bluuebunny/crossref_metadata_2025 huggingface dataset:
Two simple, brief, naturalistic activities and their impact on positive affect: feeling grateful and eating ice cream
Authors: Linley Peter Alex , Dovey Helen , de Bruin Eveline , Transler Catherine , Wilkinson Joy , Maltby John , Hurling Robert
Published: November 2013

Background

Positive psychology interventions have been shown to increase happiness and well-being, and researchers are beginning to speculate on the mechanisms through which these interventions may be effective. People are also naturally attuned to the things that will make them happier in their daily lives, and there is a case for considering how more naturalistic, everyday activities may also increase positive affect, happiness and well-being.

Methods

Study 1 involved 89 participants who completed a gratefulness activity while eating an ice cream for two days, following baseline measurement for two days. Participants completed the PANAS (Positive and Negative Affect Scale) twice per day, in the afternoon and in the evening, with the activity between these two times on the activity days. Study 2 involved 280 participants who formed four groups (gratefulness activity; ice cream consumption; gratefulness activity and ice cream consumption; control group), which undertook the relevant activity for two days. Participants completed baseline and follow-up measures, including the PANAS and the GQ-6 (Gratitude Questionnaire-6) on the day before and day following the two activity days. On the activity days themselves, participants completed the PANAS before and after their activity.

Results

In Study 1, we found that the combination of the gratefulness activity and eating ice cream led to increased positive affect. In Study 2, we explored this finding further, and found that any combination of the gratefulness activity and eating ice cream (together or alone) led to increased positive affect. The same pattern of results was observed for affect balance and the ratio of positive to negative emotions. The gratefulness activity only also led to increased gratitude as measured by the GQ-6. Results showed that even simple, naturalistic everyday activities can lead to increases in positive affect. This experience of positive affect may be one mediating pathway through which positive psychology interventions, and indeed everyday activities, are effective in enhancing happiness and well-being.

Conclusions

Researchers should consider the role of everyday activities in enhancing happiness and well-being, in addition to investigating the operational mechanisms of more formal positive psychology interventions.
Lapatinib–induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors
Authors: Chen Yun-Ju , Yeh Ming-Hsin , Yu Meng-Chieh , Wei Ya-Ling , Chen Wen-Shu , Chen Jhen-Yu , Shih Chih-Yu , Tu Chih-Yen , Chen Chia-Hung , Hsia Te-Chun , Chien Pei-Hsuan , Liu Shu-Hui , Yu Yung-Luen , Huang Wei-Chien
Published: November 2013

Introduction

Triple-negative breast cancer (TNBC), a subtype of breast cancer with negative expressions of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), is frequently diagnosed in younger women and has poor prognosis for disease-free and overall survival. Due to the lack of known oncogenic drivers for TNBC proliferation, clinical benefit from currently available targeted therapies is limited, and new therapeutic strategies are urgently needed.

Methods

Triple-negative breast cancer cell lines were treated with proteasome inhibitors in combination with lapatinib (a dual epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor). Their in vitro and in vivo viability was examined by MTT assay, clonogenic analysis, and orthotopic xenograft mice model. Luciferase reporter gene, immunoblot, and RT-qPCR, immunoprecipitation assays were used to investigate the molecular mechanisms of action.

Results

Our data showed that nuclear factor (NF)-κB activation was elicited by lapatinib, independent of EGFR/HER2 inhibition, in TNBCs. Lapatinib-induced constitutive activation of NF-κB involved Src family kinase (SFK)-dependent p65 and IκBα phosphorylations, and rendered these cells more vulnerable to NF-κB inhibition by p65 small hairpin RNA. Lapatinib but not other EGFR inhibitors synergized the anti-tumor activity of proteasome inhibitors both in vitro and in vivo. Our results suggest that treatment of TNBCs with lapatinib may enhance their oncogene addiction to NF-κB, and thus augment the anti-tumor activity of proteasome inhibitors.

Conclusions

These findings suggest that combination therapy of a proteasome inhibitor with lapatinib may benefit TNBC patients.
Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts
Authors: Pfefferle Adam D , Herschkowitz Jason I , Usary Jerry , Harrell Joshua Chuck , Spike Benjamin T , Adams Jessica R , Torres-Arzayus Maria I , Brown Myles , Egan Sean E , Wahl Geoffrey M , Rosen Jeffrey M , Perou Charles M
Published: November 2013

Background

Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models are a useful resource for studying mammary cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and should improve preclinical drug testing.

Results

Transcriptomic profiles of 27 murine models of mammary carcinoma and normal mammary tissue were determined using gene expression microarrays. Hierarchical clustering analysis identified 17 distinct murine subtypes. Cross-species analyses using three independent human breast cancer datasets identified eight murine classes that resemble specific human breast cancer subtypes. Multiple models were associated with human basal-like tumors including TgC3(1)-Tag, TgWAP-Myc and Trp53-/-. Interestingly, the TgWAPCre-Etv6 model mimicked the HER2-enriched subtype, a group of human tumors without a murine counterpart in previous comparative studies. Gene signature analysis identified hundreds of commonly expressed pathway signatures between linked mouse and human subtypes, highlighting potentially common genetic drivers of tumorigenesis.

Conclusions

This study of murine models of breast carcinoma encompasses the largest comprehensive genomic dataset to date to identify human-to-mouse disease subtype counterparts. Our approach illustrates the value of comparisons between species to identify murine models that faithfully mimic the human condition and indicates that multiple genetically engineered mouse models are needed to represent the diversity of human breast cancers. The reported trans-species associations should guide model selection during preclinical study design to ensure appropriate representatives of human disease subtypes are used.
Forced Vibration Testing and Finite Element Modeling of a Nine-Story Reinforced Concrete Flat Plate-Wall Building
Authors: Celik Ozan Cem , Sucuoğlu Haluk , Akyuz Ugurhan
Published: November 2013

Tunnel form buildings, owing to their higher construction speed and quality, lower cost, and superior earthquake resistance over that of conventional reinforced concrete buildings, have been widely used for mass housing, urban renewal, and post-earthquake reconstruction projects all over the world as well as in Turkey. However, there have been few dynamic tests performed on existing buildings with this structural system. This study investigates the dynamic structural properties of a typical nine-story reinforced concrete flat plate-wall building by forced vibration testing and develops its three-dimensional (3-D) linear elastic finite element structural model. The finite element model that uses the modulus of elasticity for concrete in ACI 318 predicts the natural vibration periods well. Mode shapes are also in good agreement with the test results. Door and window openings in the shear walls, and the basement with peripheral wall emerge as modeling considerations that have the most significant impact on structural system dynamic properties.
Coexistence of Malignant Struma Ovarii and Cervical Papillary Thyroid Carcinoma
Authors: Leong Aaron , Roche Philip J. R. , Paliouras Miltiadis , Rochon Louise , Trifiro Mark , Tamilia Michael
Published: November 2013

Context:

Struma ovarii is an uncommon monodermal teratoma in which thyroid tissue is the predominant element. Malignant transformation of struma ovarii is an even rarer occurrence.

Case Presentation:

We describe a 42-year-old woman who underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a symptomatic left pelvic mass. Histology revealed malignant struma ovarii with classical papillary thyroid carcinoma expression. Ultrasonography of the cervical neck showed thyroid micronodules and a dominant 1-cm nodule in the left thyroid lobe. As the ovarian tumor was large, the patient underwent a total thyroidectomy with the intention of administering 131I therapy in an adjuvant setting. Histology of the cervical thyroid gland revealed bilateral multifocal papillary thyroid carcinoma with extrathyroidal extension and perithyroidal lymph node metastasis.

Methods:

Morphological (microscopy), immunohistochemical (Hector Battifora mesothelial cell 1, cytokeratin-19, galectin-3), and molecular (BRAF V600E, RAS, RET-PTC) characteristics and clonality analysis of the cervical thyroid and ovarian tumors were explored to distinguish them as separate malignancies.

Results:

The thyroid-type tumors from the cervical gland and ovary were discordant in terms of tissue histology and level of cytokeratin-19 expression. The clinical features and tumor profile results supported the independent existence of these two embryologically related, although topographically distinct, malignancies.

Conclusion:

Our findings provided support for synchronous, albeit distinct, primary tumors in the ovary and cervical thyroid. “Field cancerization” and early genomic instability may explain multifocality in all thyroid-type tissue. In this regard, patients with malignant struma ovarii should undergo imaging of their thyroid gland for coexisting disease and thyroidectomy recommended for suspected malignancy or in preparation for radioiodine therapy.
Dicarbazolyldicyanobenzenes as Thermally Activated Delayed Fluorescence Emitters: Effect of Substitution Position on Photoluminescent and Electroluminescent Properties
Authors: Li Bo , Nomura Hiroko , Miyazaki Hiroshi , Zhang Qisheng , Yoshida Kou , Suzuma Yoshinori , Orita Akihiro , Otera Junzo , Adachi Chihaya
Published: November 2013

We demonstrate two efficient blue-green thermally activated delayed fluorescence (TADF) compounds comprising a dimeric phenylcarbazole and four cyano substituents on the phenyl rings. A comparison of the 2,6-dicyano-substituted derivative (26IPNDCz) with the 3,5-dicyano-substituted derivative (35IPNDCz) shows that 26IPNDCz provides a larger dihedral angle and a lower decrease in the energy difference between the first singlet and triplet excited states (ΔEST) and the TADF lifetime. An organic light-emitting diode based on 26IPNDCz afforded an external quantum efficiency of 10% with reduced efficiency roll-off.
Synthesis of Silica Vesicles with Small Sizes and Reduced Aggregation for Photodynamic Therapy
Authors: Yang Yannan , Karmakar Surajit , Yu Meihua , Popat Amirali , Yu Chengzhong
Published: November 2013

Silica vesicles (SVs) with a diameter of 30 nm and reduced aggregation have been successfully synthesized using mixed triblock copolymer surfactants as the structure-directing agents, tetraethyl orthosilicate and tetrapropyl orthosilicate as mixed silica sources. Silicon phthalocyanine dichloride (SiPC) has been loaded into SV, significantly enhancing the delivery and photodynamic therapy efficiency of SiPC into cancer cells.
Robust Superhydrophobic Zinc Oxide Film
Authors: Xin Yan , Guo Zhiguang
Published: November 2013

A robust superhydrophobic surface of hexagonal ZnO microrods with a sole microscale structure was achieved via a controlled shape-preserving hydrothermal reaction. The obtained surface showed superhydrophobic properties with good mechanical properties by means of a tribological tester, which may provide an insight into designing robust water-repellent surfaces on various substrates and offer opportunities for developing various promising applications for biomimetic superhydrophobic surfaces.
Geoscience of Climate and Energy 12. Water Quality Issues in the Oil Sands Region of the Lower Athabasca River, Alberta
Authors: Schindler David W.
Published: November 2013

I summarize the controversies about industrial pollutants in freshwaters near the oil sands industrial area of Alberta, the inadequacies in environmental monitoring that have led to widespread misconceptions, and recent attempts to correct the problems.  Adequate data are available to show that mercury, other trace metals, and polycyclic aromatic compounds are being added by industry to the Athabasca river system and its watershed, although the relative contributions of industrial development and natural sources remain in question.  Recent improvements in water monitoring by Environment Canada show promise of resolving the controversies, although independent governance for Canada’s and Alberta’s water monitoring programs in the lower Athabasca River will be necessary to rebuild public confidence in the data and their interpretation by government and industry.  I document one success story in the Athabasca River: the elimination of dioxins from pulp mills in the mid-1990s has caused a consumption advisory for fish in the river to be repealed.SOMMAIREJe présente ci-dessous un résumé des controverses concernant les polluants industriels dans les eaux douces à proximité de la zone industrielle des sables bitumineux de l'Alberta, des lacunes dans la surveillance des milieux de vie à l’origine d’idées fausses répandues, et de récentes tentatives visant à corriger les problèmes.  Des données adéquates démontrent que l’industrie ajoute du mercure et d'autres métaux traces ainsi que des composés aromatiques polycycliques dans le système fluvial de la rivière Athabasca et dans son bassin versant, bien que les contributions relatives provenant de ces activités industrielles et de sources naturelles demeurent toujours en litige.  De récentes améliorations apportées au contrôle des eaux par Environnement Canada permettent d’espérer une résolution des controverses, mais l’application d’une gouvernance indépendante des programmes de contrôle de l'eau de l'Alberta du Canada dans la partie inférieure du fleuve Athabasca sera nécessaire pour rétablir la confiance de la population à l’égard des données présentées et de leur interprétation par le gouvernement et l'industrie.  Je décrie l’histoire d’une intervention réussie dans la rivière Athabasca, soit l'élimination de dioxines provenant des usines de pâte du milieu des années 1990 et qui a abouti à l’abrogation d’un avis de limitation de la consommation de poisson dans la rivière.DOI: http://dx.doi.org/10.12789/geocanj.2013.40.012
Environmental Management of the Alberta Oil Sands: Introduction to the Special Set of Articles
Authors: Miall Andrew D.
Published: November 2013

DOI: http://dx.doi.org/10.12789/geocanj.2013.40.013
Therapeutic Effects of Suppressors of Cytokine Signaling in Diabetic Nephropathy
Authors: Liu Qingjuan , Xing Lingling , Wang Lei , Yao Fang , Liu Shuxia , Hao Jun , Liu Wei , Duan Huijun
Published: November 2013

Inflammation is an important pathophysiological mechanism in diabetic nephropathy (DN). Tubular epithelial cell-myofibroblast transdifferentiation (TEMT), which can be induced by many cytokines, is an important event in DN. Oncostatin M (OSM), an inflammatory cytokine, can induce TEMT in vitro. The suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of cytokine signaling. The purpose of this study was to investigate the role of SOCS in DN. The results demonstrated that overexpression of SOCS ameliorated proteinuria, the expression of α-SMA and OSM in tubular epithelial cells, and interstitial extracellular matrix accumulation in the renal tissue of CD-1 mice. In addition, our previous studies indicated that OSM induced TEMT by activating the JAK/STAT pathway, which could be inhibited by SOCS. These results indicate that overexpression of SOCS has a therapeutic effect in DN.
Connective Tissue Growth Factor Is Involved in Structural Retinal Vascular Changes in Long-Term Experimental Diabetes
Authors: Van Geest Rob J. , Leeuwis Jan Willem , Dendooven Amélie , Pfister Frederick , Bosch Klazien , Hoeben Kees A. , Vogels Ilse M.C. , Van der Giezen Dionne M. , Dietrich Nadine , Hammes Hans-Peter , Goldschmeding Roel , Klaassen Ingeborg , Van Noorden Cornelis J.F. , Schlingemann Reinier O.
Published: November 2013

Early retinal vascular changes in the development of diabetic retinopathy (DR) include capillary basal lamina (BL) thickening, pericyte loss and the development of acellular capillaries. Expression of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family member CCN2 or connective tissue growth factor (CTGF), a potent inducer of the expression of BL components, is upregulated early in diabetes. Diabetic mice lacking one functional CTGF allele (CTGF+/−) do not show this BL thickening. As early events in DR may be interrelated, we hypothesized that CTGF plays a role in the pathological changes of retinal capillaries other than BL thickening. We studied the effects of long-term (6-8 months) streptozotocin-induced diabetes on retinal capillary BL thickness, numbers of pericytes and the development of acellular capillaries in wild type and CTGF+/− mice. Our results show that an absence of BL thickening of retinal capillaries in long-term diabetic CTGF+/− mice is associated with reduced pericyte dropout and reduced formation of acellular capillaries. We conclude that CTGF is involved in structural retinal vascular changes in diabetic rodents. Inhibition of CTGF in the eye may therefore be protective against the development of DR.
The Minkowski problem, new constant curvature surfaces in ℝ3, and some applications
Authors: Alarcón Antonio , Souam Rabah
Published: November 2013

Let

𝔪
∈
ℕ

${\mathfrak {m}\in \mathbb {N}}$

,

𝔪
≥
2

${\mathfrak {m}\ge 2}$

, and let

{

p
j

}

j
=
1

𝔪

${\lbrace p_j\rbrace _{j=1}^\mathfrak {m}}$

be a finite subset of 𝕊2 such that

0
→

∈

ℝ
3

${\vec{0}\in \mathbb {R}^3}$

lies in its positive convex hull. In this paper we make use of the classical Minkowski problem, to show the complete family of smooth convex bodies 𝒦 in ℝ3 whose boundary surface consists of an open surface S with constant Gauss curvature (respectively, constant mean curvature) and 𝔪 planar compact discs

D
¯

1

,
...
,

D
¯

𝔪

${\overline{D}_1,\ldots ,\overline{D}_\mathfrak {m}}$

, such that the Gauss map of S is a homeomorphism onto

𝕊
2

-

{

p
j

}

j
=
1

𝔪

${\mathbb {S}^2-\lbrace p_j\rbrace _{j=1}^\mathfrak {m}}$

and

D
j

⊥

p
j

${D_j\bot p_j}$

, for all

j
.

${j.}$

We derive applications to existence of harmonic diffeomorphisms between domains of 𝕊2, existence of capillary surfaces in ℝ3, and a Hessian equation of Monge–Ampère type.
The limit of the Yang–Mills flow on semi-stable bundles
Authors: Jacob Adam
Published: November 2013

By the work of Hong and Tian it is known that given a holomorphic vector bundle E over a compact Kähler manifold X, the Yang–Mills flow converges away from an analytic singular set. If E is semi-stable, then the limiting metric is Hermitian-Einstein and will decompose the limiting bundle E
∞ into a direct sum of stable bundles. Bando and Siu prove E
∞ can be extended to a reflexive sheaf

E
^

∞

${\hat{E}_\infty }$

on all of X. In this paper, we construct an isomorphism between

E
^

∞

${\hat{E}_\infty }$

and the double dual of the stable quotients of the graded Seshadri filtration

Gr

s

(
E
)

*
*

${{\rm Gr}^{\hspace*{0.56905pt}s}(E)^{**}}$

of E.
Linear stability of Perelman's ν-entropy on symmetric spaces of compact type
Authors: Cao Huai-Dong , He Chenxu
Published: November 2013

Following [`Gaussian densities and stability for some Ricci solitons', preprint 2004], in this paper we study the linear stability of Perelman's ν-entropy on Einstein manifolds with positive Ricci curvature. We observe the equivalence between the linear stability (also called ν-stability in this paper) restricted to the transversal traceless symmetric 2-tensors and the stability of Einstein manifolds with respect to the Hilbert action. As a main application, we give a full classification of linear stability of the ν-entropy on symmetric spaces of compact type. In particular, we exhibit many more ν-stable and ν-unstable examples than previously known and also the first ν-stable examples, other than the standard spheres, whose second variations are negative definite.
Placental syndecan-1 and sulphated glycosaminoglycans are decreased in preeclampsia
Authors: Heyer-Chauhan Narinda , Ovbude Ihinosen J. , Hills Anne A. , Sullivan Mark H. , Hills Frank A.
Published: November 2013

Glycosaminoglycans are found in extracellular matrix and on the cell surface in the form of proteoglycans. There is evidence that these molecules regulate biological processes, including cell survival, migration and angiogenesis. Preeclampsia is a common pregnancy disorder associated with insufficient placental development. This study aimed to determine the concentrations of glycosaminoglycans and the proteoglycan syndecan-1 within villous trophoblast and to investigate changes associated with preeclampsia. Seventy-five placental samples collected from third trimester singleton pregnancies were divided into term placentas following labour onset, gestational age-matched placentas prior to labour onset and preterm placentas. Preterm placentas were divided into three gestational age-matched groups, spontaneous preterm labour, preterm premature rupture of membranes (PPROM) and preterm preeclampsia. Sulphated glycosaminoglycan (sGAG) concentrations in placental extracts were quantified using a modified 1,9-dimethylmethylene blue assay. Syndecan-1 expression was localised using immunohistochemistry and concentrations in placental extracts determined by immunoassay. Preterm placentas had significantly lower sGAG concentrations compared to term tissues and concentrations were significantly lower in preeclampsia compared to spontaneous preterm labour (medians 5.80 and 10.0 μg/mg protein respectively, P<0.05). Syndecan-1 expression was localised to syncytiotrophoblast and median concentrations were lower in preeclampsia compared to PPROM material (preeclampsia median = 41.7, PPROM 74.4 ng/mg tissue) but not significantly different to concentrations in spontaneous preterm labour. Multivariate analysis revealed that decreased sGAG and syndecan-1 in preeclampsia were independent of labour, gestational age and birthweight centile. These findings may provide insights into a role for these molecules in the pathophysiology of preeclampsia.
Impact of IGF(CA)19 gene polymorphism on the metabolic response to GH therapy in adult GH-deficient patients
Authors: Giavoli C , Profka E , Sala E , Filopanti M , Barbieri A M , Bergamaschi S , Ferrante E , Arosio M , Ambrosi B , Lania A G , Spada A , Beck-Peccoz P
Published: November 2013

Objective

A polymorphism in the promoter region of theIGF1gene has been linked to serum IGF1 levels, risk of diabetes, and cardiovascular diseases with conflicting results. The aim of this study was to investigate the impact of this polymorphism on the short-term (1 year,n=98) and long-term (5 years,n=50) metabolic response to recombinant human GH (rhGH) in GH-deficient (GHD) adults.

Design and methods

Prospective study on GHD adults. Different genotypes were studied by microsatellite method. According to the most frequent 192 bp allele (19 cytosine–adenosine-repeats), subjects were divided into homozygous (19/19), heterozygous (19/X), and noncarriers (X/X).

Results

Basal characteristics of patients as well as their response to rhGH in terms of decrease in body fat percentage and increase in IGF1 levels were not different in the three genotype-groups. Conversely, after 1-year rhGH, a significant worsening of insulin sensitivity (i.e. increase in fasting glucose levels and homeostasis model assessment of insulin resistance) and a significant improvement in lipid profile (i.e. reduction in total cholesterol and LDL-cholesterol) were recorded only in homozygous subjects. In the long-term, insulin sensitivity was restored in all the patients, while a significant improvement in lipid profile was observed in homozygous and heterozygous subjects, but not in noncarrier subjects. No difference in rhGH dose among groups was recorded throughout the study.

Conclusions

In GHD adults, the presence of the WT allele in the IGF1 gene promoter may enhance sensitivity to either negative or positive metabolic changes induced by rhGH.
Long-term remission and recurrence rates after first and second transsphenoidal surgery for Cushing's disease: care reality in the Munich Metropolitan Region
Authors: Dimopoulou C , Schopohl J , Rachinger W , Buchfelder M , Honegger J , Reincke M , Stalla G K
Published: November 2013

Objective

Transsphenoidal surgery (TSS) presents the treatment of choice for Cushing's disease (CD). Remission and recurrence rates vary dependent on tumor size, extension, adenoma visibility on magnetic resonance imaging, and neurosurgical expertise. Other than published from single-surgeon neurosurgical series so far, we have aimed to describe long-term remission and recurrence rates of CD in a series incorporating different neurosurgeons, trying to reflect care reality in the Munich Metropolitan Region, which is accommodated by three tertiary university and multiple, smaller neurosurgical centers.

Design

We conducted a retrospective analysis of 120 patients who underwent first and 36 patients who underwent second TSS as treatment for CD between 1990 and 2012.

Methods

Patients were divided into three groups according to remission status. Potential risk factors for recurrence, pituitary function, and strategy in persistent disease were assessed.

Results

Three outcome groups were identified according to remission status after first TSS (mean follow-up 79 months): remission, 71% (85/120), disease persistence, 29% (35/120), and disease recurrence, 34% (29/85) (mean time to recurrence 54 months). After second TSS (n=36, mean follow-up 62 months), we documented remission in 42% (15/36), disease persistence in 58% (21/36), and disease recurrence in 40% (6/15) (mean time to recurrence 42 months). Postoperative hypocortisolism after first, though not after second, TSS was associated with a lower risk of suffering disease recurrence (risk=0.72; 95% CI 0.60–0.88; exact significance (two-sided) P=0.035).

Conclusions

Our study shows higher recurrence rates of CD after first TSS than previously reported. Second TSS leads an additional 8% of the patients to long-term CD remission.
Role of UGT1A1 and ADH gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients
Authors: Filopanti M , Barbieri A M , Mantovani G , Corbetta S , Gasco V , Ragonese M , Martini C , Bogazzi F , Colao A , Ferone D , Peri A , Pigliaru F , Angeletti G , Arosio M , Beck-Peccoz P , Lania A G , Spada A
Published: November 2013

Context

Hepatotoxicity is one of the most serious adverse effects in acromegalic patients treated with pegvisomant (PEG-V). Recent studies have found an association between this adverse event and the UGT1A1 allele 28 polymorphism associated with Gilbert's syndrome.

Objective

To determine whether UGT1A1*28 and alcohol dehydrogenase (ADH) polymorphisms influence liver toxicity during PEG-V treatment.

Design and setting

Multicenter observational retrospective study conducted in 13 tertiary care endocrinology units in Italy.

Patients

A total of 112 patients with active disease resistant to somatostatin analogs (SSTa) and 108 controls were enrolled.

Interventions

Clinical and biochemical data were recorded by electronic clinical reporting forms. Blood or DNA samples were sent to the coordinating center for genotyping.

Results

No differences in genotypes between patients and controls were found. During PEG-V therapy liver function tests (LFT), abnormalities and overt hepatotoxicity developed in 17 and 4.5% of patients respectively. Logistic and linear regression analyses showed an association between LFT abnormalities during the follow-up visit and prior events of LFT abnormalities in medical history (odds ratio=1.25;P=0.04) and the number of concomitant medications, other than SSTa (B=3.9;P=0.03). No correlation between LFT alterations and UGT1A1 allele 28 as well as ADH1C and B polymorphisms was found.

Conclusions

UGT1A1 allele 28 and ADH1C and B polymorphisms do not predict increased risk of hepatotoxicity during PEG-V therapy. Conversely, patients with multi-therapies and with previous episodes of liver disease should be carefully managed, due to the observed association between these conditions and LFT abnormalities during PEG-V therapy.
Abnormal metabolic phenotype in middle-aged GH-deficient adults despite long-term recombinant human GH replacement
Authors: Claessen K M J A , Appelman-Dijkstra N M , Pereira A M , Joustra S D , de Mutsert R , Gast K B , den Heijer M , Smit J W A , Dekkers O M , Biermasz N R
Published: November 2013

Background

Adult GH deficiency (GHD) is associated with increased cardiovascular mortality. Recombinant human GH (rhGH) replacement has beneficial short-term metabolic effects. Although these positive effects sustain during longer follow-up, the prevalence of the metabolic syndrome (MS) remains increased in comparison with population data not adjusted for the higher mean BMI in GHD adults.

Objective

To explore whether middle-aged patients with proposed physiological rhGH replacement have been normalized with respect to MS and its individual components in comparison with the general population, adjusted for age, sex, and BMI.

Methods

One hundred and sixty-one GHD patients (aged 40–70 years) were studied before the start and after 5 years of rhGH replacement, and were compared with 1671 subjects (aged 45–66 years) from the general population (NEO Study).

Results

MS proportion in GHD patients was 41.0% before the start of rhGH suppletion, increasing to 53.4% after 5 years (P=0.007). Despite chronic rhGH replacement, GHD patients had a 1.3-times higher MS proportion than the general population, independently of age, sex, and BMI (95% CI 1.1–1.5, P=0.008). The GHD population showed a different metabolic profile than the general population with similar BMI: an increased risk of hypertriglyceridemia (adjusted prevalence ratio (PR) 2.0, 95% CI 1.7–2.3) and low HDL-C (adjusted PR 1.8, 95% CI 1.5–2.2), but less hyperglycemia (adjusted PR 0.5, 95% CI 0.4–0.7).

Conclusions

Despite 5 years of rhGH replacement, GHD patients still have a different metabolic profile and more frequently MS than the general population. These differences were independent of BMI, and resemble the unfavorable metabolic profile of untreated GHD patients, pointing to question the long-term benefits of rhGH replacement.
Huge Aortic Pseudoaneurysm Arising from the Aorta-Saphenous Vein Graft Anastomosis after Coronary Artery Bypass Grafting
Authors: Sahin Muslum , Yazicioglu Mehmet Vefik , Sarikaya Sabit , Turkmen Mehmet Muhsin
Published: November 2013

Pseudoaneurysm of the aortic root is a rare condition and potentially fatal if not treated. It may occur in different etiologies. In this case, we aim to show an aortic pseudoaneurysm arising from the aorta-saphenous vein graft anastomosis.
The Relationship between Low Intraoperative Hematocrit Levels during Cardiopulmonary Bypass and Postoperative Neurological Events
Authors: Yılmaz Metin , Özen Anıl , Yay Kerem , Ünal Ertekin Utku , Çiçek Ömer Faruk , Yılmaz Murat , Çatav Zeki , Ulus Tulga , Paç Mustafa
Published: November 2013

Objective: The objective of our study is to analyzewhether low intraoperative hematocrit levels have an effectupon postoperative neurological events.Methods: Our study included 140 patients who underwentisolated coronary bypass under cardiopulmonary bypassbetween 2009 and 2012. The main group of the study was70 patients with intraoperative hematocrit levels lower than22%. These patients’ 30-day postoperative neurological (particularlystroke) follow up was registered as the main data ofthe study. Another group of 70 patients possessing the samedemographic features who underwent open heart surgerywith hematocrit levels remaining above 22% were registeredas the control group for perioperative neurological data.Results: The average age of the patients with hematocritlevels below and above 22% was 56.8 Â± 5.8 years and 54.1Â± 7.3 years, respectively. The mean follow-up period of thepatients was 37.2 Â± 8.6 days. None of the patients had anyneurological postoperative sequalae. No mortalities occurred.One patient who had mild paresthesia and motor weaknessof the left hand had no pathological finding on computedtomography and was diagnosed with peripheral neuropathydue to intraoperative sternal retraction.Conclusion: Because our study revealed no cerebrovascularevents, coronary bypass surgery under cardiopulmonarybypass may be safely conducted even in patients with hematocritlevels lower than 22%.
Comparison of Conventional Technique and Ultrasonographic Mapping in Saphenous Vein Harvesting
Authors: Temizkan Veysel , Ugur Murat , Arslan Gokhan , Alp Ibrahim , Yedekci Erturk , Ucak Alper , Yilmaz Ahmet Turan
Published: November 2013

Background: Saphenous vein mapping provides accurate identification of the graft diameter, location of the harvest side, and quality of graft and also led to a selective leg skin incision. In this article, we aimed to compare patients who underwent coronary artery bypass graft (CABG) surgery with or without vein mapping.Methods: Patients who underwent CABG surgery with saphenous vein grafts (SVG) between January 2005 and January 2010 in our service were analyzed retrospectively. One hundred seventy-eight 178 SVGs were harvested with classical methods (Group A), and 136 SVGs were harvested after Doppler ultrasonography (USG) mapping (Group B).Results: In Group A, 6.7% of patients needed additional incisions for graft harvesting than planned before CABG surgery due to unsuitable vein grafts. In Group B, SVGs were harvested from left lower extremity in 16 patients, and the saphenous vein was not suitable for grafting in 1 patient due to Doppler examination. In the postoperative period, complications at the incision site were reduced in Group B.Conclusion: Preoperative vein mapping for harvesting SVGs is an effective method in reducing wound site complications, hospital stay, and hospital costs and in increasing patient comfort and satisfaction.
The Application of On-Pump Beating-Heart Surgery for Partial Atrioventricular Septal Defect: A Report of 87 Cases
Authors: Chen Lin , Hao Jia , Ma Rui-Yan , Chen Bai-Cheng , Cheng Wei , Qin Chuan , Wang Xue-Feng , Xiao Ying-Bin
Published: November 2013

Background: Partial atrioventricular septal defect (P-AVSD) is a common congenital heart disease. Because of the presence of left and right atrioventricular valve deformities and the shift in the atrioventricular node and cardiac conduction bundle, the surgical repair of P-AVSD is difficult. This study was performed to compare the effects on the coronary sinus septum in the left versus the right atrium during surgical treatment for P-AVSD and report our experiences regarding the application of on-pump beating heart surgery under mild hypothermia for patients with P-AVSD.Materials and Methods: The effects of on-pump beating heart surgery were analyzed retrospectively in 87 P-AVSD patients. Of the 87 total patients, 84 with anterior mitral leaflet cleft underwent valvuloplasty and 3 underwent mitral valve replacement. Seventy-seven patients underwent tricuspid valve annuloplasty, 2 underwent tricuspid valve replacement, and 1 underwent left superior vena cava ligation, and 3 patients with atrial fibrillation were treated with radiofrequency ablation. Patients with an ostium primum atrial septal defect underwent autologous pericardial modified Kirklin repair. Of these, 46 patients had their coronary sinus septum separated into the left atrium and 41 had their coronary sinus retained in the right atrium. Fingertip oxygen saturation was compared between patients in whom the coronary sinus was separated to the left atrium and those in whom the coronary sinus was retained in the right atrium.Results: There was 1 postoperative early death (1.15%) due to respiratory failure, and 1 patient had a III degree atrioventricular block (1.15%) and underwent implantation of a permanent pacemaker. The fingertip oxygen saturation levels of the left atrium group were 96.81 ± 3.17 preoperatively, 95.37 ± 4.62 at 7 days postoperatively, and 94.53 ± 4.95 at 3 months postoperatively. Those of the right atrium group were 98.53 ± 2.84 preoperatively, 97.19 ± 3.57 at 7 days postoperatively, and 96.89 ± 4.19 at 3 months postoperatively. During the follow-up period, which ranged from 3 months to 7 years, the cardiac function was adequately restored.Conclusions: On-pump beating heart surgery under mild hypothermia is a safe and feasible method. The retention of the coronary sinus in the right atrium might maintain oxygen saturation.
Overweight Adolescents and Life Events in Childhood
Authors: Lumeng Julie C. , Wendorf Kristen , Pesch Megan H. , Appugliese Danielle P. , Kaciroti Niko , Corwyn Robert F. , Bradley Robert H.
Published: November 2013

OBJECTIVES:

To test the association of life events in childhood with overweight risk in adolescence; to examine the effects of chronicity, timing, intensity, valence, and type of life events; and to test potential moderators.

METHODS:

Mothers of children enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Study of Early Child Care and Youth Development responded to the Life Experiences Survey at ages 4, 9, and 11 years. Using logistic regression analysis, we tested the association of experiencing many negative life events with being overweight at age 15 years, controlling for child gender, race/ethnicity, maternal education, and maternal obesity. Child gender, maternal education, maternal obesity, child’s ability to delay gratification for food, and maternal sensitivity were tested as moderators.

RESULTS:

Among the 848 study children (82% non-Hispanic white), experiencing many negative life events was associated with a higher risk of overweight (odds ratio: 1.47 [95% confidence interval: 1.04–2.10]). Greater chronicity and negative valence of the event were associated with greater overweight risk; timing of exposure and maternal reported impact of the event were not. The association was more robust for events related to family physical or mental health and among children of obese mothers and children who waited longer for food.

CONCLUSIONS:

Children who experience many negative life events are at higher risk of being overweight by age 15 years. Future work should investigate mechanisms involved in this association, particularly those connected to appetitive drive and self-regulation; these mechanisms may hold promise for obesity prevention strategies.
Serum Tocopherol Levels in Very Preterm Infants After a Single Dose of Vitamin E at Birth
Authors: Bell Edward F. , Hansen Nellie I. , Brion Luc P. , Ehrenkranz Richard A. , Kennedy Kathleen A. , Walsh Michele C. , Shankaran Seetha , Acarregui Michael J. , Johnson Karen J. , Hale Ellen C. , Messina Lynn A. , Crawford Margaret M. , Laptook Abbot R. , Goldberg Ronald N. , Van Meurs Krisa P. , Carlo Waldemar A. , Poindexter Brenda B. , Faix Roger G. , Carlton David P. , Watterberg Kristi L. , Ellsbury Dan L. , Das Abhik , Higgins Rosemary D.
Published: November 2013

OBJECTIVE:

Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage.

METHODS:

Ninety-three infants <27 weeks’ gestation and <1000 g were randomly assigned to receive a single dose of vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing.

RESULTS:

Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels <0.5 mg/dL.

CONCLUSIONS:

A 50-IU/kg dose of vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.
Comitê de publicações em estudo multicêntrico e sistema informatizado de apoio - publiELSA
Authors: Carvalho Marilia Sá , Barreto Maurício Lima , Coeli Cláudia Medina , Raposo Rafael Monteiro , Mota Eduardo Luiz Andrade , Duncan Bruce Bartholow
Published: November 2013

O comitê de publicações de um estudo multicêntrico visa organizar as propostas de artigos, garantindo: amplo acesso aos dados, qualidade e precedência. Foi desenvolvido um sistema online de informação e gerenciamento de propostas de estudos - o publiELSA - , composto por três módulos: (i) submissão e aprovação da proposta; (ii) acompanhamento da proposta aprovada; e (iii) relatórios consolidados. O primeiro permite a qualquer interessado buscar e conhecer artigos já publicados e em andamento, e submeter novas propostas. O processo de aprovação e transferência dos dados para o pesquisador responsável é organizado nessa etapa. O segundo módulo visa ao monitoramento das propostas aprovadas até sua publicação final e o terceiro permite buscas e visualização de propostas e artigos. O sistema tem aspectos inovadores, sobretudo o incentivo à cooperação entre os diversos pesquisadores, por meio da circulação de informes sobre cada proposta submetida. Estimula-se assim a interação dos diferentes olhares e experiências envolvidos nesta pesquisa.
Delineamento e implementacao do biobanco do ELSA-Brasil: estudo prospectivo na populacao brasileira
Authors: Pereira Alexandre C , Bensenor Isabela M , Fedeli Ligia M , Castilhos Cristina , Vidigal Pedro G , Maniero Viviane , Leite Claudia M , Pimentel Robercia A , Duncan Bruce B , Mill Jose Geraldo , Lotufo Paulo A
Published: November 2013

O Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) é uma coorte prospectiva multicêntrica de funcionários públicos delineada para avaliar os determinantes das doenças crônicas, principalmente a doença cardiovascular e o diabetes tipo 2. Neste artigo são descritos os principais pontos do delineamento e implementação do projeto do biobanco do ELSA-Brasil. São detalhados aspectos econômicos, políticos, logísticos e tecnológicos do estudo. O artigo também discute o protocolo final de estocagem de material biológico e as instalações implementadas para atingir esse objetivo. O processo de delineamento e implementação do biobanco do ELSA-Brasil durou três anos. Tanto os biobancos centrais quanto os locais foram constituídos de acordo com as melhores práticas de estocagem de material biológico, usando soluções tecnológicas diferentes para as diferentes necessidades previstas no estudo.
Estratégias de identificação, investigação e classificação de desfechos incidentes no ELSA-Brasil
Authors: Barreto Sandhi Maria , Ladeira Roberto Marini , Bastos Maria do Socorro Castelo Branco de Oliveira , Diniz Maria de Fátima Haueisen Sander , Jesus Elcimara Amorim de , Kelles Silvana Márcia Bruschi , Luft Vivian Cristine , Melo Enirtes Caetano Prates , Oliveira Elizabete Regina Araújo de
Published: November 2013

OBJETIVO: O artigo descreve as estratégias do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) para a manutenção da adesão dos participantes ao longo do tempo e seu seguimento adequado. Isto é fundamental para garantir a validade interna de estudos longitudinais e identificar, investigar e classificar os desfechos incidentes de interesse.MÉTODOS: A metodologia de seguimento da coorte combina contatos telefônicos anuais com re-exames e entrevistas a cada três ou quatro anos. O objetivo é identificar desfechos incidentes de natureza transitória, reversíveis ou não; desfechos finais, de natureza irreversível; bem como complicações relacionadas à evolução das doenças cardiovasculares e diabetes, principais doenças estudadas.RESULTADOS: As entrevistas telefônicas visam monitorar a saúde dos participantes e identificar possíveis eventos ocorridos, como internações hospitalares, exames ou procedimentos especializados definidos previamente. O participante também é incentivado a comunicar a ocorrência de algum evento de saúde ao Centro de Pesquisa. A partir da identificação de um potencial evento, é iniciado um processo de investigação, que inclui acesso a prontuários médicos para verificação de datas e informações detalhadas sobre aquele evento. Os documentos obtidos são analisados sem identificação do paciente, profissional ou serviço de saúde e classificados por um comitê de especialistas médicos. A classificação de desfechos incidentes adotada baseia-se em critérios internacionais consagrados, garantindo comparabilidade e reduzindo o erro de classificação deles. Além dessas estratégias, a ocorrência de desfechos poderá ser investigada por meio do relacionamento de dados com bases secundárias do Ministério da Saúde, como as de mortalidade e internações.CONCLUSÕES: A correta identificação de desfechos permitirá estimar sua incidência na coorte e investigar o efeito das exposições estudadas no ELSA-Brasil em sua linha de base e nas ondas posteriores.
Recrutamento de participantes no Estudo Longitudinal de Saude do Adulto
Authors: Aquino Estela M L , Araujo Maria Jenny , Almeida Maria da Conceicao C , Conceicao Patricia , Andrade Celia Regina de , Cade Nagela Valadao , Carvalho Marilia Sa , Figueiredo Roberta Carvalho de , Fonseca Maria de Jesus M da , Giatti Luana , Menezes Greice Maria de Souza , Nunes Maria Angelica , Souza Angelita Gomes de , Vasconcellos-Silva Paulo R , Vigo Alvaro
Published: November 2013

OBJETIVO: Apresentar as estratégias de comunicação e recrutamento no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) e discutir os resultados alcançados na constituição da coorte. MÉTODOS: As estratégias foram voltadas à divulgação, à institucionalização e ao recrutamento propriamente dito. As ações de comunicação pretenderam promover o fortalecimento de imagem institucional positiva para o estudo, a gestão de conhecimentos e o diálogo eficaz com seu público-alvo. Foi criado web site oficial visando dialogar com diferentes públicos, funcionar como difusor científico e contribuir para a consolidação da imagem do estudo perante a sociedade. RESULTADOS: Foram recrutados 16.435 mulheres e homens, servidores ativos e aposentados de seis instituições públicas de ensino e pesquisa para constituir a coorte de 15.105 participantes. As metas de recrutamento foram plenamente alcançadas nos seis centros, com leve predomínio de mulheres e daqueles mais jovens, e um pouco menos de servidores com menor escolarização. CONCLUSÕES: As estratégias utilizadas se mostraram adequadas e essenciais para o sucesso da captação e participação dos servidores.