bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS‐Dependent and HIF‐1‐Independent Manners in Mouse Embryonic Stem Cells
Authors: Kučera Jan , Netušilová Julie , Sladeček Stanislava , Lánová Martina , Vašíček Ondřej , Štefková Kateřina , Navrátilová Jarmila , Kubala Lukáš , Pacherník Jiří
Published: July 2017

Hypoxia is involved in the regulation of stem cell fate, and hypoxia‐inducible factor 1 (HIF‐1) is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES) cell maintenance. We employed wild‐type and HIF‐1α‐deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF‐1‐independent manner, while STAT3 phosphorylation remained unaffected. Downregulation of ERK could not be mimicked either by pharmacologically induced hypoxia or by the overexpression. Dual‐specificity phosphatases (DUSP) 1, 5, and 6 are hypoxia‐sensitive MAPK‐specific phosphatases involved in ERK downregulation, and protein phosphatase 2A (PP2A) regulates both ERK and Akt. However, combining multiple approaches, we revealed the limited significance of DUSPs and PP2A in the hypoxia‐mediated attenuation of ERK signaling. Interestingly, we observed a decreased reactive oxygen species (ROS) level in hypoxia and a similar phosphorylation pattern for ERK when the cells were supplemented with glutathione. Therefore, we suggest a potential role for the ROS‐dependent attenuation of ERK signaling in hypoxia, without the involvement of HIF‐1.
The Diagnostic Yield of Colonoscopy Stratified by Indications
Authors: Al-Najami I. , Rancinger C. P. , Larsen Morten Kobaek , Spolén E. , Baatrup G.
Published: July 2017

Introduction. Danish centers reserve longer time for screening colonoscopies and allocate the most experienced endoscopists to these cases. The objective of this study is to determine the diagnostic yield in colonoscopies for different indications to improve planning of colonoscopy activity and allocation of the highly skilled endoscopists. Methods. Nine hundred and ninety-nine randomly collected patients from a prospectively maintained database were grouped in defined referral indication groups. Five groups were compared in respect of the detection rate of adenomas and cancers. Results. Two hundred and eighty-nine of 1098 colonoscopies in 999 patients showed significant neoplastic findings, resulting in 591 adenoma resections. Eighty-five percent were treated with a snare resection, and 15% with endoscopic mucosa resection (EMR). Positive findings in the indication groups were (1) symptoms, 25%; (2) positive screening, 17%; (3) previous resection of adenomas, 45%; (4) previous resection of colorectal cancer, 15%; and (5) surveillance of patients with high-risk family history of cancer, 35%. Conclusion. The majority of adenomas found during colonoscopy can be treated with simple techniques. If individualized time slots are considered, the adenoma follow-up colonoscopies are likely to be the most time-consuming group with more than twice the number of adenomas detected as compared to other indications.
Circulating miRNAs in Pediatric Pulmonary Hypertension Show Promise as Biomarkers of Vascular Function
Authors: Kheyfets Vitaly O. , Sucharov Carmen C. , Truong Uyen , Dunning Jamie , Hunter Kendall , Ivy Dunbar , Miyamoto Shelley , Shandas Robin
Published: July 2017

Background/Objectives. The objective of this study was to evaluate the utility of circulating miRNAs as biomarkers of vascular function in pediatric pulmonary hypertension. Method. Fourteen pediatric pulmonary arterial hypertension patients underwent simultaneous right heart catheterization (RHC) and blood biochemical analysis. Univariate and stepwise multivariate linear regression was used to identify and correlate measures of reactive and resistive afterload with circulating miRNA levels. Furthermore, circulating miRNA candidates that classified patients according to a 20% decrease in resistive afterload in response to oxygen (O2) or inhaled nitric oxide (iNO) were identified using receiver‐operating curves. Results. Thirty‐two circulating miRNAs correlated with the pulmonary vascular resistance index (PVRi), pulmonary arterial distensibility, and PVRi decrease in response to O2 and/or iNO. Multivariate models, combining the predictive capability of multiple promising miRNA candidates, revealed a good correlation with resistive (r = 0.97, P2−tailed < 0.0001) and reactive (r = 0.86, P2−tailed < 0.005) afterloads. Bland‐Altman plots showed that 95% of the differences between multivariate models and RHC would fall within 0.13 (mmHg−min/L)m2 and 0.0085/mmHg for resistive and reactive afterloads, respectively. Circulating miR‐663 proved to be a good classifier for vascular responsiveness to acute O2 and iNO challenges. Conclusion. This study suggests that circulating miRNAs may be biomarkers to phenotype vascular function in pediatric PAH.
Unilateral Headache Status after Intra-Aortic Balloon Pump Placement
Authors: Weber Garret M. , Gass Alan L. , Parikh Shalvi B.
Published: July 2017

Introduction. Intra-aortic balloon pump (IABP) counterpulsation is a catheter-based treatment for coronary artery disease and decompensated heart failure to increase coronary blood flow and improve cardiac output. IABP is generally well tolerated, and complications are usually related to peripheral vasculature or red blood cell and platelet consumption. The usual insertion site via femoral artery renders the patient bedbound. Recently, axillary artery has been used in patients with atherosclerotic peripheral vascular disease and documented small arteries or in those awaiting transplant to ensure ambulation and prevent deconditioning. Case Report. We present a patient with ischemic cardiomyopathy and severe left ventricular dysfunction, awaiting Orthotropic Heart Transplant. His worsening intractable angina and dyspnea necessitated IABP placement via left axillary artery, significantly improving his condition. He subsequently experienced migraine-type persistent unilateral headache refractory to standard pain management. Multiple strategies were utilized to treat his pain, but the patient insisted that his pain commenced after IABP placement. Ultimately, the removal of the pump led to complete resolution with no recurrence. Conclusion. The authors hypothesize that the unilaterally directed blood flow and direct increase in cerebral perfusion from the intra-aortic balloon pump may have caused vasodilation of the extracranial arteries, leading to a persistent and debilitating headache in this susceptible patient.
Molecular Dynamics Simulation of Crack Propagation in Single-Crystal Aluminum Plate with Central Cracks
Authors: Ding Jun , Wang Lu-sheng , Song Kun , Liu Bo , Huang Xia
Published: July 2017

The crack propagation process in single-crystal aluminum plate (SCAP) with central cracks under tensile load was simulated by molecular dynamics method. Further, the effects of model size, crack length, temperature, and strain rate on strength of SCAP and crack growth were comprehensively investigated. The results showed that, with the increase of the model size, crack length, and strain rate, the plastic yield point of SCAP occurred in advance, the limit stress of plastic yield decreased, and the plastic deformability of material increased, but the temperature had less effect and sensitivity on the strength and crack propagation of SCAP. The model size affected the plastic deformation and crack growth of the material. Specifically, at small scale, the plastic deformation and crack propagation in SCAP are mainly affected through dislocation multiplication and slip. However, the plastic deformation and crack propagation are obviously affected by dislocation multiplication and twinning in larger scale.
Combined Analysis of Endothelial, Hematopoietic, and Mesenchymal Stem Cell Compartments Shows Simultaneous but Independent Effects of Age and Heart Disease
Authors: Ghem Carine , Dias Lucinara Dadda , Sant’Anna Roberto Tofani , Kalil Renato A. K. , Markoski Melissa , Nardi Nance Beyer
Published: July 2017

Clinical trials using stem cell therapy for heart diseases have not reproduced the initial positive results obtained with animal models. This might be explained by a decreased regenerative capacity of stem cells collected from the patients. This work aimed at the simultaneous investigation of endothelial stem/progenitor cells (EPCs), mesenchymal stem/progenitor cells (MSCs), and hematopoietic stem/progenitor cells (HSCs) in sternal bone marrow samples of patients with ischemic or valvular heart disease, using flow cytometry and colony assays. The study included 36 patients referred for coronary artery bypass grafting or valve replacement surgery. A decreased frequency of stem cells was observed in both groups of patients. Left ventricular dysfunction, diabetes, and intermediate risk in EuroSCORE and SYNTAX score were associated with lower EPCs frequency, and the use of aspirin andβ-blockers correlated with a higher frequency of HSCs and EPCs, respectively. Most importantly, the distribution of frequencies in the three stem cell compartments showed independent patterns. The combined investigation of the three stem cell compartments in patients with cardiovascular diseases showed that they are independently affected by the disease, suggesting the investigation of prognostic factors that may be used to determine when autologous stem cells may be used in cell therapy.
Validation of Ankle Strength Measurements by Means of a Hand-Held Dynamometer in Adult Healthy Subjects
Authors: Ancillao Andrea , Palermo Eduardo , Rossi Stefano
Published: July 2017

Uniaxial Hand-Held Dynamometer (HHD) is a low-cost device widely adopted in clinical practice to measure muscle force. HHD measurements depend on operator’s ability and joint movements. The aim of the work is to validate the use of a commercial HHD in both dorsiflexion and plantarflexion ankle strength measurements quantifying the effects of HHD misplacements and unwanted foot’s movements on the measurements. We used an optoelectronic system and a multicomponent load cell to quantify the sources of error in the manual assessment of the ankle strength due to both the operator’s ability to hold still the HHD and the transversal components of the exerted force that are usually neglected in clinical routine. Results showed that foot’s movements and angular misplacements of HHD on sagittal and horizontal planes were relevant sources of inaccuracy on the strength assessment. Moreover, ankle dorsiflexion and plantarflexion force measurements presented an inaccuracy less than 2% and higher than 10%, respectively. In conclusion, the manual use of a uniaxial HHD is not recommended for the assessment of ankle plantarflexion strength; on the contrary, it can be allowed asking the operator to pay strong attention to the HHD positioning in ankle dorsiflexion strength measurements.
Pharmacokinetics and Pharmacodynamics Evaluation of Tramadol in Thermoreversible Gels
Authors: Papini Juliana Zampoli Boava , Cereda Cíntia Maria Saia , Pedrazzoli Júnior José , Calafatti Silvana Aparecida , de Araújo Daniele Ribeiro , Tofoli Giovana Radomille
Published: July 2017

We evaluated pharmacokinetics (PK) and pharmacodynamics (PD) induced by new formulations of tramadol (TR) in thermoreversible gels. The poloxamer- (PL-) tramadol systems were prepared by direct dispersion of the drug in solutions with PL 407 and PL 188. The evaluated formulations were as follows: F1: TR 2% in aqueous solution and F2: PL 407 (20%) + PL 188 (10%) + TR 2%; F3: PL 407 (25%) + PL 188 (5%) + TR 2%; F4: PL 407 (20%) + TR 2%. New Zealand White rabbits were divided into four groups (n=6) and treated by subcutaneous route with F1, F2, F3, or F4 (10 μg·kg−1). PK evaluation used TR and M1 plasma levels. PD evaluation was performed with the measurement of both pupils’ diameters. F2 showed higher TR plasma concentration after 180 minutes and presented lower M1 concentrations at almost all evaluated periods. Areas under the curve (ASC0–480 and ASC0–∞) and clearance of F2 presented differences compared to F1. F2 presented significant correlation (Pearson correlation) between the enhancement of TR and M1 concentrations and the decrease of pupil size (miosis). Thus, F2 was effective in altering pharmacokinetics and pharmacodynamics effects of TR.
A First Report on [18F]FPRGD2 PET/CT Imaging in Multiple Myeloma
Authors: Withofs Nadia , Cousin François , De Prijck Bernard , Bonnet Christophe , Hustinx Roland , Gambhir Sanjiv S. , Beguin Yves , Caers Jo
Published: July 2017

An observational study was set up to assess the feasibility of [F18]FPRGD2 PET/CT for imaging patients with multiple myeloma (MM) and to compare its detection rate with low dose CT alone and combined [F18]NaF/[F18]FDG PET/CT images. Four patients (2 newly diagnosed patients and 2 with relapsed MM) were included and underwent whole-body PET/CT after injection of [F18]FPRGD2. The obtained images were compared with results of low dose CT and already available results of a combined [F18]NaF/[F18]FDG PET/CT. In total, 81 focal lesions (FLs) were detected with PET/CT and an underlying bone destruction or fracture was seen in 72 (89%) or 8 (10%) FLs, respectively. Fewer FLs (54%) were detected by [F18]FPRGD2 PET/CT compared to low dose CT (98%) or [F18]NaF/[F18]FDG PET/CT (70%) and all FLs detected with [F18]FPRGD2 PET were associated with an underlying bone lesion. In one newly diagnosed patient, more [F18]FPRGD2 positive lesions were seen than [F18]NaF/[F18]FDG positive lesions. This study suggests that [F18]FPRGD2 PET/CT might be less useful for the detection of myeloma lesions in patients with advanced disease as all FLs with [F18]FPRGD2 uptake were already detected with CT alone.
Cigarette Smoking and Its Hazards in Kidney Transplantation
Authors: Khalil Muhammad Abdul Mabood , Tan Jackson , Khamis Said , Khalil Muhammad AshhadUllah , Azmat Rabeea , Ullah Arslan Rahat
Published: July 2017

Cigarette smoking affects many organs. It causes vasoconstriction through activation of sympathetic nervous system which leads to elevation of blood pressure and reduction in glomerular filtration rate and filtration pressure. It also causes thickening of renal arterioles. Cigarette smoking increases the risk of microalbuminuria and accelerates progression of microalbuminuria to macroalbuminuria. Furthermore, it causes rapid loss of glomerular filtration rate in chronic kidney disease patients. After kidney donation, these factors may be injurious to the solitary kidney. Kidney donors with history of cigarette smoking are prone to develop perioperative complications, pneumonia, and wound infection. Postkidney transplantation various stressors including warm and cold ischemia time, delayed graft function, and exposure to calcineurin inhibitors may result in poor graft function. Continuation of cigarette smoking in kidney transplant recipients will add further risk. In this review, we will specifically discuss the effects of cigarette smoking on normal kidneys, live kidney donors, and kidney transplant recipients. This will include adverse effects of cigarette smoking on graft and patient survival, cardiovascular events, rejection, infections, and cancers in kidney transplant recipients. Lastly, the impact of kidney transplantation on behavior and smoking cessation will also be discussed.
The Research of Clinical Decision Support System Based on Three-Layer Knowledge Base Model
Authors: Jiang Yicheng , Qiu Bensheng , Xu Chunsheng , Li Chuanfu
Published: July 2017

In many clinical decision support systems, a two-layer knowledge base model (disease-symptom) of rule reasoning is used. This model often does not express knowledge very well since it simply infers disease from the presence of certain symptoms. In this study, we propose a three-layer knowledge base model (disease-symptom-property) to utilize more useful information in inference. The system iteratively calculates the probability of patients who may suffer from diseases based on a multisymptom naive Bayes algorithm, in which the specificity of these disease symptoms is weighted by the estimation of the degree of contribution to diagnose the disease. It significantly reduces the dependencies between attributes to apply the naive Bayes algorithm more properly. Then, the online learning process for parameter optimization of the inference engine was completed. At last, our decision support system utilizing the three-layer model was formally evaluated by two experienced doctors. By comparisons between prediction results and clinical results, our system can provide effective clinical recommendations to doctors. Moreover, we found that the three-layer model can improve the accuracy of predictions compared with the two-layer model. In light of some of the limitations of this study, we also identify and discuss several areas that need continued improvement.
A Comparison of Thermal Growing Season Indices for the Northern China during 1961–2015
Authors: Cui Linli , Shi Jun , Ma Yue
Published: July 2017

Vegetation phenology is one of the most direct and sensitive indicators of terrestrial ecosystem in response to climate change. Based on daily mean air temperature at 877 meteorological stations over northern China from 1961 to 2015, the correlations and differences for different definitions of the growing season parameters (start, end, and length of the growing season) were investigated, and results show that higher correlations of 0.81–0.93 are found when indices which do not consider frost are compared with those of the same length which include the frost criteria, and lower correlations of 0.63–0.79 are observed when the length of indices is different and one of the indices includes the frost criteria or EI 3 (10 d < 5°C) is included. Lower correlations and larger differences are generally observed in the eastern and northwestern parts while higher correlation and smaller difference appeared in the northeastern and southwestern parts of northern China; thus the applicability comparison and selection of different definitions have important influence on the identifying and counting of the timing and length of the growing season in the eastern and northwestern regions of northern China.
Abnormal Biomarkers of Homocysteine Metabolism in Neonates with Conotruncal Heart Defects
Authors: Surmiak Piotr , Baumert Małgorzata , Paprotny Magdalena
Published: July 2017

Objectives. The etiology of conotruncal heart defects (CHD) remains unknown; however relation between homocysteine, folate levels, and congenital heart disease was found. With this perspective in mind, the aim of the study was to investigate biomarkers of homosyteine metabolism pathway in mothers and their neonates with CHD.Material and Methods. Forty-three pairs of mothers and their neonates with CHD and forty pairs of mothers and neonates with nonconotruncal heart defects (non-CHD) were enrolled. The control group (CG) consisted of fifty-nine pairs of mothers and their healthy neonates. For estimating the plasma total homocysteine (tHcy), serum folates, and cobalamin levels, mothers’ venous blood samples and umbilical cord blood were taken in all groups.Results. We observed higher tHcy levels in newborns with CHD in comparison to their mothers and to neonates with non-CHD. Cobalamin levels were significantly lower in neonates with CHD compared to other children. Folates and cobalamin levels were lower in CHD mothers compared to their children.Conclusions. Elevated homocysteine levels in neonates with CHD and folate metabolism disturbances in their mothers were noticed. The observed differences in homocysteine and cobalamin levels between neonates with CHD suggest the influence of various agents disturbing homocysteine metabolic pathways.
Sequential Kinase Inhibition (Idelalisib/Ibrutinib) Induces Clinical Remission in B-Cell Prolymphocytic Leukemia Harboring a 17p Deletion
Authors: Coelho H. , Badior M. , Melo T.
Published: July 2017

B-cell prolymphocytic leukemia (B-PLL) is a rare lymphoid neoplasm with an aggressive clinical course. Treatment strategies for B-PLL remain to be established, and, until recently, alemtuzumab was the only effective therapeutic option in patients harboring 17p deletions. Herein, we describe, for the first time, a case of B-cell prolymphocytic leukemia harboring a 17p deletion in a 48-year-old man that was successfully treated sequentially with idelalisib-rituximab/ibrutinib followed by allogeneic hematopoietic stem cell transplant (allo-HSCT). After 5 months of therapy with idelalisib-rituximab, clinical remission was achieved, but the development of severe diarrhea led to its discontinuation. Subsequently, the patient was treated for 2 months with ibrutinib and the quality of the response was maintained with no severe adverse effects reported. A reduced-intensity conditioning allo-HSCT from a HLA-matched unrelated donor was performed, and, thereafter, the patient has been in complete remission for 10 months now. In conclusion, given the poor prognosis of B-PLL and the lack of effective treatment modalities, the findings here suggest that both ibrutinib and idelalisib should be considered as upfront therapy of B-PLL and as a bridge to allo-HSCT.
Reordering Features with Weights Fusion in Multiclass and Multiple-Kernel Speech Emotion Recognition
Authors: Jiang Xiaoqing , Xia Kewen , Wang Lingyin , Lin Yongliang
Published: July 2017

The selection of feature subset is a crucial aspect in speech emotion recognition problem. In this paper, a Reordering Features with Weights Fusion (RFWF) algorithm is proposed for selecting more effective and compact feature subset. The RFWF algorithm fuses the weights reflecting the relevance, complementarity, and redundancy between features and classes comprehensively and implements the reordering of features to construct feature subset with excellent emotional recognizability. A binary-tree structured multiple-kernel SVM classifier is adopted in emotion recognition. And different feature subsets are selected in different nodes of the classifier. The highest recognition accuracy of the five emotions in Berlin database is 90.549% with only 15 features selected by RFWF. The experimental results show the effectiveness of RFWF in building feature subset and the utilization of different feature subsets for specified emotions can improve the overall recognition performance.
Recurrent CSF Rhinorrhea Misdiagnosed as Chronic Allergic Rhinitis with Subsequent Development of Bacterial Meningitis
Authors: Ulrich Michael T. , Loo Lawrence K. , Ing Michael B.
Published: July 2017

Introduction. Cerebrospinal fluid (CSF) rhinorrhea results from an abnormal communication of the dura mater to the nasal mucosa. The majority of cases of CSF rhinorrhea are the result of trauma or surgery involving the skull base. Spontaneous CSF rhinorrhea is a rare clinical entity with increased risk of ascending infection. Delay in diagnosis places the patient at risk of developing meningitis. Case Presentation. A 36-year-old African American female with significant medical history of obesity and hypertension presented to the emergency department with headache, altered level of consciousness, fever, and neck stiffness. Previously, the patient was diagnosed with chronic allergic sinusitis by multiple providers. Physical exam findings and laboratory tests were consistent with bacterial meningitis. The patient was admitted and started on appropriate antibiotic therapy. The patient continued to complain of persistent unilateral clear nasal drainage. The initial report from the computerized tomography scan of the sinuses indicated findings consistent with chronic sinusitis. Magnetic resonance imaging of the orbits revealed findings consistent with CSF rhinorrhea. Otolaryngology was consulted for surgical intervention. Conclusion. Suspected CSF rhinorrhea should prompt immediate biochemical and radiologic evaluation and surgical consultation. CSF rhinorrhea places patients at risk of developing bacterial meningitis.
Untargeted DNA-Demethylation Therapy Neither Prevents Nor Attenuates Ischemia-Reperfusion-Induced Renal Fibrosis
Authors: Vervaet Benjamin A. , Moonen Lies , Godderis Lode , Poels Katrien , D'Haese Patrick C.
Published: July 2017

Background: Current treatment options for chronic kidney disease (CKD) are limited and their focus is on slowing its progression by addressing comorbidities. Fibrosis, the common histopathological process in CKD, is a major therapeutic research target. In CKD, fibroblasts are terminally activated due to alterations in their DNA-methylation pattern, particularly hypermethylation. Preventing the copying of pathological DNA-methylation patterns in proliferating fibroblasts could be a new effective therapeutic strategy for treating CKD. Methods: To evaluate the therapeutic effect of short-term treatment with the DNA-methyltransferase (DNMT)-inhibitor decitabine on fibrosis (either developing or already established), male C57Bl/6 mice underwent warm unilateral ischemia-reperfusion injury. Respectively 3 days, 3 and 6 weeks after surgery, decitabine treatment (0.25 mg/kg) was initiated for 10 days after which animals were followed up to 12 weeks after ischemia. The efficacy of therapy on fibrosis was evaluated by collagen I and tgfβ gene expression and histological quantification of collagen I staining. In addition, the effect of decitabine treatment on tubular injury (Kim-1, Ngal), inflammation (TNFa, IL6), DNA-methyltransferases (Dnmt1, 3a, and 3b), and global methylation status was determined. Results: Following ischemia there was a significant increase in fibrotic, injury, and inflammatory markers as well as an increase of the various dnmts. Although decitabine treatment transiently increased renal injury and had a moderately decreasing effect on dnmt expression and on global DNA-methylation upon immediate treatment, none of the treatment regimens succeeded in preventing, attenuating, or diminishing fibrosis in the long run. Conclusion: Administration of untargeted nucleoside analogues seems unsuitable as a first-line treatment option in developing or established CKD.
Matrix Metalloproteinase Polymorphisms in Patients with Floppy Mitral Valve/Mitral Valve Prolapse (FMV/MVP) and FMV/MVP Syndrome
Authors: Lima Sarah M. , Pitsis Antonios A. , Kelpis Timotheos G. , Shahin Mohamed H. , Langaee Taimour Y. , Cavallari Larisa H. , Theofilogiannakos Efstratios K. , Boudoulas Harisios , Boudoulas Konstantinos Dean
Published: July 2017

Background: It has been suggested that collagen abnormalities of the mitral valve are present in patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP). Genetic factors determining collagen synthesis and degradation have not been well defined in these patients. This study was undertaken to determine whether selective polymorphisms of matrix metalloproteinase-2 (MMP2) or transforming growth factor-β (TGFβ), with known or putative effects on collagen turnover, are more frequent in FMV/MVP. Methods: Single nucleotide polymorphisms (SNPs) in select genes related to collagen turnover, including MMP2 rs2285053, MMP2 rs243865, TGFβ1 rs1800469, and TGFβ2 rs900, were determined in 98 patients with FMV/MVP who had severe mitral regurgitation and compared to 99 controls. Results:MMP2 rs243865 was the only SNP significantly associated with FMV/MVP as compared to the control (odds ratio 2.07, 95% CI 1.23-3.50, p = 0.006). MMP2 rs228503 was the only SNP significantly associated with the FMV/MVP syndrome as compared to patients with FMV/MVP without the syndrome (odds ratio 2.41, 95% CI 1.08-5.40, p = 0.032). Conclusion: The frequency of certain MMP2 polymorphisms is higher in patients with the FMV/MVP syndrome and patients with FMV/MVP without the syndrome. The data suggest that a genetic predisposition that alters collagen turnover may play a role in the pathogenesis and development of FMV/MVP.
Social Birth: Rites of Passage for the Newborn
Authors: Obladen Michael
Published: July 2017

Rites of passage mark important changes during human life and, for the neonate, its transition from intrauterine life into society. Their original intent was to purify the body from blood and meconium. But the cleansing rites had a spiritual dimension from the very start. When the rites of Mesopotamian, Egyptian, Jewish, Greek, Roman, Hindu, Nordic, Muslim, Maya, and Christian cultures are briefly compared, they reveal a remarkable similarity. What most rites had in common was the cleansing of the body, or sprinkling it with water; special clothing; the exorcism of evil spirits; blessings and prayers for good spirits; and a name-giving ceremony and a feast for family, relatives, and friends. Before this rite, the infant's social existence was incomplete and it could easily be abandoned or killed, as was usual in cases of severe malformations. Infant baptism originated in the 4th century CE with the concept of original sin. Emergency baptism originated in the 12th century and had a profound influence on the development of obstetrics and neonatal care. Rites of passage defined, but also set an end to, the liminal status between life and death in a phase of high mortality and partial personhood, and granted the right to live for the infant.
A Dopamine Hypothesis of Autism Spectrum Disorder
Authors: Pavăl Denis
Published: July 2017

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis.
A High Fat Diet During Pregnancy and Lactation Induces Cardiac and Renal Abnormalities in GLUT4 +/- Male Mice
Authors: Kruse Michael , Fiallo Ariana , Tao Jianling , Susztak Katalin , Amann Kerstin , Katz Ellen B. , Charron Maureen J.
Published: July 2017

Background/Aims: Altered nutrients during the in utero (IU) and/or lactation (L) period predispose offspring to cardio-renal diseases in adulthood. This study investigates the effect of a high fat diet (HFD) fed to female mice during IU/L on gene expression patterns associated with heart and kidney failure and hypertension in male offspring. Methods: Female wild type (WT) mice were fed either a HFD or control chow (C) prior to mating with males with a genetic heterozygous deletion of GLUT4 (G4+/-, a model of peripheral insulin resistance and hypertension) and throughout IU/L. After weaning male offspring were placed on a standard rodent chow until 24 weeks of age. Results: All offspring exposed to a maternal HFD showed increased heart and kidney weight and reduced cardiac insulin responsiveness. G4+/- offspring on a HFD displayed early hypertension associated with increased renal gene expression of renin and the AT1- receptors compared to G4+/- on a C diet. This group showed decreased cardiac expression of key genes involved in fatty acid oxidation compared to WT on a C diet. Conclusions: These results indicate an interaction between a HFD diet and genotype during early life development that can enhance susceptibility to cardio-renal diseases later in life.
Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction
Authors: Chen Chang , Gao Jin-Lai , Liu Ming-Yu , Li Shan-Liang , Xuan Xiu-Chen , Zhang Xin-Zi , Zhang Xi-Yue , Wei Yuan-Yuan , Zhen Chang-Lin , Jin Jing , Shen Xin , Dong De-Li
Published: July 2017

Background/Aims: Endothelin-1 is implicated in the pathogenesis of hypertension, but the underlying mechanisms remained elusive. Our previous study found that inhibition of mitochondrial fission of smooth muscle cells suppressed phenylephrine- and high K+-induced artery constriction. Here, we studied the effects of mitochondrial fission inhibitors on endothelin-1-induced vasoconstriction. Methods: The tension of rat mesenteric arteries and thoracic aorta was measured by using a multi-wire myograph system. Mitochondrial morphology of aortic smooth muscle cells was observed by using transmission electron microscopy. Results: Dynamin-related protein-1 selective inhibitor mdivi-1 relaxed endothelin-1-induced constriction, and mdivi-1 pre-treatment prevented endothelin-1-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Mdivi-1 had a similar inhibitory effect on rat thoracic aorta. Another mitochondrial fission inhibitor dynasore showed similar effects as mdivi-1 in rat mesenteric arteries. Mdivi-1 inhibited endothelin-1-induced increase of mitochondrial fission in smooth muscle cells of rat aorta. Rho-associated protein kinase inhibitor Y-27632 which relaxed endothelin-1-induced vasoconstriction inhibited endothelin-1-induced mitochondrial fission in smooth muscle cells of rat aorta. Conclusion: Endothelin-1 increases mitochondrial fission in vascular smooth muscle cells, and mitochondrial fission inhibitors suppress endothelin-1-induced vasoconstriction.
Posthuman Community in the Edgelands
Authors: Cudworth Erika
Published: July 2017

This paper draws on a study of companion animals in human households and public spaces, deploying material gained by ethnographic observation and interviews with dog walkers in urban and rural contexts. The communities which are the subject of this study frequent public places that might be described as “Edgeland” space where dogs and “dog people” meet. It is argued the relationships between cross-species packs of people and dogs that develop over time in the routine practice of walking are micro-communities inclusive of both dogs and their human companions. These might be understood as posthuman social forms with particular characteristics of inclusivity, diversity, and reconstitution. Human members of such communities are also invested in, and defensive of, Edgeland spaces and engaged in practices of care for both human and canine walkers.
Perceptions of Insects
Authors: Lemelin Raynald Harvey , Dampier Jason , Harper Rick , Bowles Robert , Balika Debbie
Published: July 2017

A Personal Meaning of Insects Map (pmim) was administered to participants from eastern Canada and northeastern United States. In the four-phase inductive study, participant responses to insects were coded and analyzed. Responses were elicited prior to and after viewing an insect video. Responses regarding the most cited insects, negative and positive associations with insects, and suggested management and education strategies were examined. Participants also discussed how information was acquired from various sources. The findings suggest that perceptions of insects are contextualized and sometimes inaccurate relative to scientific taxonomy. Research and the development of education strategies that take into account how the general public understands (or misunderstands) insects and where it acquires its information would be better served if we were to develop management and educational tools that address human-insect encounters from various socio-cultural perspectives.
Strengthening the Evaluation of Evidence in International Criminal Trials
Authors: McDermott Yvonne
Published: July 2017

Recent studies have highlighted instances where findings of fact reached by international criminal tribunals appear not to be adequately supported by the evidence. These works have typically focused on evidential issues, such as witnesses’ fading memories, cultural differences, and more sinister aspects (such as financial incentives) as the root causes for such discrepancies. However, this article argues that these accounts are incomplete, as they do not recognise difficulties arising from the judicial evaluation of, and reasoning on, the evidential record, which poses potentially insurmountable challenges to reliable fact-finding by international criminal tribunals. This article highlights recent differences of opinion between judges on how evidence should be weighed and evaluated. It points to some issues arising from the enormity of the fact-finding role in international criminal trials and the procedural framework embraced by the international criminal tribunals. It discusses tools to assist fact-finding, and their potential applicability to international criminal trials.
Searching for Deterrence at the International Criminal Court
Authors: Dancy Geoff
Published: July 2017

Does the International Criminal Court (icc) deter acts of violence in the world? To answer this question, this article first distinguishes between three phenomena that are often confusingly grouped together under the heading of ‘deterrence’. These include the termination of ongoing civil wars (compellence), the prevention of atrocity crime recidivism (specific deterrence), and the overall prevention of war and atrocity crimes (general deterrence). The article then assesses whether state commitments to the Rome Statute and icc intervention in specific contexts can promote these three aims. It presents evidence that the icc can indeed contribute to violence prevention, though not because of its ability to sanction abusive actors. Instead, the Court’s role as a ‘stigmatizer’ in the international community has likely contributed to declines in certain types of violence over time. As such, the article concludes that the icc is more important for what it is than what it does.
Morphological and molecular study of the genus Nosopsyllus (Siphonaptera: Ceratophyllidae). Nosopsyllus barbarus () as a junior synonym of Nosopsyllus fasciatus (Bosc d’Antic, 1800)
Authors: Zurita Antonio , Callejón Rocío , de Rojas Manuel , Cutillas Cristina
Published: July 2017

In the present work, a comparative morphological and molecular study of Nosopsyllus barbarus (Jordan & Rothschild 1912) and Nosopsyllus fasciatus (Bosc, d’Antic 1800) isolated from rodents from different geographical regions (Spain, Morocco, Belgium, France and Portugal) has been carried out. The Internal Transcribed Spacers 1 and 2 (ITS1, ITS2) and partial 18S rRNA, and partial cytochrome c oxidase 1 (cox1) and cytochrome b (cytb) mtDNA sequences were determined to clarify the taxonomic status of these two species and to assess intraspecific variation and inter-specific sequence differences. In addition, a phylogenetic analysis with other species of fleas using Bayesian inference was performed. We have found morphological differences between N. barbarus and N. fasciatus that did not correspond with molecular differences. Furthermore, any of the five molecular markers used in this study was able to discriminate between the two species. Thus, based on the phylogenetic and molecular study of three nuclear markers (18S, ITS1, ITS2) and two mitochondrial markers (cox1 and cytb), as well as the concatenated dataset of both species, we concluded that morphological characters traditionally used to discriminate between the two species do not provide solid arguments for considering these two “morphospecies” as two different species. Therefore, we propose N. barbarus should be considered as a junior synonym of N. fasciatus.
The genus Arocatus in Taiwan (Hemiptera: Heteroptera: Lygaeidae)
Authors: TSAI JING-FU , RÉDEI DÁVID
Published: July 2017

Species of the genus Arocatus Spinola, 1837 (Hemiptera: Heteroptera: Lygaeidae: Lygaeinae) occurring in Taiwan are reviewed, illustrated and keyed. Arocatus elegantulus sp. nov. is described; earlier records of Caenocoris dimidiatus Breddin, 1907 from Taiwan and the Ryukyu Archipelago of Japan pertain to this new species. Arocatus pseudosericans Gao, Kondorosy & Bu, 2013 and A. nanus (Breddin, 1900) are recorded for the first time from Taiwan; earlier records of A. sericans (Stål, 1859) pertain to A. pseudosericans. The distribution of A. sericans and A. pseudosericans in Japan and Korea and the intraspecific variability of A. pseudosericans are discussed. The identification problems of the genera Arocatus, Caenocoris Fieber, 1860 and Thunbergia Horváth, 1914 are highlighted, the external male genitalia of T. cf. marginata (Thunberg, 1822) are described and illustrated, and diagnostic characters potentially suitable for distinguishing Thunbergia from Arocatus are provided.
A new Trogoderma species from Central Madagascar (Coleoptera: Dermestidae: Megatominae)
Authors: HÁVA JIŘÍ , BAŇAŘ PETR
Published: July 2017

A new species, Trogoderma sahondrae sp. nov., from Central Madagascar is described and illustrated and a key to all known Madagascan species is provided. The new species differs from other related species by the combination of colour of the elytral fasciae, structure of antennae, and male genitalia.
Comparative morphology and description of male of Dysschema amapoarum Moraes & Duarte, 2015 (Lepidoptera: Erebidae, Arctiinae)
Authors: MORAES SIMEÃO DE SOUZA , DUARTE MARCELO
Published: July 2017

The previously unknown male of Dysschema amapoarum Moraes & Duarte, 2015 from the Atlantic Rainforest of southeast Brazil is here described, with illustrations of the adult and genitalia. We also compare the habitus and morphology of D. amapoarum with three closely related species, in order to shed light on the taxonomic identity of this species.
A Framework to Decompose Wind-Driven Biases in Climate Models Applied to CCSM/CESM in the Eastern Pacific
Authors: Larson Sarah M. , Kirtman Ben P. , Vimont Daniel J.
Published: July 2017

Annual cycle biases in climate models are suspected to be largely wind driven along the equator, with winds first driving SST changes that then influence the overlying atmospheric circulation. This study utilizes an experimental approach to test the hypothesis that seasonally varying climatological wind stress directly contributes to the SST and ITCZ biases in the eastern equatorial Pacific. Results show that removing the wind stress annual cycle from the ocean forcing, without constraining the atmosphere and ocean dynamics or buoyancy coupling in the NCAR CCSM4/CESM1.2.0 models, results in a remarkable reduction in the SST annual cycle and springtime ITCZ biases. Improvements in the SST occur primarily because wind-driven errors in the variability of horizontal temperature advection are damped. The ITCZ problem is closely tied to biases in the wind-driven near-equatorial SST. Additional model experiments and analyses reveal that the contributions from zonal and meridional wind stress to the biases are locally forced within 10°S–10°N and additive, suggesting that the biases are driven by independent processes. The zonal and meridional components drive different aspects of the SST annual cycle bias and contribute to the springtime ITCZ bias in different zonal locations. Both the atmosphere and ocean components of the model, separately, are shown to produce unfavorable ocean surface conditions for the simulation of a realistic springtime ITCZ, deeming this a coupled problem. Results show that wind stress may act as a pathway for process-based errors in climate models to directly drive SST and ITCZ biases.
Calibrated Approach to Endoscopico Sinus Surgery
Authors: Lucente Frank E. , Schoenfeld Philip S.
Published: July 2017

Endoscopic sinus surgery, in which the surgeon views the nose and paranasal sinuses through a telescope, can potentially lead to loss of perspective of the patient's entire head. Preoperative computed tomographs are also taken at angles different from those encountered in the surgical setting. As a result, the appropriate angle and depth of instrument insertion can fail to be appreciated. In order to study those angles and depths in a setting that more closely resembles the clinical situation in the operating room, we have performed 15 cadaver dissections and measured 14 dimensions relevant to the endoscopic approach. We recommend that cadaver dissection be an important part of continued training in sinus surgery. We also recommend that a reference probe be placed along the floor of the nose and that endoscopic instruments be calibrated at 1-cm intervals so that the depth of insertion can be monitored by an observer or instructor.
Bronchogenic Cyst with Tracheal Involvement
Authors: Yerman Howard M. , Holinger Lauren D.
Published: July 2017

Bronchogenic cysts are uncommon developmental anomalies of the primitive foregut that can produce symptoms of ventilatory compromise in infants and children. A 2-month-old child presented with episodes of stridor and obstructive apnea due to a bronchogenic cyst compressing the trachea and causing near-total obstruction. Aspiration of the cyst during bronchoscopy resulted in severe bradycardia (from 140 to 50 beats per minute), although blood pressure was stable and oxygen saturation remained at 100 %. Subsequent elective thoracotomy revealed the cyst to be intimately associated with the vagus nerve, and vagal stimulation may have caused the bradycardia. Bronchogenic cysts, although rare, should be considered in the differential diagnosis of infants and children undergoing direct laryngoscopy and bronchoscopy for airway compromise. The endoscopic aspiration of cystic tracheal and bronchial lesions may not obviate the need for more definitive surgical treatment and, as this case demonstrates, is not free of potential hazard.
Ultrastructural Changes in Human Nasal Cilia Caused by the Common Cold and Recovery of Ciliated Epithelium
Authors: Rautiainen Markus , Kiukaanniemi Heikki , Nuutinen Juhani , Collan Yrjö
Published: July 2017

Changes in the ultrastructure of human respiratory cilia caused by the common cold were studied in 12 patients. The nasal mucosa was studied three times: on the first or second day after the beginning of symptoms, and 1 week and 3 weeks after the first biopsy. The damage was most severe at 1 week. The most remarkable finding was the loss of cilia and ciliated cells. However, the ultrastructure was usually normal, without any increase in tubular anomalies, as compared with the normal material of the previous reports. Three weeks after the beginning of the disease the number of cilia and ciliated cells had increased to nearly normal. However, as a sign of regeneration, immature short cilia (0.7 to 2.5 μm in length) were often seen. The ciliary orientation was uniform, dynein arms were normal, and there was no increase in the number of tubular anomalies. The results suggest that the impaired mucociliary function during viral infections is due to the loss of cilia and ciliated cells, rather than to ultrastructural anomalies in the cilia. The development of tubular anomalies and random ciliary orientation may require more extensive exposure to factors affecting ciliary function.