop better insecticides or blood thinners. But these goals will take further medical research. For now, the focus is on two main players in New York life: the subway and bedbugs. Scientists already have found that genetic traces of bedbugs in northern Manhattan are more closely related to those in the island's southern part, while there are bigger variations between the Upper East Side and Upper West Side. Geneticist Christopher Mason, who worked on the project, says the reason for that can be found simply by looking at a subway map: In Manhattan, for instance, subway lines run the length of the island north to south, while there's no subway link through Central Park between the East Side and the West Side. Not that bedbugs are riding the subway, noted George Amato, an evolutionary biologist at the American Museum of Natural History who also worked on bedbug project. He says New York's bedbugs "move around with people, dogs, and people's items — and they probably move most easily the way people move most easily." Amato collaborated with Mason, who works at Weill Cornell Medicine's Institute for Computational Biomedicine. A bedbug colony at the famed museum was used for the genome map. A similar map was assembled by an international research team at 36 institutions, including the University of Cincinnati. The New York team's resulting scientific paper on the subject was published Tuesday in Nature Communications. A second paper on bedbug genetics, from the University of Cincinnati, also appeared Tuesday in the same publication. To learn how the bedbug has evolved and spread, the New York team took DNA sample swabs from 1,400 city locations including subway cars, turnstiles, ticket vending kiosks, and above ground places like parks. Amato said there are many ways small fragments of the critters' DNA, or DNA of a related species, could get into the subway — clinging to the clothes of some of the 6 million daily riders and their belongings, or washed down into the stations. Amato said the first rough bedbug genetic sequence emerged about a year ago, but it took months to refine the model into an accurate genome. "Before this, people were just feeling their way through in the dark; this genome turns the light on for various areas of other research," said Amato. "Our team is now moving on to the genetics of cockroaches and other living fossils." This story has been corrected to show that fragments of bedbugs' DNA or related species' DNA were collected at subways, not whole bedbugs.

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