bluuebunny/crossref_metadata_2025 huggingface dataset:
A Biomechanical Investigation into the Absence of Leaping in the Locomotor Repertoire of the Slender Loris (Loris tardigradus)
Authors: Sellers William I.
Published: April 2017

Unlike all other primates, members of the subfamily Lorisinae are never seen to leap. To investigate the anatomical specializations that are behind the absence of leaping in their locomotor repertoire, a predictive mechanical model of leaping was developed using the lesser bushbaby, Galago moholi, as a size-matched leaping prosimian comparison. This enabled the required limb movements for a leaping slender loris to be calculated, and hence the torque and power requirements at each of the hindlimb joints. From this information, the maximum feasible leap was calculated for the slender loris morphotype, and it was found that this alone would prevent the animal from leaping a greater distance than it could walk over, so that the reduction in fitness due to an apparent loss of leaping from the behavioural repertoire can be considered to be very small.
Influence de différents agents dénaturants et de la digestion tryptique sur l’activité adénosinetriphosphatasique de la myosine de carotide de bovidé
Authors: Gaspar-Godfroid A.
Published: April 2017

Although the molecular parameters of the myosins of vertebrate striated and smooth muscles seem to be similar, the ATPase activity of the latters, however, present some peculiar features. The enzymic activity of cow carotid myosin and the extent of its aggregation are strongly influenced by the method of isolation. When prepared in absence of reducing agent, the Ca++-ATPase activity is, as in the case of other smooth muscles myosins, lower than that of striated muscle myosin and larger at high ionic strength than at low ionic strength. It reaches the activity of that of skeletal red muscle or cardiac muscle when prepared in the presence of 2 mM β-mercaptoethanol. Denaturating agents as urea, lithium bromide, ethanol and ethylene glycol, which do not influence striated muscle myosin at low concentration, considerably enhance Ca++-ATPase activity of cow carotid myosin and tonoactomyosin. Tryptic digestion also increases Ca++-ATPase activity of cow carotid myosin and tonoactomyosin; at first, overdigestion does not change this enhanced activity in the case of tonoactomyosin but lowers considerably this activity in the case of myosin. Unaggregated cow carotid H-meromyosin can be obtained if the preparation and the digestion of the myosin or the tonoactomyosin are carried out in the presence of 2 mM β- mercaptoethanol.
Inhibition of in vivo Neural Vasoconstriction by Exogenous Catecholamines
Authors: Sanders Kenton M. , Ross Gordon
Published: April 2017

Intraarterial infusions of norepinephrine and dopamine markedly attenuated the mesenteric vasoconstrictor response to periarterial nerve stimulation in anesthetized cats, but did not attenuate the response to intravenous noiepinephrine. The degree of attenuation was independent of stimulation voltage, but inversely related to frequency. The results are compatible with previous in vitro evidence that NE and DA decrease adrenergic transmitter release during nerve stimulation.
Innervation of the Canine Inferior Vena Cava
Authors: Ichikawa Tomohiro , Ishikawa Naohisa , Shigei Tatsuro
Published: April 2017

The innervation of three embryologically distinct segments of the canine inferior vena cava was investigated. These segments were termed A (supradiaphragm), B-C (intrahepatic and that between liver and renal veins), and D (infrarenal). Strips were cut from these segments, and their isometric tensions were recorded. Transmural electrical stimulation induced contractile responses in circular strips from segment B-C (66.5% of the maximum norepinephrine-induced response) and in those from D (14.4%), but not in A. These responses almost completely disappeared in the presence of phenoxybenzamine. In segment B-C, however, the remaining small contraction was markedly enhanced by neostigmine and abolished by atropine. The same phenomenon was also observed in the contraction remaining after reserpinization. Longitudinal strips from segment C responded similarly. Concentration-response curves of circular strips for acetylcholine were shifted by neostigmine markedly to the left only in segment B-C, while no significant shift occurred in A and D. It was concluded that the adrenergic innervation is remarkably dense in B-C, sparse in D, and probably lacking in A. In addition, a cholinergic excitatory innervation is present in segment B-C.
Gamma-Aminobutyric Acid-A Receptor-Mediated Suppression of 5-Hydroxytryptamine-Induced Guinea-Pig Basilar Artery Smooth Muscle Contractility
Authors: Shirakawa Junji , Hosoda Kohkichi , Taniyama Kohtaro , Matsumoto Satoshi , Tanaka Chikako
Published: April 2017

The mechansim of γ -aminobutyric acid (GABA)-induced suppression of 5-hydroxytryptamine (5HT)-induced contractility of cerebral blood vessels was studied in single smooth muscle cells isolated from the guinea-pig basilar artery. GABA reduced 5HT-induced contraction of single smooth muscle cells, and the effect of GABA was mimicked by muscimol, but not baclofen. The response of muscimol was antagonized by bicuculline, thereby indicating that GABAA receptors exist on the smooth muscle of the basilar artery. Since GABA did not change the contraction induced by the addition of Ca2+ to the Ca2+-free medium in the presence of high K+, it is unlikely that GABA inhibits the influx of extracellular Ca2+. The caffeine-induced contraction in the Ca2+-free medium was reduced by GABA, and the effect of GABA was not obtained by treatment with furosemide and in the Cl--free medium. These results indicate that GABA acts on the GABAa receptor located on smooth muscle cells and reduces the contractility of the basilar artery by suppression of the mobilization of intracellular Ca2+.
Variable Receptor Affinity and Tissue Sensitivity
Authors: Oriowo M.A. , Bevan R.D. , Bevan J.A.
Published: April 2017

Vascular smooth muscle sensitivity to norepinephrine (NE), measured by contractile responses in vitro, varied in different arteries of the rabbit and also in the same vessels in other species. There was a good correlation between variation in the affinity of NE for the α1-adrenoceptor and tissue sensitivity. The variation was continuous and probably not indicative of different receptor subtypes. Solubilization of α1-adrenoceptors from the membrane changed the affinity for specific ligands while reconstitution restored it. Taken together, these results suggest the presence of a factor(s) within the receptor microenvironment capable of modulating affinity and hence tissue sensitivity to NE. In some blood vessels, receptor number was correlated significantly with affinity of the α1-adrenoceptor for NE also. In general, the contribution of receptor number was considerably less than the affinity for NE.
Role of Potassium Channels in the Vascular Response to Endogenous and Pharmacological Vasodilators
Authors: Brayden Joseph E. , Quayle John M. , Standen Nicholas B. , Nelson Mark T.
Published: April 2017

Many endogenous and pharmacological vasodilators hyperpolarize vascular smooth muscle and this response appears to be due to an increased conductance to potassium ions. The hyperpolarization may contribute to the mechanism of dilation by causing voltage-dependent calcium channels to close. Recent evidence indicates that the response to hyperpolarizing vasodilators is mediated through activation of ATP-sensitive potassium (Katp) channels. Single Katp channels on isolated vascular smooth muscle cells are activated by cromakalim and calcitonin gene-related peptide (CGRP). This response is inhibited by glibenclainide. Cromakalim, CGRP and other vasodilators hyperpolarize and relax arteries in vitro and these responses are reversed by glibenclainide. The hypotensive effects of these agents in vivo are antagonized by glibenclainide. We propose that activation of KATP channels and the associated membrane hyperpolarization represents an important general mechanism of vasodilation.
Predictive Utility of Type and Duration of Symptoms at Initial Presentation in Patients with Mild Cognitive Impairment
Authors: Devier Deidre J. , Villemarette-Pittman Nicole , Brown Patrick , Pelton Gregory , Stern Yaakov , Sano Mary , Devanand D.P.
Published: April 2017

Background/Aims: To assess (1) the duration and symptoms present in participants with mild cognitive impairment (MCI) and (2) the impact of these variables on predicting conversion to Alzheimer’s disease (AD). Methods: Participants with MCI (n = 148) were assessed and followed systematically. Results: Decline in memory was reported as the first symptom in 118 of the cases. Converters had more symptoms (e.g. language decline, depression), and the combination of decline in memory and in performance of high-order social/cognitive activities as well as disorientation more often than nonconverters (p = 0.036). In an age-stratified Cox model, predictors of conversion to AD were shorter time since onset of memory decline and lower baseline MMSE score. Conclusions: Recent onset of memory decline with older age, decreased MMSE score, change in performance and disorientation indicate a greater likelihood of short-term conversion to AD.
Combination of Corpus Callosotomy and Vagus Nerve Stimulation in the Treatment of Refractory Epilepsy
Authors: Guillamón E. , Miró J. , Gutiérrez A. , Conde R. , Falip M. , Jaraba S. , Plans G. , Garcés M. , Villanueva V.
Published: April 2017

Background: Palliative techniques such as partial corpus callosotomy (CC) and vagus nerve stimulation (VNS) may be effective for adequate control of seizures in pharmacoresistant patients who are not candidates for resective surgery. Objective: The objective of this study was to analyze the efficacy of the combination of these two techniques in patients where the first surgery had not achieved adequate control. Materials and Methods: This is a retrospective review of 6 patients with refractory epilepsy in which both types of surgery were performed, CC and VNS. We analyzed variables such as age, sex, age at onset of epilepsy, seizure types, electroencephalogram and magnetic resonance imaging results, and number of pre- and postoperative seizures. Results: Three patients first underwent VNS and then CC, and 3 patients were treated in reverse order. All patients had some improvement after the first surgery, but they continued to experience persistent falls, so a second palliative technique was used. The mean improvement after both surgeries was 89% (90% in patients first receiving CC and 87% in patients who first underwent VNS). Conclusions: In adequately studied patients who are not optimal candidates for resective surgery, palliative surgery is a choice. The combination of VNS and CC shows good results in our series, although the right order to perform both procedures has not been defined. These results should be confirmed in a larger group of patients.
Immunology of Major Depression
Authors: Müller Norbert
Published: April 2017

High levels of several proinflammatory components of the immune system, such as interleukin-6, C-reactive protein, tumor necrosis factor (TNF)-α, or neopterin in patients suffering from major depression (MD) point to the involvement of an inflammatory process in the pathophysiology of MD. The direct and indirect effects of cytokines on neurotransmitter storage and release - mediated by microglia cells and astrocytes - are discussed. The tryptophan/kynurenine metabolism is one of the indirect mechanisms because the enzyme indoleamine 2,3-dioxygenase - a key enzyme of this metabolism in the central nervous system - is driven by pro- and anti-inflammatory cytokines and degrades serotonin. Moreover, neuroactive kynurenines such as kynurenic acid and quinolinic acid act on the glutamatergic neurotransmission as N-methyl-D-aspartate antagonists and agonists, respectively. Alterations of the serotonergic, noradrenergic and glutamatergic neurotransmission have been shown with low-level neuroinflammation and may be involved in symptom generation. Epidemiological and clinical studies show a role for inflammation as a risk factor for MD. A large-scale epidemiological study in MD clearly demonstrates that severe infections and autoimmune disorders are lifetime risk factors for MD. The vulnerability-stress-inflammation model matches with this view as stress may increase proinflammatory cytokines and even contribute to a lasting proinflammatory state. Further support comes from the therapeutic benefit of anti-inflammatory medications such as the cyclo-oxygenase-2 inhibitors, TNF-α antagonists and others, and the anti-inflammatory and immunomodulatory intrinsic effects of antidepressants.
A Sequential Comparison on the Risk of Haemorrhage with Different Sizes of Biopsy Needles for Stereotactic Brain Biopsy
Authors: Yuen Jason , Zhu Cannon X.L. , Chan Danny T.M. , Ng Rebecca Y.T. , Nia Wai , Poon Wai Sang , Ng Ho Keung , Mok Vincent C.T. , Wong Laurence K.S. , Cheung Tom C.Y. , Siu Deyond Y.W.
Published: April 2017

Aim: To compare the risk of postoperative haemorrhage with different sizes of brain biopsy needles. Patients and Method: A cohort of patients using a 2.5-mm outer diameter side-cutting biopsy needle was compared to a subsequent cohort using a 1.8-mm needle of the same type. All data were collected prospectively. A CT scan was done within 12 h after surgery. Any visible haemorrhage at the operated site was documented. Results: From 2007 to 2013, 54 stereotactic brain biopsies (all frameless except for one frame-based) were performed. The 2.5-mm group comprised 29 procedures from 2007 to 2009. The 1.8-mm group comprised the subsequent 25 procedures. The diagnostic yields were 90 and 96% in the 2.5- and the 1.8-mm group, respectively (p = 0.615). Comparing the 2.5- and the 1.8-mm group, haemorrhage was significantly reduced: incidence (72 vs. 40%, p = 0.016); size of haemorrhage (mean 7.2 vs. 2.6 mm, p = 0.002); proportion of haemorrhage size >10 mm (34.5 vs. 4%, p = 0.006). Symptomatic haemorrhage rates were 3.4 and 0.0% in the 2.5- and the 1.8-mm group, respectively (p = 1.00). Conclusion: The 1.8-mm outer diameter needle carried a lower risk of postoperative haemorrhage than the 2.5-mm one, without compromising the diagnostic yield.
Comparison of Hemodynamics after Combined Spinal-Epidural Anesthesia between Decubitus and Sitting Positions in Aged Patients Undergoing Total Hip Replacement
Authors: Han Guang , Zhao Guang-yi , Li Lu , Zhao Ping
Published: April 2017

Objective: To compare the hemodynamics after combined spinal-epidural anesthesia (CSEA) between decubitus and sitting positions in aged patients undergoing total hip replacement. Methods: A total of 80 aged patients who underwent CSEA for elective total hip replacement were randomly divided into a decubitus position group (group D) and a sitting position group (group S; each group with 40 patients). In group D, 10 mg of 0.5% bupivacaine were given into the subarachnoid space in decubitus position. In group S, 10 mg of 0.5% bupivacaine were given into the subarachnoid space in the sitting position, which was maintained for 1 min, after which the patients were in decubitus position. In both groups, the sensory block levels and changes in hemodynamics were assessed. Results: The mean arterial blood pressure was significantly higher in group S than in group D at each time point within 30 min after anesthesia. There were no significant differences in heart rate between the two groups at each time point. There was also no significant difference in the level of sensory block between the two groups 20 min after the administration of CSEA. Conclusion: For aged patients undergoing total hip replacement, CSEA is safer and more effective in the sitting position than in decubitus position.
Common Variants in Serum/Glucocorticoid Regulated Kinase 1 (SGK1) and Blood Pressure Responses to Dietary Sodium or Potassium Interventions: A family-Based Association Study
Authors: Chu Chao , Wang Yang , Wang Man , Mu Jian-jun , Liu Fu-qiang , Wang Lan , Ren Ke-yu , Wang Dan , Yuan Zu-yi
Published: April 2017

Background/Aims: Serum/Glucocorticoid Regulated Kinase 1 (SGK1) plays a significant role in regulating renal Na+ reabsorption, K+ secretion, and blood pressure (BP). This study aimed to assess the association of common genetic variants in the SGK1 gene with BP responses to controlled dietary sodium or potassium interventions. Methods: A total of 334 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially maintained a seven-day low-sodium diet (3g/day of NaCl or 51.3mmol/day of sodium), a seven-day high-sodium diet (18g/day of NaCl or 307.8 mmol/day of sodium) and a seven-day high-sodium plus potassium supplementation intervention (4.5g/day of KCl or 60mmol/day of potassium). Six single-nucleotide polymorphisms (SNPs) in the SGK1 gene were selected. Results: After adjustment for multiple testing, SNP rs9376026 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-sodium intervention (P = 0.018 and 0.022, respectively). However, the associations between selected SNPs in the SGK1 gene and BP responses to high-sodium or high-sodium plus potassium-supplementation intervention did not reach statistical significance. In addition, SNP rs9389154 and two other SNPs (rs1763509 and rs9376026) were associated respectively with systolic BP (SBP) and DBP at baseline (P = 0.040, 0.032, and 0.031, respectively). SNP rs3813344 was significantly associated with SBP, DBP, and MAP (P = 0.049, 0.015 and 0.018, respectively). Conclusion: Our study indicates that the genetic polymorphism in the SGK1 gene is significantly associated with BP responses to dietary sodium intervention.
Multiple Human Papilloma Virus Infections and Their Impact on the Development of High-Risk Cervical Lesions
Authors: Salazar Katrina L. , Zhou Haijun Steve , Xu Jiaqiong , Peterson Leif E. , Schwartz Mary R. , Mody Dina R. , Ge Yimin
Published: April 2017

Objective: Individuals are often infected with multiple genotypes of human papillomavirus (HPV) simultaneously, but the role these infections play in the development of cervical disease is not well established. This study aimed to determine the association of multiple HPV infections with high-risk cervical lesions (hrCLs). Study Design: HPV genotyping was performed on 798 SurePath specimens collected between December 1, 2009, and April 30, 2011. The cases were classified as hrCL (n = 90) or non-hrCL (n = 708) based on cytology diagnoses. The association between hrCL and HPV infection patterns was analyzed. Results: Multiple HPV infections were frequently encountered (38.2%) in the cohort. Increased frequency of hrCLs was associated with a single high-risk HPV (hrHPV) infection. An additive or synergistic effect was not observed for hrCL in multiple HPV infections. The hrCL rates appeared to decrease in various patterns of multiple HPV infections, but the reduction was not statistically significant. Conclusions: Multiple HPV infections are common with no additive or synergistic effect on the development of hrCL. Conversely, reduced hrCL rates were observed in various patterns of multiple HPV infections compared to their single-genotype infection counterparts, suggestive of possible intergenotypic competition or more effective immune response triggered by multiple infections. Further studies in larger cohorts are needed.
Cetuximab-Carboplatin-5-Fluorouracil Regimen in Elderly Patients with Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma: A French Retrospective Survey
Authors: Burgy Mickaël , Barthélémy Philippe , Lefevre François , Dupret-Bories Agnès , Truntzer Pierre , Korenbaum Clement , Flesch Henri , Bronner Guy , Borel Christian
Published: April 2017

Background: The cetuximab plus platinum-based chemotherapy regimen is a standard of care in the treatment of recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The feasibility in the elderly population is currently unknown. Methods: We performed a retrospective study in order to assess the efficacy and safety of the cetuximab plus platinum-based chemotherapy regimen in patients >65 years with recurrent or metastatic HNSCC. We performed a retrospective review of all medical records from recurrent or metastatic HNSCC patients >65 years treated with the cetuximab plus platinum-based chemotherapy regimen between September 2008 and December 2013 in our institution (Centre Paul Strauss, Strasbourg, France). Results: A total of 59 patients were identified. Carboplatin in combination with 5-fluorouracil (FU) was the only cetuximab-associated chemotherapy regimen used for treating elderly patients. The median progression-free survival was 4 months (95% confidence interval [CI]: 2.9-4.7), and the median overall survival was 9.1 months (95% CI: 6.5-13.1). Grade 3 or 4 toxicity adverse events occurred in 52% (n = 31) of the patients (mostly hematologic toxicities and infections). Conclusions: This retrospective study suggests that the cetuximab plus carboplatin-5FU chemotherapy is an effective treatment option for elderly patients with recurrent or metastatic HNSCC.
Combining Real-Time COLD- and MAMA-PCR TaqMan Techniques to Detect and Quantify R201 GNAS Mutations in the McCune-Albright Syndrome
Authors: de Sanctis Luisa , Galliano Ilaria , Montanari Paola , Matarazzo Patrizia , Tessaris Daniele , Bergallo Massimiliano
Published: April 2017

Background/Aim: The McCune-Albright syndrome (MAS) is a potentially severe disorder hallmarked by fibrous bone dysplasia, café-au-lait skin spots, and endocrine hyperfunction. It is caused by postzygotic activating mutations at the R201 codon of the GNAS gene, leading to a state of somatic mosaicism. Our aim was to improve the mutation detection rate and to quantify the presence of R201 GNAS mutations in different DNA samples from MAS patients. Methods: Real-time COLD- and MAMA-PCR TaqMan techniques were combined to search for R201 mutations in the DNA of blood or affected tissues from 16 previously molecularly characterized MAS patients, from a further 84 subjects with MAS signs who were R201 negative at RFLP analysis, and from 36 controls. The ability of this new method to provide quantitative data was tested in the serial dilution of wild-type, R201H, or R201C cloned plasmid DNA samples; the mutant abundance was measured by spectrophotometry. Results: A linear correlation between the true and the relative mutant abundance was observed until 2.5%, indicating a reliable quantification of R201 mutations. The assay’s sensitivity was 0.05%, similar to that of previously described molecular methods. Conclusion: The real-time COLD-MAMA-PCR approach is a rapid, efficient, and inexpensive molecular technique for the identification of mutant alleles poorly represented in DNA samples.
Self-Administered Tinnitus Pitch Matching versus a Conventional Audiometric Procedure
Authors: Kim Tae Su , Yakunina Natalia , Ryu Yoon-Jong , Chung Ik Joo , Nam Eui-Cheol
Published: April 2017

Objective: Obtaining an accurate tinnitus pitch match is an initial and critical requirement for tinnitus evaluation and treatment, particularly for applying tailor-made notched music training. We investigated whether computer-based self-administered tinnitus pitch matching (CSTPM) is comparable with a conventional audiometric procedure (CAP). Methods: In total, 82 patients (mean age 45.52 years; 42 females) with tonal tinnitus participated. The CAP was performed by the same audiologist using a 2-alternative forced choice method with a frequency range of 0.25-16 kHz. In the CSTPM, the subjects used personal computer software with a scrolling slider to select the sound closest to their tinnitus pitch. After each matching procedure, an octave challenge test was applied. A multivariate logistic regression was performed to determine factors associated with the difference between the CSTPM and CAP. Results: The subjects' mean hearing threshold was 21.25 ± 17.61 dB HL; the mean tinnitus handicap inventory score was 35.56 ± 24.09. The mean pitches measured with the CSTPM and CAP were 6.29 ± 4.30 and 6.98 ± 5.33 kHz, respectively. In total, 57 (69.5%) subjects matched their tinnitus with less than half an octave difference between the procedures. The results of the 2 methods correlated significantly with each other (Pearson r = 0.793, p < 0.001). Octave confusion was a significant factor affecting the difference between the procedures (odds ratio 8.92, p < 0.05). Conclusions: The CSTPM appears to be as accurate as the standard audiological procedure, and may be used instead of the CAP when octave confusion is minimized.
Vitamin D supplementation in patients with rheumatic diseases – the process of making a meta-analysis, its adversities and learningsVitamin D supplementation in patients with rheumatic diseases – the process of making a meta-analysis, its adversities and learnings
Authors: Freitas Thiago Quadrante , Franco André Silva , Bernardo Wanderley Marques , Pereira Rosa Maria Rodrigues
Published: April 2017

No abstract
Analysis of the reversibility of biliary cirrhosis in young rats submitted to biliary obstruction followed by desobstruction
Authors: Braz Maria Julia de Aro , Corbi Leonardo Ervolino , Tannuri Ana Cristina Aoun , Gonçalves Josiane de Oliveira , Serafini Suellen , Coelho Maria Cecília de Mendonça , Tannuri Uenis
Published: April 2017

In this letter to the editor of Revista de Medicina, we present a summary of our study entitled “Analysis of the reversibility of biliary cirrhosis in young rats submitted to biliary obstruction followed by desobstruction”, presented at the XXXV COMU in 2016 - 1st place of Oswaldo Cruz award, surgical area.Biliary atresia and other liver conditions are relevant in pediatric clinic, due to its progression into biliary cirrhosis and eventually, necessity for liver transplant. It is known that the period during which biliary obstruction persists is determining for the development of cirrhosis and its reversibility after a biliary drainage procedure. However, there are no time or histological markers of biliary cirrhosis reversibility. An animal model of biliary obstruction and desobstruction was employed and after histologic and molecular analysis, we concluded that, considering the high mortality rate and the improvement in histologic and molecular changes after biliary drainage in most groups, cirrhosis and its histological and molecular changes occur early after biliary obstruction, are severe and potentially fatal, but can be reversed or at least delayed after biliary drainage.
Decifrando a proveniência dos folhelhos da formação Ponta Grossa na região de Rio Verde de Mato Grosso e Coxim (MS) através de métodos petrográficos e geoquímicos
Authors: Montibeller Cibele Carolina , Zanardo Antenor , Navarro Guillermo Rafael Beltran
Published: April 2017

Na região de Rio Verde de Mato Grosso e Coxim (MS) ocorrem rochas sedimentares devonianas relacionadas à Formação Ponta Grossa. Nesta região, a Formação Ponta Grossa aflorante é constituída por um pacote de folhelhos e siltitos cinza a pretos, com níveis de siltitos argilosos sobrepostos por arenitos feldspáticos muito finos micáceos, de cores creme, verde e avermelhados. Acima dos arenitos ocorrem siltitos argilosos amarelos fracamente laminados. Quimicamente, os níveis pelíticos são classificados como folhelhos/argilitos e com composição matura, derivados principalmente de rochas ígneas intermediárias e/ou máficas. Através da utilização de diagramas discriminantes para ambientes tectônicos e de proveniência, não foi estabelecido um padrão único para as amostras da Formação Ponta Grossa, podendo ser tanto classificados como sedimentos depositados em margem passiva quanto em margem ativa. Entretanto, dado o contexto da Bacia do Paraná durante o Devoniano, os sedimentos da Formação Ponta Grossa provavelmente tiveram como fonte rochas formadas em margens ativas (arcos magmáticos), erodidas e depositadas em margem passiva (bacia intracratônica).
Socioeconomic Status Interacts with the Genetic Effect of a Chromosome 9p21.3 Common Variant to Influence Coronary Artery Calcification and Incident Coronary Events in the Heinz Nixdorf Recall Study (Risk Factors, Evaluation of Coronary Calcium, and Lifestyle)
Authors: Schmidt Börge , Frölich Stefanie , Dragano Nico , Frank Mirjam , Eisele Lewin , Pechlivanis Sonali , Forstner Andreas J. , Nöthen Markus M. , Mahabadi Amir A. , Erbel Raimund , Moebus Susanne , Jöckel Karl-Heinz
Published: April 2017

Background—

Genetic variants of a locus within the chromosome 9p21.3 region are consistently associated with coronary artery disease and coronary artery calcification (CAC). The aim of this study was to examine whether a 9p21.3 common variant interacts with socioeconomic status (SES) to influence CAC and incident coronary events in a population-based cohort.

Methods and Results—

9p21.3 single nucleotide polymorphism rs2891168 was genotyped in 4116 participants of the Heinz Nixdorf Recall study. SES indicators (education and income) and CAC were assessed at baseline. Incident coronary events were ascertained over a median follow-up of 9.3 years. Multiple regression models were fitted to estimate genetic effects on log
e
(CAC+1) and incident coronary events. Genetic effects were highest in the lower income tertile with a 53.1% (95% confidence interval, 30.6%–79.6%;
P
=1.8×10

–
7

) increase in CAC and a hazard ratio of 1.44 (95% confidence interval, 1.01–2.07;
P
=0.049) for incident coronary events per additional risk allele. After including genotype×SES interaction terms in the regression models, genotype×income interactions were observed for CAC (exp[β
g×income
]=0.85 [95% confidence interval, 0.74–0.98;
P
g×income
=0.02] per 1000€/mo increase and additional risk allele) and for incident coronary events (hazard ratio
g×income
=0.69 [95% confidence interval, 0.48–0.98;
P
g×income
=0.04] per 1000€/mo increase and additional risk allele). No interaction was observed using education as SES indicator.

Conclusions—

A 9p21.3 common variant seems to interact with SES to influence CAC and incident coronary events in a population-based cohort. This supports the hypothesis that better material, psychosocial, and lifestyle conditions enable higher SES groups to reduce the expression of their genetic susceptibility to coronary artery disease.
Exosomal MicroRNA Transfer Into Macrophages Mediates Cellular Postconditioning
Authors: de Couto Geoffrey , Gallet Romain , Cambier Linda , Jaghatspanyan Ervin , Makkar Nupur , Dawkins James Frederick , Berman Benjamin P. , Marbán Eduardo
Published: April 2017

Background:

Cardiosphere-derived cells (CDCs) confer cardioprotection in acute myocardial infarction by distinctive macrophage (Mϕ) polarization. Here we demonstrate that CDC-secreted exosomes (CDC
exo
) recapitulate the cardioprotective effects of CDC therapy known as cellular postconditioning.

Methods:

Rats and pigs underwent myocardial infarction induced by ischemia/reperfusion before intracoronary infusion of CDC
exo
, inert fibroblast exosomes (Fb
exo
; control), or vehicle. Two days later, infarct size was quantified. Macrophages were isolated from cardiac tissue or bone marrow for downstream analyses. RNA sequencing was used to determine exosome content and alterations in gene expression profiles in Mϕ.

Results:

Administration of CDC
exo
but not Fb
exo
after reperfusion reduces infarct size in rat and pig models of myocardial infarction. Furthermore, CDC
exo
reduce the number of CD68+ Mϕ within infarcted tissue and modify the polarization state of Mϕ so as to mimic that induced by CDCs. CDC
exo
are enriched in several miRNAs (including miR-146a, miR-181b, and miR-126) relative to Fb
exo
. Reverse pathway analysis of whole-transcriptome data from CDC
exo
-primed Mϕ implicated miR-181b as a significant (
P
=1.3x10
−21
) candidate mediator of CDC-induced Mϕ polarization, and PKCδ (protein kinase C δ) as a downstream target. Otherwise inert Fb
exo
loaded selectively with miR-181b alter Mϕ phenotype and confer cardioprotective efficacy in a rat model of myocardial infarction. Adoptive transfer of PKCδ-suppressed Mϕ recapitulates cardioprotection.

Conclusions:

Our data support the hypothesis that exosomal transfer of miR-181b from CDCs into Mϕ reduces PKCδ transcript levels and underlies the cardioprotective effects of CDCs administered after reperfusion.
Long‐Term Follow‐up of the PADI Trial: Percutaneous Transluminal Angioplasty Versus Drug‐Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia
Authors: Spreen Marlon I. , Martens Jasper M. , Knippenberg Bob , van Dijk Lukas C. , de Vries Jean‐Paul P. M. , Vos Jan Albert , de Borst Gert Jan , Vonken Evert‐Jan P. A. , Bijlstra Okker D. , Wever Jan J. , Statius van Eps Randolph G. , Mali Willem P. Th. M. , van Overhagen Hendrik
Published: April 2017

Background

Clinical outcomes reported after treatment of infrapopliteal lesions with drug‐eluting stents (DESs) have been more favorable compared with percutaneous transluminal angioplasty with a bailout bare metal stent (
PTA
‐
BMS
) through midterm follow‐up in patients with critical limb ischemia. In the present study, long‐term results of treatment of infrapopliteal lesions with
DESs
are presented.

Methods and Results

Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive
PTA
‐
BMS
or
DESs
with paclitaxel. Long‐term follow‐up consisted of annual assessments up to 5 years after treatment or until a clinical end point was reached. Clinical end points were major amputation (above ankle level), infrapopliteal surgical or endovascular reintervention, and death. Preserved primary patency (≤50% restenosis) of treated lesions was an additional morphological end point, assessed by duplex sonography. In total, 74 limbs (73 patients) were treated with
DESs
and 66 limbs (64 patients) were treated with
PTA
‐
BMS
. The estimated 5‐year major amputation rate was lower in the
DES
arm (19.3% versus 34.0% for
PTA
‐
BMS
;
P
=0.091). The 5‐year rates of amputation‐ and event‐free survival (survival free from major amputation or reintervention) were significantly higher in the
DES
arm compared with
PTA
‐BMS (31.8% versus 20.4%,
P
=0.043; and 26.2% versus 15.3%,
P
=0.041, respectively). Survival rates were comparable. The limited available morphological results showed higher preserved patency rates after
DESs
than after
PTA
‐
BMS
at 1, 3, and 4 years of follow‐up.

Conclusions

Both clinical and morphological long‐term results after treatment of infrapopliteal lesions in patients with critical limb ischemia are improved with
DES
compared with
PTA
‐
BMS
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00471289.
Differences in Short‐ and Long‐Term Mortality Associated With BMI Following Coronary Revascularization
Authors: Terada Tasuku , Forhan Mary , Norris Colleen M. , Qiu Weiyu , Padwal Raj , Sharma Arya M. , Nagendran Jayan , Johnson Jeffrey A.
Published: April 2017

Background

The association between obesity and mortality risks following coronary revascularization is not clear. We examined the associations of BMI (kg/m
2
) with short‐, intermediate‐, and long‐term mortality following coronary artery bypass graft surgery (
CABG
) and percutaneous coronary intervention (
PCI
) in patients with different coronary anatomy risks and diabetes mellitus status.

Methods and Results

Data from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) registry were analyzed. Using normal
BMI
(18.5–24.9) as a reference, multivariable‐adjusted hazard ratios for all‐cause mortality within 6 months, 1 year, 5 years, and 10 years were individually calculated for
CABG
and
PCI
with 4 prespecified
BMI
categories: overweight (25.0–29.9), obese class I (30.0–34.9), obese class
II
(35.0–39.9), and obese class
III
(≥40.0). The analyses were repeated after stratifying for coronary risks and diabetes mellitus status. The cohorts included 7560 and 30 258 patients for
CABG
and
PCI
, respectively. Following
PCI
, overall mortality was lower in patients with overweight and obese class I compared to those with normal
BMI
; however, 5‐ and 10‐year mortality rates were significantly higher in patients with obese class
III
with high‐risk coronary anatomy, which was primarily driven by higher mortality rates in patients without diabetes mellitus (5‐year adjusted hazard ratio, 1.78 [95%
CI
, 1.11–2.85] and 10‐year adjusted hazard ratio, 1.57 [95% CI, 1.02–2.43]). Following
CABG
, overweight was associated with lower mortality risks compared with normal
BMI
.

Conclusions

Overweight was associated with lower mortality following
CABG
and
PCI
. Greater long‐term mortality in patients with obese class
III
following
PCI
, especially in those with high‐risk coronary anatomy without diabetes mellitus, warrants further investigation.
Characteristics of Earlier Versus Delayed Presentation of Very Late Drug‐Eluting Stent Thrombosis: An Optical Coherence Tomographic Study
Authors: Lee Seung‐Yul , Ahn Jung‐Min , Mintz Gary S. , Hur Seung‐Ho , Choi So‐Yeon , Kim Sang‐Wook , Cho Jin Man , Hong Soon Jun , Kim Jin Won , Hong Young Joon , Lee Sang‐Gon , Shin Dong‐Ho , Kim Jung‐Sun , Kim Byeong‐Keuk , Ko Young‐Guk , Choi Donghoon , Jang Yangsoo , Park Seung‐Jung , Hong Myeong‐Ki
Published: April 2017

Background

The pathophysiology underlying very late drug‐eluting stent (
DES
) thrombosis is not sufficiently understood. Using optical coherence tomography, we investigated characteristics of very late stent thrombosis (
VLST
) according to different onset times.

Methods and Results

A total of 98 patients from 10 South Korean hospitals who underwent optical coherence tomography for evaluation of very late
DES
thrombosis were retrospectively included in analyses.
VLST
occurred at a median of 55.1 months after
DES
implantation. All patients were divided into 2 equal groups of earlier versus delayed presentation of
VLST
, according to median onset time. In total, 27 patients were treated with next‐generation
DES
and 71 with first‐generation
DES
. Based on optical coherence tomography findings at thrombotic sites, main
VLST
mechanisms were as follows, in descending order: neoatherosclerosis (34.7%), stent malapposition (33.7%), and uncovered struts without stent malapposition or evagination (24.5%). Compared with patients with earlier
VLST
, patients with delayed
VLST
had lower frequency of uncovered struts without stent malapposition or evagination (34.7% versus 14.3%, respectively;
P
=0.019). Conversely, the frequency of neoatherosclerosis was higher in patients with delayed versus earlier
VLST
(44.9% versus 24.5%, respectively;
P
=0.034). The frequency of stent malapposition was not different between patients with earlier and delayed
VLST
(34.7% versus 32.7%, respectively;
P
=0.831). The frequency of stent malapposition, evagination, and uncovered struts was still half of delayed
VLST
.

Conclusions

The pathological mechanisms of very late
DES
thrombosis changed over time. Delayed neointimal healing remained a substantial substrate for
VLST
, even long after
DES
implantation.
Growth Differentiation Factor 15 at 1 Month After an Acute Coronary Syndrome Is Associated With Increased Risk of Major Bleeding
Authors: Lindholm Daniel , Hagström Emil , James Stefan K. , Becker Richard C. , Cannon Christopher P. , Himmelmann Anders , Katus Hugo A. , Maurer Gerald , López‐Sendón José Luis , Steg Philippe Gabriel , Storey Robert F. , Siegbahn Agneta , Wallentin Lars
Published: April 2017

Background

Growth differentiation factor‐15 (
GDF
‐15) is related to major bleeding when measured at initial presentation in patients with acute coronary syndromes (
ACSs
) treated with dual antiplatelet therapy. It is unknown whether follow‐up measurements provide additional information. The objective of this study was to investigate whether
GDF
‐15 measured 1 month after an
ACS
provides additional information beyond the baseline levels with regard to the risk of major bleeding.

Methods and Results

GDF
‐15 was measured at baseline and at 1 month after an
ACS
in 4049 patients included in the PLATelet inhibition and patient Outcomes (PLATO) trial. The association between 1‐month
GDF
‐15 level and non–coronary artery bypass grafting surgery‐related major bleeding was assessed by a multivariable Cox model, adjusting for baseline
GDF
‐15, age, anemia, impaired renal function, history of gastrointestinal bleeding, and sex. Elevated
GDF
‐15 (>1800 ng/L) at 1 month was associated with an increased risk of non‐coronary artery bypass grafting‐related major bleeding (3.9% versus 1.2%; hazard ratio, 3.38; 95%
CI
, 1.89–6.06), independent of baseline
GDF
‐15. Patients who had elevated
GDF
‐15 levels at baseline and subsequent nonelevated
GDF
‐15 at 1 month had a similar risk as patients who had nonelevated levels at both measurements.

Conclusions

GDF
‐15 at 1 month after an
ACS
is related to the risk of bleeding during
DAPT
and provides additional information on the bleeding risk beyond baseline
GDF
‐15 levels.
GDF
‐15 levels may therefore be useful as part of decision support concerning long‐term antithrombotic treatment in patients post‐
ACS
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00391872.
Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist
Authors: Sato Kengo , Shirai Remina , Hontani Mina , Shinooka Rina , Hasegawa Akinori , Kichise Tomoki , Yamashita Tomoyuki , Yoshizawa Hayami , Watanabe Rena , Matsuyama Taka‐aki , Ishibashi‐Ueda Hatsue , Koba Shinji , Kobayashi Youichi , Hirano Tsutomu , Watanabe Takuya
Published: April 2017

Background

Kisspeptin‐10 (
KP
‐10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor,
GPR
54, have currently received much attention in relation to pre‐eclampsia. However, it still remains unknown whether
KP
‐10 could affect atherogenesis.

Methods and Results

We evaluated the effects of
KP
‐10 on human umbilical vein endothelial cells, human monocyte‐derived macrophages, human aortic smooth muscle cells in vitro, and atherosclerotic lesions in apolipoprotein E–deficient (ApoE
−/−
) mice in vivo.
KP
‐10 significantly increased the adhesion of human monocytes to human umbilical vein endothelial cells, which was significantly inhibited by pretreatment with P234, a
GPR
54 antagonist.
KP
‐10 stimulated
mRNA
expression of tumor necrosis factor‐α, interleukin‐6, monocyte chemotactic protein‐1, intercellular adhesion molecule‐1, vascular adhesion molecule‐1, and E‐selectin in human umbilical vein endothelial cells.
KP
‐10 significantly enhanced oxidized low‐density lipoprotein–induced foam cell formation associated with upregulation of
CD
36 and acyl‐CoA:cholesterol acyltransferase‐1 in human monocyte‐derived macrophages. In human aortic smooth muscle cells,
KP
‐10 significantly suppressed angiotensin
II
–induced migration and proliferation, but enhanced apoptosis and activities of matrix metalloproteinase (
MMP
)‐2 and
MMP
‐9 by upregulation of extracellular signal‐regulated kinase 1 and 2, p38, Bcl‐2‐associated X protein, and caspase‐3. Four‐week‐infusion of
KP
‐10 into ApoE
−/−
mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration and vascular inflammation as well as decreased intraplaque vascular smooth muscle cells contents. Proatherosclerotic effects of endogenous and exogenous
KP
‐10 were completely canceled by P234 infusion in ApoE
−/−
mice.

Conclusions

Our results suggest that
KP
‐10 may contribute to accelerate the progression and instability of atheromatous plaques, leading to plaque rupture. The
GPR
54 antagonist may be useful for prevention and treatment of atherosclerosis. Thus, the
KP
‐10/
GPR
54 system may serve as a novel therapeutic target for atherosclerotic diseases.
GRECOS Project (Genotyping Recurrence Risk of Stroke)
Authors: Fernández-Cadenas Israel , Mendióroz Maite , Giralt Dolors , Nafria Cristina , Garcia Elena , Carrera Caty , Gallego-Fabrega Cristina , Domingues-Montanari Sophie , Delgado Pilar , Ribó Marc , Castellanos Mar , Martínez Sergi , Freijo Marimar , Jiménez-Conde Jordi , Rubiera Marta , Alvarez-Sabín José , Molina Carlos A. , Font Maria Angels , Grau Olivares Marta , Palomeras Ernest , Perez de la Ossa Natalia , Martinez-Zabaleta Maite , Masjuan Jaime , Moniche Francisco , Canovas David , Piñana Carlos , Purroy Francisco , Cocho Dolores , Navas Inma , Tejero Carlos , Aymerich Nuria , Cullell Natalia , Muiño Elena , Serena Joaquín , Rubio Francisco , Davalos Antoni , Roquer Jaume , Arenillas Juan Francisco , Martí-Fábregas Joan , Keene Keith , Chen Wei-Min , Worrall Bradford , Sale Michele , Arboix Adrià , Krupinski Jerzy , Montaner Joan
Published: April 2017

Background and Purpose—

Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS.

Methods—

We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method.

Results—

The analyses revealed that rs1800801 in the
MGP
gene (hazard ratio, 1.33;
P
=9×10
−
03
), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (
P
=3.2×10
−
09
) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score (
P
=0.03).

Conclusions—

The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the
MGP
gene was associated with vascular recurrence in the Spanish population.