bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemogenetic Evaluation of the Mitotic Kinesin CENP-E Reveals a Critical Role in Triple-Negative Breast Cancer
Authors: Kung Pei-Pei , Martinez Ricardo , Zhu Zhou , Zager Michael , Blasina Alessandra , Rymer Isha , Hallin Jill , Xu Meirong , Carroll Christopher , Chionis John , Wells Peter , Kozminski Kirk , Fan Jeffery , Guicherit Oivin , Huang Buwen , Cui Mei , Liu Chaoting , Huang Zhongdong , Sistla Anand , Yang Jennifer , Murray Brion W.
Published: June 2014

Breast cancer patients with tumors lacking the three diagnostic markers (ER, PR, and HER2) are classified as triple-negative (primarily basal-like) and have poor prognosis because there is no disease-specific therapy available. To address this unmet medical need, gene expression analyses using more than a thousand breast cancer samples were conducted, which identified elevated centromere protein E (CENP-E) expression in the basal-a molecular subtype relative to other subtypes. CENP-E, a mitotic kinesin component of the spindle assembly checkpoint, is shown to be induced in basal-a tumor cell lines by the mitotic spindle inhibitor drug docetaxel. CENP-E knockdown by inducible shRNA reduces basal-a breast cancer cell viability. A potent, selective CENP-E inhibitor (PF-2771) was used to define the contribution of CENP-E motor function to basal-like breast cancer. Mechanistic evaluation of PF-2771 in basal-a tumor cells links CENP-E–dependent molecular events (e.g., phosphorylation of histone H3 Ser-10; phospho-HH3-Ser10) to functional outcomes (e.g., chromosomal congression defects). Across a diverse panel of breast cell lines, CENP-E inhibition by PF-2771 selectively inhibits proliferation of basal breast cancer cell lines relative to premalignant ones and its response correlates with the degree of chromosomal instability. Pharmacokinetic–pharmacodynamic efficacy analysis in a basal-a xenograft tumor model shows that PF-2771 exposure is well correlated with increased phospho-HH3-Ser10 levels and tumor growth regression. Complete tumor regression is observed in a patient-derived, basal-a breast cancer xenograft tumor model treated with PF-2771. Tumor regression is also observed with PF-2771 in a taxane-resistant basal-a model. Taken together, CENP-E may be an effective therapeutic target for patients with triple-negative/basal-a breast cancer. Mol Cancer Ther; 13(8); 2104–15. ©2014 AACR.
In Vitro and In Vivo Activity of the Low-Immunogenic Antimesothelin Immunotoxin RG7787 in Pancreatic Cancer
Authors: Hollevoet Kevin , Mason-Osann Emily , Liu Xiu-fen , Imhof-Jung Sabine , Niederfellner Gerhard , Pastan Ira
Published: June 2014

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. RG7787 is a novel low-immunogenic antimesothelin recombinant immunotoxin (RIT), engineered to overcome the limitations of SS1P, a RIT now in clinical trials. In vitro activity was evaluated on five established PDAC cell lines (KLM-1, AsPC-1, BxPC-3, Panc 3.014, and PK-1) and on PDAC cells directly established from a patient tumor (GUMC108). RG7787 had subnanomolar IC50s in most cell lines, and was significantly more active than SS1P in GUMC108, KLM-1, and Panc 3.014 cells. GUMC108 was most sensitive, with RG7787 killing >99% of the cells. In a subcutaneous KLM-1 xenograft mouse model, two cycles of 3 × 2.5 mg/kg RG7787 QOD combined with two cycles of 1 × 50 mg/kg paclitaxel induced near-complete responses, with all tumors regressing below 5 mm3 within 30 days after therapy was initiated (>95% decrease) and no significant growth increase for at least another 3 weeks. RG7787 alone gave limited but significant regressions and paclitaxel by itself arrested tumor growth. Quantifying the uptake of Alexa Fluor 647–labeled RG7787 in tumors showed that the RIT reached only 45% of KLM-1 cells, accounting in part for the limited responses. Paclitaxel did not improve RG7787 uptake, which thus cannot explain the beneficial effect of the combination therapy. In conclusion, RG7787 has high cytotoxic activity on PDAC cell lines as well as on primary patient cells. In vivo, this novel RIT gives durable near-complete tumor responses when combined with paclitaxel. RG7787 merits further evaluation for the treatment of PDAC. Mol Cancer Ther; 13(8); 2040–9. ©2014 AACR.
Expression of the miR200 Family of microRNAs in Mesothelial Cells Suppresses the Dissemination of Ovarian Cancer Cells
Authors: Sugiyama Kazuya , Kajiyama Hiroaki , Shibata Kiyosumi , Yuan Hong , Kikkawa Fumitaka , Senga Takeshi
Published: June 2014

The TGFβ-mediated alteration of the tumor microenvironment plays a crucial role in tumor progression. Mesothelial cells are the primary components of the tumor microenvironment for ovarian cancer cells; however, the exact role of TGFβ-stimulated mesothelial cells in ovarian cancer progression remains uncertain. In this report, we examined the effects of TGFβ-treated mesothelial cells on ovarian cancer progression. We show that TGFβ-stimulated human primary mesothelial cells (HPMC) are able to promote cancer cell attachment and proliferation and the activation of the promoter activities of MMP-2 and MMP-9, which are metalloproteinases necessary for tumor invasion. Expression of the miR200 family was downregulated in HPMCs by TGFβ stimulation, and restoration of the expression of miR200 family members in HPMCs suppressed cancer cell attachment and proliferation. Downregulation of the miR200 family by TGFβ induced fibronectin 1 production, which promoted cancer cell attachment to HPMCs. Finally, we demonstrated that the delivery of the miR200s to mesothelial cells in mice inhibited ovarian cancer cell implantation and dissemination. Our results suggest that alteration of the tumor microenvironment by the miR200 family could be a novel therapeutic strategy for ovarian cancer treatment. Mol Cancer Ther; 13(8); 2081–91. ©2014 AACR.
Central Fat Accumulation Associated with Metabolic Risks beyond Total Fat in Normal BMI Chinese Adults
Authors: Fu Xiaohua , Zhu Fei , Zhao Xinyu , Ma Xiaoguang , Zhu Shankuan
Published: June 2014

Objective: To investigate the association of central fat with metabolic risks in normal BMI Chinese people. Methods: Normal BMI subjects (18.5 ≤ BMI < 24, n = 520) aged 18-82 years were included. Blood pressure, triglycerides, high-density lipoprotein cholesterol and fasting plasma glucose were collected as metabolic risk factors. Dual-energy X-ray absorptiometry was used to measure total and central fat. Central fat was indicated as percent trunk fat (%TF) and android/gynoid fat ratio. Multiple adjusted regression models were applied to investigate the association of total and central fat with metabolic risk factors. The assessment values of these fat measures were further compared by receiver-operating characteristic (ROC) curves. Results: Both total and central fat were correlated with metabolic risk factors. After adjusting for BMI, the significant association of percent body fat (%BF) with metabolic risks diminished, whereas %TF and android/gynoid fat ratio were still correlated. When BMI was replaced with %BF in the models, the results remained unchanged. ROC analysis showed the areas under the curve (AUCs) of total and central fat for at least two metabolic risk factors were comparable in men. However, in women, the AUCs of %TF and android/gynoid fat ratio were significantly greater than those of BMI, %BF and waist circumference. Conclusions: Central fat accumulation had a stronger association with metabolic risks than total fat in normal BMI Chinese adults, particularly in women. Central fat had more important implications in assessing ‘metabolically obese' individuals among normal BMI subjects.
Restorative Treatment Thresholds: Factors Influencing the Treatment Thresholds and Modalities of General Dentists in Kuwait
Authors: Khalaf Mai E. , Alomari Qasem D. , Ngo Hien , Doméjean Sophie
Published: June 2014

Objectives: This study investigated the thresholds at which general dentists in Kuwait would restore approximal and occlusal carious lesions and examined the demographic characteristics of the dentists in relation to their decision making. Subjects and Methods: The study population consisted of a random sample of 185 general dentists practicing in the Ministry of Health of Kuwait. A survey questionnaire was administered. The questionnaire presented different stages and locations of carious lesions; the participants were asked to identify the stage at which a restoration is required under different conditions, the preparation technique, and their choice of restorative material. Results: For approximal carious lesions, 74 (40%) of the participants reported that they would restoratively intervene when the carious lesion reached the outer third of the dentin. A total of 91 (49.2%) reported the use of traditional class II restorations. For occlusal carious lesions, 128 (69.2%) said they would intervene when lesions reached the middle third of the dentin. 146 (78.9%) said they would remove the carious tissue only in their preparation. For both approximal and occlusal lesions, the participants preferred resin composite as the material for restoration. Conclusions: The respondents tended to delay restorative intervention until dentinal penetration of the caries. Resin restorative materials were used in conservatively prepared cavities. Participants chose a conservative approach for occlusal lesions but still believed in a traditional approach when it concerned approximal lesions. Experience, university dental education, and participation in continuous education courses were most significantly related to restorative treatment.
Increased Density of Demodex folliculorum Mites in Pregnancies with Gestational Diabetes
Authors: Keskin Kurt Raziye , Aycan Kaya Ozlem , Karateke Atilla , Silfeler Dilek Benk , Soylu Karapınar Oya , Akkoca Ayse Neslin , Hakverdi Ali Ulvi
Published: June 2014

Objective: To investigate the presence of Demodex in patients with gestational diabetes and the impact of glucose regulation on Demodex density in gestational diabetes. Subjects and Methods: The study population consisted of 33 patients with gestational diabetes and 30 pregnant women without gestational diabetes (control group). The age, parity, gestational age, and BMI of the study group were recorded and the patients were divided into 2 groups, i.e. those with regulated and unregulated glucose levels, according to their postprandial 1st- and 2nd-hour glucose values. A standardized skin surface biopsy method was used to determine if patients had Demodex folliculorum infestation (>5 mites/cm2 of skin). Results: Patients with gestational diabetes had a statistically significantly higher Demodex density compared to the control group (24.2 vs. 3.3%; p < 0.001). Furthermore, a significantly higher proportion of gestational diabetes patients with unregulated glucose levels had a higher Demodex density compared to those in the regulated subgroup (6/19 vs. 2/14; p = 0.001). Conclusion: Our study revealed that the Demodex density was increased in gestational diabetes patients. Further, poor glucose regulation could be the mechanism responsible for the increased Demodex density in gestational diabetes patients with unregulated glucose levels compared to those with regulated glucose levels.
Treatment with p33 Curtails Morbidity and Mortality in a Histone-Induced Murine Shock Model
Authors: Westman Johannes , Smeds Emanuel , Johansson Linda , Mörgelin Matthias , Olin Anders I. , Malmström Erik , Linder Adam , Herwald Heiko
Published: June 2014

Collateral damage caused by extracellular histones has an immediate impact on morbidity and mortality in many disease models. A significant increase in the levels of extracellular histones is seen in critically ill patients with trauma and sepsis. We showed that histones are released from necrotic cells in patients with invasive skin infections. Under in vitro conditions, endogenous p33, an endothelial surface protein also known as the gC1q receptor, interacts with histones released from damaged endothelial cells. Functional analyses have revealed that recombinantly expressed p33 completely neutralizes the harmful features of histones, i.e. hemolysis of erythrocytes, lysis of endothelial cells and platelet aggregation. We also noted that mice treated with a sublethal dose of histones developed severe signs of hemolysis, thrombocytopenia and lung tissue damage already 10 min after inoculation. These complications were fully counteracted when p33 was administered together with the histones. Moreover, application of p33 significantly improved survival in mice receiving an otherwise lethal dose of histones. Together, our data suggest that treatment with p33 is a promising therapeutic approach in severe infectious diseases.
Using Hospital Data and Routines to Estimate Costs and Effects of Integrative Care Programmes for Chronic Pain and Stress Disorders - a Feasibility Study
Authors: Sundberg Tobias , Falkenberg Torkel
Published: June 2014

Background: Evidence of cost and effects for comprehensive hospital-based integrative care (IC) is scarce. The aim of this study was to explore the feasibility of using local hospital data and routines to estimate costs and effects of anthroposophic IC programmes for chronic pain and stress disorders in Sweden. Methods: Retrospective analysis of one IC hospital's local administrative registry data. Main outcomes embraced patient demographics, programme duration and costs, patients' health status (EQ-5D index, 0-1) and self-rated health (EQ-5D VAS, 0-100), from hospital admittance to discharge. The use of postal questionnares for collecting follow-up data after hospital discharge was assessed. Results: The IC pain programme had 461 records, all with complete data on costs and duration: average programme cost, EUR 5,925 (95% CI 5,780-6,070), and duration, 17.8 (SD 4.7) days. The IC stress programme had 263 records, all with complete cost and duration data: programme cost, EUR 5,494 (95%CI 5,318-5,671); duration 18.0 (SD 4.7) days. From admittance to discharge, health status improved by 0.23 (95% CI 0.19-0.27) in the pain, and by 0.16 (95% CI 0.12-0.20) in the stress programme. Improvements in self-rated health were 20 (95% CI 18-22), and 21 (95% CI 18-23), respectively. There was a general decrease in questionnaire response rate after hospital discharge, whereby 27-32% of respondents had completed data after 9 months. Conclusions: It was feasible to use hospital registry data to estimate costs and show positive effects of anthroposophic IC programmes for pain and stress disorders in Sweden. Clinical implications and the need for long-term follow-up are discussed.
Nondialytic Therapy for Elderly Patients in a Critical Care Setting
Authors: Ishikawa Hideaki , Sakamoto Junichi
Published: June 2014

It is frequently necessary to admit critically ill elderly patients to intensive care units (ICUs) due to their physiological impairments and co-morbidities. Several life-sustaining therapies such as mechanical ventilation are performed as necessary treatment in these ICUs. Sometimes renal replacement therapy (i.e. dialysis) is considered for elderly patients with complicating serious renal insufficiency. However, although the necessity for dialysis is recognized, some elderly patients may not benefit from this care because of their limited life expectancy. Until recently, life-sustaining support for critically ill elderly patients in Japan has been used routinely, regardless of the medical futility. The issue of providing better end-of-life care for elderly patients even in the ICU is now being raised frequently. We therefore wish to highlight the issue of end-of-life care and decision-making in the ICU, focusing on nondialytic therapy (NDT). The aim of this article was to assess whether NDT is an acceptable optional care for critically ill elderly patients with serious kidney diseases, even in the ICU. We hope our experiences may be helpful to physicians with an interest in decision-making and end-of-life care.
Chemotherapy in Early Breast Cancer: When, How and Which One?
Authors: Schmidt Marcus
Published: June 2014

The efficacy of chemotherapy depends on the level of risk of the individual patient. Because of this, careful estimation of the risk level is mandatory. In addition to well-established clinicopathological factors, validated gene expression signatures might be useful in selected patients if all other criteria are inconclusive for therapeutic decision-making. If indicated, chemotherapy can be used either after surgery (adjuvant) or before surgery (neoadjuvant). Both approaches lead to comparable long-term survival. The neoadjuvant setting offers the additional opportunity for elaborate translational studies to develop and validate predictive biomarkers and to discover mechanisms of resistance to therapy. If possible, chemotherapy regimens should include both anthracyclines and taxanes. Docetaxel should be used every 3 weeks; better tolerability with equivalent efficacy favors the concurrent over the sequential approach. Paclitaxel, on the other hand, should be administered sequentially, either weekly or every 2 weeks. Especially, intense dose-dense sequential chemotherapy with granulocyte colony-stimulating factor support is very effective in high-risk breast cancer patients. In order to decrease toxicities, anthracycline-free regimens or a shortening of the duration of adjuvant chemotherapy are potential options that should be further explored.
Unspecific Abdominal Symptoms and Pneumobilia: A Rare Case of Gastrointestinal Obstruction
Authors: Keller Martina , Epp Carola , Meyenberger Christa , Sulz Michael Christian
Published: June 2014

The case of a 77-year-old woman with symptoms of gastric outlet obstruction is presented. Transabdominal ultrasonography findings were suspicious of Bouveret's syndrome. Upper endoscopy confirmed this diagnosis. Bouveret's syndrome is a rare complication of gallstone disease caused by a bilioenteric fistula leading to gastric outlet obstruction by a gallstone and should be suspected in any patient who presents with pneumobilia without recent endoscopic retrograde cholangiopancreatography or biliary surgery.
Duodenal Hemorrhage from Pancreatic Cancer Infiltration Controlled through Combination Therapy with Gemcitabine and S-1
Authors: Takada Ryoji , Ioka Tatsuya , Sueyoshi Hironari , Ishida Nobuko , Yamai Takuo , Fukutake Nobuyasu , Ashida Reiko , Uehara Hiroyuki , Takenaka Akemi , Tomita Yasuhiko , Katayama Kazuhiro
Published: June 2014

2.6% of pancreatic cancer patients have the primary manifestation of gastrointestinal bleeding. It is not feasible to stop the duodenal hemorrhage caused by the pancreatic cancer infiltration. A 43-year-old woman who was diagnosed as having pancreatic cancer with multiple hepatic metastases and duodenal infiltration was administered gemcitabine and S-1 combination therapy. During the chemotherapy, initially, bleeding occurred due to duodenal infiltration. However, we continued the chemotherapy and duodenal infiltration was markedly reduced in size and did not rebleed. Aggressive chemotherapy contributed to maintenance of performance status as well as improvement of quality of life for the patient.
Distress in Cancer Patients and Their Caregivers and Association with the Caregivers' Perception of Dyadic Communication
Authors: Haun Markus W. , Sklenarova Halina , Brechtel Anette , Herzog Wolfgang , Hartmann Mechthild
Published: June 2014

Background: Discrepancies within cancer-affected couples can disrupt security within the dyadic relationship during cancer treatment. This study investigated the patients' and caregivers' distress and associations between the caregivers' perception of the patients' degree of open communication and their distress. Participants and Methods: In a cross-sectional survey, 189 pairs of cancer patients (31% gastrointestinal, 34% lung, 35% urological cancers) and their partners were assessed for distress (QSC-R10), depression and anxiety (PHQ-2/GAD-2). The caregivers also reported their perception of the patients' degree of disclosure regarding cancer-relevant topics (CCAT-F Disclosure subscale), caregiver strain (CSI), and unmet needs (SCNS-P&C). Prevalences of clinically significant distress were calculated. Associations were calculated between the caregivers' and the patients' ratings and between the caregivers' distress and their perception of the patients' degree of disclosure. Results: 33% of the caregivers and 25% of the patients exhibited significant anxiety, with a tendency towards a higher frequency in the caregivers (p = 0.10). The prevalence of depression was lower but equally high in caregivers and patients. The caregivers' perceived non-disclosure by the patients was primarily associated with their anxiety (r = 0.31), disease-specific distress (r = 0.32), and psychological/emotional needs (r = 0.35). Conclusion: The identification of caregivers reporting problems in communicating with patients should be pursued in clinical practice as this might indicate that caregivers are particularly burdened.
DNA Repair Gene - XRCC1 in Relation to Genome Instability and Role in Colorectal Carcinogenesis
Authors: Nissar Saniya , Sameer Aga Syed , Rasool Roohi , Rashid Fouzia
Published: June 2014

Colorectal carcinogenesis is a multifactorial and multi-gene process, involving 3 major genetic instability pathways: chromosomal instability, microsatellite instability and CpG island methylator phenotype. Inefficient DNA repair is one of the causes of genetic instability leading to tumorigenesis. Defects in DNA repair genes are associated with cancer development. The XRCC1 gene is an important DNA repair genes and forms the component of several different damage recovery pathways, including base excision repair and single-strand breaks repair - the processes frequently involved in cancer transformation. In this review we have shed light on the structure and functioning of the XRCC1 gene and its protein, and the role played by XRCC1 in colorectal carcinogenesis.
Câncer e o microambiente tumoral
Authors: Onuchic Ana Cláudia , Chammas Roger
Published: June 2014

Antes tido como um conjunto de células alteradas em proliferação, hoje o câncer é mais bem entendido como um microambiente, em que as interações entre os elementos celulares e moleculares que o compõem são determinantes na progressão tumoral. Como resultado, a compreensão do evento neoplásico ganha complexidade crescente. A dinâmica das células tumorais passa a ser avaliada como parte de um verdadeiro tecido tumoral, sujeita a condições de vascularização, de oxigenação, de pressão intersticial e de necrose tecidual, que influenciam na cinética tumoral. Estão sendo identificados novos componentes deste nicho tumoral e as suas respectivas atuações. Entre esses integrantes, encontram-se os elementos da imunidade, cuja modulação tem sido demonstrada por uma série de pesquisas aqui revisadas, tanto no sentido da vigilância imunológica, como pressão seletiva negativa, quanto no favorecimento da progressão tumoral. Esta revisão analisará a neoplasia do ponto de vista de um microambiente tumoral, focando na participação imunológica e na cinética tumoral, expondo as principais idéias e descobertas que criaram e estão aperfeiçoando o conceito de câncer
Internações por Lúpus no estado de Alagoas: 2002-2007
Authors: Silva Ana Carolina Santos , Amorim Edla Cavalcanti , Silva Gabriela Gama , Alves Waneska Alexandra , Correia Divanise Suruagy
Published: June 2014

Objetivou-se identificar o número de internações por Lúpus no estado de Alagoas no período de 2002 a 2007 com a análise de alguns aspectos relevantes. O Banco de Dados do Sistema Único de Saúde (DATASUS) foi utilizado como fonte de dados. As variáveis abordadas foram retiradas da Ficha de Autorização Hospitalar (AIH) e analisadas no programa EPI INFO 3.5.1 através de medidas estatísticas de frequência. Nesse período, 578 pacientes com Lúpus foram internados no estado de Alagoas, prevalecendo o sexo feminino (90,3%) e a média de idade de 24,36 anos. Quanto à procedência dos pacientes com Lúpus, a maioria era da mesorregião Leste, tendo destaque a cidade de Maceió (capital do estado), origem de 50,71% dos pacientes. A capital possuiu também o maior número de internações (94,3%). A especialidade que realizou maior quantidade de diagnóstico principal e admissão de pacientes com Lúpus foi a Clínica Médica (92,05%), sendo todas essas informações compatíveis com estudos semelhantes realizados em outros estados brasileiros. O mês de maior número de internações foi março, e o período de permanência de internação dos pacientes teve média de 7,24 dias. O custo médio por paciente foi de R$121,77; por dia de internação de R$16,80; e por ano de R$115,18, sendo esses dados divergentes daqueles encontrados na literatura, que mostra um custo em se manter o paciente com Lúpus por ano no Brasil de R$ 999,00, valor significativamente superior. Foram a óbito 14 (2,4%) dos pacientes estudados. Houve prevalência do diagnóstico principal de Lúpus Eritematoso Disseminado não especificado (45,33%).
Postsystolic Shortening by Myocardial Deformation Imaging as a Sign of Cardiac Adaptation to Pressure Overload in Fetal Growth Restriction
Authors: Crispi Fàtima , Bijnens Bart , Sepulveda-Swatson Eduardo , Cruz-Lemini Monica , Rojas-Benavente Juan , Gonzalez-Tendero Anna , Garcia-Posada Raul , Rodriguez-Lopez Merida , Demicheva Elena , Sitges Marta , Gratacós Eduard
Published: June 2014

Background—

Fetal growth restriction (FGR) is associated with global adverse cardiac remodeling in utero and increased cardiovascular mortality in adulthood. Prenatal myocardial deformation has not been evaluated in FGR to date. We aimed to evaluate prenatal cardiac remodeling comprehensively in FGR including myocardial deformation imaging.

Methods and Results—

Echocardiography was performed in 37 consecutive FGR (defined as birthweight <10th centile) and 37 normally grown fetuses. A comprehensive fetal echocardiography was performed including tissue Doppler and 2-dimensional–derived strain and strain rate. Postnatal blood pressure measurement at 6 months of age was also performed. FGR cases showed signs of more globular hearts with decreased longitudinal motion (left systolic annular peak velocity: controls mean 6 cm/s [SD 1.2] versus FGR 5.3 [1]) and diastolic dysfunction (isovolumic relaxation time: controls 44 ms [6] versus FGR 52 [9]). Peak strain and strain rate values of the left ventricle were not significantly different; however, a postsystolic shortening in the basal segment of the septal ventricular wall was observed in 57% of the FGR cases and in none of controls (
P
<0.001). FGR cases with postsystolic shortening had absence of a hypertrophic response, a poorer perinatal outcome (lower gestational age and birthweight, containing all cases of perinatal mortality [8%]), and higher values of blood pressure.

Conclusions—

Myocardial deformation imaging revealed a postsystolic shortening in 57% of FGR, which supports increased pressure overload as a mechanism for cardiovascular programming in FGR. Postsystolic shortening was associated with severity and with higher blood pressure postnatally.
Myocardial Contractile Dysfunction Is Associated With Impaired Mitochondrial Function and Dynamics in Type 2 Diabetic but Not in Obese Patients
Authors: Montaigne David , Marechal Xavier , Coisne Augustin , Debry Nicolas , Modine Thomas , Fayad Georges , Potelle Charlotte , El Arid Jean-Marc , Mouton Stéphanie , Sebti Yasmine , Duez Hélène , Preau Sébastien , Remy-Jouet Isabelle , Zerimech Farid , Koussa Mohamed , Richard Vincent , Neviere Remi , Edme Jean-Louis , Lefebvre Philippe , Staels Bart
Published: June 2014

Background—

Obesity and diabetes mellitus are independently associated with the development of heart failure. In this study, we determined the respective effects of obesity, insulin resistance, and diabetes mellitus on the intrinsic contraction and mitochondrial function of the human myocardium before the onset of cardiomyopathy.

Methods and Results—

Right atrial myocardium was obtained from 141 consecutive patients presenting no sign of cardiomyopathy. We investigated ex vivo isometric contraction, mitochondrial respiration and calcium retention capacity, and respiratory chain complex activities and oxidative stress status. Diabetes mellitus was associated with a pronounced impairment of intrinsic contraction, mitochondrial dysfunction, and increased myocardial oxidative stress, regardless of weight status. In contrast, obesity was associated with less pronounced contractile dysfunction without any significant perturbation of mitochondrial function or oxidative stress status. Tested as continuous variables, glycated hemoglobin A
1C
, but neither body mass index nor the insulin resistance index (homeostasis model assessment–insulin resistance), was independently associated with cardiac mitochondrial function. Furthermore, diabetes mellitus was associated with cardiac mitochondrial network fragmentation and significantly decreased expression of the mitochondrial fusion related protein MFN1. Myocardial MFN1 content was inversely proportional to hemoglobin A
1C
.

Conclusion—

Worsening of intrinsic myocardial contraction in the transition from obesity to diabetes mellitus is likely related to worsening of cardiac mitochondrial function because impaired mitochondrial function and dynamics and contractile dysfunction are observed in diabetic patients but not in “metabolically healthy” obese patients at early stage in insulin resistance.
Early Remodeling of Perinuclear Ca
2+
Stores and Nucleoplasmic Ca
2+
Signaling During the Development of Hypertrophy and Heart Failure
Authors: Ljubojevic Senka , Radulovic Snjezana , Leitinger Gerd , Sedej Simon , Sacherer Michael , Holzer Michael , Winkler Claudia , Pritz Elisabeth , Mittler Tobias , Schmidt Albrecht , Sereinigg Michael , Wakula Paulina , Zissimopoulos Spyros , Bisping Egbert , Post Heiner , Marsche Gunther , Bossuyt Julie , Bers Donald M. , Kockskämper Jens , Pieske Burkert
Published: June 2014

Background—

A hallmark of heart failure is impaired cytoplasmic Ca
2+
handling of cardiomyocytes. It remains unknown whether specific alterations in nuclear Ca
2+
handling via altered excitation-transcription coupling contribute to the development and progression of heart failure.

Methods and Results—

Using tissue and isolated cardiomyocytes from nonfailing and failing human hearts, as well as mouse and rabbit models of hypertrophy and heart failure, we provide compelling evidence for structural and functional changes of the nuclear envelope and nuclear Ca
2+
handling in cardiomyocytes as remodeling progresses. Increased nuclear size and less frequent intrusions of the nuclear envelope into the nuclear lumen indicated altered nuclear structure that could have functional consequences. In the (peri)nuclear compartment, there was also reduced expression of Ca
2+
pumps and ryanodine receptors, increased expression of inositol-1,4,5-trisphosphate receptors, and differential orientation among these Ca
2+
transporters. These changes were associated with altered nucleoplasmic Ca
2+
handling in cardiomyocytes from hypertrophied and failing hearts, reflected as increased diastolic Ca
2+
levels with diminished and prolonged nuclear Ca
2+
transients and slowed intranuclear Ca
2+
diffusion. Altered nucleoplasmic Ca
2+
levels were translated to higher activation of nuclear Ca
2+
/calmodulin-dependent protein kinase II and nuclear export of histone deacetylases. Importantly, the nuclear Ca
2+
alterations occurred early during hypertrophy and preceded the cytoplasmic Ca
2+
changes that are typical of heart failure.

Conclusions—

During cardiac remodeling, early changes of cardiomyocyte nuclei cause altered nuclear Ca
2+
signaling implicated in hypertrophic gene program activation. Normalization of nuclear Ca
2+
regulation may therefore be a novel therapeutic approach to prevent adverse cardiac remodeling.
A Civilized Gaul: Caesar’s Portrait of Piso Aquitanus (De Bello Gallico 4.12.4-6)
Authors: Brown Robert D.
Published: June 2014

A literary analysis of the portrait of Piso Aquitanus (Gal. 4.12), a Gaul killed together with his brother in a cavalry engagement with the Usipetes and Tencteri in 55 bce. The portrait is first discussed against the literary tradition of heroic brothers in epic and in historiography. The function of the portrait is then examined in relation to the depiction of Gauls and Germans in Book Four. From this perspective, the portrayal of Piso’s courage and devotion can be seen to promote Caesar’s underlying aims of justifying, on the one hand, his harsh suppression of the barbarous Germans, and, on the other, his enlistment of “civilized” Gauls in the cause of Rome.1
Other Peoples’ Scriptures: Mythical Texts of Imagined Communities
Authors: Vishanoff David R.
Published: June 2014

The essays in this issue of Numen exemplify a shift in the comparative study of scriptures, highlighting their evanescence, their non-informative dimensions, and the ways in which they and the people who hold them sacred are reimagined across religious boundaries.
The Use of Mayan Scripture in the Americas’ First Christian Theology
Authors: Sparks Garry
Published: June 2014

This study examines the work of the Dominican Friar Domingo de Vico, specifically his theology of or for the “Indians,” the Theologia Indorum, written originally in K’iche’ Maya in 1553–1554. While scholarship in recent decades has focused on the first post-contact writings by autochthonous Americans, particularly the Popol Wuj, or Mayan “Council Book,” and the early impact of Hispano-Catholicism, little attention has been paid to the influence of indigenous religion on colonial Christianity. Therefore, this study critically examines the first use of Mayan myths in Christian literature for a more nuanced understanding of the mutual dynamics between missionaries and the missionized as well as the distinctions between missionary translation strategies in the early formative decades of first contact.
From Ministry Towards Spiritual Competence. Changing Perspectives in Spiritual Care in the Netherlands
Authors: Smeets Wim , Morice-Calkhoven Tessa
Published: June 2014

In the ‘crisis of ministry’ alternatives are considered to a worldview-based spiritual positioning of spiritual caregivers. One of the concepts in this discussion is that of spiritual competence. We addressed the question: what are the attitudes of spiritual caregivers (and their educators) towards ministry and spiritual competence? In terms of the volume the question is: to what extent does a specific denominational concept such as ministry still relate to religion as it is lived in contemporary society, more specifically in healthcare systems?

Ministry we defined as worldview representation in public and semi-public settings. There is a tension between representation and communication of religion, or, between authorisation and competence in the role of the minister. Quantitative empirical research clarified that spiritual caregivers regard the ministry positively. But they doubt their representation task, and have a multiple worldview orientation towards communication.

Spiritual competence can be situated on the level of the person, professional practice, professional identity and legitimation. This analysis can be related to, e.g. the competence profile of medical specialists and praxis-oriented models of spiritual care. Semi-structured interviews with educators of spiritual caregivers put forward a balance in personal and professional spirituality, the role of reflexivity and some basic —, core — and heuristic competencies.

Spiritual competence is at the core of the identity of spiritual care. Further research should reveal the extent to which this concept is an umbrella term, an alternative or even a substitute for ministry, conceptually and organisationally.
Semantics of Faith. Methodology and Results Regarding Young People’s Ability to Speak about their Beliefs
Authors: Faix T.
Published: June 2014

In recent years, the relationship between spirituality and youth has become a defining concept in religious discourse, and yet has also become so confused and vague that clarity is still required. Over the last two decades, any number of vast empirical surveys on the spirituality of adolescents has been undertaken in German-speaking Europe. These surveys were mostly quantitative, resulting in what Elmhorst calls: “God as semantic blank space”, demonstrating that young people are unable to talk about their spirituality. The most recent survey (2010 to 2012), commissioned by the Protestant Church of Westphalia, was conducted in the opposite fashion: Adolescents were first asked about their faith (using a qualitative survey, incorporating methods such as symbols, collages, interviews, etc.) and the young people’s concepts were then utilized for a subsequent quantitative survey. Following a short introduction outlining the problem, this article will then be subdivided into four more points: (1) The theoretical background of the research, (2) the methodology and the design of analysis and a summary of the central results, (3) a presentation of the consequences of the results for the current scholarly debate and (4) a reflection on the methodology and the conceptual approach.
Defining and Measuring the Contribution of Anglican Secondary Schools to Students’ Religious, Personal and Social Values
Authors: Francis Leslie J. , Lankshear David W. , Robbins Mandy , Village Andrew , ap Siôn Tania
Published: June 2014

The involvement of the Christian Churches within a state-maintained system of schools, as in the case of England and Wales, raises interesting and important questions regarding the concept of religion employed in this context and regarding defining and measuring the influence exerted by schools with a religious character on the students who attend such schools. Since the foundation of the National Society in 1811, Anglican schools have provided a significant contribution to the state-maintained sector of education in England and Wales and by the end of the twentieth century were providing about 25% of primary school places and nearly 5% of secondary school places. From the early 1970s, Francis and his colleagues have offered a series of studies profiling the attitudes and values of students attending Anglican schools as a way of defining and measuring the influence exerted by schools with a religious character. The present study extends previous research in three ways. It offers a comparative study by examining the responses of 1,097 year-nine and year-ten students from 4 Anglican schools with 20,348 students from 93 schools without a religious foundation. It examines a range of religious, social and personal values. It employs multilevel linear models to identify the contribution made by Anglican schools after taking into account differences within the students themselves. Of the 11 dependent variables tested, only one, self-esteem, showed any significant difference between Anglican schools and schools without a religious foundation. Students attending Anglican schools recorded a significantly lower level of self-esteem. On the other hand, there were no significant school effects identified in terms of rejection of drug use, endorsing illegal behaviours, racism, attitude toward school, conservative Christian belief or views on sexual morality (abortion, contraception, divorce, homosexuality, and sex outside marriage).
Succession Rights of Muslim Women in the Modern World: An Analytical Appraisal
Authors: Ahangar Mohd Altaf Hussain
Published: June 2014

Islam allows women the right to succession on the principle of a double share to a man and a single share to a woman. This principle is in reality an improvement on the operating law even in the 19th century wherein women were totally excluded from succession. Presently all Muslims are not governed by a uniform succession law. There are Muslim countries where the Shari‛ah is followed in theory while in reality a woman is excluded from inheritance. There are Muslim countries where Muslim women are allowed equal succession rights with men. Most non-Muslim countries have a uniform law of succession for all its citizens. This article addresses the question as to whether the modern law operating particularly in non-Muslim countries in comparison to Islamic law does better justice to nearer female heirs.
Consumer Protection under Saudi Arabia Law
Authors: Albaqme Aidh Sultan
Published: June 2014

The development of consumer protection laws in Saudi Arabia is of great significance because of the critical role that the Kingdom plays in the Gulf-Corporation Council Alliance and the fact that not many studies have been conducted on the issue of consumer protection in the Kingdom. Therefore, this article will analyse Islamic (Sharī‛ah) law as the foundation of consumer protection in Saudi Arabia and also focus on the development of consumer protection under Islamic law. The article will also compare Islamic law with other legal systems that are applied in Western nations with regard to consumer protection and advertising. Finally, the article will focus on the importance of Islamic law as a tool to ensure that the rights of consumers are respected and that adherence to religion is guaranteed.
Current Disclosure and Transparency Practices in Saudi Corporate Governance
Authors: al-Kahtani Faleh Salem
Published: June 2014

This article will investigate the current disclosure and transparency practices in the Saudi corporate governance system. The purpose of this article is to examine whether the disclosure and transparency requirements are satisfied, adequate and respected by the Saudi listed corporations. The disclosure and transparency prerequisites are also measured, and some of the main facets that have been sustained until now by the listed corporations are explored. In particular, a variety of the main disclosure and transparency ideologies that have been violated by some of the listed corporations are provided. In additional, the significance of disclosure and transparency in company annual reports is debated. The Capital Market Authority Board has consequently imposed fines on listed corporations responsible for violations. The Capital Market Authority Board has taken the defamation approach as punishment for such listed corporations.
The Enforcement of Foreign Judgments in the uae and difc Courts
Authors: Kantaria Saloni
Published: June 2014

A party seeking to enforce a foreign judgment in the uae can do so through the uae local courts or the difc courts. However, each court applies different considerations in determining whether to recognise and enforce foreign judgments from countries with which the uae has no treaty. Since there are not many countries with which the uae has a bilateral or multilateral treaty, careful consideration should be given when selecting the country whose courts will have jurisdiction over any dispute as this may have a bearing on the recognition and enforcement of any judgment in the uae. This article will assist in these considerations.
Application of the Build, Operate, Transfer (bot) Contract as a Means of Financing Development of Waqf Land: Malaysian Experience
Authors: Noor Azman bin Mohd , Yunus Saidatolakma bt Mohd
Published: June 2014

The build, operate and transfer (bot) contract has widely been applied in developing economies since the participation of private sectors has declined in the reconstruction and funding of public infrastructure. bot is a financing and operating approach, which has been practiced primarily in the area of infrastructure privatization in developing countries. Recently, application of the bot scheme has been carried out in many waqf institutions, especially Majlis Agama Islam Wilayah Persekutuan. The bot approach offers new perspectives in the field of waqf as it has the capability to enhance waqf property for the public’s benefit. Property enhancement is the major reason why waqf is enjoined by Islam. Waqf institutional involvement in developing its property and public infrastructures by way of bot contracts is proving to be a challenging exercise. This article examines the current practice of applying bot contracts in waqf institutions in general and in Majlis Agama Islam Wilayah Persekutuan in particular, with specific reference to the application of other types of contracts. In addition, the practice is discussed in terms of its compliance with the principles of Sharīʿah law. Moreover, this article aims to identify the issues, problems as well as challenges that might face waqf institutions during implementation of bot contracts.
“Natural Born Sportsmen”. Processes of Othering and Self-Charismatization of African Professional Footballers in Germany
Authors: Ungruhe Christian
Published: June 2014

At first sight, the perception of African footballers in Germany seems to be two-fold. Whereas amateur players may face racist assaults during matches time and again, open racism in professional German football has declined. Indeed, African players in the Bundesliga are frequently celebrated by fans and are icons of their clubs. However, this paper argues that the cheering of star players and forms of open racism during amateur matches are often only two extremes of a continuum since professional African footballers continue to be socially constructed as being different. Ascriptions of playing styles as elegant, powerful, and playful reflect alleged natural differences and manifest the otherness of African players. The article analyzes the historical construction of this manifestation and also discusses to what extent ascribed otherness is adopted by African footballers as a kind of “self-charismatization.”
Deep-sea Bodotriidae, Diastylidae and Pseudocumatidae (Cumacea, Crustacea) from the southeastern Atlantic
Authors: MÜHLENHARDT-SIEGEL UTE
Published: June 2014

Nine species of the family Diastylidae, two species of the family Bodotriidae and one species of the family Pseudocumatidae are present in the Diva II and Ifremer collections. Two new species were recognized and described herein. However, one of the new species has to remain in open nomenclature due to its young developmental stage. The new species are Makrokylindrus (Makrokylindrus) abyssalis, and M. (Adiastylis) sp.1. The distribution range is enlarged based on the new findings for seven species.
Nemozoma gymnosternalis sp. nov., a new anomalous species of Trogossitidae from Brazil
Authors: KOLIBÁČ JIŘÍ
Published: June 2014

Nemozoma gymnosternalis sp. nov., a new member of the tribe Trogossitini (Trogossitidae) from southeastern Brazil is described. The species is distinct in its morphological characters, namely the shortened elytra, abdominal tergites enwound with projected folds of ventrites, and modified structure of extremely shortened ovipositor. Léveillé’s assignment of Airora quadrimaculatus Léveillé, 1894 to the genus Corticotomus Sharp, 1891 is confirmed. The systematics of brachelytric species of Nemozoma Latreille, 1804 is briefly discussed. The presence of two projecting cranial horns, a structure that occurs in several unrelated beetle groups with a similar biology, is also mentioned.
Description of the larva of Philopotamus achemenus Schmid 1959 (Trichoptera: Philopotamidae) and a larval key for species of Philopotamus in Greece
Authors: KARAOUZAS IOANNIS
Published: June 2014

The larva of Philopotamus achemenus is described for the first time. The diagnostic features of the species are described and illustrated and some information regarding its ecology and world distribution is included. Furthermore, its morphological characters are compared and contrasted in an identification key for larvae of the Greek species of Philopotamus.