bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B25: Association of down-regulation of miR-193b and up-regulation of miR-196a with prognosis in gastric cancer
Authors: Sun Wenjie , Mu Yongping , Su Xiulan
Published: October 2015

Dysregulated expression of microRNAs (miRNAs) is confirmed to be closely associated with tumor development, progression, and carcinogenesis. The purpose of the present study was to determine the miRNA expression proﬁle of gastric cancer and to explore the relationship between aberrant miRNA expression and prognosis of gastric cancer in Chinese patients. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be present at significantly different expression levels in tissues from gastric cancer compared to those matched adjacent non-tumor tissues (ANTTs). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was then employed to characterize the expression patterns of miR-193b and miR-196a in total 96 snap frozen clinical gastric samples including 48 gastric cancer tissues and 48 paired ANTTs. The association between miRNA expression and clinical-pathological characteristics of patients was analyzed by binary logistic regression. We found that down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (P < 0.05), while up-expression of miR-196a was significantly correlated with poor differentiation (P = 0.022). Moreover, down-expression of miR-193b elevated cancer risk in UICC stage (adjusted odds ratio = 8.69; 95% confidence interval = 1.06-56.91; P = 0.043;). A Kaplan-Meier survival curve indicated that the patients with high fold change of down-regulated miR-193b had a significantly shorter survival time (n = 19; median survival = 29 months) compared to patients with low fold change of down-regulated miR-193b (n = 29; median survival = 54 months) (P = 0.001). Overall survival time of patients with low fold change of up-regulated miR-196a (n = 27; median survival = 52 months) was longer than that of patients with high fold change (n = 21; median survival = 46 months) (P = 0.003). Thus, miR-193b and miR-196a may be applied as novel and promising prognostic factors in gastric cancer.

Note: This abstract was not presented at the conference.

Citation Format: Wenjie Sun, Yongping Mu, Xiulan Su. Association of down-regulation of miR-193b and up-regulation of miR-196a with prognosis in gastric cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B25.
Abstract B36: Pyruvate kinase M2 regulates adipocyte differentiation and the expression of enzymes involved in glucose metabolism
Authors: Kimura Tetsuo , Bhardwaj Priya , Falcone Domenick J. , Dannenberg Andrew J. , Subbaramaiah Kotha
Published: October 2015

The number of overweight and obese individuals continues to increase in both the U.S. and worldwide. This increase has led to a significant increase in obesity-related medical problems including diabetes mellitus, cardiovascular disease and cancer. In obesity, the differentiation of adipocytes is suppressed. Although adipocyte differentiation is associated with changes in glucose metabolism, little is known about the potential of enzymes involved in glucose metabolism to modulate this process. Pyruvate kinase (PK) mediates the rate-limiting step of glycolysis. The M2 isoform of PK (PKM2) is expressed in adipocytes but its role in adipogenesis is unknown. Here we demonstrate that PKM2 regulates the differentiation of both human and mouse adipocytes. Silencing of PKM2 in preadipocytes led to increased lipid accumulation, enhanced expression of markers (FABP4, PPARgamma, C/EBPBeta) of adipocyte differentiation and caused a shift in the pattern of enzymes involved in glucose metabolism favoring the TCA cycle. Overexpression of PKM2 suppressed adipocyte differentiation. In obesity, increased numbers of macrophages are found in adipose tissue and are believed to contribute to insulin resistance. Interestingly, we found that activated macrophages produce factors that inhibit adipocyte differentiation leading to increased levels of enzymes involved in aerobic glycolysis including PKM2. Given its importance in regulating adipocyte differentiation, we investigated the mechanism by which PKM2 expression was regulated. The HIF-1alpha - c-Myc - HnRNPA1 pathway induced PKM2 in preadipocytes. The redox sensor CtBP1 was found to be a negative regulator of this pathway. Taken together, these results provide evidence that PKM2 is not only expressed in adipose tissue but is also a determinant of adipocyte differentiation. Whether pharmacologically targeting PKM2 will impact on obesity or its consequences warrants further investigation.

Citation Format: Tetsuo Kimura, Priya Bhardwaj, Domenick J. Falcone, Andrew J. Dannenberg, Kotha Subbaramaiah. Pyruvate kinase M2 regulates adipocyte differentiation and the expression of enzymes involved in glucose metabolism. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B36.
Abstract B54: Current intervention strategies in the NCI PREVENT Cancer Preclinical Drug Development Program
Authors: Shoemaker Robert H. , Dunn Barbara K. , Suen Chen , Boring Dan L. , Klein Brian D. , Miller Mark S. , Steele Vernon E.
Published: October 2015

Chemoprevention research in the Division of Cancer Prevention (DCP) was re-structured in 2011 creating the PREVENT Cancer Preclinical Drug Development Program. This Program provides for peer-review of proposals from the general research community for development of small molecules or biologicals, including vaccines, for cancer prevention or biomarkers to facilitate clinical evaluation of prevention strategies. The process for applying to the Prevent Program is described at: http://prevention.cancer.gov/programs-resources/programs/prevent. Applications are submitted twice yearly and reviewed by a panel of experts from the extramural community and NIH Scientists outside DCP and scored for scientific merit, feasibility, etc. Top scoring applications undergo secondary review and prioritization by a panel of DCP and other NIH scientists. Applications with potential for near-term clinical translation are given highest priority. Approved projects are implemented as Task Orders via a system of contracts with academic and nonprofit, independent research institutions that provide the full range of preclinical studies, including good laboratory practice toxicology, needed to support Investigational New Drug Applications. Twenty-five Task Orders addressing a range of intervention strategies have been awarded in the first two years of the Program. Small molecules targeting classic aspects of inflammation as well as newer molecular-targeted agents (n=16) are under study. Pharmacodynamic assays are coupled to efficacy studies. Immunoprevention strategies targeting tumor-associated antigens as well as antigens from cancer-associated infectious agents (n=6) are being pursued. Preliminary data from current projects will be presented. The PREVENT Cancer Program has engaged a broad cross-section of investigators, supporting preclinical development of agents addressing a wide variety of cancer prevention strategies.

Citation Format: Robert H. Shoemaker, Barbara K. Dunn, Chen Suen, Dan L. Boring, Brian D. Klein, Mark S. Miller, Vernon E. Steele. Current intervention strategies in the NCI PREVENT Cancer Preclinical Drug Development Program. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B54.
Abstract CN01-01: Big challenges of big data: Biomedical science in the petabyte era
Authors: Shyr Yu
Published: October 2015

Next-generation sequencing technologies (NGS) have exploded in popularity in recent years thanks to their ability to produce an enormous volume of data quickly and at relatively low cost compared to traditional sequencing methods such as Sanger sequencing. The emergence of NGS has pushed forward the goal of personalized medicine, but looking at the entire scope of a study from experimental design to data analysis to the ultimate goal of dose selection based on a patient's genome reveals many more challenges. Sample size for RNA-seq studies has been a persistent problem that has only recently received attention. Sequencing data analysis packages are numerous and constantly in development, but without a clear gold standard, they can be more overwhelming than helpful. Finally, this genomic information must be seamlessly integrated with clinical information for the knowledge to be useable by practitioners before the goal of personalized medicine can become a reality.

Citation Format: Yu Shyr. Big challenges of big data: Biomedical science in the petabyte era. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN01-01.
Abstract CN07-02: Obesity, inflammation, and breast cancer
Authors: Dannenberg Andrew J.
Published: October 2015

Obesity is a risk factor for the development of several malignancies including hormone receptor–positive breast cancer in postmenopausal women and has been associated with an increased risk of recurrence and reduced survival. Chronic inflammation increases the risk of multiple tumor types. A link between obesity, breast inflammation and hormone receptor-positive breast cancer was previously unknown. Obesity causes subclinical inflammation in visceral and subcutaneous white adipose tissue, characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures (CLS). Estrogen synthesis is catalyzed by aromatase, which is encoded by CYP19. We found increased numbers of CLS, activation of the NF-kappaB transcription factor, increased levels of pro-inflammatory mediators and elevated aromatase levels in the mammary glands of obese mice. These preclinical findings raised the possibility that the obesity-inflammation-aromatase axis is important for breast carcinogenesis. Importantly, these findings have now been translated to women. Breast tissue was obtained from women who underwent surgery. CLS of the breast (CLS-B) were found in approximately 50% of patient samples. The severity of breast inflammation correlated with both body mass index and adipocyte size. Menopause is an independent determinant of CLS-B. Consistent with our preclinical findings, increased NF-κB binding activity, increased levels of pro-inflammatory mediators and elevated aromatase expression and activity were found in the inflamed breast tissue of overweight and obese women. Collectively, our results suggest that the obesity-inflammation-aromatase axis is present in the breast tissue of most overweight and obese women and is likely to contribute to the increased risk of hormone receptor-positive breast cancer. The discovery of the connection between obesity, breast inflammation and changes in the expression of genes linked to breast cancer provides a mechanistic rationale for the development of behavioral, dietary and pharmacological strategies to reduce the risk of breast cancer. Non-invasive biomarkers of adipose inflammation are needed to both identify at-risk individuals and monitor the efficacy of interventions aimed at attenuating inflamed adipose tissue. Recent progress in the development of blood biomarkers of breast adipose inflammation will be reviewed.

Citation Format: Andrew J. Dannenberg. Obesity, inflammation, and breast cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN07-02.
Abstract CN11-02: Impact for the menopausal transition on skeletal and breast health
Authors: Cauley Jane A.
Published: October 2015

Women spend about one-third of their lifespan in the postmenopausal period. Menopause represents a vulnerable time in a woman's life for a number of reason, in particular, for her skeletal health. Estrogen deficiency associated with menopause increases bone remodeling leading to an imbalance between bone formation and bone resorption. The Study of Women's Health Across the Nation (SWAN) is an ongoing multicenter study designed to investigate a broad range physiological, psychosocial and social issues for women at midlife. The long range goal was to distinguish ovarian aging from chronological aging. Skeletal health was a particular focus of SWAN. At baseline, all 3302 women were age 42-52 years and pre- or early perimenopausal, having had a menstrual period within 3-months of study entry. A 10-year longitudinal analysis was conducted in a subset of 242 African American, 384 Caucasian, 117 Chinese and 119 Japanese women for whom a final menstrual period (FMP) could be defined. Bone loss was not evident during the pretransmenopausal state (between 5-years and 1-year prior to the FMP). Bone mineral density (BMD) loss began 1-year prior to FMP and slowed 2 years after FMP. Cumulative loss was greatest in Asian women and slowest in African American women. The 10-year cumulative loss of lumbar spine BMD was 10.6%, most of which was lost in the transmenopause period.

This menopause associated estrogen deficiency might also influence breast density, a major risk factor for breast cancer. An ancillary study to SWAN focused on breast density: 1007 women from 3 sites were included. Mammograms that were taken 2-years before baseline up to 2-years after the 6th annual follow-up visit were retrospectively obtained and graded for breast density. Findings from the SWAN breast density include the observation that greater parity and younger age at first birth were inversely associated with breast density and may support a mechanism for parity and breast cancer through breast density. Smokers had lower breast density supporting an anti-estrogenic effect on breast tissue. The percentage of breast density decreased with increasing body mass index over time.

In conclusion, the SWAN study provides important insights into menopausal health.

Citation Format: Jane A. Cauley. Impact for the menopausal transition on skeletal and breast health. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN11-02.
Abstract PR09: Intermittent dosing regimens maintain efficacy of several cancer preventing drugs
Authors: Steele Vernon E. , Grubbs Clinton J. , Lubet Ronald A.
Published: October 2015

Many potential chemopreventive drugs have adverse effects on human subjects when given daily. One strategy to alleviate these adverse events is to give the drugs on an intermittent dosing schedule. Such intermittent dosing has proven effective in other settings to reduce toxicity with limited effect on efficacy. Two animal models were used: the rat methylnitrosourea (MNU) - induced mammary cancer model and the rat hydroxy-butyl(butyl)-nitrosamine (OH-BBN) -induced urinary bladder cancer model. For the mammary study female Sprague-Dawley rats were given 75 mg of MNU/kg body weight at 50 days of age and five days later the EGFR inhibitors, Erlotinib, Gefitinib or Lapatinib were administered either daily or once a week at two dose levels. Multiplicity of ER-positive mammary cancers was followed weekly for four months. For the urinary bladder study female Fischer 344 rats were given 150 mg OH-BBN/gavage twice weekly beginning at 56 days of age and continuing for 8 weeks. Two weeks after the last OH-BBN treatment the rats were given naproxen either daily, one week on/one week off, or 3 weeks on/3 weeks off. Bladders were excised after 8 months of naproxen treatment and bladders with tumors were excised and weighed. EGFR inhibitors and the NSAID, Naproxen, have similar efficacy when given intermittently compared to daily. The EGFR antagonists, Erlotinib and Lapatinib, decreased mammary cancer multiplicity by 90% given daily and 75 % given weekly. The NSAID, naproxen, decreased large bladder cancers by about 65-80% given either daily, one week on/one week off or 3 weeks on/3 weeks off. Therefore intermittent dosing can be used for agents in two different mechanistic classes in animal mammary and bladder cancer models to lower toxicity, yet show little reduction in chemoprevention efficacy compared to daily dosing. Intermittent dosing schedules in the clinic should reduce EGFR mediated rash and NSAID induced gastric toxicity clinically while retaining efficacy.

Citation Format: Vernon E. Steele, Clinton J. Grubbs, Ronald A. Lubet. Intermittent dosing regimens maintain efficacy of several cancer preventing drugs. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PR09.
T-cell–based Immunotherapy: Adoptive Cell Transfer and Checkpoint Inhibition
Authors: Houot Roch , Schultz Liora Michal , Marabelle Aurélien , Kohrt Holbrook
Published: October 2015

Tumor immunotherapy has had demonstrable efficacy in patients with cancer. The most promising results have been with T-cell–based therapies. These include adoptive cell transfer of tumor-infiltrating lymphocytes, genetically engineered T cells, and immune checkpoint inhibitor antibodies. In this review, we describe the different T-cell–based strategies currently in clinical trials and put their applications, present and future, into perspective. Cancer Immunol Res; 3(10); 1115–22. ©2015 AACR.
A Case Study of Fixed-Effects and Random-Effects Meta-Analysis Models for Genome-Wide Association Studies in Celiac Disease
Authors: Ahn Richard S. , Garner Chad
Published: October 2015

Background/Aims: Amongst the many approaches to genome-wide association study (GWAS) meta-analysis (MA), the most popular methods are based on fixed-effects (FE) modeling because it tends to be the statistically most powerful approach in the absence of heterogeneity. However, FE-based MA ignores the potential heterogeneity that may exist between studies. The purpose of our analysis was to test whether results from random effects (RE)-based methods that account for heterogeneity differed significantly from the results that were originally published. Methods: We reanalyzed two GWAS FE-based MAs of celiac disease with RE-based methods: (1) a two-stage GWAS MA that includes 9,451 celiac disease cases and 16,434 controls from 12 collections and (2) a single-stage GWAS MA using a custom dense genotyping platform to capture low-frequency and rare variants in 12,041 cases and 12,228 controls from 7 collections. Results: We present evidence that SNPs at loci that were previously reported to be genome-wide significant (GWS; p < 5 × 10-8) in either the two-stage GWAS MA or the single-stage GWAS MA were not GWS when heterogeneity was accounted for by an RE MA method. Conclusion: This case study highlights the strengths of RE MA methods in the presence of heterogeneity and of pooled FE methods.
Copy Number Variations in DISC1 and DISC1-Interacting Partners in Major Mental Illness
Authors: Johnstone Mandy , Maclean Alan , Heyrman Lien , Lenaerts An-Sofie , Nordin Annelie , Nilsson Lars-Göran , De Rijk Peter , Goossens Dirk , Adolfsson Rolf , St. Clair David M. , Hall Jeremy , Lawrie Stephen M. , McIntosh Andrew M. , Del-Favero Jurgen , Blackwood Douglas H.R. , Pickard Benjamin S.
Published: October 2015

Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification. Here, we report the finding of rare CNVs in DISC1, NDE1 (together with adjacent genes within the 16p13.11 duplication), NDEL1 (including the overlapping MYH10 gene) and CIT. Our findings provide further evidence for involvement of DISC1 and its interaction partners in neuropsychiatric disorders and also for a role of structural variants in the aetiology of these devastating diseases.
Pharmacogenetic Effect of Complement Factor H Gene Polymorphism in Response to the Initial Intravitreal Injection of Bevacizumab for Wet Age-Related Macular Degeneration
Authors: Medina Flavio Mac Cord , Alves Lopes da Motta Augusto , Takahashi Walter Y. , Carricondo Pedro Carlos , dos Santos Motta Mario Martins , Melo Monica B. , Vasconcellos Jose Paulo C.
Published: October 2015

Purpose: To compare the functional and morphological response to the initial intravitreal (IVT) injection of bevacizumab in exudative age-related macular degeneration (AMD) patients with the complement factor H (CFH) gene polymorphism T1277C in the Brazilian population. Methods: Twenty-five unrelated patients with treatment-naive exudative AMD underwent an IVT injection of 1.25 mg bevacizumab at the initial presentation (D0) and were reexamined 7 days (D7) and 28 days (D28) later. The time and extent of visual acuity (VA) and central retinal thickness (CRT) changes were evaluated according to the presence of the T1277C polymorphism. Results: In the homozygous risk group (CC), VA improvement was detected mostly from D7 to D28, while in the heterozygous (CT) and homozygous for the wild-type allele (TT) groups, functional response occurred earlier, from D0 to D7. Morphological response to the first IVT injection of bevacizumab was significant in the CT and TT groups, while the CC group presented no significant change in CRT up to D28. Conclusion: The CC variant of the CFH gene polymorphism T1277C is related to delayed functional and limited morphological response to the initial IVT injection of bevacizumab in exudative AMD patients in a sample of the Brazilian population.
Lower Risk of Cancer in the Areas Inhabited by the German Minority in the Region of Opole, Poland
Authors: Chawińska Ewa , Tukiendorf Andrzej , Miszczyk Leszek
Published: October 2015

Background: The lower risk of cancer in the areas inhabited by the German minority in the region of Opole, Poland, at the turn of the 1980's and 1990's has been already reported. A reanalysis of the present-day data was conducted. Patients and Methods: All the cancer cases (at all sites combined) registered within the years 2008-2012 with data collected by the Regional Cancer Registry in Opole were analyzed in this study. To estimate the risk of cancer in different spatial contexts, such as trends, clusters, and levels, modern geostatistical tools were applied. Results: A statistically significant reduction of the cancer risk was reported in administrative units with ≥ 10% of the German minority. Average decreases in relative risk of 13% in men and 16% in women were estimated. The geographical patterns of the estimates are illustrated. Conclusions: The observed differences in the risk of cancer between the ethnic groups (Germans and repatriates) confirm a historical trend of the disease in the region of Opole, Poland. Some genetic, nutritional, or cultural aspects together with economic issues may play a role in the specified spatial disease patterns.
Lower Hydrogen Sulfide Is Associated with Cardiovascular Mortality, Which Involves cPKCβII/Akt Pathway in Chronic Hemodialysis Patients
Authors: Feng Su-Juan , Li Han , Wang Shi-Xiang
Published: October 2015

Background/Aims: To evaluate the relationship between plasma hydrogen sulfide (H2S) and cardiovascular risk markers, including pulse pressure (PP), left ventricular mass index (LVMI) and intima-media thickness (IMT), and mortality in chronic hemodialysis (CHD) patients and further investigate the underlying cardiovascular protection mechanism of H2S. Methods: CHD patients, 113 of them, were studied. Plasma H2S was measured through zinc acetate reaction. cPKCβII membrane translocation and phosphorylation of Akt were detected by western blot. Results: Lower plasma H2S level in CHD patients was predictor of an increased PP, LVMI and IMT. Patients with lower H2S had a lower survival at the end of the study. H2S was an independent predictor of all-cause and cardiovascular mortality when adjusted for other risk factors. CHD patients with lower H2S showed an increase of cPKCβII activation, but phosphorylation of Akt decreased. The level of VCAM-1 and ICAM-1 increased significantly. Conclusions: Lower plasma H2S in CHD patients is associated with cardiovascular risk factors and mortality, which may be mediated by the cPKCβII/Akt pathway and further VCAM-1/ICAM-1 upregulation.
Is the Post-Radical Prostatectomy Gleason Score a Valid Predictor of Mortality after Neoadjuvant Hormonal Treatment?
Authors: Froehner Michael , Propping Stefan , Koch Rainer , Borkowetz Angelika , Liebeheim Dorothea , Toma Marieta , Baretton Gustavo B. , Wirth Manfred P.
Published: October 2015

Purpose: To evaluate the validity of the Gleason score after neoadjuvant hormonal treatment as predictor of disease-specific mortality after radical prostatectomy. Patients and Methods: A total of 2,880 patients with a complete data set and a mean follow-up of 10.3 years were studied; 425 of them (15%) had a history of hormonal treatment prior to surgery. The cumulative incidence of deaths from prostate cancer was determined by univariate and multivariate competing risk analysis. Cox proportional hazard models for competing risks were used to study combined effects of the variables on prostate cancer-specific mortality. Results: A higher portion of specimens with a history of neoadjuvant hormonal treatment were assigned Gleason scores of 8-10 (28 vs. 17%, p < 0.0001). The mortality curves in the Gleason score strata <8 vs. 8-10 were at large congruent in patients with and without neoadjuvant hormonal treatment. In patients with neoadjuvant hormonal treatment, a Gleason score of 8-10 was an independent predictor of prostate cancer-specific mortality; the hazard ratio was, however, somewhat lower than in patients without neoadjuvant hormonal treatment. Conclusion: This study suggests that the prognostic value of the post-radical prostatectomy Gleason score is not meaningfully jeopardized by heterogeneous neoadjuvant hormonal treatment in a routine clinical setting.
Endometrial Cancer with Sarcoidosis in Regional Lymph Nodes: A Case Report
Authors: Tamauchi Satoshi , Shimomura Yuji , Hayakawa Hiromi
Published: October 2015

Sarcoidosis is a chronic, multisystemic disease commonly affecting the lungs and lymphatic system and is characterized by the formation of noncaseating granulomas. Although several reports are available on cases developing both sarcoidosis and cancer metachronously, cases of simultaneous diagnosis of these diseases have rarely been reported. A 67-year-old woman diagnosed with endometrial cancer had developed systemic lymph node swelling, including bilateral hilar, paraaortic, and a few pelvic lymph nodes, as observed on preoperative imaging. During surgery, frozen sections of a paraaortic lymph node were examined, revealing noncaseating granulomas compatible with sarcoidosis. Next, modified radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy were performed. Postoperative pathological analysis revealed endometrioid adenocarcinoma of the uterus, and no metastasis but noncaseating granulomas were detected in the resected lymph nodes. Postoperatively, we identified cutaneous sarcoidosis and uveitis in the presence of a tuberculin-negative test. On the basis of these findings, we diagnosed the patients with endometrial cancer complicated by sarcoidosis. She underwent adjuvant chemotherapy, and at the 1-year follow-up, the lymph node swelling due to sarcoidosis was stable, and no recurrence of the cancer was observed. This turned out to be a case of early endometrial cancer mimicking advanced cancer by sarcoidosis. Histological confirmation and additional examination for sarcoidosis are necessary in cancer patients suspected of sarcoidosis.
Absence of in vitro Procoagulant Activity in Immunoglobulin Preparations due to Activated Coagulation Factors
Authors: Oviedo Adriana E. , Bernardi María E. , Guglielmone Hugo A. , Vitali María S.
Published: October 2015

Background: Immunoglobulin (IG) products, including intravenous (IVIG) or subcutaneous (SCIG) immunoglobulins are considered safe and effective for medical therapy; however, a sudden and unexpected increase in thromboembolic events (TE) after administration of certain batches of IVIG products has been attributed to the presence of activated coagulation factors, mainly factor XIa. Our aims were to examine the presence of enduring procoagulant activity during the manufacturing process of IGs, with special focus on monitoring factor XIa, and to evaluate the presence of in vitro procoagulant activity attributed to coagulation factors in different lots of IVIG and SCIG. Methods: Samples of different steps of IG purification, 19 lots of IVIG and 9 of SCIG were analyzed and compared with 1 commercial preparation of IVIG and 2 of SCIG, respectively. Factors II, VII, IX, XI and XIa and non-activated partial thromboplastin time (NAPTT) were assayed. Results: The levels of factors II, VII, IX, X and XI were non-quantifiable once fraction II had been re-dissolved and in all analyzed lots of IVIG and SCIG. The level of factor XIa at that point was under the detection limits of the assay, and NAPTT yielded values greater than the control during the purification process. In SCIG, we detected higher concentrations of factor XIa in the commercial products, which reached values up to 5 times higher than the average amounts found in the 9 batches produced by UNC-Hemoderivados. Factor XIa in commercial IVIG reached levels slightly higher than those of the 19 batches produced by UNC-Hemoderivados. Conclusion: IVIG and SCIG manufactured by UNC-Hemoderivados showed a lack of thrombogenic potential, as demonstrated not only by the laboratory data obtained in this study but also by the absence of any reports of TE registered by the post marketing pharmacovigilance department.
Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman
Authors: Lestelle Valentin , de Coster Claire , Sarran Anthony , Poizat Flora , Delpero Jean-Robert , Raoul Jean-Luc
Published: October 2015

We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.
Increased Steroid Excretion in Children with Extremely Low Birth Weight at a Median Age of 9.8 years
Authors: Gohlke Bettina , Wudy Stefan A. , Stutte Sonja , Bartmann Peter , Hartmann Michaela F. , Woelfle Joachim
Published: October 2015

Background: Events during foetal or early extrauterine life may affect bodily structure and/or functions and even pave the way for adult diseases. Aims: To find whether extremely low birth weight (ELBW) infants differ from healthy controls regarding the excretion of steroid metabolites. Methods: The study compared 17 female and 10 male ELBW infants, all prepubertal, aged 8-11 years, birth weight <1,000 g, with 27 age- and sex-matched controls. All were healthy at the time of the study. Height, weight and BMI did not differ between the groups. Results were adjusted according to body surface area. 36 urinary steroid metabolites were quantified by gas chromatography-mass spectrometry. Results: In the ELBW girls 33/36 steroid metabolites were higher (19 significantly) than in the controls. All 36 steroid metabolites were higher in the ELBW boys (9 significantly) than in the controls. Sums of mineralocorticoid precursors, metabolites descriptive for cortisol and parameters of adrenal androgen production were significantly higher in ELBW infants (both sexes). Only the sum of the metabolites known to be illustrative for adrenal 11β-hydroxysteroid dehydrogenase activity was not different. Conclusion: Prepubertal ELBW children have an augmented urinary excretion of adrenal androgens, cortisol and mineralocorticoid precursors. These findings corroborate and help to explain the link between early-life adversity and subsequent adrenocortical function.
Nasopalpebral Schwannomas and Human Immunodeficiency Virus Infection
Authors: Handra-Luca Adriana , Haddar Djamel , Morin Anne-Sophie
Published: October 2015

Objective: To report a case of a schwannoma of nasopalpebral location, occurring in a human immunodeficiency virus (HIV)-positive patient. Clinical Presentation and Intervention: A 55-year-old man presented with a nasopalpebral painless tumefaction, pneumopathy and HIV-related immunodepression after stopping combination antiretroviral therapy. Magnetic resonance imaging showed subcutaneous masses, with contrast enhancement of the left nose pyramid, internal cantus and inferior palpebral area, suspicious of Kaposi sarcoma. The resected specimen showed schwannoma histology, with tumor cells expressing S100 protein and WT1. Conclusion: The features of a rare case of facial schwannoma of nasopalpebral location in an HIV-positive patient are reported. The diagnosis may be difficult before microscopic examination, with imaging features suggesting a Kaposi sarcoma.
Hipertensão renovascular na arterite de Takayasu: um relato de caso
Authors: Braz Maria Julia De Aro , Corbi Leonardo Ervolino , Bortolotto Luiz Aparecido , Giorgi Dante Marcelo Antigas
Published: October 2015

Arterite de Takayasu é uma doença inflamatória crônica, de etiologia pouco conhecida, que acomete mais frequentemente mulheres jovens, na vigésima ou trigésima décadas de vida, sendo mais prevalente no Japão, Sudeste Asiático, Índia e México. A doença afeta principalmente aorta, seus maiores ramos e artérias pulmonares, ocasionando estenose, oclusão e, menos frequentemente, dilatação e formação de aneurismas. O envolvimento de artérias renais é o mais comum nos casos em que se observa acometimento de artérias viscerais, sendo encontrado em 24 a 68% deles. Estenose de artéria renal gera hipoperfusão renal, ativação do sistema renina-angiotensina-aldosterona e retenção de sódio, modificando débito cardíaco e resistência vascular periférica. A consequente elevação dos níveis pressóricos caracteriza a hipertensão renovascular, que ocorre quando a estenose da artéria é superior a 70%, sendo uma das causas mais comuns de hipertensão secundária, sobretudo em jovens. O manejo do paciente com arterite de Takayasu inclui medidas farmacológicas para controle pressórico e terapêutica intervencionista por tratamento percutâneo ou revascularização cirúrgica do território em isquemia. Será descrito o caso de um paciente com hipertensão de difícil controle por estenose de artéria renal, decorrente de arterite de Takayasu, submetido a tratamento percutâneo.[...]
O pré-condicionamento com solução salina hipertônica reduz o stress oxidativo na isquemia reperfusão hepática com hipotermia
Authors: Boas Mariana Da Silva Villas , Figueira Estela Regina Ramos , Rocha Filho Joel Avancini , D’Albuquerque Luiz Augusto Carneiro
Published: October 2015

A lesão isquemia/reperfusão (IR) hepática desencadeia uma reação inflamatória que influencia diretamente na sobrevivência do enxerto após o transplante de fígado. A hipotermia reduz drasticamente a lesão IR, sendo a base da preservação dos órgãos. No entanto, outras estratégias são necessárias para aumentar a viabilidade do enxerto. Em trabalho anterior realizado no nosso LIM, foi demonstrado que a solução salina hipertônica(SSH) reduz a lesão hepática após a IR hepática normotérmica. O objetivo deste estudo foi avaliar os efeitos do condicionamento do fígado com SSH na IR hepática com hipotermia tópica do fígado. [...]
Dose–Response Relationship Between Physical Activity and Risk of Heart Failure
Authors: Pandey Ambarish , Garg Sushil , Khunger Monica , Darden Douglas , Ayers Colby , Kumbhani Dharam J. , Mayo Helen G. , de Lemos James A. , Berry Jarett D.
Published: October 2015

Background—

Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose–response association between PA and HF risk has not been reported previously.

Methods and Results—

Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose–response relationships between PA and HF risk were assessed with random-effects models. Generalized least-squares regression models were used to assess the quantitative relationship between PA (metabolic equivalent [MET]–min/wk) and HF risk across studies reporting quantitative PA estimates. Twelve prospective cohort studies with 20 203 HF events among 370 460 participants (53.5% women; median follow-up, 13 years) were included. The highest levels of PA were associated with significantly reduced risk of HF (pooled hazard ratio for highest versus lowest PA, 0.70; 95% confidence interval, 0.67–0.73). Compared with participants reporting no leisure-time PA, those who engaged in guideline-recommended minimum levels of PA (500 MET-min/wk; 2008 US federal guidelines) had modest reductions in HF risk (pooled hazard ratio, 0.90; 95% confidence interval, 0.87–0.92). In contrast, a substantial risk reduction was observed among individuals who engaged in PA at twice (hazard ratio for 1000 MET-min/wk, 0.81; 95% confidence interval, 0.77–0.86) and 4 times (hazard ratio for 2000 MET-min/wk, 0.65; 95% confidence interval, 0.58–0.73) the minimum guideline-recommended levels.

Conclusions—

There is an inverse dose–response relationship between PA and HF risk. Doses of PA in excess of the guideline-recommended minimum PA levels may be required for more substantial reductions in HF risk.
Human Trafficking in Nahum
Authors: Cook Gregory D.
Published: October 2015

Nahum has come under recent censure for the term זונה (3:4). Scholars have argued that calling Nineveh a prostitute does not fit the brutal Neo-Assyrian Empire. This article argues that the book of Nahum charges Nineveh with multi-national human trafficking. Assyrian practices conform to the United Nations definition of human trafficking. The methods Assyria used to recruit, transport, and prostitute peoples match methods of modern slavers. The title זונה therefore is used because the city acted as a spiritual madam. Vast populations were kidnapped for economic purposes and much of the labor, money, and people acquired through conquest were used to serve the Assyrian pantheon.
Aeschylus and the Binding of the Tyrant
Authors: Picariello Damien K. , Saxonhouse Arlene W.
Published: October 2015

In Aeschylus’ Prometheus Bound, the playwright depicts the punishment of Prometheus by the tyrannical Zeus. Zeus’ subordinates understand his tyranny to be characterized by an absolute freedom of action. Yet the tyrant’s absolute freedom as ruler is called into question by insecurity of his position and by his dependence on Prometheus’ knowledge. We find in the Prometheus Bound a model of tyrannical rule riddled with contradictions: The tyrant’s claim to total control and absolute freedom is in tension with a reality characterized by insecurity, impotence, and constraint. We contrast this model of rule with the model found in Aeschylus’ Suppliant Maidens, in which the King, agreeing to be bound by the wishes of his subjects, nevertheless preserves for himself a certain freedom of action that the tyrannical ruler lacks.
Aristotle’s Pambasileia and the Metaphysics of Monarchy
Authors: Atack Carol
Published: October 2015

Aristotle’s account of kingship in Politics 3 responds to the rich discourse on kingship that permeates Greek political thought (notably in the works of Herodotus, Xenophon and Isocrates), in which the king is the paradigm of virtue, and also the instantiator and guarantor of order, linking the political microcosm to the macrocosm of the universe. Both models, in separating the individual king from the collective citizenry, invite further, more abstract thought on the importance of the king in the foundation of the polity, whether the king can be considered part of, or separate from, the polis, and the relationship between polis and universe. In addressing these aspects of kingship theories, Aristotle explores a ‘metaphysics of monarchy’, part of the long-running mereological problem of parts and wholes in the construction of the polis, and connecting his account of kingship to his thought on citizenship and distributive justice within the polis.
Senecio eliseae (Compositae, Senecioneae), a new species from the southern Ecuadorian Andes
Authors: Calvo Joel
Published: October 2015

Senecio eliseae is described as a new species from the southern Ecuadorian Andes. It is a suffrutescent herb characterized by erect branches that are leaved only in the upper half, yellow discoid nodding capitula, and glandular-hirsute indumentum on the stem, leaves, and synflorescence. Detailed photographs of plants from the type locality are provided.
A revision of the genus Belciana Walker, 1862 with description of three new species (Lepidoptera, Noctuidae: Pantheinae) from East and South East Asia. Revision of Pantheinae, contribution XII
Authors: Behounek G. , HAN H.L. , Kononenko V.S.
Published: October 2015

The Oriental Pantheinae genus Belciana Walker, 1862 is revised. Three new species, B. hreblayi sp. n., B. sulawesiana sp. n., B. pinratanai sp. n., from Taiwan, Indonesia and Thailand, are described. Five new combinations in the genus Diphteroides Bethune-Baker, 1906 are proposed: Diphteroides caerulea (Hampson, 1926) comb. n., D. habroscia (Prout, 1924) comb. n., D. patricolor (Prout, 1924) comb. n., D. serrata Bethune-Baker, 1906, D. subserrata (Prout, 1924) comb. n. and D. sophronia (Prout, 1924) comb. n. The extensive diagnoses of known species of Belciana are given. The imagines, male and female genitalia are illustrated. The checklist of the genus Belciana in East Asia is presented.
Taxonomic notes on Holcobunus Roewer, 1910, with descriptions of three new species, and new records for Holcobunus nigripalpis Roewer, 1910
(Opiliones: Eupnoi: Sclerosomatidae)
Authors: TOURINHO ANA LÚCIA , PINTO-DA-ROCHA RICARDO , BRAGAGNOLO CIBELE
Published: October 2015

Three new Brazilian species of Holcobunus Roewer, 1910 are described, thus increasing the total number of species in the genus to five: Holcobunus bicornutus Mello-Leitão, 1940, H. nigripalpis Roewer, 1910, Holcobunus dissimilis sp. nov. (type locality: Espírito Santo, Santa Teresa, Reserva Biologia Augusto Ruschi), Holcobunus ibitirama sp. nov. (type locality: Espírito Santo, Ibitirama, Santa Marta, close to Parque Nacional Caparaó), and Holcobunus uaisoh sp. nov. (type locality: Minas Gerais, Fervedouro, Parque Estadual Serra do Brigadeiro). A new record for Holcobunus nigripalpis Roewer, 1910 from Minas Gerais is also provided and the morphological variation in both penis and somatic morphology in the genus are presented and discussed. These observations enhance our understanding of both the diversity and distribution of Holcobunus.
A Local Meshless Method for Approximating 3D Wind Fields
Authors: Pepper Darrell W. , Waters Jiajia
Published: October 2015

An efficient, mesh-free numerical method has been developed for creating 3D wind fields using data from meteorological towers. Node points are placed within a region of interest, generally based upon topological features. Since meshless methods do not require connective mesh generation, storage is greatly reduced, permitting implementation of the code using MATLAB on a personal computer. Utilizing locally collocated nodes and radial basis functions, a 3D wind can be quickly created that satisfies mass consistency. The meshless method yields close approximations to results obtained with mesh-dependent finite-difference, finite-volume, and finite-element techniques.
Educating Amid Uncertainty
Authors: Kraft Matthew A. , Papay John P. , Johnson Susan Moore , Charner-Laird Megin , Ng Monica , Reinhorn Stefanie
Published: October 2015

Purpose: We examine how uncertainty, both about students and the context in which they are taught, remains a persistent condition of teachers’ work in high-poverty, urban schools. We describe six schools’ organizational responses to these uncertainties, analyze how these responses reflect open- versus closed-system approaches, and examine how this orientation affects teachers’ work. Research Methods: We draw on interviews with a diverse set of 95 teachers and administrators across a purposive sample of six high-poverty, urban schools in one district. We analyzed these interviews by drafting thematic summaries, coding interview transcripts, creating data-analytic matrices, and writing analytic memos. Findings: We find that students introduced considerable uncertainty into teachers’ work. Although most teachers we spoke with embraced the challenges of their work and the expanded responsibilities that it entailed, they recognized that their individual efforts were not sufficient to succeed. Teachers consistently spoke about the need for organizational responses that addressed the environmental uncertainty of working with students from low-income families whose experience in school often has been unsuccessful. We describe four types of organizational responses—coordinated instructional supports, systems to promote order and discipline, socioemotional supports for students, and efforts to engage parents—and illustrate how these responses affected teachers’ ability to manage the uncertainty introduced by their environment. Conclusions: Traditional public schools are open systems and require systematic organizational responses to address the uncertainty introduced by their environments. Uncoordinated individual efforts alone are not sufficient to meet the needs of students in high-poverty urban communities.