bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular and Molecular Mechanisms of Autoimmune Hepatitis
Authors: Webb G.J. , Hirschfield G.M. , Krawitt E.L. , Gershwin M.E.
Published: November 2017

Autoimmune hepatitis is an uncommon idiopathic syndrome of immune-mediated destruction of hepatocytes, typically associated with autoantibodies. The disease etiology is incompletely understood but includes a clear association with human leukocyte antigen (HLA) variants and other non-HLA gene variants, female sex, and the environment. Pathologically, there is a CD4+ T cell–rich lymphocytic inflammatory infiltrate with variable hepatocyte necrosis and subsequent hepatic fibrosis. Attempts to understand pathogenesis are informed by several monogenetic syndromes that may include autoimmune liver injury, by several drug and environmental agents that have been identified as triggers in a minority of cases, by human studies that point toward a central role for CD4+ effector and regulatory T cells, and by animal models of the disease. Nonspecific immunosuppression is the current standard therapy. Further understanding of the disease's cellular and molecular mechanisms may assist in the design of better-targeted therapies, aid the limitation of adverse effects from therapy, and inform individualized risk assessment and prognostication.
Src family kinase inhibitors blunt PACAP-induced PAC1 receptor endocytosis, phosphorylation of ERK, and the increase in cardiac neuron excitability
Authors: Tompkins John D. , Clason Todd A. , Buttolph Thomas R. , Girard Beatrice M. , Linden Anne K. , Hardwick Jean C. , Merriam Laura A. , May Victor , Parsons Rodney L.
Published: November 2017

Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors ( Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. However, additional mechanisms responsible for the enhanced excitability are activated following internalization of the PAC1 receptor and endosomal signaling. Src family kinases play critical roles mediating endocytosis of many trophic factor and G protein-coupled receptors. The present study investigated whether Src family kinases also support the PACAP-induced PAC1 receptor internalization, phosphorylation of ERK, and enhanced neuronal excitability. Using human embryonic kidney cells stably expressing a green fluorescent protein-tagged PAC1 receptor, treatment with the Src family kinase inhibitor PP2 (10 µM) markedly reduced the PACAP-induced PAC1 receptor internalization, and in parallel, both PP2 and Src inhibitor 1 (Src-1, 2 µM) reduced ERK activation determined by Western blot analysis. In contrast, Src family kinase inhibitors did not eliminate a PACAP-induced rise in global calcium generated by inositol (1,4,5)-trisphosphate-induced release of calcium from endoplasmic reticulum stores. From confocal analysis of phosphorylated ERK immunostaining, PP2 treatment significantly attenuated PACAP activation of ERK in neurons within cardiac ganglia whole mount preparations. Intracellular recordings demonstrated that PP2 also significantly blunted a PACAP-induced increase in cardiac neuron excitability. These studies demonstrate Src-related kinase activity in PAC1 receptor internalization, activation of MEK/ERK signaling, and regulation of neuronal excitability. The present results provide further support for the importance of PAC1 receptor endosomal signaling as a key mechanism regulating cellular function.
Microvascular insulin resistance in skeletal muscle and brain occurs early in the development of juvenile obesity in pigs
Authors: Olver T. Dylan , Grunewald Zachary I. , Jurrissen Thomas J. , MacPherson Rebecca E. K. , LeBlanc Paul J. , Schnurbusch Teagan R. , Czajkowski Alana M. , Laughlin M. Harold , Rector R. Scott , Bender Shawn B. , Walters Eric M. , Emter Craig A. , Padilla Jaume
Published: November 2017

Impaired microvascular insulin signaling may develop before overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signaling manifests in skeletal muscle (triceps), brain (prefrontal cortex), and corresponding vasculatures, and that depressed insulin-induced vasodilation is reversible with acute inhibition of protein kinase Cβ (PKCβ). Juvenile Ossabaw miniature swine (3.5 mo of age) were divided into two groups: lean control ( n = 6) and obese ( n = 6). Obesity was induced by feeding the animals a high-fat/high-fructose corn syrup/high-cholesterol diet for 10 wk. Juvenile obesity was characterized by excess body mass, hyperglycemia, physical inactivity (accelerometer), and marked lipid accumulation in the skeletal muscle, with no evidence of overt atherosclerotic lesions in athero-prone regions, such as the abdominal aorta. Endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) vasomotor responses in the brachial and carotid arteries (wire myography), as well as in the skeletal muscle resistance and 2A pial arterioles (pressure myography) were unaltered, but insulin-induced microvascular vasodilation was impaired in the obese group. Blunted insulin-stimulated vasodilation, which was reversed with acute PKCβ inhibition (LY333-531), occurred alongside decreased tissue perfusion, as well as reduced insulin-stimulated Akt signaling in the prefrontal cortex, but not the triceps. In the early stages of juvenile obesity development, the microvasculature and prefrontal cortex exhibit impaired insulin signaling. Such adaptations may underscore vascular and neurological derangements associated with juvenile obesity.
The Role of Sphingosine-1-Phosphate and Ceramide-1-Phosphate in Inflammation and Cancer
Authors: Hait Nitai C. , Maiti Aparna
Published: November 2017

Inflammation is part of our body’s response to tissue injury and pathogens. It helps to recruit various immune cells to the site of inflammation and activates the production of mediators to mobilize systemic protective processes. However, chronic inflammation can increase the risk of diseases like cancer. Apart from cytokines and chemokines, lipid mediators, particularly sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), contribute to inflammation and cancer. S1P is an important player in inflammation-associated colon cancer progression. On the other hand, C1P has been recognized to be involved in cancer cell growth, migration, survival, and inflammation. However, whether C1P is involved in inflammation-associated cancer is not yet established. In contrast, few studies have also suggested that S1P and C1P are involved in anti-inflammatory pathways regulated in certain cell types. Ceramide is the substrate for ceramide kinase (CERK) to yield C1P, and sphingosine is phosphorylated to S1P by sphingosine kinases (SphKs). Biological functions of sphingolipid metabolites have been studied extensively. Ceramide is associated with cell growth inhibition and enhancement of apoptosis while S1P and C1P are associated with enhancement of cell growth and survival. Altogether, S1P and C1P are important regulators of ceramide level and cell fate. This review focuses on S1P and C1P involvement in inflammation and cancer with emphasis on recent progress in the field.
Relationships among Tomistoma schlegelii in Malaysia Based on Cyt b-Control Region Gene Analysis
Authors: Md Adzhar Muhammad Amirul Arib , Hassan Ruhana
Published: November 2017

Tomistoma schlegelii is a slender snout crocodile, secretive in nature which is currently under Appendix I of Convention on International Trade in Endangered Species of Wild Flora and Fauna (CITES). Limited information is currently available on its wild population, especially in Malaysia. Thus this study aims to describe genetic relationship of T. schlegelii populations from Malaysia which was done using partial sequencing of Cytochrome b-control region mtDNA gene. The study reveals that the genetic diversity among T. schlegelii is high, ranging from 0.16% to 3.34%, suggesting healthy populations. Analysis showed that there is gene flow among populations (Da = 1.71% to 2.21%) within Western Sarawak, Peninsular Malaysia, and other geographical regions coherent with Sundaland theory, suggesting that there is ancient river system connecting the two regions of Peninsular Malaysia and West Borneo when the Sunda Shelf was exposed. Unique haplotypes had been observed in Northern Sarawak (SAM01 and SAM02) as well as in Sumatera; thus each T. schlegelii deserved its own management strategies to ensure the survival of the species.
Effect of Cap-Lenticule Diameter Difference on the Visual Outcome and Higher-Order Aberrations in SMILE: 0.4 mm versus 1.0 mm
Authors: Torun Acar Banu , Acar Suphi
Published: November 2017

Purpose. To evaluate the effect of cap-lenticule diameter difference (CLDD) on the visual outcome and higher-order aberrations (HOAs) of small-incision lenticule extraction (SMILE). Methods. A total of 132 patients who had bilateral SMILE for myopia or myopic astigmatism were included. The CLDD was 0.4 mm in 54 patients (group 1) and 1.0 mm in 78 patients (group 2). The refractive parameters, uncorrected (UDVA) and corrected distance visual acuity (CDVA), and HOAs were determined preoperatively and during six months follow-up. Results. Group 1 had better CDVA (in logMAR) compared to group 2 at day 1 (−0.07 ± 0.07 versus 0.04 ± 0.07, resp.; p<0.001) and week 1 (−0.07 ± 0.07 versus –0.04 ± 0.07, resp.; p=0.001). The visual acuity improved more in group 1 than in group 2. The UDVA (in logMAR) was 0.07 ± 0.07 and 0.29 ± 0.09 at day 1 (p<0.001) and −0.08 ± 0.07 and −0.06 ± 0.06 at six months (p=0.038) in group 1 and group 2, respectively. Group 1 was associated with significantly less induction of HOAs (0.24 ± 0.08 μm and 0.32 ± 0.26 μm, resp.; p=0.002). Conclusions. In SMILE, 0.4 mm CLDD is associated with better visual outcome and less induction of HOAs than 1.0 mm. Narrow CLDD should be considered in SMILE to increase the visual acuity particularly in the early postoperative period.
Growth Patterns in the Irish Pyridoxine Nonresponsive Homocystinuria Population and the Influence of Metabolic Control and Protein Intake
Authors: Purcell Orla , Coughlan Aoife , Grant Tim , McNulty Jenny , Clark Anne , Deverell Deirdre , Mayne Philip , Hughes Joanne , Monavari Ahmad , Knerr Ina , Crushell Ellen
Published: November 2017

A low methionine diet is the mainstay of treatment for pyridoxine nonresponsive homocystinuria (HCU). There are various guidelines for recommended protein intakes for HCU and clinical practice varies. Poor growth has been associated with low cystine levels. This retrospective review of 48 Irish pyridoxine nonresponsive HCU patients assessed weight, height, body mass index (BMI), protein intake, and metabolic control up to 18 years at nine set time points. Patients diagnosed through newborn screening (NBS) were compared to late diagnosed (LD) patients. At 18 years the LD group (n=12, mean age at diagnosis 5.09 years) were heavier (estimated effect +4.97 Kg,P=0.0058) and taller (estimated effect +7.97 cmP=0.0204) than the NBS group (n=36). There was no difference in growth rate between the groups after 10 years of age. The HCU population were heavier and taller than the general population by one standard deviation with no difference in BMI. There was no association between intermittently low cystine levels and height. Three protein intake guidelines were compared; there was no difference in adult height between those who met the lowest of the guidelines (Genetic Metabolic Dietitians International) and those with a higher protein intake.
Fear of Falling and Cognitive Impairments in Elderly People with Hip Fractures
Authors: Kasai Mari , Meguro Kenichi , Ozawa Hiroshi , Kumai Keiichi , Imaizumi Hideki , Minegishi Hanae , Oi Hideki , Oizumi Akira , Yamashiro Masahiro , Matsuda Michimasa , Tanaka Masahiko , Itoi Eiji
Published: November 2017

Background/Aim: The purpose of this study was to investigate the estimated prevalence of dementia and the relationship between cognitive impairment and fear of falling in patients with hip fractures. Methods: Analysis 1 included 100 patients with hip fractures. Analysis 2 included a subgroup of subjects with ≥75 years of functional independence: 46 patients with hip fractures and 46 control subjects without hip fractures, and presence or absence of dementia. We used an informant-rated questionnaire including the AD8 for screening for dementia, the Barthel Index for assessing activities of daily living, and the Short Falls Efficacy Scale-International (FES-I) for assessing fear of falling. Results: The estimated prevalence of dementia was 66% in patients with hip fractures. There were significant fracture and dementia effects, with significant covariate effects of age and gender on the Short FES-I scores. Conclusion: Our results suggested that more than two-thirds of patients with hip fractures had dementia. Fear of falling may reflect not only physical functions but also cognitive impairments.
A Small Supernumerary Marker Derived from the Pericentromeric Region of Chromosome 5: Case Report and Delineation of Partial Trisomy 5p Phenotype
Authors: Camerota Letizia , Pitzianti Mariabernarda , Postorivo Diana , Nardone Anna M. , Ligas Claudio , Moretti Costanzo , Pasini Augusto , Brancati Francesco
Published: November 2017

A 17-year-old girl presented with a distinct phenotype mainly featuring craniofacial dysmorphism, including a disproportioned large, round, elongated face; hypertelorism; deep-set eyes with short palpebral fissures; obesity (BMI 37), and a neuropsychiatric disorder with high-functioning autism. Postnatal conventional cytogenetic analyses from peripheral blood revealed a mosaic small supernumerary marker chromosome (sSMC) with a mos 47,XX,+mar[7]/46,XX[43] karyotype. By cenM-FISH technique, the sSMC was identified as a ring derivative of chromosome 5. Metaphase FISH analysis with a set of dedicated probes defined its origin from the pericentromeric region of chromosome 5, including the NIPBL gene at 5p13.2. Such sSMCs, exceedingly rare in the literature, underlie proximal trisomy 5p. In order to delineate a core phenotype of proximal trisomy 5p, we compared our patient's features with those of 6 patients found in the literature with similar der(5) chromosomes. Furthermore, a dozen individuals with 5p13 (micro)duplication syndrome was compared and discussed. We identified highly distinctive craniofacial dysmorphism, obesity, and intellectual disability and/or autism spectrum disorder as typical features of proximal 5p trisomy. In the critical region (band 5p13), the NIPBL gene is likely to be a major determinant of the neurobehavioral phenotype, and its presence at the sSMC level may be relevant to predict clinical outcome.
Polyperspektivität in der Medizin: Dilemma oder Chance? Zur Ganzheitlichkeit der Homöopathie Hahnemanns
Authors: Schmidt Josef M.
Published: November 2017

Die von Samuel Hahnemann (1755-1843) begründete Homöopathie lässt sich heute aus den verschiedensten Perspektiven betrachten und beurteilen - bedingt durch interne Differenzierungen, externe kritische Einwände sowie einschlägige Forschungsergebnisse aus fast allen Natur- und Geisteswissenschaften. Die kulturgeschichtlichen Wurzeln der jetzt in allen Bereichen, auch in der Medizin, überbordenden Polyperspektivität liegen im Abendland einerseits im traditionellen monotheistischen Wahrheitsbegriff der jüdisch-christlichen Religion, andererseits in einem seit der Aufklärung sich beschleunigenden Rationalisierungs- und Dekonstruktionsprozess innerhalb der Wissenschaften selbst. Sozioökonomische Auswirkungen der zunehmenden Unsicherheit und Überforderung reichen von Orientierungslosigkeit und Delegitimierung der Wissenschaften bis zur Herrschaft von Zahlen und Algorithmen. Zur Bewältigung dieser Herausforderung bieten sich theoretisch etwa die Philosophie des Jainismus (Anekantavada, Syadvada, Nayavada) oder Friedrich Nietzsches an, praktisch vor allem Platons Staatsphilosophie sowie die christliche Trinitätslehre. Indem auch Hahnemanns Homöopathie-Konzeption die Dimensionen Mythos, Logos und Ethos umfasst, bietet sein Ansatz ein seit 200 Jahren bewährtes Paradigma, mit dem Polyperspektivitätsdilemma auf eine praktische, realistische und kreative Weise fertig zu werden.
MMP-9 and Its Regulators TIMP-1 and EMMPRIN in Patients with Acute ST-Elevation Myocardial Infarction: A NORDISTEMI Substudy
Authors: Opstad Trine Baur , Seljeflot Ingebjørg , Bøhmer Ellen , Arnesen Harald , Halvorsen Sigrun
Published: November 2017

Objectives: The extracellular matrix is involved in wound repair after acute myocardial infarction (AMI). We investigated whether matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and the MMP inducer (EMMPRIN) are associated with infarct size, left ventricular function, and clinical outcome in ST-elevation-MI (STEMI). Methods: In 243 STEMI patients, circulating EMMPRIN, MMP-9, and TIMP-1 were analyzed 3 days and 3 months post-AMI. Infarct size and left ventricular ejection fraction were assessed by single-photon emission computed tomography (SPECT) (n = 230/226) and MRI (n = 111/167) at 3 months. Results: EMMPRIN, MMP-9, and TIMP-1 levels and the MMP-9/TIMP-1 ratio declined from day 3 to 3 months (p < 0.001, all). TIMP-1 levels at day 3 correlated significantly with SPECT- and MRI-based infarct size, troponin T (p < 0.04, all), and amino-terminal pro-B-type natriuretic peptide (NT-proBNP; p < 0.001). The upper quartile of day 3 TIMP-1 levels showed an adjusted odds ratio of 5.0 (95% confidence interval 1.2-20.6) for having a large infarct size. An insignificant relationship between MMP-9 and clinical events within 1 year (death, AMI, or stroke) (n = 15) was observed, probably due to the lack of statistical power. Conclusion: The decline in EMMPRIN, MMP-9, and TIMP-1 3 months after acute STEMI is probably due to initial acute-phase processes. The associations between TIMP-1, infarct size, and NT-proBNP indicate a role for TIMP-1 in cardiac remodeling.
Evaluation of Temporal Virological Responses to Interferon-α-2b plus Ribavirin among Genotype 3a Hepatitis C Virus-Infected Patients
Authors: Raza Abida , Ovais Muhammad , Aziz Hafsa , Anwar Asim , Irfan Javaid , Ahmad Irshad , Mukhtar Muhammad
Published: November 2017

Objectives: The present study aimed to examine the impact of rapid virological response (RVR) and early virological response (EVR) on sustained virological response (SVR) in chronic hepatitis C genotype 3a individuals. Methods: The patients were given antiviral therapy with IFN-α-2b, 3 million units 3 times a week and 800-1,200 mg of ribavirin daily adjusted to the patient's body weight (<60 kg 800 mg day−1, and >60 kg 1,200 day−1). The patients received this combination therapy for 24 weeks. The patients were evaluated for their viral load at week 4, 12, and 24 using RT-PCR. Results: Out of 1,471 patients, 43.3% showed a negative viral load in week 4, demonstrating RVR, whereas 56.6% maintained a high viral load. These were further separated based on viral reduction in their plasma: either negative for HCV-RNA at week 12 (n = 575), manifesting EVR, or showing a 2-log reduction in HCV viral load classified as partial EVR (PEVR; n = 259). The PEVR response was less (29.7%) compared with RVR (85.9%) and EVR (69.0%), although nonresponders were found in both groups. Conclusions: Individuals incompliant with their treatment who have a higher RVR significantly influence their SVR towards a better remission that can be treated within a short duration with standard treatment.
Can Water Exchange Improve Patient Tolerance in Unsedated Colonoscopy A Prospective Comparative Study
Authors: Azevedo Richard , Leitão Cátia , Pinto João , Ribeiro Helena , Pereira Flávio , Caldeira Ana , Banhudo António
Published: November 2017

Background & Aims: Unsedated colonoscopy can be painful, poorly tolerated by patients, and associated with unsatisfactory technical performance. Previous studies report an advantage of water exchange over conventional air insufflation in reducing pain during unsedated colonoscopy. Our goal was to analyze the impact of water exchange colonoscopy on the level of maximum pain reported by patients submitted to unsedated colonoscopy, compared to conventional air insufflation. Methods: We performed a single-center, patient-blinded, prospective randomized comparative study, where patients were either allocated to the water group, in which the method of colonoscopy used was water exchange, or the standard air group, in which the examination was accomplished with air insufflation. Results: A total of 141 patients were randomized, 70 to the water and 71 to the air group. The maximum level of pain reported by patients during unsedated colonoscopy, measured by a numeric scale of pain (0-10), was significantly lower in the water group (3.39 ± 2.32), compared to the air group (4.94 ± 2.10), p < 0.001. The rate of painless colonoscopy was significantly higher in the water group (12.9 vs. 1.4%, p = 0.009). There were no significant differences between the two groups regarding indications for the procedure, quality of bowel preparation, cecal intubation time, withdrawal time, number of position changes, adenoma detection rate, and postprocedural complications. Only the number of abdominal compressions was significantly different, showing that water exchange decreases the number of compressions needed during colonoscopy. Conclusions: Water exchange was a safe and equally effective alternative to conventional unsedated colonoscopy, associated with less intraprocedural pain without impairing key performance measures.
Opioid Receptors Contribute to Antinociceptive Effect of Tianeptine on Colorectal Distension-Induced Visceral Pain in Rats
Authors: Bilge S. Sırrı , İlkaya Fatih , Darakcı Özge , Çiftcioğlu Engin , Bozkurt Ayhan
Published: November 2017

Tianeptine is a clinically effective atypical antidepressant with distinct neurochemical properties. In this study, we aimed to investigate the contribution of opioid receptors in the antinociceptive effect of tianeptine on visceral pain in awake rats and to differentiate the subtype and the localization (central and/or peripheral) of these opioid receptors involved in this antinociception. Visceromotor response to noxious colorectal distension (CRD) was quantified with electromyographic recordings, obtained from previously implanted electrodes into the external oblique musculature of rats under anesthesia, before and after tianeptine administration. The opioid receptor antagonist naloxone hydrochloride (NLX) and peripherally restricted opioid receptor antagonist naloxone methiodide (NLXM) were administered intravenously 10 min before tianeptine (10 mg/kg, i.v.). The antinociceptive effect of tianeptine was abolished by NLX (1 and 2 mg/kg, i.v.), but was partially reduced by NLXM (1 and 2 mg/kg, i.v.). A µ-opioid receptor-selective dose (0.03 mg/kg, i.v.) of NLX, but not NLXM, significantly inhibited the antinociceptive effect of tianeptine. Our results suggest that antinociceptive effect of tianeptine on CRD-induced visceral nociception in rats involves the activation of both central and peripheral opioid receptors.
Pycnogenol® bei Erkrankungen des venösen Systems - eine systematische Übersicht
Authors: Rohdewald Peter
Published: November 2017

Hintergrund: Die chronisch venöse Insuffizienz (CVI) ist eine weit verbreitete, durch Ödeme der Unterschenkel gekennzeichnete Krankheit. Das Vein Consult Program schätzte auf der Basis von 91 000 untersuchten Personen die Prävalenz der Erkrankung auf 60%. Ein Extrakt aus der Rinde der französischen Meereskiefer, Pinus pinasterAiton, subsp. atlantica (Pycnogenol®), bietet sich aufgrund seiner wundheilenden, antientzündlichen und die Mikrozirkulation anregenden Eigenschaften für die Behandlung von CVI-Symptomen, Ulzera und hämorrhoidalen Symptomen an. Methoden: Patienten beiderlei Geschlechts mit CVI-Symptomen, Hämorrhoiden und Ulzera wurden in Studien aufgenommen und mit 100-360 mg Pycnogenol täglich für 1-12 Monate behandelt. Ödeme der unteren Extremitäten wurden mit der Wasserverdrängungsmethode oder durch Ermittlung des Knöchelumfangs objektiviert. Symptome der CVI wurden nach Schweregrad beurteilt. Ergebnisse: 15 klinische Studien mit 475 CVI-Patienten zeigten nach 100-360 mg Pycnogenol täglich übereinstimmend eine Symptomverbesserung und Ödemreduktion. 100-150 mg des Kiefernrindenextraktes waren Kompressionsstrümpfen und einigen Venentherapeutika überlegen. Oral und topisch eingesetztes Pycnogenol beschleunigte die Heilung von Ulzera und hämorrhoidalen Episoden. Eine gesteigerte Elastizität variköser Venen nach Einnahme von 150 mg Pycnogenol wurde an Venensegmenten ex vivo demonstriert. Leichte unerwünschte Effekte traten mit der gleichen Häufigkeit wie unter Placebo auf. Schlussfolgerungen: Pycnogenol bietet eine sichere und effektive Option für die orale Behandlung venöser Ödeme. Die kombinierte topische und orale Anwendung von Pycnogenol beschleunigt die Abheilung venöser und diabetischer Ulzera und von Hämorrhoiden.
Chloroquine Autophagic Inhibition Rebalances Th17/Treg-Mediated Immunity and Ameliorates Systemic Lupus Erythematosus
Authors: An Ning , Chen Yanwen , Wang Chao , Yang Chen , Wu Zhi-hong , Xue Jing , Ye Lin , Wang Shujun , Liu Hua-feng , Pan Qingjun
Published: November 2017

Background: Imbalanced cellular immunity is critical to the pathogenesis of systemic lupus erythematosus (SLE). Recently, autophagy has emerged as a key homeostatic mechanism in T lymphocytes. This study was conducted to explore the impact of autophagy on the Th17/ regulatory T (Treg) immune imbalance in SLE. Methods: Peripheral Th17 and Treg cells from newly diagnosed patients with SLE and healthy controls were detected by flow cytometry. Additionally, the effects of chloroquine (CQ) autophagic inhibition on the Th17/Treg immune response were investigated in vitro. In addition, hydroxychloroquine (HCQ) treatment of the Th17/Treg immune response and the disease progression of lupus MRL/lpr mice were studied in vivo. Results: Compared with healthy controls, both peripheral Th17 and Treg cells of patients with SLE exhibited activated autophagy, resulting in a heightened Th17 proinflammatory response and diminished Treg immunosuppression. Furthermore, in vitro experiments indicated that CQ autophagic inhibition effectively rebalanced the Th17/Treg immune responses in patients with SLE. In vivo studies of MRL/lpr mice similarly confirmed that HCQ treatment decisively inhibited the autophagy of Th17/Treg cellular subsets, restoring the immune balance, lowering the serum levels of inflammatory cytokines and autoantibodies, and improving renal histopathology. Conclusion: Activated autophagy contributed to the Th17/Treg immune imbalance in SLE, and chloroquine autophagic inhibition rebalanced Th17/ Treg-mediated immunity and ameliorated SLE.
Catheter Ablation of Idiopathic Left Posterior Fascicular Ventricular Tachycardia
Authors: Ma Wei , Lu Fengmin , Shehata Michael , Wang Xunzhang , Zhang Fan , Chen Bingwei , Wu Dongyan , He Le , Sun Shan , Cheng Aijuan , Ding Jun , Cong Hongliang , Xu Jing
Published: November 2017

Background

We report the 12-lead ECG morphology of left posterior fascicular ventricular tachycardia (LPF-VT) and the relationship between His-ventricular (HV) interval and site of origin in LPF-VT.

Methods and Results

We studied 41 patients who underwent successful catheter ablation of LPF-VT with HV interval >0 ms (n=8; proximal-LPF group), HV interval 0 to −15 ms (n=15; middle-LPF group), and HV interval <–15 ms (n=18; distal-LPF group). The earliest mapped presystolic potential (PP)-QRS interval was 34.1±4.2, 24.5±3.2, and 19.4±2.8 ms in proximal-, middle-, and distal-LPF groups. The earliest PP ratio (PP-QRS interval during VT/HV interval during sinus rhythm) was 0.59±0.05, 0.45±0.07, and 0.31±0.05 in the proximal-, middle-, and distal-LPF groups. There were statistically significant differences between the 3 groups in earliest PP ratio, and there was close correlation between the HV interval during LPF-VT and earliest PP ratio. The QRS duration in the proximal-LPF group (114±6 ms) was significantly narrower compared with the middle-LPF group (128±5 ms) and distal-LPF group (140±6 ms). In leads I and V6, the ratio of R/S tended to be greater in the proximal-LPF group compared with the other 2 groups. QRS duration, the ratio of R/S in leads V6, and lead I could predict a proximal or distal origin site of LPF-VT with high sensitivity and specificity.

Conclusion

The HV interval and 12-lead ECG morphology of LPF-VT may help predict the successful site of origin and prove useful in guiding an effective ablation strategy.
Relationship of Echocardiographic
Z
Scores Adjusted for Body Surface Area to Age, Sex, Race, and Ethnicity
Authors: Lopez Leo , Colan Steven , Stylianou Mario , Granger Suzanne , Trachtenberg Felicia , Frommelt Peter , Pearson Gail , Camarda Joseph , Cnota James , Cohen Meryl , Dragulescu Andreea , Frommelt Michele , Garuba Olukayode , Johnson Tiffanie , Lai Wyman , Mahgerefteh Joseph , Pignatelli Ricardo , Prakash Ashwin , Sachdeva Ritu , Soriano Brian , Soslow Jonathan , Spurney Christopher , Srivastava Shubhika , Taylor Carolyn , Thankavel Poonam , van der Velde Mary , Minich LuAnn
Published: November 2017

Background—

Published nomograms of pediatric echocardiographic measurements are limited by insufficient sample size to assess the effects of age, sex, race, and ethnicity. Variable methodologies have resulted in a wide range of
Z
scores for a single measurement. This multicenter study sought to determine
Z
scores for common measurements adjusted for body surface area (BSA) and stratified by age, sex, race, and ethnicity.

Methods and Results—

Data collected from healthy nonobese children ≤18 years of age at 19 centers with a normal echocardiogram included age, sex, race, ethnicity, height, weight, echocardiographic images, and measurements performed at the Core Laboratory.
Z
score models involved indexed parameters (X/BSA
α
) that were normally distributed without residual dependence on BSA. The models were tested for the effects of age, sex, race, and ethnicity. Raw measurements from models with and without these effects were compared, and <5% difference was considered clinically insignificant because interobserver variability for echocardiographic measurements are reported as ≥5% difference. Of the 3566 subjects, 90% had measurable images. Appropriate BSA transformations (BSA
α
) were selected for each measurement. Multivariable regression revealed statistically significant effects by age, sex, race, and ethnicity for all outcomes, but all effects were clinically insignificant based on comparisons of models with and without the effects, resulting in
Z
scores independent of age, sex, race, and ethnicity for each measurement.

Conclusions—

Echocardiographic
Z
scores based on BSA were derived from a large, diverse, and healthy North American population. Age, sex, race, and ethnicity have small effects on the
Z
scores that are statistically significant but not clinically important.
Association Between Leukocyte Telomere Length and the Risk of Incident Atrial Fibrillation: The Framingham Heart Study
Authors: Staerk Laila , Wang Biqi , Lunetta Kathryn L. , Helm Robert H. , Ko Darae , Sherer Jason A. , Ellinor Patrick T. , Lubitz Steven A. , McManus David D. , Vasan Ramachandran S. , Benjamin Emelia J. , Trinquart Ludovic
Published: November 2017

Background

Advancing age is a prominent risk factor for atrial fibrillation (
AF
). Shorter telomere length is a biomarker of biological aging, but the link between shorter telomere length and increased risk of
AF
remains unclear. We examined the association between shorter leukocyte telomere length (
LTL
) and incident
AF
.

Methods and Results

We included
AF
‐free participants from the observational Framingham Heart Study Offspring cohort from 1995 to 1998, who had
LTL
measurements. We examined the association between baseline
LTL
and incident
AF
with multivariable Cox models adjusted for age, sex, current smoking, height, weight, systolic and diastolic blood pressure, use of antihypertensive medication, diabetes mellitus, history of myocardial infarction, and history of heart failure. The study sample comprised 1143
AF
‐free participants (52.8% women), with mean age of 60±8 years. The mean
LTL
at baseline was 6.95±0.57 kb. During 15.1±4.2 years mean follow‐up, 184 participants (64 women) developed
AF
. Chronological age was associated with increased risk of
AF
(hazard ratio per 10‐year increase, 2.16; 95% confidence interval, 1.71–2.72). There was no significant association between
LTL
and incident
AF
(hazard ratio per 1 SD decrease
LTL
, 1.01; 95% confidence interval, 0.86–1.19). Our study was observational in nature; hence, we could not exclude residual confounding and we were unable to establish causal pathways.

Conclusions

In our moderate‐sized community‐based cohort, we did not find evidence for a significant association between
LTL
and risk of incident
AF
.
Reading God’s Will? Function and Status of Oracle Interpreters in Ancient Jewish and Greek Texts
Authors: Tervanotko Hanna
Published: November 2017

There is a rising scholarly consensus that consulting the divine will did not altogether cease in the Second Temple period. Rather, it took different forms, and one was consulting the divine will via existing texts. Meanwhile, the identity of such interpreters remains unclear. This paper explores the possible identities of interpreters by comparing the figures that interpret Jewish oracles with the chresmologoi that appear in ancient Greek compositions. Such a comparison provides new insights into the divinatory use of written oracles. The interpreters of the Jewish and Greek texts operated at least partly in similar ways. While their methods of interrogating the oracles are somewhat alike, Jewish interpreters enjoyed a status similar to that of prophetic figures, whereas Greek interpreters operated more independently and without a similarly evident divine mandate.
Reading, Writing, and Memorizing Together: Reading Culture in Ancient Judaism and the Dead Sea Scrolls in a Mediterranean Context
Authors: Popović Mladen
Published: November 2017

This article focuses on reading culture as an aspect of the Dead Sea Scrolls textual community in its ancient Mediterranean context. On the basis of comparative evidence, the article approaches reading in ancient Judaism as a multi-dimensional and deeply social activity by taking reading aloud, writing, and memorizing as intertwined practices occurring in group reading events. The evidence discussed, such as from Philo of Alexandria, the first-century ce Theodotus inscription from Jerusalem, and 1QS 6:6–8, reflects certain aspects of reading cultures shared between different Jewish communities in the ancient Mediterranean during the Hellenistic and early Roman periods. In addition, it is argued that features such as scribal marks in manuscripts, evidence such as the writing of excerpts, manuscripts such as 4Q159 and 4Q265, or note-taking in 4Q175 and other such manuscripts should be considered within the context of the ancient procedure of reading by intellectual or scholarly readers. Moreover, the article suggests that the Genesis Apocryphon actually preserves a glimpse of the scrolls’ elite reading culture described in a text from Hellenistic-period Judaea.
Rediscovered Gravestones from a Destroyed Jewish Cemetery in Ostróg: The Case of Two Inscriptions of 1445
Authors: Fishel Alexandra , Nosonovsky Michael
Published: November 2017

The earliest extant gravestone inscriptions from Western Ukraine are from the 16th century; however, some perished monuments of the 15th century have been mentioned in literature. Among these are two 1445 inscriptions from Ostróg published by M. Biber in 1907. The Jewish cemetery in Ostróg was destroyed in 1968, and the two gravestones did not survive. However, several hundreds of gravestones from the destroyed cemetery in Ostróg have been found recently and there are several 17th–19th century epitaphs published by Biber among them. In addition, several photographs of the cemetery and its monuments are kept in the depositary of a local museum, including one presumed 1445 inscription. We have compared these materials with those published by Biber and thus have been able to re-evaluate the authenticity of the 1445 epitaphs. One of them turns out to be of 1520, while the date of the other one remains questionable.
Biafra and Abuse of Power in I.N.C. Aniebo’s Rearguard Actions
Authors: Gomba Obari
Published: November 2017

The Nigerian civil war has left a lasting impact on the politics of Nigeria. It has also provided material for I.N.C. Aniebo’s Rearguard Actions. Given the prior success of his novel The Anonymity of Sacrifice, this collection of short stories expands his creative portfolio on the subject of war. Over and above the predilection of Biafran discourse for blaming others for Biafra’s failure, Aniebo’s depiction of the war calls attention to the failings of Biafra itself. On the strength of Aniebo’s stories, this paper seeks to examine the nature of the abuse of power in Biafra and to show how such abuse helped precipitate the collapse of the breakaway nation-state.
Transculturalism, Otherness, Exile, and Identity in Chimamanda Ngozi Adichie’s Americanah
Authors: Nwanyanwu Augustine Uka
Published: November 2017

Today African literature exhibits and incorporates the decentred realities of African writers themselves as they negotiate and engage with multifarious forms of diaspora experience, dislocation, otherness, displacement, identity, and exile. National cultures in the twenty-first century have undergone significant decentralization. New African writing is now generated in and outside Africa by writers who themselves are products of transcultural forms and must now interrogate existence in global cities, transnational cultures, and the challenges of immigrants in these cities. Very few novels explore the theme of otherness and identity with as much insight as Adichie’s Americanah. The novel brings together opposing cultural forms, at once transcending and celebrating the local, and exploring spaces for the self where identity and otherness can be viewed and clarified. This article endeavours to show how African emigrants seek to affirm, manipulate, and define identity, reclaiming a space for self where migrant culture is marginalized. Adichie’s exemplary focus on transcultural engagement in Americanah provides an accurate representation of present-day African literary production in its dialectical dance between national and international particularities.
Genital Morphology of Winged and Wingless Males in the Ant Genus Cardiocondyla (Formicidae, Myrmicinae)
Authors: Schmidt Christine V. , Heinze Jürgen
Published: November 2017

The myrmicine ant genusCardiocondylais characterized by a peculiar male diphenism with winged disperser males and wingless, “ergatoid” fighter males. Here we describe and illustrate the morphology of the male external genitalia of 13 species of this genus. Several characters, especially the parossiculus of the volsella and the medial face of the paramere, vary between different species groups and might be useful to clarify the infrageneric taxonomy ofCardiocondyla. External genitalia between different phenotypes of a species differ primarily in size. All examined males, both winged and ergatoid, have a parameral hook that resembles a structure described inNesomyrmexmales but apparently is absent in other studied myrmicine ants. The presence and absence of this hook might be useful for future studies on the relationships within the myrmicine tribe Crematogastrini.
Detention and Its Reforms in the prc
Authors: Biddulph Sarah , Nesossi Elisa , Sapio Flora , Trevaskes Susan
Published: November 2017

This article reviews forms of detention and their reforms in the People’s Republic of China (prc). We examine the changing scope and uses of both administrative and criminal detention powers in the reform period and the impact of changing politics, ideology, and law in reform of both detention powers and institutions.

In Part 1, we focus on the continuities and discontinuities in the ideology of punishment, the perceived role and uses of detention in shaping society and in social control. In Part 2, we explore the factors relevant to the reform or abolition of range of administrative detention powers. We seek to understand how reforms have occurred, where they have stalled and where they are now possible. We ask how relevant these considerations are to the reform of criminal detention powers and find some distinctive features, not least of which is the comparative rigidity brought about by legal codification. We also note that reform to some administrative detention powers has been accompanied by an expansion in the criminal justice system. Our analysis illustrates that not only is there a wide range of people that the Party-state considers deserve to be placed outside of society, but also that in contemporary China detention is still considered to be a very useful form of social management and control.
Deep-water bony fishes collected by the B/O Miguel Oliver on the shelf edge of Pacific Central America: an annotated, illustrated and DNA-barcoded checklist
Authors: ROBERTSON D. ROSS , ANGULO ARTURO , BALDWIN CAROLE C. , PITASSY DIANE , DRISKELL AMY , WEIGT LEE , NAVARRO IGNACIO J.F.
Published: November 2017

An annotated and photographically illustrated checklist with DNA barcodes of the species of bony fishes collected during a month-long research cruise of the Spanish Research vessel B/O Miguel Oliver is presented. The vessel made trawls on the continental shelf of the Pacific coast of Central America, in November-December 2010, at depths of 108–1625 m. This list, based on 707 specimens (of a total of 876 specimens collected during the whole expedition), includes 129 species belonging to 15 orders, 61 families, and 97 genera. New information is presented on the geographical distributions of more than a third of those species, with 29 species (22.4%) representing new records from Central American waters and 17 species (13.2%) having expanded latitudinal ranges. Data on capture depths demonstrate increased depth ranges due to new minimum and/or maximum known depths for 31 species, i.e. 24% of those captured. Tissue samples from frozen specimens were used to obtain DNA barcodes of 682 (96.5%) individuals belonging to 118 species (91.4% of those recorded here), which have been made publically available in Genbank. Those data include barcodes for 84 species (65.1% of the total collected, and 77.1% of those for which barcodes were obtained) and 30 genera (30.9% of those collected) for which no species barcodes have been previously published. Barcodes of 54 species represent the first genetic sequences of any type published for those species. The abundance of new data indicate that there is still much to learn about the composition and geographical and depth distributions of the fish fauna of the shelf edge and continental slope of this region.
Rapid Weakening of Tropical Cyclones in Monsoon Gyres over the Tropical Western North Pacific
Authors: Liang Jia , Wu Liguang , Gu Guojun
Published: November 2017

As one major source of forecasting errors in tropical cyclone intensity, rapid weakening of tropical cyclones [an intensity reduction of 20 kt (1 kt = 0.51 m s−1) or more over a 24-h period] over the tropical open ocean can result from the interaction between tropical cyclones and monsoon gyres. This study aims to examine rapid weakening events occurring in monsoon gyres in the tropical western North Pacific (WNP) basin during May–October 2000–14.

Although less than one-third of rapid weakening events happened in the tropical WNP basin south of 25°N, more than 40% of them were associated with monsoon gyres. About 85% of rapid weakening events in monsoon gyres occurred in September and October. The rapid weakening events associated with monsoon gyres are usually observed near the center of monsoon gyres when tropical cyclone tracks make a sudden northward turn. The gyres can enlarge the outer size of tropical cyclones and tend to induce prolonged rapid weakening events with an average duration of 33.2 h. Large-scale environmental factors, including sea surface temperature changes, vertical wind shear, and midlevel environmental humidity, are not primary contributors to them, suggesting the possible effect of monsoon gyres on these rapid weakening events by modulating the tropical cyclone structure. This conclusion is conducive to improving operational forecasts of tropical cyclone intensity.
Diagnosing Human-Induced Dynamic and Thermodynamic Drivers of Extreme Rainfall
Authors: Cheng Linyin , Hoerling Martin , Smith Lesley , Eischeid Jon
Published: November 2017

Factors responsible for extreme monthly rainfall over Texas and Oklahoma during May 2015 are assessed. The event had a return period of at least 400 years, in contrast to the prior record, which was roughly a 100-yr event. The event challenges attribution science to disentangle factors because it occurred during a strong El Niño, a natural pattern of variability that affects the region’s springtime rains, and during the warmest global mean temperatures since 1880. Effects of each factor are diagnosed, as is the interplay between El Niño dynamics and human-induced climate change.

Analysis of historical climate simulations reveals that El Niño was a necessary condition for monthly rains to occur having the severity of May 2015. The model results herein further reveal that a 2015 magnitude event, whether conditioned on El Niño or not, was made neither more intense nor more likely to be due to human-induced climate change over the past century.

The intensity of extreme May rainfall over Texas and Oklahoma , analogous to the 2015 event, increases by roughly 5% by the latter half of the twenty-first century. No material changes occur in either El Niño–related teleconnections or in overall atmospheric dynamics during extreme May rainfall over the twenty-first century. The increased severity of Texas/Oklahoma May rainfall events in the future is principally due to thermodynamic driving, although much less than implied by simple Clausius–Clapeyron scaling arguments given a projected 23% increase in atmospheric precipitable water vapor. Other thermodynamic factors are identified that act in opposition to the increase in atmospheric water vapor, thereby reducing the effectiveness of overall thermodynamic driving of extreme May rainfall changes over Texas and Oklahoma.
Between world culture and local context
Authors: Brankovic Jelena
Published: November 2017

World society theory argues that actor empowerment in local contexts is driven primarily by the expanding world culture, rendering alternative explanations weaker in comparison. This article explores one such alternative explanation and offers an account of actor empowerment which highlights the role of identity constructed in local interaction. The article imports insights from identity theory to show how identities constructed in interaction may complement those derived from the world culture. To explore the phenomenon of theoretical interest, the case of a historical empowerment of Serbian universities in the post-2000 period, as an actor in the national higher education governance, is considered.