bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview of Experimental and Clinical Findings regarding the Neuroprotective Effects of Cerebral Ischemic Postconditioning
Authors: Ma Di , Feng Liangshu , Deng Fang , Feng Jia-Chun
Published: April 2017

Research on attenuating the structural and functional deficits observed following ischemia-reperfusion has become increasingly focused on the therapeutic potential of ischemic postconditioning. In recent years, various methods and animal models of ischemic postconditioning have been utilized. The results of these numerous studies have indicated that the mechanisms underlying the neuroprotective effects of ischemic postconditioning may involve reductions in the generation of free radicals and inhibition of calcium overload, as well as the release of endogenous active substances, alterations in membrane channel function, and activation of protein kinases. Here we review the novel discovery, mechanism, key factors, and clinical application of ischemic postconditioning and discuss its implications for future research and problem of clinical practice.
Modeling Anomalous Diffusion by a Subordinated Integrated Brownian Motion
Authors: Shi Long , Xiao Aiguo
Published: April 2017

We consider a particular type of continuous time random walk where the jump lengths between subsequent waiting times are correlated. In a continuum limit, the process can be defined by an integrated Brownian motion subordinated by an inverse α-stable subordinator. We compute the mean square displacement of the proposed process and show that the process exhibits subdiffusion when 0<α<1/3, normal diffusion when α=1/3, and superdiffusion when 1/3<α<1. The time-averaged mean square displacement is also employed to show weak ergodicity breaking occurring in the proposed process. An extension to the fractional case is also considered.
Curvature-Induced Spatial Ordering of Composition in Lipid Membranes
Authors: Katz Shimrit , Givli Sefi
Published: April 2017

Phase segregation of membranal components, such as proteins, lipids, and cholesterols, leads to the formation of aggregates or domains that are rich in specific constituents. This process is important in the interaction of the cell with its surroundings and in determining the cell’s behavior and fate. Motivated by published experiments on curvature-modulated phase separation in lipid membranes, we formulate a mathematical model aiming at studying the spatial ordering of composition in a two-component biomembrane that is subjected to a prescribed (imposed) geometry. Based on this model, we identified key nondimensional quantities that govern the biomembrane response and performed numerical simulations to quantitatively explore their influence. We reproduce published experimental observations and extend them to surfaces with geometric features (imposed geometry) and lipid phases beyond those used in the experiments. In addition, we demonstrate the possibility for curvature-modulated phase separation above the critical temperature and propose a systematic procedure to determine which mechanism, the difference in bending stiffness or difference in spontaneous curvatures of the two phases, dominates the coupling between shape and composition.
Recovery of Abnormal ABR in Neonates and Infants at Risk of Hearing Loss
Authors: Psarommatis Ioannis , Voudouris Charalampos , Kapetanakis Ioannis , Athanasiadi Faselida , Douros Konstantinos
Published: April 2017

The purpose of this retrospective study is to present the clinical experience of a single institution on the recovery of ABR thresholds in a large population of neonates and infants at risk of hearing loss. Potential prognostic factors associated with this phenomenon were also investigated. Out of 2248 high risk infants, 384 had abnormal ABR at initial hearing evaluation and 168 of them had absent ABR or a threshold ≥80 dBnHL. From this subgroup, a significant percentage showed complete or partial recovery on reexamination (32.7% and 9.3%, resp.), performed 4–6 months later. The presence of normal otoacoustic emissions was associated with the ABR restoration on reexamination. Moreover, the very young age at the initial hearing screening seems to be related to higher probabilities of false positive ABR. The potential recovery of hearing in HR infants raises concerns about the very early cochlear implantation in HR infants less than one year. Such a treatment modality should be decided cautiously and only after obtaining valid and stable objective and subjective hearing thresholds. This holds especially true for infants showing an auditory neuropathy profile, as they presented a much greater probability of ABR recovery.
On Improving the Performance of Dynamic DCVSL Circuits
Authors: Bajpai Pratibha , Pandey Neeta , Gupta Kirti , Bagga Shrey , Panda Jeebananda
Published: April 2017

This contribution aims at improving the performance of Dynamic Differential Cascode Voltage Switch Logic (Dy-DCVSL) and Enhanced Dynamic Differential Cascode Voltage Switch Logic (EDCVSL) and suggests three architectures for the same. The first architecture uses transmission gates (TG) to reduce the logic tree depth and width, which results in speed improvement. As leakage is a dominant issue in lower technology nodes, the second architecture is proposed by adapting the leakage control technique (LECTOR) in Dy-DCVSL and EDCVSL. The third proposed architecture combines features of both the first and the second architectures. The operation of the proposed architectures has been verified through extensive simulations with different CMOS submicron technology nodes (90 nm, 65 nm, and 45 nm). The delay of the gates based on the first architecture remains almost the same for different functionalities. It is also observed that Dy-DCVSL gates are 1.6 to 1.4 times faster than their conventional counterpart. The gates based on the second architecture show a maximum of 74.3% leakage power reduction. Also, it is observed that the percentage of reduction in leakage power increases with technology scaling. Lastly, the gates based on the third architecture achieve similar leakage power reduction values to the second one but are not able to exhibit the same speed advantage as achieved with the first architecture.
3D Evaluation of Maxillary Sinus Using Computed Tomography: A Sexual Dimorphic Study
Authors: Bangi Balaji Babu , Ginjupally Uday , Nadendla Lakshmi Kavitha , Vadla Bhavana
Published: April 2017

Purpose. Gender determination is considered to be an important step in the reconstruction of the biological profile in forensic medicine. Maxillary sinus can be used for identification of sex when other methods are indecisive. Computed tomography (CT) provides an excellent method for examining maxillary sinuses. Hence the aim of the study was to determine the accuracy of gender determination using maxillary sinus with CT. Materials and Methods. CT images were used to measure the mediolateral, superoinferior, and anteroposterior dimensions and the volume of the maxillary sinuses in 100 patients (50 males and 50 females) to determine the gender of an individual for forensic identification. Discriminative analysis was done using the values derived and the t-test for independent samples was used to compare these values in males and females. Results. The accuracy rate was found to be 84% in males and 92% in females with the mean accuracy of 88%. Conclusion. Our study concludes that gender determination can be done using measurements of maxillary sinus through CT when other methods are unavailable. The prediction rate can be increased by including volume of the maxillary sinus.
Toxicity of Nickel Oxide Nanoparticles on a Freshwater Green Algal Strain ofChlorella vulgaris
Authors: Oukarroum Abdallah , Zaidi Wassila , Samadani Mahshid , Dewez David
Published: April 2017

A freshwater microalga strain ofChlorella vulgariswas used to investigate toxic effects induced by nickel oxide nanoparticles (NiO-NPs) in suspension. Algal cells were exposed during 96 h to 0–100 mg L−1of NiO-NPs and analyzed by flow cytometry. Physicochemical characterization of nanoparticles in tested media showed a soluble fraction (free Ni2+) of only 6.42% for 100 mg L−1of NiO-NPs, indicating the low solubility capacity of these NPs. Toxicity analysis showed cellular alterations which were related to NiO-NPs concentration, such as inhibition in cell division (relative cell size and granularity), deterioration of the photosynthetic apparatus (chlorophyll synthesis and photochemical reactions of photosynthesis), and oxidative stress (ROS production). The change in cellular viability demonstrated to be a very sensitive biomarker of NiO-NPs toxicity with EC50of 13.7 mg L−1. Analysis by TEM and X-ray confirmed that NiO-NPs were able to cross biological membranes and to accumulate inside algal cells. Therefore, this study provides a characterization of both physicochemical and toxicological properties of NiO-NPs suspensions in tested media. The use of the freshwater strain ofC. vulgarisdemonstrated to be a sensitive bioindicator of NiO-NPs toxicity on the viability of green algae.
3D Numerical and Experimental Study on Paraffin Wax Melting in Thermal Storage for the Nozzle-and-Shell, Tube-and-Shell, and Reducer-and-Shell Models
Authors: Korawan Agus Dwi , Soeparman Sudjito , Wijayanti Widya , Widhiyanuriyawan Denny
Published: April 2017

Paraffin melting experienced in the nozzle-and-shell, tube-and-shell, and reducer-and-shell models in thermal storage with 3D numerical and experimental approach has been studied. The numerical study aims to evaluate the melting process and discover temperature distribution, liquid-solid interface, liquid fraction, and the average surface Nusselt number, while the aim of this experimental study is to determine the distribution of melting temperature. The comparison of temperature distribution between the numerical approach and experimental one indicates a good agreement. The comparison result between the three models shows that the melting process of the nozzle-and-shell model is the best, followed by tube-and-shell and reducer-and-shell models, successively. To finish the melting process, the time required is 6130 s for the nozzle-and-shell model, while tube-and-shell model requires 8210 s and reducer-and-shell model requires 12280 s.
Energy Balance Modulation Impacts Epigenetic Reprogramming, ERα and ERβ Expression, and Mammary Tumor Development in MMTV-neu Transgenic Mice
Authors: Rossi Emily L. , Dunlap Sarah M. , Bowers Laura W. , Khatib Subreen A. , Doerstling Steven S. , Smith Laura A. , Ford Nikki A. , Holley Darcy , Brown Powel H. , Estecio Marcos R. , Kusewitt Donna F. , deGraffenried Linda A. , Bultman Scott J. , Hursting Stephen D.
Published: April 2017

The association between obesity and breast cancer risk and prognosis is well established in estrogen receptor (ER)-positive disease but less clear in HER2-positive disease. Here, we report preclinical evidence suggesting weight maintenance through calorie restriction (CR) may limit risk of HER2-positive breast cancer. In female MMTV-HER2/neu transgenic mice, we found that ERα and ERβ expression, mammary tumorigenesis, and survival are energy balance dependent in association with epigenetic reprogramming. Mice were randomized to receive a CR, overweight-inducing, or diet-induced obesity regimen (n = 27/group). Subsets of mice (n = 4/group/time point) were euthanized after 1, 3, and 5 months to characterize diet-dependent metabolic, transcriptional, and epigenetic perturbations. Remaining mice were followed up to 22 months. Relative to the overweight and diet-induced obesity regimens, CR decreased body weight, adiposity, and serum metabolic hormones as expected and also elicited an increase in mammary ERα and ERβ expression. Increased DNA methylation accompanied this pattern, particularly at CpG dinucleotides located within binding or flanking regions for the transcriptional regulator CCCTC-binding factor of ESR1 and ESR2, consistent with sustained transcriptional activation of ERα and ERβ. Mammary expression of the DNA methylation enzyme DNMT1 was stable in CR mice but increased over time in overweight and diet-induced obesity mice, suggesting CR obviates epigenetic alterations concurrent with chronic excess energy intake. In the survival study, CR elicited a significant suppression in spontaneous mammary tumorigenesis. Overall, our findings suggest a mechanistic rationale to prevent or reverse excess body weight as a strategy to reduce HER2-positive breast cancer risk. Cancer Res; 77(9); 2500–11. ©2017 AACR.
The Role of Platelet Function Analyzer Testing in Cardiac Surgery Transfusion Management
Authors: Bogdanic Dejana , Karanovic Nenad , Mratinovic-Mikulandra Jela , Paukovic-Sekulic Branka , Brnic Dijana , Marinovic Ivanka , Nonkovic Diana , Bogdanic Nikolina
Published: April 2017

Background: Identifying high-risk patients for transfusion after cardiac operations would alter postoperative management. The aim of this study was to investigate closure time (CT) measured by platelet function analyzer (PFA) for prediction of bleeding and transfusions. Methods: 66 patients were scheduled for coronary artery bypass graft (CABG) surgery and 30 patients for valve repair and replacement (non-CABG). Measurements of PFA-100® CT for collagen and adenosine diphosphate (cADP) and collagen and epinephrine (cEPI) were performed 15 min after protamine administration. Blood loss was measured, and the amount of transfusion products was recorded postoperatively. Results: The study demonstrated significant differences between CABG patients with cADP-CT ≥ 118 s and those with cADP-CT < 118 s with regard to blood loss for 24 h (p = 0.001) and blood loss for 25-48 h (p = 0.003) as well as fresh frozen plasma (p = 0.015), platelet (p > 0.001) and red blood cell (p = 0.002) units given in 48 postoperative h. There were no differences cardiopulmonary bypass when was applied. In non-CABG patients, there were no differences in blood loss and transfusion requirements with respect to cADP-CT and cEPI-CT. Conclusion: Postoperative platelet dysfunction measured by a prolonged cADP-CT was significant predictor of blood loss and transfusion in CABG patients.
Mechanisms of Optic Nerve Invasion in Primary Choroidal Melanoma
Authors: Szalai Eszter , Wells Jill R. , Grossniklaus Hans E.
Published: April 2017

Aim: The aim of this study was to assess morphological risk factors associated with optic nerve invasion of choroidal melanoma and to identify possible mechanisms of optic nerve invasion. Methods: Medical charts and histology slides of patients with primary choroidal melanoma who were treated by enucleation/exenteration and whose pathology showed optic nerve invasion were reviewed. Results: Twenty-one patients (mean age: 65.67 ± 14.72 years) with primary uveal melanoma arising from the choroid were included in this analysis. A peripapillary location was present in 86% of the cases. Four types of optic nerve invasion were identified: transvitreal invasion (10%); retinal invasion (23%); direct peripapillary invasion (57%); and a combined mechanism (10%). Optic nerve invasion was prelaminar in 67%, laminar in 10%, and retrolaminar in 23% of the cases. Significantly higher largest basal diameter (p = 0.021) and tumor thickness values (p = 0.017) and higher rates of vortex vein (p = 0.022) and retinal invasion (p = 0.007) were observed in the transvitreal/retinal invasion groups when compared to the direct peripapillary invasion group. Conclusions: A peripapillary tumor location was the most common mechanism of optic nerve invasion of choroidal melanoma. In 43% of the cases, other mechanisms including transvitreal and retinal invasion resulted in optic nerve invasion.
Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related Adverse Events
Authors: Imafuku Keisuke , Yoshino Koji , Yamaguchi Kei , Tsuboi Satoshi , Ohara Kuniaki , Hata Hiroo
Published: April 2017

Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs) associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD) pattern. Oral corticosteroids improved chest shadow of CT scan in both cases. However, when nivolumab was re-administrated, case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From our cases, it is difficult to re-administrate nivolumab for the patients with pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve their symptoms.
Circulating Exosomal MicroRNA-21 as a Biomarker in Each Tumor Stage of Colorectal Cancer
Authors: Tsukamoto Mitsuo , Iinuma Hisae , Yagi Takahiro , Matsuda Keiji , Hashiguchi Yojiro
Published: April 2017

Objective: We clarified the predictive and prognostic value of circulating plasma exosomal microRNA-21 (miR-21) in each TNM stage of colorectal cancer (CRC) patients. Methods: The microRNA (miRNA) profiles of the plasma exosomes, primary tumor tissues, and liver metastasis tissues from the same CRC patients were examined using a microarray. For validation analysis, the plasma exosome samples from 326 CRC patients were measured by TaqMan miRNA assays. Results: In the miRNA microarray analyses, miR-21 showed the highest upregulation in exosomes, primary tumor tissues, and liver metastasis tissues. Significant correlations were demonstrated between exosomal miR-21 and tissue miR-21 levels. As for the relationship to the pathological condition, exosomal miR-21 showed a significant association with liver metastasis and TNM stage. The overall survival (OS) rates and disease-free survival (DFS) rates in high-exosomal-miR-21 patients were significantly worse than those in low-miR-21 patients. Exosomal miR-21 levels were an independent prognostic factor for OS and DFS in CRC patients with TNM stage II or III, and for OS in patients with TNM stage IV. Conclusion: Plasma exosomal miR-21 levels are a useful biomarker for the prediction of recurrence and poor prognosis in CRC patients with TNM stage II, III, or IV.
Thromboelastometry and Thrombelastography Analysis under Normal Physiological Conditions - Systematic Review
Authors: Adler Marcel , Ivic Sandra , Bodmer Nicolas S. , ten Cate Hugo , Bachmann Lucas M. , Wuillemin Walter A. , Nagler Michael
Published: April 2017

Background: Studies investigating thromboelastometry or thrombelastography analyses in a physiological context are scattered and not easy to access. Objective: To systematically retrieve and describe published reports studying healthy subjects and targeting at the correlation of ROTEM® and TEG® measurements with conventional parameters of hemostasis. Methods: Systematic Review: Papers were searched in Medline, Scopus and the Science Citation Index database. Reference lists of included studies and of reviews were screened. To be included papers had to report ROTEM or TEG data on healthy subjects. Two reviewers screened papers for inclusion, read full texts of potentially relevant papers, and extracted data of included papers. Results: Searches identified 1,721 records of which 1,713 were either excluded immediately or after reading the full text. The remaining 8 studies enrolled 632 subjects. The association of conventional parameters of hemostasis with ROTEM and with TEG was investigated in one and two studies, respectively. Overall correlation was limited and ranged from 0.0 to 0.40 (total thrombus generation vs. fibrinogen; clotting time INTEM vs. activated partial thromboplastin time). Conclusions: Studies assessing the relationship between thromboelastometry or thromboelastography analyses and conventional parameters of hemostasis in healthy subjects remains scarce, and correlations are limited. Further research is needed to understand the physiology of thromboelastometry and thromboelastography parameters.
Six-Year Outcome of Opioid Maintenance Treatment in Heroin-Dependent Patients: Results from a Naturalistic Study in a Nationally Representative Sample
Authors: Soyka Michael , Strehle Jens , Rehm Jürgen , Bühringer Gerhard , Wittchen Hans-Ulrich
Published: April 2017

Background: In many countries, the opioid agonists, buprenorphine and methadone, are licensed for maintenance treatment of opioid dependence. Many short-term studies have been performed, but little is known about long-term effects. Therefore, this study described over 6 years (1) mortality, retention and abstinence rates and (2) changes in concomitant drug use and somatic and mental health. Methods: A prevalence sample of n = 2,694 maintenance patients, recruited from a nationally representative sample of n = 223 substitution doctors, was evaluated in a 6-year prospective-longitudinal naturalistic study. At 72 months, n = 1,624 patients were assessed for outcome; 1,147 had full outcome data, 346 primary outcome data and 131 had died; 660 individuals were lost to follow-up. Results: The 6-year retention rate was 76.6%; the average mortality rate was 1.1%. During follow-up, 9.4% of patients became “abstinent” and 1.9% were referred for drug-free addiction treatment. Concomitant drug use decreased and somatic health status and social parameters improved. Conclusions: The study provides further evidence for the efficacy and safety of maintenance treatment with opioid agonists. In the long term, the number of opioid-free patients is low and most patients are more or less continuously under opioid maintenance therapy. Further implications are discussed.
Financial Toxicity of Cancer Drugs: Possible Remedies from an Ethical Perspective
Authors: Marckmann Georg , in der Schmitten Jürgen
Published: April 2017

Spiraling costs of cancer treatments have become a major concern for the payers in the health care system and for individual patients suffering from the cancer drugs' financial toxicity. This article discusses possible solutions from an ethical perspective. First, it gives some orientation about what constitutes a fair price for innovative anticancer agents. While a definitive answer remains difficult, there are good reasons to enter into price negotiations with the pharmaceutical companies to align the price with the R&D costs and the added value of the product. Information about the drug's cost-effectiveness should be available, a fixed threshold, however, seems ethically problematic. Rather, a ‘signal cost-effectiveness threshold' should indicate when the drug price requires special justification. Further strategies include an improved benefit assessment after market authorization by independent publicly financed studies, which will provide a valid basis for price negotiations and clinical decision-making at the micro level. Last but not least, cancer treatments should be tailored not only to the biology of the tumor but also to the preferences of the patient. Primarily mandated by the respect for autonomy, promoting patient-centered care has the potential to improve quality of care and enable a wise use of scarce health care resources.
Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway
Authors: Huang Ren-hong , Quan Ying-jun , Chen Jin-hong , Wang Ting-feng , Xu Ming , Ye Min , Yuan Hao , Zhang Chong-jie , Liu Xiao-jian , Min Zhi-jun
Published: April 2017

Background: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy. Methods: HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used to investigate the formation of autophagosomes. Results: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. Conclusion: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC.
Osteopontin, Bone Morphogenetic Protein-4, and Vitamin D Receptor Gene Polymorphisms in the Susceptibility and Clinical Severity of Spinal Tuberculosis
Authors: Wang Guohua , Xie Liangyi , Hu Jianzhong , Lu Hongbin , Liu Xiangyang , Cao Yong , Liu Bin , Zhang Yi , Shen Xiongjie
Published: April 2017

Background/Aims: Spinal tuberculosis (TB) is a common and dangerous form of extrapulmonary TB with unclear mechanisms in its occurrence and progression. This study investigated the clinical significances of bone morphogenetic protein-4 (BMP-4), osteopontin (OPN), and vitamin D receptor (VDR) gene polymorphism, mRNA and protein expression in spinal TB patients. Methods: BMP-4 and OPN gene polymorphisms were detected by direct DNA sequencing, while VDR-FokI polymorphisms were analyzed using PCR-RFLP. mRNA and protein expression was measured using real-time PCR and Western blot, respectively. Results: A significant lower frequency of TT genotype and T allele at 6007C>T polymorphism in BMP-4 gene; higher frequency of GG genotype and G allele at -66T>G polymorphism in OPN gene, and higher frequency of the ff genotype and f allele at the VDR-FokI polymorphism were observed in patients with spinal TB compared to controls. TT genotype of 6007C>T polymorphism correlated with a lower BMP-4 mRNA and protein expression, -66GG genotype correlated with a high OPN mRNA and protein expression, and ff genotype correlated with the lower VDR mRNA and protein levels in the intervertebral disc tissues. The TT genotype and low BMP-4 gene expression; the -66GG genotype and high OPN gene expression; and the ff genotype and low VDR gene expression significantly correlated with the clinical severity of spinal TB. Conclusion: The 6007C>T polymorphism of BMP-4, -66T>G polymorphism of OPN, and VDR-FokI polymorphism are the susceptible factors of spinal TB and indicators of the clinical severity. These three genes may collaborate in the development of spinal TB.
Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells
Authors: Samuel Sherin , Zhang Kuo , Tang Yi-Da , Gerdes A. Martin , Carrillo-Sepulveda Maria Alicia
Published: April 2017

Background/Aims: Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. Methods: Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP). Results: Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Conclusion: Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation.
Streblid bat flies on phyllostomid bats from an island off the coast of São Paulo, Brazil
Authors: Dornelles Guilherme Douglas Piel , Graciolli Gustavo
Published: April 2017

Streblidae is the family of bloodsucking flies, mostly tropical and subtropical, that are obligate ectoparasites of bats. A high number of these fly species are found in the Atlantic Forest, but there is little information about their quantitative descriptors. In this paper, we describe the prevalence, mean intensity, and infracommunities of streblid bat flies on phyllostomid bats from the Parque Estadual da Ilha do Cardoso, São Paulo state, Brazil. Surveys were conducted from July 1990 to July 1991 in distinct places of the island, with a total of 454 flies of 30 species collected from 132 bats of 15 species. From those, we found 44 host-parasite associations and 31 infracommunities that suffered variations due to accidental associations or contaminations. With our results, the number of Streblidae species increased from 31 to 36 in São Paulo State.
Una especie nueva de rana del género Chiasmocleis (Microhylidae: Gastrophryninae) de la Cordillera del Cóndor, Ecuador
Authors: Almendáriz Cabezas Ana de Lourdes , Brito M. Jorge , Batallas Revelo Diego Alejandro , Vaca-Guerrero Jorge , Ron Santiago R.
Published: April 2017

We describe a new species of frog of the genus Chiasmocleis from the montane forests of southeastern Ecuador, at the western slopes of Cordillera del Cóndor, between 1,224‑1,630 m of elevation. Based on new sequences of mitochondrial and nuclear DNA we present phylogenetic relationships of the new species and its congeners. The phylogeny shows a close relationship to C. antenori, C. carvalhoi, C. magnova and C. tridactyla. The new species is part of a clade of species that were previously assigned to the genus Syncope. This clade has a sister relationship to a clade that contains all remaining species of Chiasmocleis. The new species differs from its congeners by its reddish-brown to dark-brown (sepia) dorsum with minute yellowish-white spots. Chiasmocleis parkeri sp. nov. is similar to Chiasmocleis antenori in lacking digit I of both hands and feet but Chiasmocleis parkeri differs in coloration, arrangement and size of pale spots, and the absence of a pale line in the canthal region. We describe the calls, which are characterized by having non-pulsed notes, and we provide ecological data from the type locality and adjacent areas.
Towards a review of the decapod crustacea from the remote oceanic archipelago of Trindade and Martin Vaz, south Atlantic Ocean: new records and notes on ecology and zoogeography
Authors: Tavares Marcos Domingos Siqueira , Carvalho Leina , Mendonça Junior Joel Braga de
Published: April 2017

The remoteness of the Trindade and Martin Vaz young volcanic archipelago (TMV) raises questions about the source of its marine benthic fauna and levels of endemism. Addressing these questions requires a comprehensive knowledge of the taxonomic composition of the marine fauna of the islands. A five-year survey in the shallow marine waters (up to 30 m) and a literature review on the data published for TMV have been conducted to document the biodiversity of the benthic fauna. Here we report on ten new records of decapod crustaceans from TMV: Gnathophyllum americanum and Thor amboinensis are circumtropical in distribution, whereas Stenopus hispidus, Gnathophylloides mineri and Parribacus antarcticus are disjunct circumtropical species as their distribution in the Atlantic Ocean is limited eastwardly to TMV or Ascension Island (S. hispidus), therefore, do not extending into the eastern Atlantic. Gnathophyllum circellum and Thor manningi are western Atlantic species, with G. circellum previously known only from the Caribbean Sea. Pontonia manningi, Tuleariocaris neglecta and Enoplometopus antillensis are amphi-Atlantic in distribution. Two of the above species are recorded from the southwestern Atlantic for the first time: Gnathophyllum circellum and Tuleariocaris neglecta. These new records corroborate that the marine benthic invertebrate fauna of the TMV archipelago is actually a mosaic of amphi-Atlantic, eastern Atlantic, central Atlantic (insular), endemic and circumtropical species, with a strong western Atlantic component.
Social Integration and Reduced Risk of Coronary Heart Disease in Women
Authors: Chang Shun-Chiao , Glymour Maria , Cornelis Marilyn , Walter Stefan , Rimm Eric B. , Tchetgen Tchetgen Eric , Kawachi Ichiro , Kubzansky Laura D.
Published: April 2017

Rationale:

Higher social integration is associated with lower cardiovascular mortality; however, whether it is associated with incident coronary heart disease (CHD), especially in women, and whether associations differ by case fatality are unclear.

Objectives:

This study sought to examine the associations between social integration and risk of incident CHD in a large female prospective cohort.

Methods and Results:

Seventy-six thousand three hundred and sixty-two women in the Nurses’ Health Study, free of CHD and stroke at baseline (1992), were followed until 2014. Social integration was assessed by a simplified Berkman–Syme Social Network Index every 4 years. End points included nonfatal myocardial infarction and fatal CHD. Two thousand three hundred and seventy-two incident CHD events occurred throughout follow-up. Adjusting for demographic, health/medical risk factors, and depressive symptoms, being socially integrated was significantly associated with lower CHD risk, particularly fatal CHD. The most socially integrated women had a hazard ratio of 0.55 (95% confidence interval, 0.41–0.73) of developing fatal CHD compared with those least socially integrated (
P
for trend <0.0001). When additionally adjusting for lifestyle behaviors, findings for fatal CHD were maintained but attenuated (
P
for trend =0.02), whereas the significant associations no longer remained for nonfatal myocardial infarction. The inverse associations between social integration and nonfatal myocardial infarction risk were largely explained by health-promoting behaviors, particularly through differences in cigarette smoking; however, the association with fatal CHD risk remained after accounting for these behaviors and, thus, may involve more direct biological mechanisms.

Conclusions:

Social integration is inversely associated with CHD incidence in women, but is largely explained by lifestyle/behavioral pathways.
Methodological Rigor in Preclinical Cardiovascular Studies
Authors: Ramirez F. Daniel , Motazedian Pouya , Jung Richard G. , Di Santo Pietro , MacDonald Zachary D. , Moreland Robert , Simard Trevor , Clancy Aisling A. , Russo Juan J. , Welch Vivian A. , Wells George A. , Hibbert Benjamin
Published: April 2017

Rationale:

Methodological sources of bias and suboptimal reporting contribute to irreproducibility in preclinical science and may negatively affect research translation. Randomization, blinding, sample size estimation, and considering sex as a biological variable are deemed crucial study design elements to maximize the quality and predictive value of preclinical experiments.

Objective:

To examine the prevalence and temporal patterns of recommended study design element implementation in preclinical cardiovascular research.

Methods and Results:

All articles published over a 10-year period in 5 leading cardiovascular journals were reviewed. Reports of in vivo experiments in nonhuman mammals describing pathophysiology, genetics, or therapeutic interventions relevant to specific cardiovascular disorders were identified. Data on study design and animal model use were collected. Citations at 60 months were additionally examined as a surrogate measure of research impact in a prespecified subset of studies, stratified by individual and cumulative study design elements. Of 28 636 articles screened, 3396 met inclusion criteria. Randomization was reported in 21.8%, blinding in 32.7%, and sample size estimation in 2.3%. Temporal and disease-specific analyses show that the implementation of these study design elements has overall not appreciably increased over the past decade, except in preclinical stroke research, which has uniquely demonstrated significant improvements in methodological rigor. In a subset of 1681 preclinical studies, randomization, blinding, sample size estimation, and inclusion of both sexes were not associated with increased citations at 60 months.

Conclusions:

Methodological shortcomings are prevalent in preclinical cardiovascular research, have not substantially improved over the past 10 years, and may be overlooked when basing subsequent studies. Resultant risks of bias and threats to study validity have the potential to hinder progress in cardiovascular medicine as preclinical research often precedes and informs clinical trials. Stroke research quality has uniquely improved in recent years, warranting a closer examination for interventions to model in other cardiovascular fields.
Vascular Stiffness in Children With Chronic Kidney Disease
Authors: Savant Jonathan D. , Betoko Aisha , Meyers Kevin E.C. , Mitsnefes Mark , Flynn Joseph T. , Townsend Raymond R. , Greenbaum Larry A. , Dart Allison , Warady Bradley , Furth Susan L.
Published: April 2017

Carotid-femoral pulse wave velocity (cfPWV) is a measure of arterial stiffness associated with cardiovascular events in the general population and in adults with chronic kidney disease. However, few data exist regarding cfPWV in children with chronic kidney disease. We compared observed cfPWV assessed via applanation tonometry in children enrolled in the CKiD cohort study (Chronic Kidney Disease in Children) to normative data in healthy children and examined risk factors associated with elevated cfPWV. cfPWV Z score for height/gender and age/gender was calculated from and compared with published pediatric norms. Multivariable linear regression was used to assess the relationship between cfPWV and age, gender, race, body mass index, diagnosis, urine protein–creatinine ratio, mean arterial pressure, heart rate, number of antihypertensive medications, uric acid, and serum low-density lipoprotein. Of the 95 participants with measured cfPWV, 60% were male, 19% were black, 46% had glomerular cause of chronic kidney disease, 22% had urine protein–creatinine ratio 0.5 to 2.0 mg/mg and 9% had >2.0 mg/mg, mean age was 15.1 years, average mean arterial pressure was 80 mm Hg, and median glomerular filtration rate was 63 mL/min per 1.73 m
2
. Mean cfPWV was 5.0 m/s (SD, 0.8 m/s); mean cfPWV Z score by height/gender norms was −0.1 (SD, 1.1). cfPWV increased significantly with age, mean arterial pressure, and black race in multivariable analysis; no other variables, including glomerular filtration rate, were independently associated with cfPWV. In this pediatric cohort with mild kidney dysfunction, arterial stiffness was comparable to that of normal children. Future research is needed to examine the impact of chronic kidney disease progression on arterial stiffness and associated cardiovascular parameters in children.
Maternal Antihypertensive Medication Use and Congenital Heart Defects
Authors: Fisher Sarah C. , Van Zutphen Alissa R. , Werler Martha M. , Lin Angela E. , Romitti Paul A. , Druschel Charlotte M. , Browne Marilyn L.
Published: April 2017

Previous NBDPS (National Birth Defects Prevention Study) findings from 1997 to 2003 suggested that maternal antihypertensive use was associated with congenital heart defects (CHDs). We re-examined associations between specific antihypertensive medication classes and specific CHDs with additional NBDPS data from 2004 to 2011. After excluding mothers missing hypertension information or who reported pregestational diabetes mellitus, a multiple birth, or antihypertensive use but no hypertension, we compared self-reported maternal exposure data on 10 625 CHD cases and 11 137 nonmalformed controls. We calculated adjusted odds ratios [95% confidence intervals] to estimate the risk of specific CHDs associated with antihypertensive use during the month before conception through the third month of pregnancy, controlling for maternal age, race/ethnicity, body mass index, first trimester cigarette smoking, and NBDPS site. Overall, 164 (1.5%) case mothers and 102 (0.9%) control mothers reported early pregnancy antihypertensive use for their hypertension. We observed increased risk of 4 CHD phenotypes, regardless of antihypertensive medication class reported: coarctation of the aorta (2.50 [1.52–4.11]), pulmonary valve stenosis (2.19 [1.44–3.34]), perimembranous ventricular septal defect (1.90 [1.09–3.31]), and secundum atrial septal defect (1.94 [1.36–2.79]). The associations for these phenotypes were statistically significant for mothers who reported β-blocker use or renin–angiotensin system blocker use; estimates for other antihypertensive medication classes were generally based on fewer exposed cases and were less stable but remained elevated. Our results support and expand on earlier NBDPS findings that antihypertensive medication use may be associated with increased risk of specific CHDs, although we cannot completely rule out confounding by underlying disease characteristics.
Cardioprotective Effects of Intracoronary Morphine in ST‐Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: A Prospective, Randomized Trial
Authors: Gwag Hye Bin , Kim Eun Kyoung , Park Taek Kyu , Lee Joo Myung , Yang Jeong Hoon , Song Young Bin , Choi Jin‐Ho , Choi Seung‐Hyuk , Lee Sang Hoon , Chang Sung‐A , Park Sung‐Ji , Lee Sang‐Chol , Park Seung Woo , Jang Woo Jin , Lee Mirae , Chun Woo Jung , Oh Ju Hyeon , Park Yong Hwan , Choe Yeon Hyeon , Gwon Hyeon‐Cheol , Hahn Joo‐Yong
Published: April 2017

Background

A cardioprotective role of morphine acting via opioid receptors has been demonstrated, and previous preclinical studies have reported that morphine could reduce reperfusion injury and myocardial infarct size in a way similar to that of ischemic periconditioning. This study aimed to evaluate the effect of intracoronary morphine on myocardial infarct size in patients with
ST
‐elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Methods and Results

This study was designed as a 2‐center, prospective, randomized, open‐label, blinded end point trial. A total of 91
ST
‐elevation myocardial infarction patients with thrombolysis in myocardial infarction flow grade of 0 to 1 undergoing primary percutaneous coronary intervention were randomly assigned to a morphine or control group at a 1:1 ratio. The morphine group received 3 mg of morphine sulfate diluted with 3 mL of normal saline, and the control group received 3 mL of normal saline into a coronary artery immediately after restoration of coronary flow. The primary end point was myocardial infarct size assessed by cardiac magnetic resonance imaging The cardiac magnetic resonance images were evaluated for 42 and 38 patients in the morphine and control groups, respectively. Myocardial infarct size was not different between the 2 groups (25.6±11.2% versus 24.6±10.5%,
P
=0.77), nor was the extent of microvascular obstruction or myocardial salvage index (6.0±6.3% versus 5.1±4.6%,
P
=0.91; 31.1±15.2% versus 30.3±10.9%,
P
=0.75, respectively). There was no difference in peak creatine kinase‐
MB
level, final thrombolysis in myocardial infarction flow, myocardial brush grade, or complete resolution of
ST
‐segment.

Conclusions

Intracoronary morphine administration could not reduce myocardial infarct size in
ST
‐elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01738100.
Predictors for Symptomatic Intracranial Hemorrhage After Endovascular Treatment of Acute Ischemic Stroke
Authors: Hao Yonggang , Yang Dong , Wang Huaiming , Zi Wenjie , Zhang Meng , Geng Yu , Zhou Zhiming , Wang Wei , Xu Haowen , Tian Xiguang , Lv Penghua , Liu Yuxiu , Xiong Yunyun , Liu Xinfeng , Xu Gelin , Liu Chengchun , Shi Zongjie , Zhang Jinhua , Lin Hang , Lin Min , Hu Zhen , Deng Xiaorong , Wan Yue , Zhang Jiandong , Shi Zhonghua , Qu Mirui , Huang Xianjun , Quan Tao , Guan Sheng , Chen Lin , Li Xiaobo , Wang Shuiping , Yang Shiquan , Liu Wenhua , Wei Dan , Wang Zhen , Liu Xintong , Guo Fuqiang , Yang Shu , Zheng Dequan , Wu Xinyu , Zeng Youfu , Tu Mingyi , Jin Ping , Liu Yong , Li Hua , Fang Jiayang , Xiao Guodong
Published: April 2017

Background and Purpose—

Symptomatic intracranial hemorrhage (SICH) pose a major safety concern for endovascular treatment of acute ischemic stroke. This study aimed to evaluate the risk and related factors of SICH after endovascular treatment in a real-world practice.

Methods—

Patients with stroke treated with stent-like retrievers for recanalizing a blocked artery in anterior circulation were enrolled from 21 stroke centers in China. Intracranial hemorrhage was classified as symptomatic and asymptomatic ones according to Heidelberg Bleeding Classification. Logistic regression was used to identify predictors for SICH.

Results—

Of the 632 enrolled patients, 101 (16.0%) were diagnosed with SICH within 72 hours after endovascular treatment. Ninety-day mortality was higher in patients with SICH than in patients without SICH (65.3% versus 18.8%;
P
<0.001). On multivariate analysis, baseline neutrophil ratio >0.83 (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.24–3.46), pretreatment Alberta Stroke Program Early Computed Tomography Score of <6 (OR, 2.27; 95% CI, 1.24–4.14), stroke of cardioembolism type (OR, 1.91; 95% CI, 1.13–3.25), poor collateral circulation (OR, 1.97; 95% CI, 1.16–3.36), delay from symptoms onset to groin puncture >270 minutes (OR, 1.70; 95% CI, 1.03–2.80), >3 passes with retriever (OR, 2.55; 95% CI, 1.40–4.65) were associated with SICH after endovascular treatment.

Conclusions—

Incidence of SICH after thrombectomy is higher in Asian patients with acute ischemic stroke. Cardioembolic stroke, poor collateral circulation, delayed endovascular treatment, multiple passes with stent retriever device, lower pretreatment Alberta Stroke Program Early Computed Tomography Score, higher baseline neutrophil ratio may increase the risk of SICH.