bluuebunny/crossref_metadata_2025 huggingface dataset:
The Value of ABCD2F Scoring System (ABCD2 Combined with Atrial Fibrillation) to Predict 90-Day Recurrent Brain Stroke
Authors: Almasi Mostafa , Hodjati Firoozabadi Nader , Ghasemi Faeze , Chardoli Mojtaba
Published: August 2016

Background. The ABCD2 score is now identified as a useful clinical prediction rule to determine the risk for stroke in the days following brain ischemic attacks.Aim. The present study aimed to introduce a new scoring system named “ABCD2F” and compare its value with the previous ABCD2 system to predict recurrent ischemic stroke within 90 days of the initial cerebrovascular accident (CVA).Methods. 138 consecutive patients with the final diagnosis of ischemic CVA or TIAs who referred to emergency ward of Rasoul-e-Akram general hospital in Tehran from September 2012 to December 2013 were eligible. By adding a new score in the presence of atrial fibrillation to ABCD2 system, the new scoring system as ABCD2F was introduced and the risk stratification was done again on this new system.Results. The area under the curve for ABCD2 was 0.434 and for ABCD2F it was 0.452 indicating low value of both systems for assessing recurrence of stroke within 90 days of primary event. Multivariable logistic regression analysis showed that none of the baseline factors could predict 90-day recurrent stroke.Conclusion. ABCD2 and/or atrial fibrillation are not good scoring candidates for assessing the risk of recurrent stroke within first 90 days.
Sectional Category of the Ganea Fibrations and Higher Relative Category
Authors: Doeraene Jean-Paul
Published: August 2016

We first compute James’ sectional category (secat) of the Ganea map gk of any map ιX in terms of the sectional category of ιX: we show that secat gk is the integer part of secat ιX/(k+1). Next we compute the relative category (relcat) of gk. In order to do this, we introduce the relative category of order k (relcatk) of a map and show that relcat gk is the integer part of relcatkιX/(k+1). Then we establish some inequalities linking secat and relcat of any order: we show that secat ιX⩽relcatkιX⩽secat ιX+k+1 and relcatkιX⩽relcatk+1ιX⩽relcatkιX+1. We give examples that show that these inequalities may be strict.
Efficacy of Traditional Chinese Medicine in Xerostomia and Quality of Life during Radiotherapy for Head and Neck Cancer: A Prospective Pilot Study
Authors: Hsu Pei-Yu , Yang Sien-Hung , Tsang Ngan-Ming , Fan Kang-Hsing , Hsieh Chia-Hsun , Lin Jr-Rung , Hong Ji-Hong , Lin Yung-Chang , Chen Hsing-Yu , Yang Cheng-Tao , Yang Ching-Wei , Chen Jiun-Liang
Published: August 2016

Xerostomia is one of the most common acute and late complications of radiotherapy for head and neck cancer, and it affects quality of life. We conducted a prospective study to evaluate the efficacy of traditional Chinese medicine (TCM) in toxicities and quality of life during radiotherapy. Head and neck cancer patients who were scheduled for radiotherapy were checked for inclusion/exclusion criteria before enrollment. Patients in the study group (inpatients) were hospitalized in a Chinese medicine ward and received concomitant TCM intervention during radiotherapy, while those in the control group (outpatients) received only conventional cancer treatments at the Western outpatient department. The primary end point was amelioration of postradiotherapy side effects. The secondary end points were quality of life during the cancer therapy and occurrence of adverse events following the TCM treatments. Thirty inpatients and 50 outpatients completed the study. Compared to the control group, those in the TCM group had decreased severity of xerostomia. There was no treatment‐related impairment of renal or hepatic function among TCM group. Although better outcomes of social contact, dyspnea, physical and emotional function, and financial problems were found in the TCM group, we need further confirmation about the impact of hospitalization itself on these results.
Treatment of Bone Losses in Revision Total Hip and Knee Arthroplasty Using Trabecular Metal: Current Literature
Authors: Cottino Umberto , Rosso Federica , Dettoni Federico , Bruzzone Matteo , Bonasia Davide Edoardo , Rossi Roberto
Published: August 2016

Revision Total Knee or Hip Arthroplasty is challenging procedures for surgeons usually characterized by bone loss. There are different options available to treat those bone losses. However, there is still a concern on the stability of bone-implant interface, which is mandatory to achieve good long-term results in prosthetic implants. Recently, porous tantalum has been introduced, with the aim of improving the bone-implant interface fixation and implant primary stability. Different solutions for the treatment of bone defects in both revision Total Knee and Hip Arthroplasty have been proposed. In revision Total Hip Arthroplasty (THA) tantalum shells can be used to treat Paprosky type III defects also, because of their mechanical properties. Similarly, trabecular metal has been proposed in revision Total Knee Arthroplasty (TKA), being considered a viable option to treat severe type 2 or 3 defects. The aim of this paper is to review the mechanical properties and characteristics of tantalum. Furthermore, we will discuss its role in treating bone defects in both revision THA and TKA, as well as the outcome reported in literature.
Computing the Pseudoinverse of Specific Toeplitz Matrices Using Rank-One Updates
Authors: Stanimirović Predrag S. , Katsikis Vasilios N. , Stojanović Igor
Published: August 2016

Application of the pure rank-one update algorithm as well as a combination of rank-one updates and the Sherman-Morrison formula in computing the Moore-Penrose inverse of the particular Toeplitz matrix is investigated in the present paper. Such Toeplitz matrices appear in the image restoration process and in many scientific areas that use the convolution. Four different approaches are developed, implemented, and tested on a number of numerical experiments.
Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins
Authors: Ruiz-Ramírez Angélica , López-Acosta Ocarol , Barrios-Maya Miguel Angel , El-Hafidi Mohammed
Published: August 2016

Metabolic diseases such as obesity, metabolic syndrome, and type II diabetes are often characterized by increased reactive oxygen species (ROS) generation in mitochondrial respiratory complexes, associated with fat accumulation in cardiomyocytes, skeletal muscle, and hepatocytes. Several rodents studies showed that lipid accumulation in cardiac myocytes produces lipotoxicity that causes apoptosis and leads to heart failure, a dynamic pathological process. Meanwhile, several tissues including cardiac tissue develop an adaptive mechanism against oxidative stress and lipotoxicity by overexpressing uncoupling proteins (UCPs), specific mitochondrial membrane proteins. In heart from rodent and human with obesity, UCP2 and UCP3 may protect cardiomyocytes from death and from a state progressing to heart failure by downregulating programmed cell death. UCP activation may affect cytochrome c and proapoptotic protein release from mitochondria by reducing ROS generation and apoptotic cell death. Therefore the aim of this review is to discuss recent findings regarding the role that UCPs play in cardiomyocyte survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote heart protection.
Variation of Main Phenophases in Phenological Calendar in East China and Their Response to Climate Change
Authors: Zheng Fengyi , Tao Zexing , Liu Yachen , Xu Yunjia , Dai Junhu , Ge Quansheng
Published: August 2016

Based on the phenological data from China Phenological Observation Network, we compiled the phenological calendars of 3 phenological observation stations (Shanghai, Nanjing, and Hefei) in East China for 1987–1996 and 2003–2012 according to the sequences of mean phenophases. We calculated the correlated coefficient and the root mean square error (RMSE) between phenophases and the beginning of meteorological seasons to determine the beginning date of phenological season. By comparing new phenological calendars with the old ones, we discussed the variation of phenophases and their responses to temperature. The conclusions are as follows. (1) The beginning dates of spring and summer advanced, while those of autumn and winter delayed. Thus, summers got longer and winters got shorter. (2) The beginning time of the four phenological seasons was advancing during 1987–1996, while it was delaying during 2003–2012. (3) Most spring and summer phenophases occur earlier and most autumn and winter phenophases occur later in 2003–2012 than in 1987–1996. (4) The beginning time of phenological seasons was significantly correlated with temperature. The phenological sensitivities to temperature ranged from −6.49 to −6.55 days/°C in spring, −3.65 to −5.02 days/°C in summer, 8.13 to 10.27 days/°C in autumn, and 4.76 to 10.00 days/°C in winter.
Simulation and Analysis of Uncooled Microbolometer for Serial Readout Architecture
Authors: Alhussein Musaed , Haider Syed Irtaza
Published: August 2016

A detailed thermal behavior and theoretical analysis of uncooled resistive microbolometer is presented along with the proposed thermal imager simulator. An accurate model of a thermal detector is required to design a readout circuit that can compensate for the noise due to process variability and self-heating. This paper presents a realistic simulation model of microbolometer that addresses the fixed pattern noise, Johnson noise, and self-heating. Different simulations were performed to study the impact of infrared power and bias power on the performance of microbolometers. The microbolometers were biased with different bias currents along with different thermal parameters of the reference microbolometer to analyze the impact of self-heating on the thermal image. The proposed thermal imager simulator is used as a tool to visually analyze the impact of noise on the quality of a thermal image. This simulator not only helps in compensating the noise prior to the implementation in Analog Design Environment, but also can be used as a platform to explore different readout architectures. In this work, serial readout architecture was simulated with a row of blind microbolometers that served as a reference. Moreover, the algorithm for the proposed thermal imager simulator is presented.
A Wideband End-Fire Conformal Vivaldi Antenna Array Mounted on a Dielectric Cone
Authors: Li Zengrui , Kang Xiaole , Su Jianxun , Guo Qingxin , Yang Yaoqing (Lamar) , Wang Junhong
Published: August 2016

The characteristics of a novel antipodal Vivaldi antenna array mounted on a dielectric cone are presented. By employing antipodal Vivaldi antenna element, the antenna array shows ultrawide bandwidth and end-fire radiation characteristics. Our simulations show that the cone curvature has an obvious influence on the performance of the conformal antenna, in terms of both the bandwidth and the radiation patterns. The thickness and permittivity of the dielectric cone have an effect on the bandwidth of the conformal antenna. Measurement results of both single antenna and conformal antenna array show a good agreement with the simulated results. The measured conformal antenna can achieve a −10 dBS11with bandwidth of 2.2–12 GHz and demonstrate a typical end-fire radiation beam. These findings provide useful guidelines and insights for the design of wideband end-fire antennas mounted on a dielectric cone.
Antitumor Properties of an IgG2-Enhanced Next-Generation MET Monoclonal Antibody That Degrades Wild-Type and Mutant MET Receptors
Authors: Yang Yan , Mandiyan Sreekala , Robinson Brett S. , McMahon Gerald
Published: August 2016

A sound rationale exists for antibody targeting of the MET receptor tyrosine kinase, but therapeutic agents that can broadly block HGF ligand binding and exon 14–mutated or amplified MET to induce receptor degradation have yet to be reported. Here we report the identification of several MET monoclonal antibodies (mAb) that block MET-dependent signaling and tumor growth. In particular, the MET mAb KTN0073 and KTN0074 bind the Sema/PSI domain, at overlapping but distinct epitopes, preventing HGF interaction with MET and triggering receptor ubiquitination and degradation. Notably, both mAbs also triggered degradation of oncogenic MET exon 14 mutants, which propagate more durable MET signals due to a defect in receptor degradation. Mechanistic investigations showed that both mAbs engaged a pathway distinct from HGF-induced receptor degradation and protease-mediated shedding, independently of signaling driven by the exon 14–encoded sequences in the intracellular juxtamembrane region of the MET receptor. Grafting the mAb variable regions onto the IgG2 constant region dramatically enhanced the tumor inhibitory activities of KTN0073 but not KTN0074, suggesting a specific influence of antibody isotype of the epitopes for these two MET mAbs. Overall, our results highlight KTN0073 as a novel IgG2-based MET mAb that acts through exon 14–independent mechanisms to degrade the MET receptor, potentially offering a therapeutic tool to treat a broader range of human tumors where MET is exon 14 mutated or amplified. Cancer Res; 76(19); 5788–97. ©2016 AACR.
Abscopal Effects of Radiotherapy Are Enhanced by Combined Immunostimulatory mAbs and Are Dependent on CD8 T Cells and Crosspriming
Authors: Rodriguez-Ruiz María E. , Rodriguez Inmaculada , Garasa Saray , Barbes Benigno , Solorzano Jose Luis , Perez-Gracia Jose Luis , Labiano Sara , Sanmamed Miguel F. , Azpilikueta Arantza , Bolaños Elixabet , Sanchez-Paulete Alfonso R. , Aznar M. Angela , Rouzaut Ana , Schalper Kurt A. , Jure-Kunkel Maria , Melero Ignacio
Published: August 2016

Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory mAbs to act both on irradiated tumor lesions and on distant, nonirradiated tumor sites. The combination of radiotherapy with immunostimulatory anti-PD1 and anti-CD137 mAbs was conducive to favorable effects on distant nonirradiated tumor lesions as observed in transplanted MC38 (colorectal cancer), B16OVA (melanoma), and 4T1 (breast cancer) models. The therapeutic activity was crucially performed by CD8 T cells, as found in selective depletion experiments. Moreover, the integrities of BATF-3–dependent dendritic cells specialized in crosspresentation/crosspriming of antigens to CD8+ T cells and of the type I IFN system were absolute requirements for the antitumor effects to occur. The irradiation regimen induced immune infiltrate changes in the irradiated and nonirradiated lesions featured by reductions in the total content of effector T cells, Tregs, and myeloid-derived suppressor cells, while effector T cells expressed more intracellular IFNγ in both the irradiated and contralateral tumors. Importantly, 48 hours after irradiation, CD8+ TILs showed brighter expression of CD137 and PD1, thereby displaying more target molecules for the corresponding mAbs. Likewise, PD1 and CD137 were induced on tumor-infiltrating lymphocytes from surgically excised human carcinomas that were irradiated ex vivo. These mechanisms involving crosspriming and CD8 T cells advocate clinical development of immunotherapy combinations with anti-PD1 plus anti-CD137 mAbs that can be synergistically accompanied by radiotherapy strategies, even if the disease is left outside the field of irradiation. Cancer Res; 76(20); 5994–6005. ©2016 AACR.
The Greater Genomic Landscape: The Heterogeneous Evolution of Cancer
Authors: Almassalha Luay M. , Bauer Greta M. , Chandler John E. , Gladstein Scott , Szleifer Igal , Roy Hemant K. , Backman Vadim
Published: August 2016

Results have historically shown a broad plasticity in the origin of tumors and their functions, with significant heterogeneity observed in both morphologies and functional capabilities. Largely unknown, however, are the mechanisms by which these variations occur and how these events influence tumor formation and behavior. Contemporary views on the origin of tumors focus mainly on the role of particular sets of driver transformations, mutational or epigenetic, with the occurrence of the observed heterogeneity as an accidental byproduct of oncogenesis. As such, we present a hypothesis that tumors form due to heterogeneous adaptive selection in response to environmental stress through intrinsic genomic sampling mechanisms. Specifically, we propose that eukaryotic cells intrinsically explore their available genomic information, the greater genomic landscape (GGL), in response to stress under normal conditions, long before the formation of a cancerous lesion. Finally, considering the influence of chromatin heterogeneity on the GGL, we propose a new class of compounds, chromatin-protective therapies (CPT), which target the physical variations in chromatin topology. In this approach, CPTs reduce the overall information space available to limit the formation of tumors or the development of drug-resistant phenotypes. Cancer Res; 76(19); 5605–9. ©2016 AACR.
Found in Translation: Maximizing the Clinical Relevance of Nonclinical Oncology Studies
Authors: Spilker Mary E. , Chen Xiaoying , Visswanathan Ravi , Vage Chandra , Yamazaki Shinji , Li Gang , Lucas Judy , Bradshaw-Pierce Erica L. , Vicini Paolo
Published: August 2016

Purpose: The translation of nonclinical oncology studies is a subject of continuous debate. We propose that translational oncology studies need to optimize both pharmacokinetic (drug exposure) and pharmacodynamic (xenograft model) aspects. While improvements in pharmacodynamic translatability can be obtained by choosing cell lines or patient-derived xenograft models closer to the clinical indication, significant ambiguity and variability exists when optimizing the pharmacokinetic translation of small molecule and biotherapeutic agents.

Experimental Design and Results: In this work, we propose a pharmacokinetic-based strategy to select nonclinical doses for approved drug molecules. We define a clinically relevant dose (CRD) as the dosing regimen in mice that most closely approximates the relevant pharmacokinetic metric in humans. Such metrics include area under the time–concentration curve and maximal or minimal concentrations within the dosing interval. The methodology is applied to six drugs, including targeted agents and chemotherapeutics, small and large molecules (erlotinib, dasatinib, vismodegib, trastuzumab, irinotecan, and capecitabine). The resulting efficacy response at the CRD is compared with clinical responses.

Conclusions: We conclude that nonclinical studies designed with the appropriate CRDs of approved drug molecules will maximize the translatability of efficacy results, which is critical when testing approved and investigational agents in combination. Clin Cancer Res; 23(4); 1080–90. ©2016 AACR.
Higher Order Chromatin Modulator Cohesin SA1 Is an Early Biomarker for Colon Carcinogenesis: Race-Specific Implications
Authors: Wali Ramesh K. , Momi Navneet , Dela Cruz Mart , Calderwood Audrey H. , Stypula-Cyrus Yolanda , Almassalha Luay , Chhaparia Anuj , Weber Christopher R. , Radosevich Andrew , Tiwari Ashish K. , Latif Bilal , Backman Vadim , Roy Hemant K.
Published: August 2016

Alterations in high order chromatin, with concomitant modulation in gene expression, are one of the earliest events in the development of colorectal cancer. Cohesins are a family of proteins that modulate high-order chromatin, although the role in colorectal cancer remains incompletely understood. We, therefore, assessed the role of cohesin SA1 in colorectal cancer biology and as a biomarker focusing in particular on the increased incidence/mortality of colorectal cancer among African-Americans. Immunohistochemistry on tissue arrays revealed dramatically decreased SA1 expression in both adenomas (62%; P = 0.001) and adenocarcinomas (75%; P = 0.0001). RT-PCR performed in endoscopically normal rectal biopsies (n = 78) revealed a profound decrease in SA1 expression in adenoma-harboring patients (field carcinogenesis) compared with those who were neoplasia-free (47%; P = 0.03). From a racial perspective, colorectal cancer tissues from Caucasians had 56% higher SA1 expression than in African-Americans. This was mirrored in field carcinogenesis where healthy Caucasians expressed more SA1 at baseline compared with matched African-American subjects (73%; P = 0.003). However, as a biomarker for colorectal cancer risk, the diagnostic performance as assessed by area under ROC curve was greater in African-Americans (AUROC = 0.724) than in Caucasians (AUROC = 0.585). From a biologic perspective, SA1 modulation of high-order chromatin was demonstrated with both biophotonic (nanocytology) and chromatin accessibility [micrococcal nuclease (MNase)] assays in SA1-knockdown HT29 colorectal cancer cells. The functional consequences were underscored by increased proliferation (WST-1; P = 0.0002, colony formation; P = 0.001) in the SA1-knockdown HT29 cells. These results provide the first evidence indicating a tumor suppressor role of SA1 in early colon carcinogenesis and as a risk stratification biomarker giving potential insights into biologic basis of racial disparities in colorectal cancer. Cancer Prev Res; 9(11); 844–54. ©2016 AACR.
Reduction of MDSCs with All-trans Retinoic Acid Improves CAR Therapy Efficacy for Sarcomas
Authors: Long Adrienne H. , Highfill Steven L. , Cui Yongzhi , Smith Jillian P. , Walker Alec J. , Ramakrishna Sneha , El-Etriby Rana , Galli Susana , Tsokos Maria G. , Orentas Rimas J. , Mackall Crystal L.
Published: August 2016

Genetically engineered T cells expressing CD19-specific chimeric antigen receptors (CAR) have shown impressive activity against B-cell malignancies, and preliminary results suggest that T cells expressing a first-generation disialoganglioside (GD2)-specific CAR can also provide clinical benefit in patients with neuroblastoma. We sought to assess the potential of GD2-CAR therapies to treat pediatric sarcomas. We observed that 18 of 18 (100%) of osteosarcomas, 2 of 15 (13%) of rhabdomyosarcomas, and 7 of 35 (20%) of Ewing sarcomas expressed GD2. T cells engineered to express a third-generation GD2-CAR incorporating the 14g2a-scFv with the CD28, OX40, and CD3ζ signaling domains (14g2a.CD28.OX40.ζ) mediated efficient and comparable lysis of both GD2+ sarcoma and neuroblastoma cell lines in vitro. However, in xenograft models, GD2-CAR T cells had no antitumor effect against GD2+ sarcoma, despite effectively controlling GD2+ neuroblastoma. We observed that pediatric sarcoma xenografts, but not neuroblastoma xenografts, induced large populations of monocytic and granulocytic murine myeloid-derived suppressor cells (MDSC) that inhibited human CAR T-cell responses in vitro. Treatment of sarcoma-bearing mice with all-trans retinoic acid (ATRA) largely eradicated monocytic MDSCs and diminished the suppressive capacity of granulocytic MDSCs. Combined therapy using GD2-CAR T cells plus ATRA significantly improved antitumor efficacy against sarcoma xenografts. We conclude that retinoids provide a clinically accessible class of agents capable of diminishing the suppressive effects of MDSCs, and that co-administration of retinoids may enhance the efficacy of CAR therapies targeting solid tumors. Cancer Immunol Res; 4(10); 869–80. ©2016 AACR.
Empirically Derived Dietary Patterns and Hypertension Likelihood: A Meta-Analysis
Authors: Wang Cui-Jiang , Shen You-Xia , Liu Yun
Published: August 2016

Background/Aims: Dietary patterns, which represent whole-diet and a complex integration of food and nutrient, have been reported to play an important role in the development of hypertension. However, the results have yielded conflicting findings. Herein, we performed this meta-analysis to evaluate the associations between different dietary patterns and the likelihood of hypertension. Methods: MEDLINE and EBSCO were searched to identify relevant articles published until the end of March 2016. A random-effects model was used to account for possible heterogeneity between studies.A total of twenty-seven studies met the inclusion criteria and were included in this meta-analysis. Results: There was evidence of a decreased likelihood for hypertension in the highest compared with the lowest categories of healthy pattern (odds ratio (OR)=0.81; 95% confidence interval(CI): 0.67-0.97; P=0.02). An increased likelihood of hypertension was shown for the highest compared with the lowest category of heavy drinking pattern (OR=1.62; 95% CI: 1.16-2.26; P=0.004), whereas no statistically significant association with western-style and light-moderate drinking pattern were observed(OR=1.04, 95% CI: 0.83-1.31; OR=1.20, 95% CI:0.94- 1.53; P>0.05). Conclusions: Our results of this systematic review and meta-analysis suggest that dietary pattern may be associated with the likelihood of hypertension.
Serum Potassium Profile and Associated Factors in Incident Peritoneal Dialysis Patients
Authors: Liu Ying , Cheng Ben-Chung , Lee Wen-Chin , Li Lung-Chih , Lee Chih-Hsiung , Chang Wen Xiu , Chen Jin-Bor
Published: August 2016

Background/Aims: Abnormal potassium profiles are common in peritoneal dialysis (PD) patients. We studied the factors associated with serum potassium profiles in incident PD patients. Methods: Patients were enrolled from two hospital-facilitated PD centers from May 2013 to May 2016 and January 2009 to December 2015. A total of 319 incident PD patients were examined for factors associated with serum potassium profile. Average serum potassium levels were obtained for analysis during the first 3 months after PD initiation. Clinically factors and parameters associated with PD were assessed by logistic regression. Results: There were 168 men and 151 women (mean age, 50.8 years). Blood urea nitrogen (BUN), creatinine (Cr), and intact parathyroid hormone levels were significantly increased in patients in the higher serum potassium group. There were no significant risk factors for hypokalemia, including sex, age, diabetes, blood examination parameters, medication use, or PD-related parameters by multivariate logistic regression analysis. BUN (adjusted odds ratio [OR] 1.02, 95% CI 1.01-1.03, p = 0.001) and Cr (adjusted OR 1.08, 95% CI 1.01-1.16, p = 0.029) levels were significant risk factors for hyperkalemia by multivariate logistic regression analysis. Conclusion: Hyperkalemia and blood BUN and Cr levels were significantly associated in incident PD patients.
Direct Renin Inhibitor is Better than Angiotensin II Receptor Blocker for Intrarenal Arterioles
Authors: Nagai Yohko , Nakanishi Kazushige , Yamanaka Nobuaki
Published: August 2016

Background/Aims: We have reported that the long-term administration of angiotensin II receptor blockers (ARBs) induced unusual proliferative changes of renal afferent arteriolar smooth muscle cells (SMCs) in rats, associated with the overproduction of renin. In this study, we examined that a direct renin inhibitor (DRI: Aliskilen; Novartis Pharma Co, USA) might induce different changes on afferent arteriolar walls compared to ARBs. Method: Twenty one 6-weeks-old male spontaneous hypertensive rats (SHRs) were divided into the following three groups: high-dose DRI group (n=7), low-dose DRI group (n=5) and control group (n=9). The rats were fed a standard diet (0.4%NaCl) containing high-dose (150mg/kg/day), low-dose (30mg/kg/day) DRI and without DRI for 12 weeks. The kidneys were examined by histological and immunohistochemical studies. Systolic blood pressure, 24-h urine samples and blood samples were also examined. Results: The afferent arteriolar SMC walls in the two DRI groups showed no proliferative changes. The positive renin expression area was the largest in the high-dose DRI group among the three groups (14.3±4.0µm2, 6.7±2.0µm2, 2.6±0.9µm2/glomerlus, p=0.020, p=0.008, p=0.017, respectively). Conclusion: The long-term DRI administration increases tissue and circulatory renin; however, afferent arteriolar proliferative changes as shown in ARBs were not induced.
Hepatitis B e Antigen Expression by Hepatitis B Virus Subgenotype A1 Relative to Subgenotypes A2 and D3 in Cultured Hepatocellular Carcinoma (Huh7) Cells
Authors: Bhoola Nimisha Harshadrai , Kramvis Anna
Published: August 2016

Background: Hepatitis B virus (HBV) is hyperendemic in southern Africa, with subgenotype A1 prevailing. The precore/core (preC/C) region of A1, encoding for hepatitis B e antigen (HBeAg), has unique sequence characteristics, differentiating it from subgenotypes A2 and D3. Our aim was to follow the expression of HBeAg in vitro by the three subgenotypes. Methods: Huh7 cells were transfected with plasmids belonging to subgenotypes A1, A2, and D3. Using indirect immunofluorescence, the expression of HBeAg was followed, as was the activation of the unfolded protein response (UPR) and subsequent activation of apoptosis. Results and Conclusions: Following transfection with D3, HBeAg passed through the secretory pathway earlier than cells transfected with genotype A. Cells transfected with A1 showed a lower expression of the preC/C precursor in the secretory pathway and a higher co-localization in the nucleus. Cells transfected with A1 showed greater endoplasmic reticulum (ER) stress and an earlier, prolonged activation of the UPR seen by the higher activity of three ER-localized transmembrane transducers (double-stranded RNA-dependent protein kinase-like ER kinase, activating transcription factor 6, and inositol-requiring enzyme 1), on day 3 compared to day 5. Moreover, our study also found that cells transfected with A1 had increased apoptosis.
Caveolin-1 Plays an Important Role in the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Cardiomyocytes
Authors: Chen Ying , Wang Chunxia , Huang Qiang , Wu Dan , Cao Jianing , Xu Xin , Yang Chengjian , Li Xun
Published: August 2016

Objectives: Accumulating evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) may transdifferentiate into cardiomyocytes, making BMSCs a promising source of cardiomyocytes for transplantation. However, little is known about the molecular mechanisms underlying myogenic conversion of BMSCs. Methods: This study was designed to investigate the functional role of caveolin-1 in the cardiomyocyte differentiation of BMSCs and to explore the potential underlying molecular mechanisms. Results: BMSC differentiation was induced by treatment with 10 μM 5-azacytidine, and immunofluorescence assay showed that the expression of cardiomyocyte marker cardiac troponin T (cTnT) was significantly increased compared with a control group. Meanwhile, an increased caveolin-1 expression was found during the 5-azacytidine-induced BMSC differentiation. Additionally, the role of caveolin-1 in the differentiation process was then studied by using caveolin-1 siRNAs. We found that silencing caveolin-1 during induction remarkably enhanced the expression of cardiomyocyte marker genes, including cTnT, Nkx2.5 (cardiac-specific transcription factor), α-cardiac actin and α-myosin heavy chain (α-MHC). Moreover, we observed that downregulation of caveolin-1 was accompanied by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. Conclusions: Taken together, these findings demonstrate that caveolin-1 plays an important role in the differentiation of BMSCs into cardiomyocytes in conjunction with the STAT3 pathway.
Transport and Catabolism of Pentitols by Listeria monocytogenes
Authors: Kentache Takfarinas , Milohanic Eliane , Cao Thanh Nguyen , Mokhtari Abdelhamid , Aké Francine Moussan , Ma Pham Que Mai , Joyet Philippe , Deutscher Josef
Published: August 2016

Transposon insertion into Listeria monocytogenes lmo2665, which encodes an EIIC of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS), was found to prevent D-arabitol utilization. We confirm this result with a deletion mutant and show that Lmo2665 is also required for D-xylitol utilization. We therefore called this protein EIICAxl. Both pentitols are probably catabolized via the pentose phosphate pathway (PPP) because lmo2665 belongs to an operon, which encodes the three PTSAxl components, two sugar-P dehydrogenases, and most PPP enzymes. The two dehydrogenases oxidize the pentitol-phosphates produced during PTS-catalyzed transport to the PPP intermediate xylulose-5-P. L. monocytogenes contains another PTS, which exhibits significant sequence identity to PTSAxl. Its genes are also part of an operon encoding PPP enzymes. Deletion of the EIIC-encoding gene (lmo0508) affected neither D-arabitol nor D-xylitol utilization, although D-arabitol induces the expression of this operon. Both operons are controlled by MtlR/LicR-type transcription activators (Lmo2668 and Lmo0501, respectively). Phosphorylation of Lmo0501 by the soluble PTSAxl components probably explains why D-arabitol also induces the second pentitol operon. Listerial virulence genes are submitted to strong repression by PTS sugars, such as glucose. However, D-arabitol inhibited virulence gene expression only at high concentrations, probably owing to its less efficient utilization compared to glucose.
Impact of Pulmonary Artery Catheter Use on Short- and Long-Term Mortality in Patients with Cardiogenic Shock
Authors: Rossello Xavier , Vila Montserrat , Rivas-Lasarte Mercedes , Ferrero-Gregori Andreu , Sans-Roselló Jordi , Duran-Cambra Albert , Sionis Alessandro
Published: August 2016

Objectives: The impact of pulmonary artery catheterization (PAC) on survival in patients with cardiogenic shock (CS) is not well established. This study aimed to assess whether Swan-Ganz catheter monitoring is related to short- and long-term mortality in patients with CS. Methods: One hundred and twenty-nine consecutive patients with a first admission for CS were prospectively enrolled in a single-center registry between December 2005 and May 2009, and were subsequently followed up over 5.3 years. Results: PAC was used in 64% of all patients with a mean age of 68 years (65% men). After adjustment for age, gender and the presence of CS upon admission, PAC was associated with lower short-term mortality [hazard ratio (HR) = 0.55, 95% confidence interval (CI) 0.35-0.86, p = 0.008] as well as lower mortality rates in the long-term follow-up (HR = 0.63, 95% CI 0.41-0.97, p = 0.035). In a subgroup analysis, the use of PAC was associated with reduced mortality in patients without acute coronary syndrome (ACS), i.e. 49% in the Swan-Ganz group vs. 82% (p = 0.010), but there was no difference within the ACS group. Conclusions: The use of PAC in patients with CS was associated with lower short- and long-term mortality rates after adjustment for age, gender and the presence of shock upon admission. This benefit was only significant in those patients without ACS.
Telehealthcare for Chronic Obstructive Pulmonary Disease in Switzerland Is Feasible and Appreciated by Patients
Authors: Rassouli Frank , Pfister Maurus , Widmer Sandra , Baty Florent , Burger Barbara , Brutsche Martin H.
Published: August 2016

Background: Earlier detection of acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) could reduce emergency admissions and hospitalisations. Studies investigating COPD management programs supported by telehealthcare (THC) have shown conflicting results. Objectives: To test the feasibility, safety and acceptance of THC for COPD. Methods: Patients daily filled out an online questionnaire focused on the detection of AECOPD. The THC platform is integrated in a comprehensive electronic patient data repository, which has to be available for all patients in Switzerland by law by 2017. The study team called the patient by phone in case of suspected AECOPD. Results: Of 339 screened patients, 14% were included. Main reasons for exclusion were missing technical equipment and unwillingness to participate in a study (50%). Data completeness was 88%; 94% completed the study. The current THC approach triggered 230 telephone calls, which led to the verification of 60 AECOPD in 22 patients. Three AECOPD were not detected. Sensitivity, specificity, positive and negative predictive value of the questionnaire-based THC approach in detecting AECOPD was 95, 98, 26 and 99.9%, respectively. Overall patient satisfaction in respect to their health condition improved significantly (VAS 8-8.7; p = 0.002). Conclusions: Adding THC to state-of-the-art COPD management is feasible in a selected subgroup of patients. We estimate that up to 50% of COPD patients could be eligible for a THC strategy. Patient compliance, acceptance and satisfaction were very high. With the proposed approach, we missed only very few AECOPD events. However, a telephone-based verification of THC alerts was required. Overall, in this proof-of-concept study, we experienced a positive effort-to-benefit ratio.
Distal 7q11.23 Duplication, an Emerging Microduplication Syndrome: A Case Report and Further Characterisation
Authors: Faundes Víctor , Santa María Lorena , Morales Paulina , Curotto Bianca , Parraguez María M.
Published: August 2016

Chromosome 7q11.23 duplication syndrome is a well-recognised syndrome which involves the duplication of the same genes located in the Williams-Beuren critical region. However, in 2010, 4 patients were reported with a microduplication only in the HIP1 and YWHAG genes. We refer to this as a distal 7q11.23 duplication (dup7q11.23D). Here, we report the fifth de novo patient with dup7q11.23D, whose symptoms may be explained by YWHAG overexpression as was demonstrated recently in mice and obese patients. Finally, further studies will be necessary to delineate this emerging microduplication syndrome.
COPD und Klangtherapie: Pilotstudie zur Wirksamkeit einer Behandlung mit Körpertambura bei COPD-Patienten
Authors: Hartwig Bernhard , Schmidt Stefan , Hartwig Isabella
Published: August 2016

Hintergrund: Erkrankungen der Atemorgane treten mit steigendem Alter öfter auf, nehmen weltweit zu und sind häufige Ursachen für Morbidität und Mortalität. In dieser Pilotstudie wurde der Frage nachgegangen, ob eine einmalige 10-minütige Behandlung mit einer Körpertambura eine signifikante und effektive Verbesserung der Lungenfunktion von Patienten mit chronisch-obstruktiver Lungenerkrankung (COPD; GOLD-Stadium A oder B) erbringen kann. Patienten und Methoden: 54 Probanden konnten je zur Hälfte in eine Behandlungsgruppe (Körpertambura) und eine aktive Kontrollgruppe (Atemtherapie) randomisiert werden. Eine Bestimmung der Lungenfunktionsmessparameter «Einsekundenkapazität» (FEV1) und «inspiratorische Vitalkapazität» (IVC) zu den Zeitpunkten T1 (Baseline), T2 (direkt nach Behandlung) und als Follow-up etwa 3 Wochen nach T1 (T3). Ergebnisse: Die Behandlungsgruppe zeigte sich der Kontrollgruppe in beiden Werten signifikant überlegen. Die Zeit-×-Gruppe-Interaktion (Varianzanalyse) ergab p = 0,001 (FEV1) bzw. p = 0,04 (IVC). Die Behandlungsgruppe zeigte bei beiden Werten eine Verbesserung von klinischer Relevanz. Schlussfolgerung: Diese Ergebnisse zeigen, dass die Klangbehandlung mittels einer Körpertambura - neben den schulmedizinischen, leitliniengerechten Therapien - eine zusätzliche, nebenwirkungsarme, aber durchaus klinisch wirksame Option für die Behandlung von COPD-Patienten darstellen kann, um deren Lebensqualität zu stabilisieren und zu verbessern.
Актуальність застосування фітопрепаратів як лікувально-профілактичних засобів у пародонтологічних хворих
Authors: Dvulit I. P.
Published: August 2016

The article presents the use of data analysis of herbal remedies in dentistry, namely in periodontal patients. Particular attention is paid to the relevance of the use of medicinal plants and preparations based thereon, in the treatment and prevention of inflammatory and degenerative periodontal disease. Powered by some of the most effective medicinal plants and herbal remedies, techniques and efect their use in patients with periodontal tissue pathology that proves their healing properties and the impact hight efective as therapeutic and prophylactic agents.
Oсобливості клінічного перебігу захворювань пародонта у хворих із різною супутньою патологією
Authors: Boytsanyuk S. I. , Zaliznyak M. S. , Chorniy N. V. , Manashchuk N. V. , Chorniy A. V.
Published: August 2016

This article provides a comparative analysis of the prevalence, diagnostical patterns, clinical course of periodontal diseases on the background of burn disease, osteoarthritis, ulcerative colitis and pancreatitis.
Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening
Authors: van Eupen Marcelle G.A. , Schram Miranda T. , van Sloten Thomas T. , Scheijen Jean , Sep Simone J.S. , van der Kallen Carla J. , Dagnelie Pieter C. , Koster Annemarie , Schaper Nicolaas , Henry Ronald M.A. , Kroon Abraham A. , Smit Andries J. , Stehouwer Coen D.A. , Schalkwijk Casper G.
Published: August 2016

Arterial stiffening, as characterized by an increase in carotid–femoral pulse-wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid–femoral pulse-wave velocity (sβ 0.10; 95% confidence interval, 0.03–0.17 and 0.10; 0.04–0.16, respectively) and central pulse pressure (sβ 0.08; 95% confidence interval 0.01–0.15 and 0.07; 0.01–0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid–femoral pulse-wave velocity were more pronounced in individuals with type 2 diabetes mellitus (
P
-interaction<0.10). These results support the hypothesis that accumulation of advanced glycation end products is involved in arterial stiffening and may explain part of the increased risk of cardiovascular disease in individuals with type 2 diabetes mellitus.
A Disintegrin and Metalloprotease-17 Regulates Pressure Overload–Induced Myocardial Hypertrophy and Dysfunction Through Proteolytic Processing of Integrin β1
Authors: Fan Dong , Takawale Abhijit , Shen Mengcheng , Samokhvalov Victor , Basu Ratnadeep , Patel Vaibhav , Wang Xiuhua , Fernandez-Patron Carlos , Seubert John M. , Oudit Gavin Y. , Kassiri Zamaneh
Published: August 2016

A disintegrin and metalloprotease-17 (ADAM17) belongs to a family of transmembrane enzymes, and it can mediate ectodomain shedding of several membrane-bound molecules. ADAM17 levels are elevated in patients with hypertrophic and dilated cardiomyopathy; however, its direct role in hypertrophic cardiomyopathy is unknown. Cardiomyocyte-specific ADAM17 knockdown mice (ADAM17
flox/flox
/αMHC-Cre; ADAM17
f/f
/Cre) and littermates with intact ADAM17 levels (ADAM17
f/f
) were subjected to cardiac pressure–overload by transverse aortic constriction. Cardiac function/architecture was assessed by echocardiography at 2 and 5 weeks post transverse aortic constriction. ADAM17 knockdown enhanced myocardial hypertrophy, fibrosis, more severe left ventricular dilation, and systolic dysfunction at 5 weeks post transverse aortic constriction. Pressure overload–induced upregulation of integrin β1 was much greater with ADAM17 knockdown, concomitant with the greater activation of the focal adhesion kinase pathway, suggesting that integrin β1 could be a substrate for ADAM17. ADAM17 knockdown did not alter other cardiomyocyte integrins, integrin α5 or α7, and HB-EGF (heparin-bound epidermal growth factor), another potential substrate for ADAM17, remained unaltered after pressure overload. ADAM17-mediated cleavage of integrin β1 was confirmed by an in vitro assay. Intriguingly, ADAM17 knockdown did not affect the myocardial hypertrophy induced by a subpressor dose of angiotensin II, which occurs independent from the integrin β1–mediated pathway. ADAM17-knockdown enhanced the hypertrophic response to cyclic mechanical stretching in neonatal rat cardiomyocytes. This study reports a novel cardioprotective function for ADAM17 in pressure overload cardiomyopathy, where loss of ADAM17 promotes hypertrophy by reducing the cleavage of cardiac integrin β1, a novel substrate for ADAM17. This function of ADAM17 is selective for pressure overload–induced myocardial hypertrophy and dysfunction, and not agonist-induced hypertrophy.
Poor Reliability of Wrist Blood Pressure Self-Measurement at Home
Authors: Casiglia Edoardo , Tikhonoff Valérie , Albertini Federica , Palatini Paolo
Published: August 2016

The reliability of blood pressure measurement with wrist devices, which has not previously been assessed under real-life circumstances in general population, is dependent on correct positioning of the wrist device at heart level. We determined whether an error was present when blood pressure was self-measured at the wrist in 721 unselected subjects from the general population. After training, blood pressure was measured in the office and self-measured at home with an upper-arm device (the UA-767 Plus) and a wrist device (the UB-542, not provided with a position sensor). The upper-arm−wrist blood pressure difference detected in the office was used as the reference measurement. The discrepancy between office and home differences was the home measurement error. In the office, systolic blood pressure was 2.5% lower at wrist than at arm (
P
=0.002), whereas at home, systolic and diastolic blood pressures were higher at wrist than at arm (+5.6% and +5.4%, respectively;
P
<0.0001 for both); 621 subjects had home measurement error of at least ±5 mm Hg and 455 of at least ±10 mm Hg (bad measurers). In multivariable linear regression, a lower cognitive pattern independently determined both the systolic and the diastolic home measurement error and a longer forearm the systolic error only. This was confirmed by logistic regression having bad measurers as dependent variable. The use of wrist devices for home self-measurement, therefore, leads to frequent detection of falsely elevated blood pressure values likely because of a poor memory and rendition of the instructions, leading to the wrong position of the wrist.
Genetic evidence for multiple paternity in the critically endangered Cuban crocodile (Crocodylus rhombifer)
Authors: Milián-García Yoamel , Jensen Evelyn L. , Mena Sheila Ribalta , Pérez Fleitas Etiam , Sosa Rodríguez Gustavo , Guerra Manchena Leiter , Espinosa López Georgina , Russello Michael A.
Published: August 2016

Conservation strategies can be most effective when factors influencing the persistence of populations are well-understood, including aspects of reproductive biology such as mating system. Crocodylians have been traditionally associated with a polygynous mating system, with genetic studies revealing multiple paternity of clutches in several species. The endemic Cuban crocodile,Crocodylus rhombifer, is currently listed as Critically Endangered, and is one of the least understood crocodylian species in terms of its mating behavior. Here, we tested a hypothesis of multiple paternity in the Cuban crocodile by collecting genotypic data at nine microsatellite loci for 102 hatchlings from five nests sampled at the Zapata Swamp captive breeding facility and analyzing them in relation to data previously collected for 137 putative parents. All five nests showed evidence of multiple paternity based on the numbers of alleles per locus, with sibship analyses reconstructing all nests as having four to six full-sib family groups. Accordingly, mean pairwise relatedness values per nest ranged from 0.21 to 0.39, largely intermediate between theoretical expected values for half-siblings (0.25) and full-siblings (0.50). It is not possible to differentiate whether the multiple paternity of a nest was due to multiple matings during the same breeding season, or a result of sperm storage. Our results reveal that theC. rhombifermating system is likely best characterized as promiscuous and suggest that the standard practice of enforcing a 1:2 sex ratio at the captive breeding facility should be altered in order to better maintain a demographically and genetically healthy ex situ population.