bluuebunny/crossref_metadata_2025 huggingface dataset:
Attitudes of Nonpalliative Care Nurses towards Palliative Care
Authors: Tait Victoria , Higgs Megan , Magann Linda , Dixon Joanne , Davis Jan Maree , Fernandez Ritin
Published: January 2015

The quality of palliative care given to terminally ill patients and their family members can be directly impacted by the attitudes that nurses hold towards palliative care. This study aimed to investigate the attitudes of nonpalliative care nurses towards death and dying in the context of palliative care. Nurses working within the medical aged care, cardiology and respiratory wards at two metropolitan teaching hospitals in Sydney completed the Frommelt Attitudes Towards Care of the Dying (FATCOD) scale, an anonymous self-administered questionnaire, and a twelve-item demographic questionnaire. A total of 95 completed surveys were used in the final analysis. The total FATCOD score was 119.8±11.1, patient FATCOD was 79.6±8.6, and family FATCOD was 40.2±4.4. Of significance, the professional variables designation and role were associated with attitudes in the total FATCOD and country of birth, designation, highest level of education, and role were associated with attitudes towards the patient FATCOD. Scores for communication between the nurse and the terminally ill patient were poor. Health care facilities should focus on developing strategies to improve the communication skills among nonpalliative care nurses in order to optimize patient outcomes.
Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location inBRCA1/2Carriers
Authors: Lecarpentier Julie , Noguès Catherine , Mouret-Fourme Emmanuelle , Buecher Bruno , Gauthier-Villars Marion , Stoppa-Lyonnet Dominique , Bonadona Valérie , Fricker Jean-Pierre , Berthet Pascaline , Caron Olivier , Coupier Isabelle , Pujol Pascal , Faivre Laurence , Gesta Paul , Eisinger François , Mari Véronique , Gladieff Laurence , Lortholary Alain , Luporsi Elisabeth , Leroux Dominique , Venat-Bouvet Laurence , Maugard Christine M. , Colas Chrystelle , Tinat Julie , Lasset Christine , Andrieu Nadine
Published: January 2015

Background: Mutations in BRCA1/2 confer a high risk of breast cancer, but literature values of this risk vary. A genotype–phenotype correlation has been found in both genes, and the effect of reproductive factors differs according to mutation location. Therefore, we hypothesize that such a variation may exist for other factors related to estrogen exposure.

Methods: We used a weighted Cox regression model to assess variation in breast cancer risk with these factors using location of mutation in homogeneous breast cancer risk region of BRCA1/2 in the GENEPSO study.

Results: We found that late age at menarche reduced breast cancer risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 65% and 73%, respectively). Among premenopausal women, overweight was associated with a 45% decrease in risk whereas underweight was associated with an increased risk (HR, 2.40). A natural menopause, mainly after age 50, was associated with a high breast cancer risk (HR, 2.46), and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause.

Conclusions: As observed in the general population, a late menarche, a long or a short menstrual cycle, over- or underweight, and being postmenopausal were associated with breast cancer risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the “high-risk” zones.

Impact: Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 24(4); 698–707. ©2015 AACR.
Sequence Variation in Mature MicroRNA-499 Confers Unfavorable Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy
Authors: Qiu Fuman , Yang Lei , Ling Xiaoxuan , Yang Rongrong , Yang Xiaorong , Zhang Lisha , Fang Wenxiang , Xie Chenli , Huang Dongsheng , Zhou Yifeng , Lu Jiachun
Published: January 2015

Purpose: This study was implemented to investigate the associations between SNP in mature microRNA (miRNA) sequence and lung cancer prognosis and to verify the function of those SNP.

Experimental Design: Eight SNPs (rs3746444T>C in hsa-mir-499, rs4919510C>G in hsa-mir-608, rs13299349G>A in hsa-mir-3152, rs12220909G>C in hsa-mir-4293, rs2168518G>A in hsa-mir-4513, rs8078913T>C in hsa-mir-4520a, rs11237828T>C in hsa-mir-5579, and rs9295535T>C in hsa-mir-5689) were analyzed in a southern Chinese population with 576 patients with lung cancer, and the significant results were validated in two additional cohorts of 346 and 368 patients, respectively. A series of experiments were performed to evaluate the relevancies of those potentially functional SNPs.

Results: We found that the microRNA-499 rs3746444T>C polymorphism exhibited a consistently poor prognosis for patients with lung cancer in the discovery set [HR, 1.24; 95% confidence interval (CI), 1.02–1.49; P = 0.028], in the validation set I (HR, 1.31; 95% CI, 1.01–1.71; P = 0.048) and in the validation set II (HR, 1.45; 95% CI, 1.12–1.86; P = 0.004). The adverse effect of CT/CC variants was more remarkable in patients receiving platinum-based chemotherapy. Further functional assays demonstrated that the rs3746444C variant allele influences the expression of several cancer-related genes and affects lung cancer cells' proliferation and tumor growth in vivo and in vitro via the cisplatinum resistance.

Conclusion: Our findings suggested that the rs3746444T>C polymorphism in mature miR-499 sequence could contribute to poor prognosis by modulating cancer-related genes' expression and thus involve tumorigenesis and anti-chemotherapy, which may be a useful biomarker to predict lung cancer patients' prognosis. Clin Cancer Res; 21(7); 1602–13. ©2015 AACR.
Global Promoter Methylation Analysis Reveals Novel Candidate Tumor Suppressor Genes in Natural Killer Cell Lymphoma
Authors: Küçük Can , Hu Xiaozhou , Jiang Bei , Klinkebiel David , Geng Huimin , Gong Qiang , Bouska Alyssa , Iqbal Javeed , Gaulard Philippe , McKeithan Timothy W. , Chan Wing C.
Published: January 2015

Purpose: To identify tumor suppressor genes epigenetically silenced by promoter hypermethylation in extranodal natural killer cell lymphoma (NKCL).

Experimental Design: Promoter methylation was analyzed with global and locus-specific methylation assays in NKCL cases and NK cell lines. Gene expression profiles were used to identify genes for which aberrant promoter methylation was associated with transcriptional silencing. Selected DNA methylations were validated by RRBS, pyrosequencing, or q-MSP. Decitabine treatment was performed to evaluate reactivation of methylated genes. The tumor suppressor effect of silenced genes was evaluated functionally by reintroducing them into NK cell lines.

Results: We observed significant promoter hypermethylation in most NKCL samples compared with normal NK cells. Correlation of global promoter methylation with gene expression profiles identified 95 genes with strong evidence for being silenced because of promoter methylation, including BCL2L11 (BIM), DAPK1, PTPN6 (SHP1), TET2, SOCS6, and ASNS. Known tumor suppressor genes were significantly overrepresented in this set of genes. Decitabine treatment of NK cell lines was associated with reexpression of all 10 selected methylated and silenced genes. Ectopic expression of frequently silenced BIM in two BIM-nonexpressing NK cell lines led to increased apoptosis and eventual elimination of BIM-transduced cells. It also sensitized these cell lines to chemotherapy-induced apoptosis. Similarly, reintroduction of SOCS6 significantly inhibited growth in SOCS6-nonexpressing NK cell lines. NK cell lines lacking ASNS expression showed increased sensitivity to treatment with l-asparaginase. Reintroduction of ASNS reduced drug sensitivity.

Conclusion: Promoter region hypermethylation is frequent in NKCL, and aberrantly methylated genes are pathologically and clinically significant. Clin Cancer Res; 21(7); 1699–711. ©2015 AACR.
Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study
Authors: Besse Benjamin , Le Moulec Sylvestre , Mazières Julien , Senellart Hélène , Barlesi Fabrice , Chouaid Christos , Dansin Eric , Bérard Henri , Falchero Lionel , Gervais Radj , Robinet Gilles , Ruppert Anne-Marie , Schott Roland , Léna Hervé , Clément-Duchêne Christelle , Quantin Xavier , Souquet Pierre Jean , Trédaniel Jean , Moro-Sibilot Denis , Pérol Maurice , Madroszyk Anne-Catherine , Soria Jean-Charles
Published: January 2015

Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-naïve or pretreated patients with non–small cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup.

Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0–1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve ×6) and paclitaxel (200 mg/m2) every 3 weeks (B + CP), or second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B + CP) or more than two (B + E) intracranial hemorrhages.

Results: In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7–7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n = 24), efficacy results for the second-line B + E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0–8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae.

Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases. Clin Cancer Res; 21(8); 1896–903. ©2015 AACR.
HOTAIR Long Noncoding RNA Promotes Gastric Cancer Metastasis through Suppression of Poly r(C)-Binding Protein (PCBP) 1
Authors: Zhang Zi-Zhen , Shen Zhi-Yong , Shen Yan-Ying , Zhao En-Hao , Wang Ming , Wang Chao-Jie , Cao Hui , Xu Jia
Published: January 2015

The objective of this study was to evaluate the role of HOTAIR long noncoding RNA in gastric cancer metastasis. We analyzed HOTAIR expression levels by real-time reverse transcription PCR and Northern blot analysis in 100 gastric tissues (50 gastric cancer tissues and 50 adjacent normal mucosa), and in four gastric cancer cell lines. Transient RNAi-mediated knockdown and pcDNA-mediated overexpression of HOTAIR were performed. Stable shRNA-mediated knockdown and lentiviral-mediated overexpression of HOTAIR were to study the role of HOTAIR on in vivo tumorigenicity and metastatic burden in the context of xenograft assays. Proteomic profiling was performed to decipher differential protein expression in cells with different HOTAIR expression levels. One of the differentially regulated proteins, Poly r(C)-binding protein (PCBP) 1, was subsequently validated and its function evaluated through xenograft assays. Expression of HOTAIR was significantly higher in cancerous tissues than in adjacent normal mucosa. HOTAIR expression levels dictated in vitro and in vivo tumorigenicity and metastatic potential in these cells. PCBP1 and HOTAIR have an inverse relationship, both at expression level and in function. A direct interaction between the two was confirmed through RNA immunoprecipitation coupled with quantitative real-time PCR. PCBP1 was confirmed to be an inhibitor of gastric cancer pathogenesis and as functionally opposite to HOTAIR long noncoding RNA. In conclusion, HOTAIR expression may serve as a potentially important disease biomarker for the identification of high-risk gastric cancer patients. Moreover, our findings provide mechanistic evidence for HOTAIR overexpression and PCBP1 downregulation and the ensuing malignant phenotype in both cultured and xenograft gastric cancer cells. Mol Cancer Ther; 14(5); 1162–70. ©2015 AACR.
Comparison of Retroperitoneoscopic and Transperitoneal Laparoscopic Adrenalectomy for Right-Sided Benign Tumors: A Single-Institute Experience
Authors: Chiang Po Hui , Yu Cheng Jen , Lee Wei Ching , Wang Hung Jen , Hsu Wu Chi
Published: January 2015

Introduction: There is a lack of data regarding the appropriateness of transperitoneal and retroperitoneal approaches for right-sided laparoscopic adrenalectomy. The aim of this study was to determine whether there is any difference between right-sided transperitoneal laparoscopic adrenalectomy (TLA) and retroperitoneal laparoscopic adrenalectomy (RLA). Material and Methods: Our surgery database was reviewed to identify patients who underwent right-sided laparoscopic adrenalectomy with a retroperitoneal or transperitoneal approach since 2000. Fifty-five patients were enrolled (31 RLA and 24 TLA). Patient characteristics, as well as operative and perioperative details, were compared between the two groups. Results: There was no difference in patient characteristics between the groups. There was a statistically significant difference (p = 0.02) in blood loss (31.7 ± 16.4 vs. 56.9 ± 65.5 ml) between RLA and TLA when the patient's BMI was >26. There was no significant difference in operative time, conversion to open surgery, length of hospitalization, or time to oral intake between the groups. Conclusions: Right-sided laparoscopic adrenalectomy can be performed safely and effectively via either RLA or TLA. Surgeons can adopt either approach with confidence depending on their preference if they are familiar with that approach.
Effects of Oatmeal and Corn Flakes Cereal Breakfasts on Satiety, Gastric Emptying, Glucose, and Appetite-Related Hormones
Authors: Geliebter Allan , Grillot Charlotte L. , Aviram-Friedman Roni , Haq Sakeena , Yahav Eric , Hashim Sami A.
Published: January 2015

Objective: The extent to which different types of breakfasts affect appetite and food intake is unclear. To assess the satiety effects of a high-fiber cereal, we compared oatmeal, isocaloric corn flakes, and water. Subjects/Methods: Thirty-six subjects (18 lean, 18 overweight) were assigned to three conditions in a randomized sequence on different days. Ratings of hunger and fullness were obtained concurrently with blood samples for measuring concentrations of glucose, insulin, glucagon, leptin, and acetaminophen (gastric emptying tracer). Appetite was assessed by calculating the area under the curve (AUC) for fullness and hunger, and by measuring food intake of an ad libitum lunch meal at 180 min. Results: Lunch meal intake was lowest after consuming oatmeal (p < 0.00001), which was lower for overweight subjects than lean subjects (p = 0.007). Fullness AUC was greatest (p = 0.00001), and hunger AUC lowest (p < 0.001) after consuming oatmeal. At 180 min, blood glucose was lowest after the corn flakes (p = 0.0001). Insulin AUC was greater for both cereals than water (p < 0.00001). Leptin AUC and glucagon AUC values did not differ between conditions. Acetaminophen concentrations peaked latest after consuming oatmeal (p = 0.046), reflecting slower gastric emptying. Conclusions: Satiety was greater and ad libitum test meal intake lower after consuming oatmeal than after corn flakes, especially in the overweight subjects.
Beneficial Effects of a Semi-Intensive Stroke Unit are Beyond the Monitor
Authors: Cereda Carlo W. , George Paul M. , Pelloni Lorenzo S. , Gandolfi-Decristophoris Paola , Mlynash Michael , Biancon Montaperto Lucia , Limoni Costanzo , Stojanova Vesna , Malacrida Roberto , Städler Claudio , Bassetti Claudio L.
Published: January 2015

Background and Purpose: Precise mechanisms underlying the effectiveness of the stroke unit (SU) are not fully established. Studies that compare monitored stroke units (semi-intensive type, SI-SU) versus an intensive care unit (ICU)-based mobile stroke team (MST-ICU) are lacking. Although inequalities in access to stroke unit care are globally improving, acute stroke patients may be admitted to Intensive Care Units for monitoring and followed by a mobile stroke team in hospital's lacking an SU with continuous cardiovascular monitoring. We aimed at comparing the stroke outcome between SI-SU and MST-ICU and hypothesized that the benefits of SI-SU are driven by additional elements other than cardiovascular monitoring, which is equally offered in both care systems. Methods: In a single-center setting, we compared the unfavorable outcomes (dependency and mortality) at 3 months in consecutive patients with ischemic stroke or spontaneous intracerebral hemorrhage admitted to a stroke unit with semi-intensive monitoring (SI-SU) to a cohort of stroke patients hospitalized in an ICU and followed by a mobile stroke team (MST-ICU) during an equal observation period of 27 months. Secondary objectives included comparing mortality and the proportion of patients with excellent outcomes (modified Rankin Score (mRS) 0-1). Equal cardiovascular monitoring was offered in patients admitted in both SI-SU and MST-ICU. Results: 458 patients were treated in the SI-SU and compared to the MST-ICU (n = 370) cohort. The proportion of death and dependency after 3 months was significantly improved for patients in the SI-SU compared to MST-ICU (p < 0.001; aOR = 0.45; 95% CI: 0.31-0.65). The shift analysis of the mRS distribution showed significant shift to the lower mRS in the SI-SU group, p < 0.001. The proportion of mortality in patients after 3 months also differed between the MST-ICU and the SI-SU (p < 0.05), but after adjusting for confounders this association was not significant (aOR = 0.59; 95% CI: 0.31-1.13). The proportion of patients with excellent outcome was higher in the SI-SU (59.4 vs. 44.9%, p < 0.001) but the relationship was no more significant after adjustment (aOR = 1.17; 95% CI: 0.87-1.5). Conclusions: Our study shows that moving from a stroke team in a monitored setting (ICU) to an organized stroke unit leads to a significant reduction in the 3 months unfavorable outcome in patients with an acute ischemic or hemorrhagic stroke. Cardiovascular monitoring is indispensable, but benefits of a semi-intensive Stroke Unit are driven by additional elements beyond intensive cardiovascular monitoring. This observation supports the ongoing development of Stroke Centers for efficient stroke care.
SRS06, a New Semisynthetic Andrographolide Derivative with Improved Anticancer Potency and Selectivity, Inhibits Nuclear Factor-κB Nuclear Binding in the A549 Non-Small Cell Lung Cancer Cell Line
Authors: Lim Jonathan Chee Woei , Jeyaraj Ethel Jeyaseela , Sagineedu Sreenivasa Rao , Wong Wai Shiu Fred , Stanslas Johnson
Published: January 2015

Background: Andrographolide has been reported with anticancer and anti-inflammatory properties through the inhibition of the activity of signaling molecules such as v-Src, nuclear factor-κB (NF-κB), STAT3, and PI3K. NF-κB has been proven to promote cancer cell survival, and targeting this pathway will halt the growth of cancer cells. Efforts have been made to produce semisynthetic derivatives of andrographolide with improved anticancer potency and selectivity. Subsequently, the effect of a selected derivative, 3,14,19-tripropionylandrographolide (SRS06), was tested for its action against NF-κB. Methods: Screening against 60 US National Cancer Institute (NCI) human cancer cell lines representing leukemia and non-small cell lung (NSCL), colon, CNS, melanoma, ovarian, renal, prostate, and breast cancers was performed to determine the tumor type selectivity and potency of SRS06. Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and sulforhodamine B assays were used to determine the in vitro anticancer activity, while Western blot studies were performed to ascertain the inhibitory effect of SRS06 on the NF-κB signaling cascade. The TransAM™ p65 assay kit was used to determine NF-κB p65 DNA binding activity in the NSCL cancer cell line A549. Results: From the NCI screening, SRS06 was found to exhibit potent growth-inhibitory effects on multiple cancer cell lines with 10-fold lower 50% growth inhibition (GI50) compared with andrographolide. It was also discerned that the compound preferentially targeted melanoma, CNS, renal, colon, ovarian, prostate, and NSCL cancer cell lines. The DNA fragmentation assay indicated that the main mode of cell death of SRS06-treated A549 cells was via apoptosis. At 5 µmol/l the compound decreased NF-κB protein expression and caused a significant reduction in the nuclear p65 DNA binding activity. Conclusion: SRS06 displayed improved anticancer selectivity and potency when compared with andrographolide. We alluded its anticancer activity to its effect of inhibiting NF-κB nuclear binding.
Mipomersen, an Antisense Oligonucleotide to Apolipoprotein B-100, Reduces Lipoprotein(a) in Various Populations With Hypercholesterolemia
Authors: Santos Raul D. , Raal Frederick J. , Catapano Alberico L. , Witztum Joseph L. , Steinhagen-Thiessen Elisabeth , Tsimikas Sotirios
Published: January 2015

Objective—

Lp(a) is an independent, causal, genetic risk factor for cardiovascular disease and aortic stenosis. Current pharmacological lipid-lowering therapies do not optimally lower Lp(a), particularly in patients with familial hypercholesterolemia (FH).

Approach and Results—

In 4 phase III trials, 382 patients on maximally tolerated lipid-lowering therapy were randomized 2:1 to weekly subcutaneous mipomersen 200 mg (n=256) or placebo (n=126) for 26 weeks. Populations included homozygous FH, heterozygous FH with concomitant coronary artery disease (CAD), severe hypercholesterolemia, and hypercholesterolemia at high risk for CAD. Lp(a) was measured 8× between baseline and week 28 inclusive. Of the 382 patients, 57% and 44% had baseline Lp(a) levels >30 and >50 mg/dL, respectively. In the pooled analysis, the mean percent decrease (median, interquartile range in Lp(a) at 28 weeks was significantly greater in the mipomersen group compared with placebo (−26.4 [−42.8, −5.4] versus −0.0 [−10.7, 15.3];
P
<0.001). In the mipomersen group in patients with Lp(a) levels >30 or >50 mg/dL, attainment of Lp(a) values ≤30 or ≤50 mg/dL was most frequent in homozygous FH and severe hypercholesterolemia patients. In the combined groups, modest correlations were present between percent change in apolipoprotein B-100 and Lp(a) (
r
=0.43;
P
<0.001) and low-density lipoprotein cholesterol and Lp(a) (
r
=0.36;
P
<0.001) plasma levels.

Conclusions—

Mipomersen consistently and effectively reduced Lp(a) levels in patients with a variety of lipid abnormalities and cardiovascular risk. Modest correlations were present between apolipoprotein B-100 and Lp(a) lowering but the mechanistic relevance mediating Lp(a) reduction is currently unknown.
Gestational Diabetes Mellitus Impairs Fetal Endothelial Cell Functions Through a Mechanism Involving MicroRNA-101 and Histone Methyltransferase Enhancer of Zester Homolog-2
Authors: Floris Ilaria , Descamps Betty , Vardeu Antonella , Mitić Tijana , Posadino Anna Maria , Shantikumar Saran , Sala-Newby Graciela , Capobianco Gianpiero , Mangialardi Giuseppe , Howard Lynsey , Dessole Salvatore , Urrutia Raul , Pintus Gianfranco , Emanueli Costanza
Published: January 2015

Objective—

Gestational diabetes mellitus (GDM) produces fetal hyperglycemia with increased lifelong risks for the exposed offspring of cardiovascular and other diseases. Epigenetic mechanisms induce long-term gene expression changes in response to in utero environmental perturbations. Moreover, microRNAs (miRs) control the function of endothelial cells (ECs) under physiological and pathological conditions and can target the epigenetic machinery. We investigated the functional and expressional effect of GDM on human fetal ECs of the umbilical cord vein (HUVECs). We focused on miR-101 and 1 of its targets, enhancer of zester homolog-2 (EZH2), which trimethylates the lysine 27 of histone 3, thus repressing gene transcription. EZH2 exists as isoforms α and β.

Approach and Results—

HUVECs were prepared from GDM or healthy pregnancies and tested in apoptosis, migration, and Matrigel assays. GDM-HUVECs demonstrated decreased functional capacities, increased miR-101 expression, and reduced EZH2- β and trimethylation of histone H3 on lysine 27 levels. MiR-101 inhibition increased EZH2 expression and improved GDM-HUVEC function. Healthy HUVECs were exposed to high or normal
d
-glucose concentration for 48 hours and then tested for miR-101 and EZH2 expression. Similar to GDM, high glucose increased miR-101 expression. Chromatin immunoprecipitation using an antibody for EZH2 followed by polymerase chain reaction analyses for miR-101 gene promoter regions showed that both GDM and high glucose concentration reduced EZH2 binding to the miR-101 locus in HUVECs. Moreover, EZH2-β overexpression inhibited miR-101 promoter activity in HUVECs.

Conclusions—

GDM impairs HUVEC function via miR-101 upregulation. EZH2 is both a transcriptional inhibitor and a target gene of miR-101 in HUVECs, and it contributes to some of the miR-101-induced defects of GDM-HUVECs.
Impaired Integrin β3 Delays Endothelial Cell Regeneration and Contributes to Arteriovenous Graft Failure in Mice
Authors: Liang Ming , Wang Yun , Liang Anlin , Dong Jin-Fei , Du Jie , Cheng Jizhong
Published: January 2015

Objective—

Neointima formation is associated with stenosis and subsequent thrombosis in arteriovenous grafts (AVGs). A role of integrin β3 in the neointima formation of AVGs remains poorly understood.

Approach and Results—

In integrin β3
−/−
mice, we found significantly accelerated occlusion of AVGs compared with the wild-type mice. This is caused by the development of neointima and lack of endothelial regeneration. The latter is a direct consequence of impaired functions of circulating angiogenic cells (CACs) and platelets in integrin β3
−/−
mice. Evidence suggests the involvement of platelet regulating CAC homing to and differentiation at graft sites via transforming growth factor-β1 and Notch signaling pathway. First, CACs deficient of integrin β3 impaired adhesion activity toward exposed subendothelium. Second, platelets from integrin β3
−/−
mice failed to sufficiently stimulate CACs to differentiate into mature endothelial cells. Finally, we found that transforming growth factor-β1 level was increased in platelets from integrin β3
−/−
mice and resulted in enhanced Notch1 activation in CACs in AVGs. These results demonstrate that integrin β3 is critical for endothelial cell homing and differentiation. The increased transforming growth factor-β1 and Notch1 signaling mediates integrin β3
−/−
-induced AVG occlusion. This accelerated occlusion of AVGs was reversed in integrin β3
−/−
mice transplanted with the bone marrow from wild-type mice.

Conclusions—

Our results suggest that boosting integrin β3 function in the endothelial cells and platelets could prevent neointima and thrombosis in AVGs.
Dimorphic Effects of Transforming Growth Factor-β Signaling During Aortic Aneurysm Progression in Mice Suggest a Combinatorial Therapy for Marfan Syndrome
Authors: Cook Jason R. , Clayton Nicholas P. , Carta Luca , Galatioto Josephine , Chiu Emily , Smaldone Silvia , Nelson Carol A. , Cheng Seng H. , Wentworth Bruce M. , Ramirez Francesco
Published: January 2015

Objective—

Studies of mice with mild Marfan syndrome (MFS) have correlated the development of thoracic aortic aneurysm (TAA) with improper stimulation of noncanonical (Erk-mediated) TGFβ signaling by the angiotensin type I receptor (AT1r). This correlation was largely based on comparable TAA modifications by either systemic TGFβ neutralization or AT1r antagonism. However, subsequent investigations have called into question some key aspects of this mechanism of arterial disease in MFS. To resolve these controversial points, here we made a head-to-head comparison of the therapeutic benefits of TGFβ neutralization and AT1r antagonism in mice with progressively severe MFS (
Fbn1

mgR/mgR

mice).

Approach and Results—

Aneurysm growth, media degeneration, aortic levels of phosphorylated Erk and Smad proteins and the average survival of
Fbn1

mgR/mgR

mice were compared after a ≈3-month-long treatment with placebo and either the AT1r antagonist losartan or the TGFβ-neutralizing antibody 1D11. In contrast to the beneficial effect of losartan, TGFβ neutralization either exacerbated or mitigated TAA formation depending on whether treatment was initiated before (postnatal day 16; P16) or after (P45) aneurysm formation, respectively. Biochemical evidence-related aneurysm growth with Erk-mediated AT1r signaling, and medial degeneration with TGFβ hyperactivity that was in part AT1r dependent. Importantly, P16-initiated treatment with losartan combined with P45-initiated administration of 1D11 prevented death of
Fbn1

mgR/mgR

mice from ruptured TAA.

Conclusions—

By demonstrating that promiscuous AT1r and TGFβ drive partially overlapping processes of arterial disease in MFS mice, our study argues for a therapeutic strategy against TAA that targets both signaling pathways although sparing the early protective role of TGFβ.
Myocardin Regulates Vascular Smooth Muscle Cell Inflammatory Activation and Disease
Authors: Ackers-Johnson Matthew , Talasila Amarnath , Sage Andrew P. , Long Xiaochun , Bot Ilze , Morrell Nicholas W. , Bennett Martin R. , Miano Joseph M. , Sinha Sanjay
Published: January 2015

Objective—

Atherosclerosis, the cause of 50% of deaths in westernized societies, is widely regarded as a chronic vascular inflammatory disease. Vascular smooth muscle cell (VSMC) inflammatory activation in response to local proinflammatory stimuli contributes to disease progression and is a pervasive feature in developing atherosclerotic plaques. Therefore, it is of considerable therapeutic importance to identify mechanisms that regulate the VSMC inflammatory response.

Approach and Results—

We report that myocardin, a powerful myogenic transcriptional coactivator, negatively regulates VSMC inflammatory activation and vascular disease. Myocardin levels are reduced during atherosclerosis, in association with phenotypic switching of smooth muscle cells. Myocardin deficiency accelerates atherogenesis in hypercholesterolemic apolipoprotein E
−/−
mice. Conversely, increased myocardin expression potently abrogates the induction of an array of inflammatory cytokines, chemokines, and adhesion molecules in VSMCs. Expression of myocardin in VSMCs reduces lipid uptake, macrophage interaction, chemotaxis, and macrophage-endothelial tethering in vitro, and attenuates monocyte accumulation within developing lesions in vivo. These results demonstrate that endogenous levels of myocardin are a critical regulator of vessel inflammation.

Conclusions—

We propose myocardin as a guardian of the contractile, noninflammatory VSMC phenotype, with loss of myocardin representing a critical permissive step in the process of phenotypic transition and inflammatory activation, at the onset of vascular disease.
Anti-Inflammatory and Antiatherogenic Effects of the NLRP3 Inflammasome Inhibitor Arglabin in ApoE
2
.Ki Mice Fed a High-Fat Diet
Authors: Abderrazak Amna , Couchie Dominique , Mahmood Dler Faieeq Darweesh , Elhage Rima , Vindis Cécile , Laffargue Muriel , Matéo Véronique , Büchele Berthold , Ayala Monica Rubio , El Gaafary Menna , Syrovets Tatiana , Slimane Mohamed-Naceur , Friguet Bertrand , Fulop Tamas , Simmet Thomas , El Hadri Khadija , Rouis Mustapha
Published: January 2015

Background—

This study was designed to evaluate the effect of arglabin on the NLRP3 inflammasome inhibition and atherosclerotic lesion in ApoE
2
Ki mice fed a high-fat Western-type diet.

Methods and Results—

Arglabin was purified, and its chemical identity was confirmed by mass spectrometry. It inhibited, in a concentration-dependent manner, interleukin (IL)-1β and IL-18, but not IL-6 and IL-12, production in lipopolysaccharide and cholesterol crystal–activated cultured mouse peritoneal macrophages, with a maximum effect at ≈50 nmol/L and EC
50
values for both cytokines of ≈ 10 nmol/L. Lipopolysaccharide and cholesterol crystals did not induce IL-1β and IL-18 production in Nlrp3
−/−
macrophages. In addition, arglabin activated autophagy as evidenced by the increase in LC3-II protein. Intraperitoneal injection of arglabin (2.5 ng/g body weight twice daily for 13 weeks) into female ApoE
2
.Ki mice fed a high-fat diet resulted in a decreased IL-1β plasma level compared with vehicle-treated mice (5.2±1.0 versus 11.7±1.1 pg/mL). Surprisingly, arglabin also reduced plasma levels of total cholesterol and triglycerides to 41% and 42%, respectively. Moreover, arglabin oriented the proinflammatory M1 macrophages into the anti-inflammatory M2 phenotype in spleen and arterial lesions. Finally, arglabin treatment markedly reduced the median lesion areas in the sinus and whole aorta to 54% (
P
=0.02) and 41% (
P
=0.02), respectively.

Conclusions—

Arglabin reduces inflammation and plasma lipids, increases autophagy, and orients tissue macrophages into an anti-inflammatory phenotype in ApoE
2
.Ki mice fed a high-fat diet. Consequently, a marked reduction in atherosclerotic lesions was observed. Thus, arglabin may represent a promising new drug to treat inflammation and atherosclerosis.
Effect of Patching on Reducing Restenosis in the Carotid Revascularization Endarterectomy Versus Stenting Trial
Authors: Malas Mahmoud , Glebova Natalia O. , Hughes Susan E. , Voeks Jenifer H. , Qazi Umair , Moore Wesley S. , Lal Brajesh K. , Howard George , Llinas Rafael , Brott Thomas G.
Published: January 2015

Background and Purpose—

The purpose is to determine whether patching during carotid endarterectomy (CEA) affects the perioperative and long-term risks of restenosis, stroke, death, and myocardial infarction as compared with primary closure.

Methods—

We identified all patients who were randomized and underwent CEA in Carotid Revascularization Endarterectomy versus Stenting Trial. CEA patients who received a patch were compared with patients who underwent CEA with primary closure without a patch. We compared periprocedural and 4-year event rates, 2-year restenosis rates, and rates of reoperation between the 2 groups. We further analyzed results by surgeon specialty.

Results—

There were 1151 patients who underwent CEA (753 [65%] with patch and 329 [29%] with primary closure). We excluded 44 patients who underwent eversion CEA and 25 patients missing CEA data (5%). Patch use differed by surgeon specialty: 89% of vascular surgeons, 6% of neurosurgeons, and 76% of thoracic surgeons patched. Comparing patients who received a patch versus those who did not, there was a significant reduction in the 2-year risk of restenosis, and this persisted after adjustment by surgeon specialty (hazard ratio, 0.35; 95% confidence interval, 0.16–0.74;
P
=0.006). There were no significant differences in the rates of periprocedural stroke and death (hazard ratio, 1.58; 95% confidence interval, 0.33–7.58;
P
=0.57), in immediate reoperation (hazard ratio, 0.6; 95% confidence interval, 0.16–2.27;
P
=0.45), or in the 4-year risk of ipsilateral stroke (hazard ratio, 1.23; 95% confidence interval, 0.42–3.63;
P
=0.71).

Conclusions—

Patch closure in CEA is associated with reduction in restenosis although it is not associated with improved clinical outcomes. Thus, more widespread use of patching should be considered to improve long-term durability.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00004732.
Effect of dietary protein level and salinity on growth, survival, enzymatic activities and amino-acid composition of the white shrimp Litopenaeus vannamei (Boone, 1931) juveniles
Authors: Sui Liying , Ma Guannan , Deng Yuangao
Published: January 2015

Litopenaeus vannamei (Boone, 1931) postlarvae with average initial body weight of 0.089 g were reared in 75-litre PVC tanks for 40 days at salinities of 30 and 60 g l−1. The shrimps were fed compound feed containing protein levels of 35, 40, 45 and 50%, respectively. Salinity had a remarkable effect on growth and survival of L. vannamei juveniles. Higher survival rate and lower growth were observed at 60 g l−1 salinity. Dietary protein level affected the survival and growth of juveniles at both salinities, increased with dietary protein levels in the range of 35 to 45%, but decreased slightly with 50% dietary protein. Broken line analysis showed that the estimated optimal dietary protein levels at salinities of 30 and 60 g l−1 were 45.93 and 46.74%, respectively. Higher salinity resulted in an increased moisture content, ash and crude protein content in the shrimp muscle tissue. The amino acid contents in the shrimp muscle tissue were generally higher at 60 g l−1 salinity and increased dietary protein level led to higher protein content, except with 50% dietary protein. At salinity 60 g l−1, the soluble protein content and activities of glutamic oxalacetic transferase (GOT) and glutamic pyruvic transaminase (GPT) in shrimp muscle tissue were higher, while catalase (CAT) activities were lower. Farming of L. vannamei at a marginal culture salinity (60 g l−1) is feasible though the shrimps were likely exposed to stressful conditions. Reduced growth rate at higher salinity may be attributed to the higher total ammonium (TAN) concentration in the culture medium and extra energy consumption for osmoregulation at hypersaline conditions.
New species of Xiphocentron Brauer 1870 (Trichoptera: Xiphocentronidae) from Northeastern Brazil
Authors: VILARINO ALBANE , CALOR ADOLFO R.
Published: January 2015

Two new species of Xiphocentron (Trichoptera: Xiphocentronidae) from Northeastern Brazil are diagnosed, described, and illustrated. Xiphocentron (Antillotrichia) kamakan n. sp. has inferior appendages each with a shape discontinuity (twist) between the first and second articles of inferior appendage, similar to that found in X. (Antillotrichia) rhamnes Schmid 1982, X. (Antillotrichia) serestus Schmid 1982, and X. (Antillotrichia) mnesteus Schmid 1982; however, it can be distinguished from these species by each inferior appendage having two darkly sclerotized spinulous regions ventrally on the basomesal and midmesal margins. Xiphocentron (Antillotrichia) maiteae n. sp. can be differentiated from all other congeners by having the basoventral margin of each inferior appendage strongly produced posterad. A key to males of Brazilian species of Xiphocentron is provided.
Description of the male of Oxyporus bautistae Márquez & Asiain (Coleoptera: Staphylinidae, Oxyporinae)
Authors: NAVARRETE-HEREDIA JOSÉ LUIS , MÁRQUEZ JUAN
Published: January 2015

The male of Oxyporus bautistae Márquez and Asiain, 2006 is described based on one specimen from San José del Pacífico, southern Oaxaca, Mexico. Oxyporus bautistae shares with O. mexicanus Fauvel, 1865 the bicolored color pattern in legs (black and orange). The male of O. bautistae has six black spots on tergites and the female has only two black spots; but we cannot explain whether the number of black spots represents a sexual character or individual variation.
A striking new treehopper genus Mutilifolia (Hemiptera: Membracidae: Smiliinae: Telamonini), from Costa Rica
Authors: WALLACE MATTHEW S.
Published: January 2015

A new treehopper genus from Costa Rica, Mutilifolia, based on M. nishidai, new species, is described and illustrated. Mutilifolia is considered a member of the subfamily Smiliinae, tribe Telamonini based on characteristics of the pronotum, fore- and hind wing venation, and female genitalia. This genus superficially resembles the telamonine genera Antianthe, Archasia, and Hemicardiacus due to the highly elevated, foliaceous, and largely green pronotum, but the male style clasp of Mutilifolia with two recurved teeth differs greatly from the styles of any other presently known telamonine. Further collecting of treehoppers in the mountainous regions of Central America and Mexico, areas often neglected by collectors, may yield additional new Telamonini taxa.
Mortonagrion megabinluyog spec. nov. from Brunei (Odonata: Zygoptera: Coenagrionidae)
Authors: DOW RORY A. , CHOONG CHEE YEN
Published: January 2015

M. megabinluyog spec. nov. is described from a location in Brunei on the island of Borneo. Additional illustrations of its sister species M. astamii are provided.
Remarks on the name Cercomacra Sclater, 1858 (Aves: Thamnophilidae) and its type species
Authors: RAPOSO MARCOS A. , TELLO JOSÉ G. , DICKINSON EDWARD C. , BRITO GUILHERME R. R.
Published: January 2015

A recent molecular phylogeny of Cercomacra Sclater, 1858 found the genus to be polyphyletic (Tello et al. 2014). Two non-sister clades in putative Cercomacra were uncovered: Cercomacra sensu stricto, including Cercomacra manu Fitzpatrick & Willard, 1990, C. brasiliana Hellmayr, 1905, C. cinerascens (Sclater, 1857), C. melanaria (Ménétries, 1835), C. ferdinandi Snethlage, 1928, C. carbonaria Sclater & Salvin, 1873 and C. nigricans Sclater, 1858; and Cercomacroides Tello & Raposo, 2014, including Cercomacroides nigrescens (Cabanis & Heine, 1859), C. laeta (Todd, 1920), C. parkeri (Graves, 1997), C. tyrannina (Sclater, 1855) and C. serva (Sclater, 1858). This split required a prior re-examination of the apparently difficult facts surrounding the name of the type species of Cercomacra to ensure that the appropriate group would retain that name leaving the balance to the new genus-group name, Cercomacroides. The findings of that re-examination are nomenclatural rather than taxonomic and are complex enough to deserve a historical explanation, which is presented here. In summary, Hellmayr (1905) was correct in clarifying the identity of the type species chosen by Sclater (1890), but he did not suggest any nomenclatural action to fix the misidentified type species. Subsequent information provided by Cory & Hellmayr (1924) regarding the type specimen of Cercomacra brasiliana was incorrect, and the holotype is not in St. Petersburg as they implied.
Defining Sudden Stratospheric Warmings
Authors: Butler Amy H. , Seidel Dian J. , Hardiman Steven C. , Butchart Neal , Birner Thomas , Match Aaron
Published: January 2015

Sudden stratospheric warmings (SSWs) are large, rapid temperature rises in the winter polar stratosphere, occurring predominantly in the Northern Hemisphere. Major SSWs are also associated with a reversal of the climatological westerly zonal-mean zonal winds. Circulation anomalies associated with SSWs can descend into the troposphere with substantial surface weather impacts, such as wintertime extreme cold air outbreaks. After their discovery in 1952, SSWs were classified by the World Meteorological Organization. An examination of literature suggests that a single, original reference for an exact definition of SSWs is elusive, but in many references a definition involves the reversal of the meridional temperature gradient and, for major warmings, the reversal of the zonal circulation poleward of 60° latitude at 10 hPa.

Though versions of this definition are still commonly used to detect SSWs, the details of the definition and its implementation remain ambiguous. In addition, other SSW definitions have been used in the last few decades, resulting in inconsistent classification of SSW events. We seek to answer the questions: How has the SSW definition changed, and how sensitive is the detection of SSWs to the definition used? For what kind of analysis is a “standard” definition useful? We argue that a standard SSW definition is necessary for maintaining a consistent and robust metric to assess polar stratospheric wintertime variability in climate models and other statistical applications. To provide a basis for, and to encourage participation in, a communitywide discussion currently underway, we explore what criteria are important for a standard definition and propose possible ways to update the definition.
On Serial Observation Processing in Localized Ensemble Kalman Filters
Authors: Nerger Lars
Published: January 2015

Ensemble square root filters can either assimilate all observations that are available at a given time at once, or assimilate the observations in batches or one at a time. For large-scale models, the filters are typically applied with a localized analysis step. This study demonstrates that the interaction of serial observation processing and localization can destabilize the analysis process, and it examines under which conditions the instability becomes significant. The instability results from a repeated inconsistent update of the state error covariance matrix that is caused by the localization. The inconsistency is present in all ensemble Kalman filters, except for the classical ensemble Kalman filter with perturbed observations. With serial observation processing, its effect is small in cases when the assimilation changes the ensemble of model states only slightly. However, when the assimilation has a strong effect on the state estimates, the interaction of localization and serial observation processing can significantly deteriorate the filter performance. In realistic large-scale applications, when the assimilation changes the states only slightly and when the distribution of the observations is irregular and changing over time, the instability is likely not significant.
Respect as an engine for new ideas: Linking respectful engagement, relational information processing and creativity among employees and teams
Authors: Carmeli Abraham , Dutton Jane E , Hardin Ashley E
Published: January 2015

In four studies we examine whether and why respectfully engaging with other organizational members can augment creativity for individuals and teams. We develop and test a model in which respectful engagement among organizational members facilitates relational information processing, which in turn results in enhanced creative behaviors. We found a similar pattern across all four studies – respectful engagement is indirectly related, through relational information processing, to creative behavior at both the individual and team levels. These findings underscore the importance of respectful engagement in facilitating relational information processing and fostering creative behaviors at both the individual and team levels.
The role of relatives in pathways to care of patients with a first episode of psychosis
Authors: Del Vecchio Valeria , Luciano Mario , Sampogna Gaia , De Rosa Corrado , Giacco Domenico , Tarricone Ilaria , Catapano Francesco , Fiorillo Andrea
Published: January 2015

Aims:

To explore the role of relatives in pathways to care of patients with a recent onset of psychosis.

Methods:

A total of 34 consecutive patients and their relatives from the Department of Psychiatry of the University of Naples SUN participated in the study. Pathways to care were retrospectively evaluated by administering the Pathways to Care Form and the Nottingham Onset Schedule (NOS) to patients, relatives and treating physicians. Relatives were addressed with the Family Involvement in Pathways to care Schedule (FIPS).

Results:

Duration of untreated illness (DUI) and duration of untreated psychosis (DUP) were 145.4 (±141.9) and 33.3 (±54.0) weeks, respectively. Help-seeking delay was 17.6 (±45.0) weeks. The first request for help was made by relatives in 76% of cases. Among health professionals, general practitioners were those most frequently contacted, followed by psychiatrists, neurologists or psychologists. Stigma and wrong attribution of psychotic symptoms were the main reasons for help-seeking delays.

Conclusions:

Relatives play a crucial role in pathways to care of patients with psychosis. DUI and DUP could be reduced by interventions aimed at increasing knowledge of early symptoms in the general population, and by the provision of psychiatric consultations in non-stigmatizing settings for young people with psychological distress.