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*Departments of Pathology and Laboratory Medicine §Public Health, Weill Cornell Medical College †Department of Urology, Lefrak Center of Robotic Surgery, Weill Cornell Medical College and New York Presbyterian Hospitals, New York, NY ‡Department of Urology, Tulane University School of Medicine, New Orleans, LA.
Next-generation DNA and RNA sequencing requires intact nucleic acids from high-quality human tissue samples to better elucidate the molecular basis of cancer. We have developed a prostate biobanking protocol to acquire suitable samples for sequencing without compromising the accuracy of clinical diagnosis. To assess the clinical implications of implementing this protocol, we evaluated 105 consecutive radical prostatectomy specimens from November 2008 to February 2009. Alternating levels of prostate samples were submitted to Surgical Pathology as formalin-fixed, paraffin-embedded blocks and to the institutional biobank as frozen blocks. Differences in reported pathologic characteristics between clinical and procured specimens were compared. Clinical staging and grading were not affected by the biobank protocol. Tumor foci on frozen hematoxylin and eosin slides were identified and high-density tumor foci were scored and processed for DNA and RNA extractions for sequencing. Both DNA and RNA were extracted from 22 cases of 44 with high-density tumor foci. Eighty-two percent (18/22) of the samples passed rigorous quality control steps for DNA and RNA sequencing. To date, DNA extracted from 7 cases has undergone whole-genome sequencing, and RNA from 18 cases has been RNA sequenced. This protocol provides prostate tissue for high-throughput biomedical research and confirms the feasibility of actively integrating prostate cancer into The Cancer Genome Atlas Program, a member of the International Cancer Genome Consortium.
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OBJECTIVE: To establish reference values for Doppler velocimetry of the ophthalmic artery (OA) and the central retinal artery (CRA) in low-risk pregnancy. METHOD: Between January 2008 and March 2009, 63 low-risk pregnant women underwent an ultrasound scan every 2weeks at the Women's Hospital, Campinas, Brazil, to determine the resistance index (RI), pulsatility index (PI), and peak systolic velocity of both arteries, in addition to the flow velocity of the second peak and peak ratio (PR) of the OA. For analysis, linear regression was used with mixed models for longitudinal data, coefficient of determination, and estimates of the 5th and 95th percentiles for each parameter at each gestational age. Intra- and inter-observer variability was evaluated via the intraclass correlation coefficient. RESULTS: There was a trend of a reduction with gestational age in PI and RI of the OA, and PI of the CRA, but not in PR of the OA; and the respective reference values were established. Intra- and inter-observer variability was considered satisfactory. CONCLUSION: Unilateral assessment of the orbital Doppler velocimetry is feasible. Establishment of reference values showed a negative correlation between gestational age and PI and RI of the OA, and PI of the CRA. The method demonstrated satisfactory reproducibility.
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Department of Biomedical Sciences-Section Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.
The flat foot in childhood is a condition frequently observed in orthopedic practice but it is still debated when and in which patients surgical corrective treatment is appropriate; recently, the application of poly-L-lactic-acid (PLLA) screws was proposed. The present study investigates a group of 33 patients treated with PLLA expansion endorthesis in order to evaluate the deformity correction. Clinical and radiological outcomes in patients were correlated with: a) morphological characterization of screws both before and after being removed from patients, when necessary; b) histological and bio-molecular evaluation of degradation processes of the implants, focusing attention on the correlation between the cellular cohort involved in inflammatory reaction and the bio-absorption degree of PLLA screws. Deformity correction was mostly achieved, with minimal need of screw removal; the results obtained clearly show the occurrence of chronic rather than acute inflammation in removed screw specimens. At the histological level, after biomaterial implantation, the sequence of events occurring in the surrounding tissues ultimately ends in the formation of foreign body giant cells (FBGCs) at the tissue/material interface; but the mechanisms which influence the fate of screw implants, i.e. the resolution of acute inflammation rather than the progression towards chronic inflammation, are of crucial importance for biodegradable materials like "polylactic acid". In fact, the FBGC response ensures a long-term mechanism which eliminates the foreign material from the body, but at the same time the implications of prolonged FBGC responses, which generate negative side effects, could significantly impede the healing progress.
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Department of Obstetrics and Gynaecology, School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo , Brazil.
The objective was to determine the cross-sectional area of the umbilical cord, its diameter and the diameter of its vessels to establish a reference curve for these parameters during pregnancy, through a prospective cross-sectional study, including 2,310 low-risk pregnancies between 12 and 40 weeks' gestation. Means and standard deviations (SDs), plus the 10th, 50th and 90th percentiles for each measurement were calculated using polynomial regression analysis. Mann-Whitney, Kruskal-Wallis and Wilcoxon tests were used for statistical analysis. These parameters increased significantly with gestational age. The area of the cord also varied significantly with parity. Their new reference curves for low risk pregnancies were calculated using polynomial regression, and an almost linear increase in values was found up to 32 weeks of pregnancy, tending to stabilise from then onwards. The regression equation of the umbilical cord area according to gestational age (GA) was:-1.417 + 0.3026*GA-0.008*GA(2)+ 0.000007*GA(3) and the degree of adjustment (R(2)) was 0.89.
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CISAS, University of Padua, I-35131 Padova, Italy. elettra.mari@unipd.it
We introduce a new optical vortex coronagraph (OVC) method to determine the angular distance between two sources when the separation is sub-Rayleigh. We have found a direct relationship between the position of the minima and the source angular separation. A priori knowledge about the location of the two sources is not required. The superresolution capabilities of an OVC, equipped with an ℓ = 2 N-step spiral phase plate in its optical path, were investigated numerically. The results of these investigations show that a fraction of the light, increasing with N, from the secondary source can be detected with a sub-Rayleigh resolution of at least 0.1 λ/D.
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Department of Urology, Weill Cornell Medical College, New York, NY, USA Centre for Integrative Biology (CIBIO), University of Trento, Trento, Italy Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
Barbieri C E, Demichelis F & Rubin M A (2012) Histopathology 60, 187-198 Molecular genetics of prostate cancer: emerging appreciation of genetic complexity The emergence of Next Generation Sequencing is providing novel insights into cancer genomes as part of large-scale efforts by the International Cancer Genome Consortium (ICGC), as well as individual Genome Centers. Studies performing whole genome or whole exome DNA sequencing are remarkable both for the alterations discovered and equally important for the infrequent nature of recurrent mutations. Current understanding of the prostate cancer (PCa) genome is based on extensive RNA-sequencing for novel gene fusions and the first whole genome sequencing effort. The emerging data suggest that there are few recurrent genetic mutations. Surprisingly, the PCa genome undergoes frequent large-scale genomic rearrangements that could not have been predicted using previous DNA sequencing approaches, or even whole exome sequencing approaches. These large-scale rearrangements appear not to occur randomly, but demonstrate patterns leading to the 'chained' juxtaposition of known oncogenes. Future efforts in DNA sequencing will help to determine the recurrent nature of these genomic rearrangements, their association with other alterations and their effect on PCa disease progression. These discoveries raise the possibility that PCa might soon transition from a poorly understood, clinically heterogeneous disease to a collection of homogeneous subtypes identifiable by molecular criteria, and perhaps vulnerable to targeted therapies.
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Department of General and Environmental Physiology, University of Bari, Bari, Italy.
We screened human kidney-derived multipotent CD133+/CD24+ ARPCs for the possible expression of all 13 aquaporin isoforms cloned in humans. Interestingly, we found that ARPCs expressed both AQP5 mRNA and mature protein. This novel finding prompted us to investigate the presence of AQP5 in situ in kidney. We report here the novel finding that AQP5 is expressed in human, rat and mouse kidney at the apical membrane of type-B intercalated cells. AQP5 is expressed in the renal cortex and completely absent from the medulla. Immunocytochemical analysis using segment- and cell type-specific markers unambiguously indicated that AQP5 is expressed throughout the collecting system at the apical membrane of type-B intercalated cells, where it co-localizes with pendrin. No basolateral AQPs were detected in type-B intercalated cells, suggesting that AQP5 is unlikely to be involved in the net trans-epithelial water reabsorption occurring in the distal tubule. An intriguing hypothesis is that AQP5 may serve an osmosensor for the composition of the fluid coming from the thick ascending limb. Future studies will unravel the physiological role of AQP5 in the kidney.
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Department ofEconomia S. Cognetti de Martiis, University of Torino, Via Po, 53, 10124 Torino, Italy. cinzia.barbieri@unito.it
The goal of this study is to inform those potentially interested (researchers, farmers, industry and public bodies) in the medicinal and aromatic properties, and profitability of Perilla frutescens (L.) Britton (Lamiaceae). Perilla, a medicinal and edible plant of Asian origin, was recently introduced to the Piedmont Region in the north-west of Italy. P. frutescens is commonly known for its anti-allergic, anti-tumor, and anti-oxidant properties. It is also widely used as human food. We collected a variety of data on Perilla crops in the Piedmont Region, including: agricultural practices, crop profitability, and its value as a bee plant. Our results suggest that ease of cultivation, approximate break-even economics, medicinal claims, and value for bees all contribute to make Perilla of economic interest in Italy.
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Max Planck Research Group on Comparative Population Linguistics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
Burkina Faso is located in the heart of West Africa and is representative of local structured patterns of human variability. Here different cultures and languages are found in geographic contiguity, as a result of several waves of migration and the succession of long- and short-term empires. However, historical documentation for this area is only partial, focusing predominantly on the recent empires, and linguistic surveys lack the power to fully elucidate the social context of contact-induced changes.In this paper we report Y chromosomal data and complete mtDNA genome sequences for ten populations from Burkina Faso whose languages belong to two very distantly related branches of the Niger-Congo phylum, the Gur and Mande language families. In addition, two further populations, the Mande-speaking Mandenka from Senegal and the Yoruba from Nigeria, were included for regional comparison. We focus on the different historical trajectories undergone by the maternal and paternal lineages. Our results reveal a striking structure in the paternal line which matches the linguistic affiliation of the ethnolinguistic groups, in contrast to near-complete homogeneity of the populations in the maternal line. However, while the ancient structure along linguistic lines is apparent in the Y-chromosomal haplogroup affiliation, this has clearly been overlain by more recent migrations, as shown by significant correlations between genetic distances based on Y-STRs and geographic distances between the populations, as well as by patterns of shared haplotypes. Using the complete mtDNA sequences we are able to reconstruct population size variation in the past, showing a strong sign of expansion in concomitance with the Holocene Climate Optimum approximately 12,000-10,000 years ago, which has been suggested as the cause of the spread of the Niger Congo phylum in the area. However, subsequent climatic fluctuations do not appear to have had an impact on the demography of the inhabitants of West Africa, probably reflecting the adaptive advantages of cultural innovations such as pastoralism and agriculture.
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Fresenius Medical Care, Bad Homburg, Germany.
The Balanced Scorecard (BSC) is a validated tool to monitor enterprise performances against specific objectives. Through the choice and the evaluation of strategic Key Performance Indicators (KPIs), it provides a measure of the past company's outcome and allows planning future managerial strategies. The Fresenius Medical Care (FME) BSC makes use of 30 KPIs for a continuous quality improvement strategy within its dialysis clinics. Each KPI is monthly associated to a score that summarizes the clinic efficiency for that month. Standard statistical methods are currently used to analyze the BSC data and to give a comprehensive view of the corporate improvements to the top management. We herein propose the Self-Organizing Maps (SOMs) as an innovative approach to extrapolate information from the FME BSC data and to present it in an easy-readable informative form. A SOM is a computational technique that allows projecting high-dimensional datasets to a two-dimensional space (map), thus providing a compressed representation. The SOM unsupervised (self-organizing) training procedure results in a map that preserves similarity relations existing in the original dataset; in this way, the information contained in the high-dimensional space can be more easily visualized and understood. The present work demonstrates the effectiveness of the SOM approach in extracting useful information from the 30-dimensional BSC dataset: indeed, SOMs enabled both to highlight expected relationships between the KPIs and to uncover results not predictable with traditional analyses. Hence we suggest SOMs as a reliable complementary approach to the standard methods for BSC interpretation.
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2012-05-17 09:38:08 © BioInfoBank Institute