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Cancers assume a variety of distinct histologies and may originate from a myriad of sites including solid organs, hematopoietic cells, and connective tissue. Clinical decision making based on consensus guidelines such as NCCN is often predicated on a specific histologic and anatomic diagnosis, supported by clinical features and pathologist interpretation of morphology and immunohistochemical (IHC) staining patterns. However, in patients with nonspecific morphologic and IHC findings—in addition to ambiguous clinical presentations such as recurrence versus new primary—a definitive diagnosis may not be possible, resulting in the patient being categorized as having a cancer of unknown primary (CUP). Therapeutic options and clinical outcomes are poor for CUP patients, with a median survival of 8-11 months. Here we describe and validate the Tempus Tumor Origin (Tempus TO) assay, an RNA-seq-based machine learning classifier capable of discriminating between 68 clinically relevant cancer subtypes. We show that the Tempus TO model is 91% accurate when assessed on retrospectively and prospectively held out cohorts of containing 9,210 samples with known diagnoses. When evaluated on a cohort of CUPs, the model recapitulated established associations between genomic alterations and cancer subtype. Combining diagnostic prediction tests (e.g., Tempus TO) with sequencing-based variant reporting (e.g., Tempus xT) may expand therapeutic options for patients with cancers of unknown primary or uncertain histology.

Background Nowadays, due to the increasing number of adult orthodontic applicants, who also have multiple dental restorations, it is important to have the ability to bond an orthodontic appliance to restoration surfaces. Objectives The aim of this paper was to determine the shear bond strength of ceramic brackets of 3 different base designs bonded to amalgam and composite restorations after using different surface treatment methods in vitro. Material and methods In an in vitro study, the surfaces of 180 amalgam and composite specimens were prepared by using sandblasting and the erbium, chromium-doped yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser irradiation. Ceramic brackets of 3 base designs, including Star, Cross and Slot, for upper central teeth were bonded to amalgam and composite surfaces by using Transbond™ XT Light Cure Adhesive. All specimens were incubated at a temperature of 37°C for 1 week, and then subjected to shear bond strength tests after 1,000 cycles of thermal cycling. The bond strength of the groups was analyzed by means of the one-way and two-way analysis of variance (ANOVA), and the comparison of the 2 groups was made with Tukey's test. Residual adhesives were also determined by a 4-part criterion (0-3) in different groups and the results were analyzed with the χ2 test. Results There was a significant difference in the shear bond strength of brackets of 3 base designs bonded to amalgam and composite surfaces with different surface treatment. Conclusions According to the results of this study, all surface treatment methods and different bracket base designs were able to provide sufficient shear bond strength on composite and amalgam surfaces. As far as the bracket base design is concerned, the use of each of the 3 base designs in the amalgam group brought desirable results in terms of the adhesive remnant index (ARI) and shear bond strength values; the use of the Star base design in the composite group proved to be suitable.

Colon polypectomy can require an injection of a submucosal lifting agent to fully visualize and completely remove the polyp. To the best of our knowledge, this is the largest morphologic series on the novel lifting agents Eleview and Orise. The study consisted of 1 polypectomy and 8 colon resections from 9 patients: 6 women, 3 men (mean age=64 y); Orise=6, Eleview=3; the median time interval between injection and resection=16 weeks. Pathologic diagnoses of the polyps included tubular adenoma (n=4), tubulovillous adenoma (n=4), and sessile serrated adenoma/polyp (n=1). We report that a histologically processed Orise aliquot from the manufacturer showed similar histology to that seen in the specimens from patients with confirmed Orise injection. The morphology of the agents in the patient specimens changed with time status postinjection: immediate resection of the lifting agent showed basophilic, amorphous, and bubbly-extracellular material with prominent hemorrhage, and resection ∼3 months after lifting agent injection showed prominent hyalinized, pink-amorphous ribbons and globules with a foreign body giant cell reaction and fibrosis. The epicenter of the lifting agents was in the submucosa, and the agents were neither refractile nor polarizable. Because of the morphologic overlap with amyloid, 5 cases were stained with Congo Red, and all cases were negative. In conclusion, awareness of the morphology of these new lifting agents is important for accurate diagnosis and to avoid the diagnostic pitfall of amyloid. These lesions can be definitively distinguished from amyloid by their nonreactivity on a Congo Red and familiarity with their characteristic clinicopathologic presentation.

Background Pancreatoblastoma (PBL) is a rare malignant pancreatic tumor seen predominantly in childhood, and its cytologic diagnosis remains challenging. Methods Twelve fine-needle-aspirations from 11 adults were analyzed. Results In total, 6 men and 5 women (median age, 45 years; age range, 32-60 years) had tumors measuring a median 5.6 cm (range, 2.5-12 cm) located in the pancreatic head (n = 7) or tail (n = 4), including 3 with familial adenomatous polyposis (FAP)/FAP-related syndromes and 4 with metastasis at diagnosis. The median follow-up was 39.8 months (range, 0.8-348 months), and 5 patients died of disease. The original cytology diagnoses were: PBL (n = 2), neuroendocrine neoplasm (n = 2), poorly differentiated neuroendocrine carcinoma (n = 2), well differentiated neuroendocrine tumor (n = 1), poorly differentiated carcinoma (n = 2), "positive for malignancy" (n = 1), acinar cell carcinoma (n = 1), and epithelioid neoplasm with endocrine and acinar differentiation versus PBL (n = 1). Universal cytopathologic findings included hypercellularity; 3-dimensional clusters; and single, monotonous, blast-like cells that were from 1.5 to 2.0 times the size of red blood cells with high nuclear-to-cytoplasmic ratio, fine chromatin, small, distinct nucleoli, and a resemblance to well differentiated neuroendocrine tumor and poorly differentiated neuroendocrine carcinoma. Branching pseudopapillae (n = 7) and grooved nuclei (n = 3) raised the differential diagnosis of solid-pseudopapillary neoplasm, but with more atypia. Uncommon features included pleomorphism (n = 4) and numerous mitoses (n = 1). Squamoid morules were seen on smears (n = 5) or cell blocks (n = 6) in 70% of patients and were characterized by epithelioid cells with elongated, streaming nuclei, fine chromatin, absent nucleoli, and positive nuclear β-catenin (n = 6 of 8). The median Ki-67 index was 21% (range, 2%-70%), and neuroendocrine marker expression was common (100%), but acinar markers were variable (63%). Conclusions A combination of cytologic findings in PBL, including a predominant population of primitive blast-like cells, subtle squamoid morules, frequent neuroendocrine and variable acinar phenotype, should facilitate accurate cytologic diagnosis and distinction from common mimics.

2625 Background: Neuroendocrine neoplasms (NENs) encompass a rare group of tumors arising in nearly any organ site. Patients with advanced-stage NENs have limited treatment options, and molecular profiling is not routinely performed in NENs. However, given tissue-agnostic FDA approvals for immunotherapy in biomarker-selected solid tumors, we sought to assess the frequency of TMB-H and MSI-H in NENs by organ site and in comparison to non-NEN counterparts. Methods: We retrospectively analyzed de-identified records from the Tempus database of NENs sequenced with the Tempus xT assay (DNA-seq of 595-648 genes at 500x coverage). Patients were included if their primary cancer arose in the lungs, GI tract (esophagus, stomach, small bowel, colon, rectum), pancreas, or prostate. Histologic diagnoses were grouped as NENs (including high grade or low/intermediate grade), and non-NENs (e.g. adenocarcinoma, squamous cell carcinoma) based on data abstracted from pathology reports. TMB-H was defined as ≥ 10 mutations/megabase. MSI-H was calculated as previously published (PMID: 31570899). Statistical comparisons were limited to groups of 10 or larger. Results: We characterized a total of 1,477 NENs from the following anatomic sites: lung (64%, N=951), pancreas (15%, N= 220), GI (15%, N= 224) and prostate (6%, N=82). TMB-H was most common in NENs arising in the lungs (17%, N=155), followed by the pancreas (5.4%, N=11), GI tract (4.8%, N=10), and prostate (3.8%, N=3) (p< 0.001). Overall, TMB-H was more common in high-grade NENs compared to low/int-grade NENs [17% (N=147) vs. 6.2% (N=31), P

Lung cancer is the leading cause of cancer-related death worldwide. It is divided into sub-categories based upon morphology, immunostaining pattern, biology, molecular profile, and/or treatment options. Up until the early 2000s when driver mutations with targeted therapies were identified in a subset of adenocarcinomas, the most critical distinction of lung carcinomas was driven by differences in treatment between small cell carcinoma (SCC) and nonsmall cell lung carcinoma (NSCLC). The distinction between SCC and NSCLC remains critical in the 21st century for management, especially for advanced stage cancer. In the vast majority of cases, morphological features are sufficient to separate SCC from other types of lung cancers. In some instances, however, cytomorphological features and immunohistochemical overlap with other tumors, limited sample availability, and/or crush artifact pose diagnostic challenges. The aim of this review is to highlight salient features of SCC and ancillary studies to distinguish it from common and uncommon potential mimickers, as well as provide updates in genomics and management.

To evaluate the impact that an electronic ordering system has on the rate of rejection of blood type and screen testing samples and the impact on the number of ABO blood-type discrepancies over a 4-year period.An electronic ordering system was implemented in May 2011. Rejection rates along with reasons for rejection were tracked between January 2010 and December 2013.A total of 40,104 blood samples were received during this period, of which 706 (1.8%) were rejected for the following reasons: 382 (54.0%) unsigned samples, 235 (33.0%) mislabeled samples, 57 (8.0%) unsigned requisitions, 18 (2.5%) incorrect tubes, and 14 (1.9%) ABO discrepancies. Of the samples, 2.5% were rejected in the year prior to implementing the electronic ordering system compared with 1.2% in the year following implementation ( P .0001).Our data demonstrate that implementation of an electronic ordering system significantly decreased the rate of blood sample rejection.

Background Enamel demineralization and white spot lesions around orthodontic brackets is a common problem associated with fixed orthodontic treatment. Glass ionomer cements (GICs) are commonly used for bracket bonding and recently, bioactive glass (BAG) was added to GICs to enhance deposition of calcium phosphate in adjacent dental structure. This study sought to assess the effect of addition of BAG particles to resin modified GIC (RMGIC) on enamel demineralization under orthodontic brackets. Material and methods In this in vitro, experimental study, 60 sound human premolars were immersed in distilled water at 6°C. The teeth were randomly divided into three groups. Using a sticker, a window measuring 7x7 mm was created on the buccal surface. The remaining surfaces were coated with nail varnish twice with a 3-hour interval. After 24 hours, the stickers were removed. Brackets were bonded to tooth surfaces using Transbond XT (control), Fuji II LC RMGIC and Fuji II LC containing 30% BAG particles. To induce acid attacks, the teeth were immersed in demineralizing solution for 6 hours. For pH cycling, the teeth were then immersed in remineralizing solution for 18 hours. This process was repeated for 21 days. Next, the teeth were longitudinally sectioned into two halves and the depth of demineralization was measured from the deepest point to the surface under a polarized light microscope. Data were analyzed using one-way ANOVA, and pairwise comparisons were carried out using Tukey's test. Results The mean depth of demineralization was 73.8±22.29, 118.08±29.42 and 182.98±20.69 µm in the BAG, RMGIC and Transbond XT groups, respectively. One-way ANOVA showed significant differences in terms of depth of demineralization among the three groups (P=0.0001). Tukey's test revealed significant differences in depth of demineralization. Conclusions Addition of BAG to RMGIC can significantly decrease the depth of enamel demineralization under orthodontic brackets in vitro. Key words:Remineralization, demineralization, orthodontic brackets, bioactive glass, resin modified glass ionomer cement.

Introduction: Occupational exposure with polluted sharp equipment usually occurs during procedures such as transfusion of blood and blood products, blood sampling, disposal of needles, and collection of polluted sharp materials. Considering the fact that students have less work experience and lower practical skills, they are more vulnerable to work-related infections. The present study was conducted to determine and compare the awareness of nursing, midwifery, and surgical technology students about occupational exposure management.Methods: This descriptive-analytical cross-sectional study was conducted on 221 students of nursing, midwifery, and surgical technology selected using the stratified random sampling in 2016. Data gathering tool was a researcher-made questionnaire including the students' demographic characteristics and awareness about occupational exposure management. Data were analyzed by SPSS18 using descriptive and analytical statistical tests.Results: Our findings showed that the mean scores of awareness about occupational exposure management were not significantly different among the nursing, midwifery, and surgical technology students (p value = 0.435). We observed that the students' age and educational level were significantly correlated with their scores of awareness about occupational exposure management (p value < 0.001).Conclusions: Results of the present study indicated poor awareness of the students about in-time management of occupational exposure. Measures such as educational workshops on preventive aspects in occupational exposure, observance of safety principles and comprehensive standards for accurate measurement of viral markers should be taken. Individual health profiles should be designed for each student to improve the occupational exposure management.

G6PD deficiency is the most common human enzymopathy, particularly in individuals of African descent. Its epidemiology has not been studied in the Dominican Republic, where many individuals have African ancestry. HIV-infected patients are at risk for adverse effects from G6PD deficiency due to receiving prophylaxis with oxidative drugs, which can induce hemolysis in G6PD-deficient patients. We determined the prevalence of G6PD deficiency, as well as the spectrum of variants, in HIV-infected patients at the Clínica de Familia La Romana, a free HIV clinic in the Dominican Republic. A medical history, chart review, and G6PD testing were performed for 238 consenting HIV-positive adults. A qualitative assay (Trinity Biotech), performed at the clinic, was assessed for color change at 30 and 60 minutes. All blood samples were also shipped to our home institution for quantifying enzyme activity (Trinity Biotech) and molecular testing by Sanger sequencing. The threshold for G6PD deficiency was 5.42 U/g hemoglobin (Hb; i.e. The overall prevalence of G6PD deficiency was 8.8% and was similar in males (9.3% [9/97]) and females (8.5% [12/141]), but higher in Haitians (18% [9/50]) as compared to Dominicans (6.4% [12/187]; p=0.01), determined by maternal country of birth. All G6PD-deficient subjects carried the “African” variant (G6PD A-). ∼60% of patients had received and ∼15% were currently on trimethoprim-sulfamethoxazole (TMP-SMX), regardless of G6PD status. Two G6PD-normal patients received Dapsone after TMP-SMX was stopped for allergy or anemia. Univariate analysis identified variables associated with G6PD deficiency in this cohort. A multivariable logistic regression model identified three variables that predicted G6PD status (p Screening for G6PD deficiency in the developing world is further complicated by lack of access to confirmatory testing. Detecting heterozygous females with intermediate, or even normal, G6PD activity is a diagnostic challenge for enzyme assays. To diagnose heterozygotes definitively, all G6PD exons were sequenced for all subjects with G6PD activity near or below the threshold, with discordant qualitative and quantitative Results, and for selected controls. Of 55 subjects sequenced, 29 had at least one G6PD A- allele. The G6PD A+ allele, also associated with African ancestry, was the only other variant detected. Overall, the 3 Methods agreed well when subjects had low or high G6PD activity, with uncertainty near the quantitative threshold for G6PD deficiency. The sequencing assay detected the G6PD A- allele in all subjects found to be G6PD-deficient by the quantitative assay, but also identified 8 heterozygous females with normal enzyme activity. The qualitative assay, whose sensitivity was increased by assessing color change at 30 minutes, was able to detect the majority (12/19) of heterozygous females, but 6 were heterozygotes with normal enzyme activity. Nonetheless, because genotype does not directly correlate with clinical severity, low activity remains the gold standard for diagnosing G6PD deficiency. Therefore, optimizing qualitative enzyme assays to detect biochemically deficient patients in conjunction with using clinical screening to increase pretest probability may together improve the diagnosis of clinically relevant G6PD deficiency in resource-limited settings. Disclosures: No relevant conflicts of interest to declare.

Background: Interest and motivation toward field of study is necessary for success in that field and educational environment is an effective factor on this interest. Objective: The aim of present study was to assess Qazvin Dental School students’ interest in their field of study and its relationships with the educational environment. Methods: In this cross-sectional descriptive trial study, 96 students with the entering years of 2010- 2013 were selected by the census sampling method in the Qazvin Dental School and assessed by questionnaire that validity and reliability confirmed in previous studies. Demographic data, interests toward field of study and factor of education environments were determined and reported by frequency and percent indices. Scores of 0-4 were assigned to answers of the participants. The effects of the parameters on the interest and education environments scores were analyzed by the regression analysis. Findings: Among students, 56.4% were interested in their field of study. Also, 56.4% believed that most of the member of staff used new methods in their educational program. 86.1% of students considered their participation on the educational decision-makings regarding their own status less. The parameters of gender (P

PURPOSE To investigate if a platelet inhibitor (aurintricarboxylic acid [ATA]) and a heparin-mimicking antagonist (RG-13577) of basic fibroblast growth factor 2 (bFGF2) could be combined as a stable compound and attached to conventional bare metal stents to hinder thrombus formation and inflammatory reactions of stenting. METHODS Fifteen domestic pigs were stented with RG-13577/ATA-coated (n=6), ATA-coated (n=12), and bare metal stents (n=12) in the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. All surviving pigs were evaluated with contrast angiography and intravascular ultrasonography (IVUS) after 4 weeks. Histological analysis of the stented arteries was performed after hematoxylin-eosin staining. Tissue factor (TF) staining and scanning electron microscopy (SEM) were performed in animals with acute stent thrombosis. RESULTS Five of the 6 animals receiving an RG-13577/ATA-coated stent experienced acute stent thrombosis, while no adverse events occurred in the animals of the other 2 groups. Follow-up angiography did not show significant in-stent stenosis in either bare or ATA-coated stents. However, histomorphometry revealed larger neointimal area (3.54+/-0.69 mm2 versus 1.82+/-0.27 mm2, p

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancers in the United States. The five-year survival rate for patients with PDAC remains dismal. Identification of biomarkers for early diagnosis of PDAC and pre-cancer pancreatic intraepithelial neoplasia (PanIN) lesions with risk of progression to PDAC is critically needed. We hypothesized that differentially expressed genes and regulatory pathways in PanIN and PDAC compared to normal duct epithelium (ND) may represent biomarkers of development of malignancy. We used Affymetrix Human Transcriptome Arrays 2.0 to establish gene expressionprofiles in ND, low-grade PanIN, and PDAC epithelium. Total RNA was isolated after laser capture microdissection (LCM) of frozen tissue sections and then used for producing hybridization-ready DNA. Hybridization quality control was performed with Expression Console 1.4 software and background corrected/normalized data were analyzed with Transcriptome Analysis Console (TAC) 3.1 and the ASSIGN algorithm. We tested RNA from 22 LCM samples (9 PDACs, 5 PanINs, and 8 ND), including 4 matched trios of ND, PanIN and PDAC from the same patients. Differential expression analysis with one-way between subject ANOVA revealed over 2000 genes differentially expressed in PDAC and PanIN vs. ND group (filter criteria up/down >2; ANOVA p1.5; ANOVA p Citation Format: Elena V. Komissarova, Jorge Sepulveda, Sarawut Kongkarnka, Maryam Shirazi, Brynn Levy, Claudia Cujar, Antonia R. Sepulveda. Human transcriptome alterations in pre-cancer and cancer epithelium identify candidate biomarkers of progression to pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 714. doi:10.1158/1538-7445.AM2017-714

Background: Concerning the prevalence of test anxiety among nursing students and presence of stress in nursing education years, this study was conducted to determine the effect of progressive muscle relaxation method on test anxiety among nursing students of Isfahan University of Medical Sciences in 2013. Materials and Methods: This was a quasi-experimental study conducted in three stages on 49 male and female nursing students divided into two groups (study and control). In the pre-test stage, demographic data and Sarason anxiety questionnaires were filled by 94 students (of terms 3 and 4). Then, in the intervention stage, the students having test anxiety were assigned to two groups (study and control), and the progressive muscle relaxation method was performed in the experiment group in four sessions. Then, the students did this method two times a day until final exams, immediately following which they filled the self-reported checklists. On the first day of the final exams, test anxiety questionnaire was filled by the two groups again. The collected data were analyzed by the statistical tests, i.e. χ2, paired t-test, independent sample t-test, Mann–Whitney and Wilcoxon tests, using SPSS 18. Results: Independent t-test showed a significant difference in the mean scores of test anxiety after intervention between the two groups of study and control (P = 0.00), but this difference was not significant before intervention (P = 0.76). Also, in the study group, there was a significant difference in the mean scores of test anxiety before and after intervention (P = 0.00), but this difference was not significant in the control group (P = 0.09). Mann–Whitney test showed no significant difference in categorization of test anxiety scores before intervention in the study and control groups (P = 0.60), but the difference was significant after intervention (P = 0.00). Wilcoxon test showed a significant difference in categorization of test anxiety scores in the study group before and after intervention (P = 0.00), but the difference was not significant in the control group (P = 0.083). Conclusions: Generally, the results showed that performing progressive muscle relaxation method was effective in reducing test anxiety among nursing students. It is suggested to conduct educational programs concerning this method in the faculties of nursing to decrease the test anxiety of nursing students.

X-linked congenital generalized hypertrichosis (Online Mendelian Inheritance in Man 307150) is an extremely rare condition of hair overgrowth on different body sites. We previously reported linkage in a large Mexican family with X-linked congenital generalized hypertrichosis cosegregating with deafness and with dental and palate anomalies to Xq24-27. Using SNP oligonucleotide microarray analysis and whole-genome sequencing, we identified a 389-kb interchromosomal insertion at an extragenic palindrome site at Xq27.1 that completely cosegregates with the disease. Among the genes surrounding the insertion, we found that Fibroblast Growth Factor 13 ( FGF13 ) mRNA levels were significantly reduced in affected individuals, and immunofluorescence staining revealed a striking decrease in FGF13 localization throughout the outer root sheath of affected hair follicles. Taken together, our findings suggest a role for FGF13 in hair follicle growth and in the hair cycle.

We present an analysis of near-infrared integral field unit spectroscopy of the 8 o'clock arc, a gravitationally lensed Lyman break galaxy, taken with SINFONI. We explore the shape of the spatially-resolved H\beta\ profile and demonstrate that we can decompose it into three components that partially overlap (spatially) but are distinguishable when we include dynamical information. We use existing B and H imaging from the Hubble Space Telescope to construct a rigorous lens model using a Bayesian grid based lens modelling technique. We apply this lens model to the SINFONI data cube to construct the de-lensed H\beta\ line-flux velocity and velocity dispersion maps of the galaxy. We find that the 8 o'clock arc has a complex velocity field that is not simply explained by a single rotating disk. The H\beta\ profile of the galaxy shows a blue-shifted wing suggesting gas outflows of ~ 200 km s^{-1}. We confirm that the 8 o'clock arc lies on the stellar mass--oxygen abundance--SFR plane found locally, but it has nevertheless significantly different gas surface density (a factor of 2--4 higher) and electron density in the ionized gas (five times higher) from those in similar nearby galaxies, possibly indicating a higher density interstellar medium for this galaxy., Comment: 23 pages, 25 figures

Aim: To test the hypothesis that microdeletions or microduplications below the resolution of a standard karyotype may be a significant cause of highly skewed X-inactivation (HSXI) in women without a cytogenetically detected X-chromosome anomaly. Methods: Cases were women with HSXI, defined as ≥85% of cells in a blood sample with the same active allele at the HUMARA locus. The skewing in controls ranged from 50 to Results: Cases and controls did not differ in the frequency of X-chromosome copy number changes ≥100 kb or in the frequency of copy number changes that contained genes. However, one woman with HSXI >90% in blood and left and right buccal smears had a 5.5-Mb deletion in Xp22.2p22.1. This deletion could affect the viability of male conceptions and may have led to the dysmorphology found in female carriers. Conclusion: HSXI in a blood sample is rarely due to X-chromosome copy number changes detectable by microarray.

Cytogenetic testing using genomic microarrays presents a clinical challenge when data regarding the phenotypic consequences of the genomic alteration are not available. We describe a chromosome 13q32.3 duplication discovered by microarray testing in a fetus with a prenatally detected apparently balanced de novo translocation 46,XY,t(2;13)(q37;q32). Microarray analysis on the fetal DNA showed duplications of 384 kb and 564 kb at the breakpoint regions on chromosomes 2q37.3 and 13q32.3, respectively. There were no disease-associated genes in the duplicated region on chromosome 2q37. The duplicated region on chromosome 13q contains the ZIC2 gene. Haploinsufficiency of ZIC2 is known to cause holoprosencephaly and other brain malformations. Studies in the mouse models have suggested that over expression of ZIC2 may also lead to brain malformations. Fetal MRI of the brain was normal and the family elected to continue the pregnancy. An apparently normal baby was born at term. At 3 months of age a physical exam showed no abnormalities and no developmental delay. This report shows that duplication of ZIC2 is not necessarily associated with brain malformations. We also describe the phenotype from four additional patients with duplications of the region of chromosome 13 containing ZIC2 and three previously described patients with supernumerary marker chromosomes derived from distal chromosome 13. None of the eight patients had holoprosencephaly or brain malformations, indicating that duplication of ZIC2 is not associated with brain anomalies. This information will be useful for counseling in other occurrences of this duplication identified by microarray.

The differential diagnosis of myoglobinuria includes multiple etiologies, such as infection, inflammation, trauma, endocrinopathies, drugs toxicity, and primary metabolic disorders. Metabolic myopathies can be due to inherited disorders of glycogen metabolism or to defects of fatty acid oxidation. Primary respiratory chain dysfunction is a rare cause of myoglobinuria but it has been described in sporadic cases with mutations in genes encoding cytochrome b or cytochrome c oxidase (COX) subunits, and in 4 cases with tRNA mutations. We describe a 39-year-old woman with myalgia and exercise-related recurrent myoglobinuria, who harbored a novel mitochondrial DNA mutation at nucleotide 4281 (m.4281A > G) in the tRNA-isoleucine gene. Her muscle biopsy revealed ragged-red and COX-deficient fibers. No deletions or duplication were detected by Southern blot analysis. The m.4281A > G mutation was present in the patient’s muscle with a mutation load of 46% and was detected in trace amounts in urine and cheek mucosa. Single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient (65%) than in normal fibers (45%). This novel mutation has to be added to the molecular causes of recurrent myoglobinuria.

Inhibition of IL-1beta convertase has been shown to decrease inflammation and apoptosis, which are features of the neointimal development after vascular interventions. The aim of our study was to reduce neointimal proliferation after stenting of the porcine coronary artery, using the irreversible IL-1beta convertase and caspase-1 inhibitor acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloromethyl-ketone (Ac-YVAD-cmk). Before coronary stent implantation, 8 pigs received an intracoronary infusion of 50 mg Ac-YVAD-cmk into the left coronary artery (group 1, n = 8), while 8 animals served as untreated controls (group 2). After 4 weeks, coronary angiography and intracoronary ultrasound (IVUS) with 3D measurements were performed. IVUS revealed a smaller in-stent intimal volume (27.3 +/- 11.6 vs. 75.8 +/- 18.4 mm3, p0.005) and a decreased maximal percentage area stenosis (36.1 +/- 8.5 vs. 69.0 +/- 8.2%, p0.001) in group 1 vs. group 2. A smaller maximal neointimal thickness (0.63 +/- 0.28 vs. 1.75 +/- 0.94 mm, p0.005) and a decreased maximal neointimal area (2.14 +/- 1.29 vs. 5.03 +/- 1.92 mm2, p0.005), assessed by computerized planimetry, were found in group 1 vs. group 2. Lower apoptotic indices of the neointimal cells were observed in the treated animals (3.0 vs. 13.4% of total intimal cells, p0.05). The coronary arterial tissue IL-1beta level was significantly decreased in the animals treated with Ac-YVAD-cmk (0.254 +/- 0.162 vs. 0.463 +/- 0.307 pg/mg protein, p0.05), and exhibited a positive linear correlation (r = 0.581, p = 0.013) with the in-stent plaque volume. In conclusion, intracoronary administration of Ac-YVAD-cmk before coronary artery stenting results in significantly decreased neointimal hyperplasia due to the inhibition of local IL-1beta production and decreased neointimal apoptosis.

BACKGROUND Biodegradable stent coatings provide a potential for local drug delivery at the time of vascular injury, while possible tissue toxicity is avoided through constant degradation, leaving behind a bare metal stent. DESIGN Serial three-dimensional (3D) intravascular ultrasonographic results on bare Megaflex stents and biodegradable polymer-coated Megaflex stents (Hyper stents) (Eurocor, Bonn, Germany) were compared 1 and 4 weeks after intracoronary implantation in pigs. METHODS Under general anaesthesia, the left anterior descending and circumflex coronary arteries of domestic pigs were stented with Megaflex and Hyper stents, using right femoral artery access. Control coronary angiography and intravascular ultrasonography (IVUS) were performed 1 and 4 weeks after stent implantation using left femoral artery access and right carotid artery access. After recording of angiographic and IVUS data, the pigs were allowed to recover. RESULTS The 1- and 4-week IVUS follow-ups revealed less neointima formation with Hyper stents than with Megaflex stents: 1-week intimal volume, 11.8+/-0.93 compared with 15.02+/-4.18 mm3, P=0.065; intimal area, 0.81+/-0.06 compared with 1.1+/-0.16 mm2, P =0.003; maximal intimal thickness, 0.12+/-0.01 compared with 0.14+/-0.02 mm, P =0.049; 4-week intimal volume, 12.4+/-1.77 compared with 27.32+/-12.79 mm3, P =0.016; intimal area, 0.82+/-0.12 compared with 1.95+/-0.65 mm2, P=0.003; and maximal intimal thickness, 0.13+/-0.04 compared with 0.30+/-0.10 mm, P=0.003. CONCLUSIONS Implantation of biodegradable polymer-coated (Hyper) stents results in significantly less neointima formation 1 and 4 weeks after intracoronary implantation than with bare Megaflex stents. Taking advantage of the good collateralization of femoral and carotid arteries of pigs, the use of different arterial accesses allows serial angiographic and 3D IVUS measurements on neointimal development without sacrificing the animals.

Inhibition of IL-1β convertase has been shown to decrease inflammation and apoptosis, which are features of the neointimal development after vascular interventions. The aim of our study was to reduce neointimal proliferation after stenting of the porcine coronary artery, using the irreversible IL-1β convertase and caspase-1 inhibitor acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloromethyl-ketone (Ac-YVAD-cmk). Before coronary stent implantation, 8 pigs received an intracoronary infusion of 50 mg Ac-YVAD-cmk into the left coronary artery (group 1, n = 8), while 8 animals served as untreated controls (group 2). After 4 weeks, coronary angiography and intracoronary ultrasound (IVUS) with 3D measurements were performed. IVUS revealed a smaller in-stent intimai volume (27.3 ±11.6 vs. 75.8 ± 18.4 mm3, p < 0.005) and a decreased maximal percentage area stenosis (36.1 ± 8.5 vs. 69.0 ± 8.2%, p < 0.001) in group 1 vs. group 2. A smaller maximal neointimal thickness (0.63 ± 0.28 vs. 1.75 ± 0.94 mm, p < 0.005) and a decreased maximal neointimal area (2.14 ± 1.29 vs. 5.03 ± 1.92 mm2, p < 0.005), assessed by computerized planimetry, were found in group 1 vs. group 2. Lower apoptotic indices of the neointimal cells were observed in the treated animals (3.0 vs. 13.4% of total intimai cells, p < 0.05). The coronary arterial tissue IL-1β level was significantly decreased in the animals treated with Ac-YVAD-cmk (0.254 ± 0.162 vs. 0.463 ± 0.307 pg/mg protein, p < 0.05), and exhibited a positive linear correlation (r = 0.581, p = 0.013) with the in-stent plaque volume. In conclusion, intracoronary administration of Ac-YVAD-cmk before coronary artery stenting results in significantly decreased neointimal hyperplasia due to the inhibition of local IL-lβ production and decreased neointimal apoptosis. (Mol Cell Biochem 249: 39–43, 2003)

BACKGROUND We evaluated the usefulness of intravascular ultrasound (IVUS) in the non-uniform distribution of in-stent neointimal hyperplasia, comparing macroscopic measurements with IVUS-guided histomorphometry. METHODS Coronary stenting was performed in 45 left coronaries of 39 pigs, using 18 Tenax (Biotronik Gmbh and Co., Berlin, Germany), 11 bare Genius (Eurocor, Bonn, Germany), 10 polymer-coated Genius (Eurocor) and six Biodivysio Matrix LO (Biodivysio Ltd, Farnham, Surrey, UK) stents. After 4 weeks, coronary angiography and IVUS with automatic pullback were performed. IVUS images were analysed using three-dimensional analysis (EchoPlaque 2; INDEC Systems Inc., Mountain View, California, USA). The stented segments were formalin fixed, embedded in Technovit 9100 and cut to 4-8 microm thick slides. The most diseased in-stent segment was 4.49 +/- 4.54 mm away from the distal stent edge assessed by IVUS. Sections of these segments were stained for histomorphometry. RESULTS A significant correlation was found between IVUS-guided histomorphometry and three-dimensional IVUS measurements of maximal intimal thickness (r = 0.6985, P < 0.005) and area (r = 0.7736, P < 0.001). Macroscopic measurements resulted in comparable maximal intimal thickness (0.83 +/- 0.43 mm compared with 0.81 +/- 0.46 mm) and area (4.44 +/- 1.73 mm2 compared with 3.45 +/- 1.55 mm2) by IVUS and histomorphometry, respectively. Although stent length, diameter, nominal inflation pressure and time and injury score did not differ between the stents, bare Genius stents resulted in significant smaller neointimal volume compared to Tenax, polymer-coated Genius and Biodivysio stents: 24.46 +/- 4.98 mm3 compared with 59.18 +/- 26.41, 60.46 +/- 10.03 and 61.41 +/- 16.27 mm3, respectively (P < 0.05). CONCLUSION The significant correlation between IVUS-guided histomorphometry and IVUS measurements confirms the usefulness of IVUS in evaluation of experimental in-stent restenosis. Implantation of bare Genius stents resulted in significant lower neointimal hyperplasia compared to Tenax, polymer-coated Genius or phosphorylcholine-coated Biodivysio stents.

The density of the warm ionized gas in high-redshift galaxies is known to be higher than what is typical in local galaxies on similar scales. At the same time, the mean global properties of the high- and low-redshift galaxies are quite different. Here, we present a detailed differential analysis of the ionization parameters of 14 star-forming galaxies at redshift 2.6-3.4, compiled from the literature. For each of those high-redshift galaxies, we construct a comparison sample of low-redshift galaxies closely matched in specific star formation rate (sSFR) and stellar mass, thus ensuring that their global physical conditions are similar to the high-redshift galaxy. We find that the median log [OIII] 5007/ [OII] 3727 line ratio of the high-redshift galaxies is 0.5 dex higher than their local counterparts. We construct a new calibration between the [OIII] 5007/ [OII] 3727 emission line ratio and ionization parameter to estimate the difference between the ionization parameters in the high and low-redshift samples. Using this, we show that the typical density of the warm ionized gas in star-forming regions decreases by a median factor of $7.1^{+10.2}_{-5.4}$ from z ~ 3.3 to z ~ 0 at fixed mass and sSFR. We show that metallicity differences cannot explain the observed density differences. Because the high- and low-redshift samples are comparable in size, we infer that the relationship between star formation rate density and gas density must have been significantly less efficient at z ~2-3 than what is observed in nearby galaxies with similar levels of star formation activity., 16 pages, 6 figures, accepted for publication in ApJ

We present an analysis of the lensed Lyman Break Galaxy (LBG), the 8 o'clock arc, at redshift 2.735. We reduced Near-IR IFU data from SINFONI on VLT covering λ= 2900 Å to 6500 Å in the rest-frame. From this we recovered the Hβ map and the spatially-resolved Hβ profile which are shown in the right plot in Fig. 1. We can see that Hβ shows different profiles at different spatial pixels and it is composed of multiple components. To study the de-lensed morphology of the galaxy we make use of existing B & H band imaging from the HST. Based on this we constructed a rigorous lens model for the system using the Bayesian grid based lens modeling technique presented by Vegetti & Koopmans (2009, MNRAS, 392, 945). In order to obtain a robust lens model, we first considered the high resolution B band HST image (rest-frame UV, left plot in Fig. 1) and then used this modeling to reconstruct the Hβ line map of the galaxy. We then present the de-lensed Hβ line map, velocity and velocity dispersion maps of this LBG galaxy.

Introduction Depression is a well known health problem worldwide. Prevalence of depressive disorders varies in different societies. Aim to determine the prevalence of depressive disorders and some associated factors in Rasht City (Northern part of Iran). Materials and methods 4020 subjects were selected among 394925 residents of Rasht aged between 18–70 during 2003 – 2004. In the first phase, subjects were screened by Beck's Depression Inventory. In the second phase, those who scored more than 15 were assessed through semi-structured psychiatric interview (DSMIV-TR). Socio-demographic characteristics including age, gender, marital status, educational level, and socio-economic class were recorded as well. Results 9.5% of samples (63% female and 37% male) were diagnosed by depressive disorders. The prevalence of minor depressive disorder, dysthymia and major depressive disorder was 5%, 2/5%, and 1% respectively. Socio-economic class was significantly associated with both depressive symptoms based on BDI score (p < 0.001) and depressive disorders based on clinical interview (p < 0.001). Conclusion Comparing to other studies, this study revealed that prevalence of dysthymic and minor depressive disorder were more than major depressive disorder, and low socio-economic class was the most significant risk factor associated with depression. Regarding our study limitations, researchers and policy makers should not consider our findings as conclusive results. Findings of this study could be applied by researchers using analytical methodology to assess relationship between depressive disorders and associated factors.

Introduction Little is known about catatonia associated with lead intoxication. Case presentation A retired printing house worker man presented with one week history of refusal to eat and mutism. He was treated with possible diagnosis of catatonia with administration of Lorazepam 3 mg P.O. daily. Significant improvement occurred after 48 hours. In further examinations, there was no evidence of physical and mental disorders while impairment in neuropsychiatry test, identification of Dohle body, basophilic stippling and toxic granulation in peripheral blood smear and blood lead level of 12.8 μg/dl were recorded. Conclusion Possibly, lead intoxication results in changes in neurotransmitter system that leads to catatonia. Lorazepam improves patient’s condition through changes in this system.