Citations

AbstractOrbital meningiomas can be classified as primary optic nerve sheath (ON) meningiomas, primary intraorbital ectopic (Ob) meningiomas and spheno‐orbital (Sph‐Ob) meningiomas based on anatomic site. Single‐nucleotide polymorphism (SNP)‐based array analysis with the Illumina 300K platform was performed on formalin‐fixed, paraffin‐embedded tissue from 19 orbital meningiomas (5 ON, 4 Ob and 10 Sph‐Ob meningiomas). Tumors were World Health Organization (WHO) grade I except for two grade II meningiomas, and one was NF2‐associated. We found genomic alterations in 68% (13 of 19) of orbital meningiomas. Sph‐Ob tumors frequently exhibited monosomy 22/22q loss (70%; 7/10) and deletion of chromosome 1p, 6q and 19p (50% each; 5/10). Among genetic alterations, loss of chromosome 1p and 6q were more frequent in clinically progressive tumors. Chromosome 22q loss also was detected in the majority of Ob meningiomas (75%; 3/4) but was infrequent in ON meningiomas (20%; 1/5). In general, Ob tumors had fewer chromosome alterations than Sph‐Ob and ON tumors. Unlike Sph‐Ob meningiomas, most of the Ob and ON meningiomas did not progress even after incomplete excision, although follow‐up was limited in some cases. Our study suggests that ON, Ob and Sph‐Ob meningiomas are three molecularly distinct entities. Our results also suggest that molecular subclassification may have prognostic implications.

BACKGROUND AND OBJECTIVE: Pediatrics has embraced technology-enhanced simulation (TES) as an educational modality, but its effectiveness for pediatric education remains unclear. The objective of this study was to describe the characteristics and evaluate the effectiveness of TES for pediatric education. METHODS: This review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. A systematic search of Medline, Embase, CINAHL, ERIC, Web of Science, Scopus, key journals, and previous review bibliographies through May 2011 and an updated Medline search through October 2013 were conducted. Original research articles in any language evaluating the use of TES for educating health care providers at any stage, where the content solely focuses on patients 18 years or younger, were selected. Reviewers working in duplicate abstracted information on learners, clinical topic, instructional design, study quality, and outcomes. We coded skills (simulated setting) separately for time and nontime measures and similarly classified patient care behaviors and patient effects. RESULTS: We identified 57 studies (3666 learners) using TES to teach pediatrics. Effect sizes (ESs) were pooled by using a random-effects model. Among studies comparing TES with no intervention, pooled ESs were large for outcomes of knowledge, nontime skills (eg, performance in simulated setting), behaviors with patients, and time to task completion (ES = 0.80–1.91). Studies comparing the use of high versus low physical realism simulators showed small to moderate effects favoring high physical realism (ES = 0.31–0.70). CONCLUSIONS: TES for pediatric education is associated with large ESs in comparison with no intervention. Future research should include comparative studies that identify optimal instructional methods and incorporate pediatric-specific issues into educational interventions.

Abstract Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients can be a good model for studying human diseases and for future therapeutic regenerative medicine. Current initiatives to establish human iPSC (hiPSC) banking face challenges in recruiting large numbers of donors with diverse diseased, genetic, and phenotypic representations. In this study, we describe the efficient derivation of transgene-free hiPSCs from human finger-prick blood. Finger-prick sample collection can be performed on a “do-it-yourself” basis by donors and sent to the hiPSC facility for reprogramming. We show that single-drop volumes of finger-prick samples are sufficient for performing cellular reprogramming, DNA sequencing, and blood serotyping in parallel. Our novel strategy has the potential to facilitate the development of large-scale hiPSC banking worldwide.

Abstract Despite the high incidence and mortality of prostate cancer, the etiology of this disease is not fully understood. In this study, we develop functional evidence for CBP and PTEN interaction in prostate cancer based on findings of their correlate expression in the human disease. Cbppc−/−;Ptenpc+/− mice exhibited higher cell proliferation in the prostate and an early onset of high-grade prostatic intraepithelial neoplasia. Levels of EZH2 methyltransferase were increased along with its Thr350 phosphorylation in both mouse Cbp−/−; Pten+/− and human prostate cancer cells. CBP loss and PTEN deficiency cooperated to trigger a switch from K27-acetylated histone H3 to K27-trimethylated bulk histones in a manner associated with decreased expression of the growth inhibitory EZH2 target genes DAB2IP, p27KIP1, and p21CIP1. Conversely, treatment with the histone deacetylase inhibitor panobinostat reversed this switch, in a manner associated with tumor suppression in Cbppc−/−;Ptenpc+/− mice. Our findings show how CBP and PTEN interact to mediate tumor suppression in the prostate, establishing a central role for histone modification in the etiology of prostate cancer and providing a rationale for clinical evaluation of epigenetic-targeted therapy in patients with prostate cancer. Cancer Res; 74(7); 2050–61. ©2014 AACR.

Interstitial cells of Cajal (ICC) act as pacemaker cells in the gastrointestinal tract by generating electrical slow waves to regulate rhythmic smooth muscle contractions. Intrinsic Ca 2+ oscillations in ICC appear to produce the slow waves by activating pacemaker currents, currently thought to be carried by the Ca 2+ -activated Cl − channel anoctamin 1 (Ano1). In this article we present a novel model of small intestinal ICC pacemaker activity that incorporates store-operated Ca 2+ entry and a new model of Ano1 current. A series of simulations were carried out with the ICC model to investigate current controversies about the reversal potential of the Ano1 Cl − current in ICC and to predict the characteristics of the other ion channels that are necessary to generate slow waves. The model results show that Ano1 is a plausible pacemaker channel when coupled to a store-operated Ca 2+ channel but suggest that small cyclical depolarizations may still occur in ICC in Ano1 knockout mice. The results predict that voltage-dependent Ca 2+ current is likely to be negligible during the slow wave plateau phase. The model shows that the Cl − equilibrium potential is an important modulator of slow wave morphology, highlighting the need for a better understanding of Cl − dynamics in ICC.

ObjectivesAnalyze the effect of ipsilateral submandibular gland preservation on patients undergoing concurrent neck dissection and transoral surgery for oropharyngeal squamous cell carcinoma. Evaluate for (1) intraoperative and postoperative communications between the oropharynx and neck and (2) oncologic outcomes.Study DesignRetrospective chart review of prospectively collected data.SettingTertiary academic referral center.Methods and SubjectsRetrospective chart review of patients undergoing transoral laser resection of oropharyngeal squamous cell carcinoma with simultaneous neck dissection(s) for primary, persistent, recurrent, and second primary disease between January 1999 and February 2013. Data analyzed for operative technique, pathologic diagnosis, postoperative course, complications, and oncologic outcomes.ResultsOverall 253 patients were identified. Of these, 96 patients underwent ipsilateral submandibular gland preservation and 157 underwent ipsilateral submandibular gland removal at the time of neck dissection. The prevalence of intraoperative communication between the neck and oropharynx was significantly lower in cases with submandibular gland preservation (2/96, 2.08%) compared to those with submandibular gland removal (22/157, 14.13%). No postoperative leaks occurred in the gland preservation group (0/96, 0%) compared to a leak prevalence of 8.92% (14/157) when the gland was removed (P =. 0041). There was no difference in local, regional, or distant disease recurrence between submandibular gland preservation and gland removal. Similarly, Kaplan‐Meier analysis showed no difference in disease free survival, disease specific survival, or overall survival.ConclusionsSubmandibular gland preservation during neck dissection in patients undergoing transoral surgery for oropharyngeal squamous cell carcinoma significantly reduces the risk of intraoperative and postoperative salivary leaks without compromising oncologic outcomes.

S ‐transform (ST) is a time–frequency representation (TFR) that is popularly used in a variety of applications, but prohibitive in both storage and computation for large time series. This study proposes a one‐dimensional fast time–frequency transform (FTFT‐1D) which generates a highly compressed form of the ST directly, without the need to compute the complete ST matrix initially and compress it subsequently. The compression technique used in the FTFT‐1D helps in storage, transmission and visualisation of the ST. The FTFT‐1D encodes the TFR information uniformly and finds the local spectrum instantaneously and accurately. It is useful for real‐time applications such as monitoring, control and filtering. In addition, the FTFT‐1D is memory efficient, robust and adaptive in nature.

AbstractBackground: It is widely accepted that chronic inflammation plays a role in the etiology of colorectal cancer. Using a two-stage design, we examined the associations between colorectal cancer and common variation in 37 key genes in the inflammation and innate immunity pathways.Methods: In the discovery stage, 2,322 discordant sibships (2,535 cases, 3,915 sibling controls) from the Colorectal Cancer Family Registry were genotyped for more than 600 tagSNPs and 99 single-nucleotide polymorphisms (SNP) were selected for further examination based on strength of association. In the second stage, 351 SNPs tagging gene regions covered by the 99 SNPs were tested in 4,783 Multiethnic Cohort subjects (2,153 cases, 2,630 controls).Results: The association between rs9858822 in the PPARG gene and colorectal cancer was statistically significant at the end of the second stage (OR per allele = 1.36, Bonferroni-adjusted P = 0.045), based on the “effective” number of markers in stage II (n = 306). The risk allele C was common (frequency 0.3) in African Americans but rare (frequency < 0.03) in whites, Japanese Americans, Latinos, and Native Hawaiians. No statistically significant heterogeneity of effects across race/ethnicity, body mass index (BMI) levels, regular aspirin use, or pack-years of smoking was detected for this SNP. Suggestive associations were also observed for several SNPs in close vicinity to rs9858822.Conclusions: Our results provide new evidence of association between PPARG variants and colorectal cancer risk.Impact: Further replication in independent samples is warranted. Cancer Epidemiol Biomarkers Prev; 22(11); 2094–101. ©2013 AACR.

Background and Purpose— Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke. Methods— The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10 296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14 549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research–generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived. Conclusions— The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.