bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in transient elastography in early cirrhotic patients after receiving nonselective B‐blocker for primary variceal bleeding prophylaxis: Three‐month follow up
Authors: Piyachaturawat Panida , Siramolpiwat Sith , Sonsiri Kanokwan , Tangkijvanich Pisit , Treeprasertsuk Sombat
Published: July 2018

Background and Aim

A nonselective B‐blocker (NSBB) is recommended for primary prophylaxis of variceal bleeding. The impact of treatment with NSBB on modulating transient elastography (TE) has not been reported. The aim of the study is to investigate the effect of NSBB treatment on TE in early cirrhotic patients.

Methods

In this prospective study, we enrolled all early cirrhotic patients who underwent esophagogastroduodenoscopy (EGD) and showed small esophageal varices (EV) at our institute for a period of 1 year. The TE and heart rate (HR) of all participants were measured before and 3 months after receiving NSBB.

Results

Thirty‐nine patients receiving propanolol for 3 months were analyzed. There were 16 patients in the HR responder group (41%) and 23 patients in the HR nonresponder group (59%). The reduction of TE was preferably found in the HR responder group compared with the HR nonresponder group, in which mean changes in TE were −5.6 and −0.7 kPa, respectively (P = 0.23). In addition, we categorized the patients using their TE responses. Twenty‐five patients (64.1%) showed reduced TE during the follow‐up period, in which the mean TE value change was −2.94 kPa. Using correlation analysis, TE and HR responses were insignificantly correlated (r = 0.23, P = 0.15).

Conclusion

The NSBB administered for 3 months mainly improved TE value in early cirrhotic patients even though the changes of HR and TE did not correlate. Further study is needed to confirm whether the monitoring of TE change may be a better predictor for pharmacological response than the HR response.
Regularity and h‐polynomials of monomial ideals
Authors: Hibi Takayuki , Matsuda Kazunori
Published: July 2018

Let denote the polynomial ring in n variables over a field K with each and let be a homogeneous ideal of S with . The Hilbert series of is of the form , where with is the h‐polynomial of . It is known that, when is Cohen–Macaulay, one has , where is the (Castelnuovo–Mumford) regularity of . In the present paper, given arbitrary integers r and s with and , a monomial ideal I of with for which and will be constructed. Furthermore, we give a class of edge ideals of Cameron–Walker graphs with for which is not Cohen–Macaulay.
Pelvic floor dysfunction in women with fibromyalgia and control subjects: Prevalence and impact on overall symptomatology and psychosocial function
Authors: Carrillo‐Izquierdo Maria Dolores , Slim Mahmoud , Hidalgo‐Tallon Javier , Calandre Elena P.
Published: July 2018

Aims

To evaluate the prevalence, distress, and impact of pelvic floor dysfunction (PFD) symptomatology in women with fibromyalgia and control women. We also aimed to evaluate the impact of PFD symptomatology on several psychosocial measures such as mood, sleep, pain, and quality of life.

Methods

We conducted a cross‐sectional study in women with fibromyalgia and control women from the general population. Using a structured survey, we collected sociodemographic and clinical data, assessed the prevalence of PFD and evaluated the distress (PFDI‐20) and the impact (PFIQ‐7) caused by its symptomatology. Using Spanish‐validated questionnaires, we also evaluated mood and sleep disturbances, bodily pain, and quality of life in subjects with and without PFD. In participants with fibromyalgia, we assessed the severity and impact of the disease using the Fibromyalgia Impact Questionnaire (FIQR).

Results

Two hundred and twenty‐six patients with fibromyalgia and 222 control women completed the surveys. Two hundred and twenty patients (93%) and 140 controls (63%) reported PFD‐related symptoms. Both the scores of distress (143.1 ± 5.7 vs 96.1 ± 4.8, P < 0.0001) and impact (122.4 ± 5.6 vs 100.6 ± 6.4, P < 0.0001) caused by PFD symptoms were significantly higher in women with fibromyalgia than in controls. There was a significant positive relationship between fibromyalgia severity and both PFDI‐20 (r2 = 0.32, P < 0.0001) and PFIQ‐7 scores (r2 = 0.375, P < 0.0001). Depression severity, sleep disturbances, bodily pain, and low quality of life were highest in women with fibromyalgia and PFD and lowest in control women without PFD.

Conclusions

PFD‐related symptoms were significantly more frequent in women with fibromyalgia than in controls. PFD symptomatology, when present, negatively influenced mood, sleep quality, and quality of life of both patients with fibromyalgia and controls.
Re: De‐novo abnormal uteroplacental circulation in third trimester: pregnancy outcome and pathological implications. J. Binder, C. Monaghan, B. Thilaganathan, S. Carta and A. Khalil. Ultrasound Obstet Gynecol 2018; 52: 60–65.
Authors: Morales‐Roselló J.
Published: July 2018

Linked Comment: Ultrasound Obstet Gynecol 2018; 52: 60–65
Management of respiratory complications in a western lowland gorilla (Gorilla gorilla gorilla) born by cesarean section
Authors: Thurber Mary I. , Greenberg Mark , Weiss Dawn , Richardson Lynn , Stallard Andrew , Lamberski Nadine
Published: July 2018

A female western lowland gorilla (Gorilla gorilla gorilla) infant was delivered by cesarean section (C‐section) to an 18‐year‐old primiparous dam after prolonged labor. The infant required resuscitation at birth and was hospitalized for management of pneumonia and associated respiratory distress secondary to the aspiration of meconium‐stained amniotic fluid. The infant received nine days of intensive care with respiratory support, antibiotics, intravenous fluid therapy, anti‐inflammatory drugs, bronchodilators, and chest physiotherapy. Respiratory support included nasal continuous positive airway pressure (CPAP), and supplemental oxygen. Complications included right lung atelectasis secondary to bronchial obstruction and pneumonia. Following the resolution of pneumonia, visual reintroductions with the troop were initiated. The dam was given a medical lactation supplement (metoclopramide) and her mammary glands were stimulated to increase milk production. After several days of visual and olfactory introductions, the infant was successfully physically reintroduced to her dam at 12 days of age; the dam showed appropriate maternal response and nursing of the infant. The infant had appropriate growth and development, and 4 years later, has no evidence of negative side effects of neonatal respiratory disease. This is the first reported case of management of neonatal gorilla respiratory disease associated with a C‐section, with successful reintroduction to the family group after hospitalization.
Relative response to digital tablet devices and painting as sensory enrichment in captive chimpanzees
Authors: Grunauer Priscilla P. , Walguarnery Justin W.
Published: July 2018

Digital devices, including tablet computers and other touchscreens, can potentially serve as flexible and convenient means for providing behavioral enrichment activities to captive primates. Despite increased interest in incorporating technology into enrichment programs, no direct quantitative comparison has previously been made between the effectiveness of typical tactile enrichment activities and enrichment activities on digital devices. One way in which these activities differ is in the degree of controllability afforded the animals in interacting with the enrichment objects, since digital devices will be limiting to varying degrees based on the particulars of software and the interface format. This study compared the effects of painting with brush on paper to those of a painting application on a digital tablet device (iPad™) in eight group‐living chimpanzees at the Honolulu Zoo. Observations were analyzed across baseline, enrichment, and post‐enrichment periods to measure significant differences in the reduction of displacement and stereotypic behaviors. We found that the digital tablet device running an application that permits production of semi‐automated visualizations, was as effective as painting with brush on paper in reducing some stereotypic and displacement behaviors, including yawning and self‐picking. However, the digital tablet was not as effective in reducing other displacement behaviors, nor was it as effective in retaining the chimpanzee's attention. These results confirm a useful role for digital devices in enrichment programs but suggest a need to assess individual device applications in their capacity to promote greater controllability and sensory breadth of the enrichment experience.
Incoherent conductivity of holographic charge density waves
Authors: Goutéraux Blaise , Jokela Niko , Pönni Arttu
Published: July 2018

Abstract

The DC resistivity of charge density waves weakly-pinned by disorder is controlled by diffusive, incoherent processes rather than slow momentum relaxation. The corresponding incoherent conductivity can be computed in the limit of zero disorder. We compute this transport coefficient in holographic spatially modulated breaking translations spontaneously. As a by-product of our analysis, we clarify how the boundary heat current is obtained from a conserved bulk current, defined as a suitable generalization of the Iyer-Wald Noether current of the appropriate Killing vector.
The topologically twisted index of $$ \mathcal{N} $$ = 4 super-Yang-Mills on T 2 × S2 and the elliptic genus
Authors: Hong Junho , Liu James T.
Published: July 2018

Abstract

We examine the topologically twisted index of

$$ \mathcal{N} $$

N

= 4 super-Yang-Mills with gauge group SU(N ) on T
2×S
2, and demonstrate that it receives contributions from multiple sectors corresponding to the freely acting orbifolds T
2/ℤ
m
 × ℤ
n
where N = mn. After summing over these sectors, the index can be expressed as the elliptic genus of a twodimensional

$$ \mathcal{N} $$

N

= (0, 2) theory resulting from Kaluza-Klein reduction on S
2. This provides an alternate path to the ‘high-temperature’ limit of the index, and confirms the connection to the right-moving central charge of the

$$ \mathcal{N} $$

N

= (0, 2) theory.
Presenting Archaeology and Heritage at a UNESCO World Heritage Site: Gorée Island, Senegal
Authors: Thiaw Ibrahima , Wait Gerry
Published: July 2018

Gorée Island is Senegal's first site on the UNESCO World Heritage List. It is associated with the infamous Atlantic slave trade, and over the past few decades, Gorée has become a prime destination for global tourism, particularly for the African diaspora from the New World but also for many Europeans and African nationals. Today, Gorée is a forum where different stakeholders battle over the role, place, and significance of the island in the Atlantic slave trade and its enduring legacies in the present. While Gorée owes much of its reputation to its heritage, including architecture, archaeology, and monuments, recent controversies over site preservation and policy compliance raised questions about heritage presentation and consumption. This article analyzes stakeholders’ attitudes toward archaeology and heritage to gain insights on how they are presented and consumed by different stakeholders and eventually destroyed by them as well. The discussion shows ambiguous attitudes toward site presentation and preservation, which might be linked either to stakeholders’ subjectivities or hypocrisy or to poor and uncoordinated communication strategies by heritage professionals.
A Framework to Assess the Quality of Non-traditional Articles in the Field of Disaster Response and Management
Authors: Hall Mary , Cartwright Chris , Lee Andrew C. K.
Published: July 2018

Objective

While carrying out a scoping review of earthquake response, we found that there is no universal standardized approach for assessing the quality of disaster evidence, much of which is variable or not peer reviewed. With the lack of a framework to ascertain the value and validity of this literature, there is a danger that valuable insights may be lost. We propose a theoretical framework that may, with further validation, address this gap.

Methods

Existing frameworks – quality of reporting of meta-analyses (QUORUM), meta-analysis of observational studies in epidemiology (MOOSE), the Cochrane assessment of bias, Critical Appraisal Skills Programme (CASP) checklists, strengthening the reporting of observation studies in epidemiology (STROBE), and consensus guidelines on reports of field interventions in disasters and emergencies (CONFIDE)–were analyzed to identify key domains of quality. Supporting statements, based on these existing frameworks were developed for each domain to form an overall theoretical framework of quality. This was piloted on a data set of publications from a separate scoping review.

Results

Four domains of quality were identified: robustness, generalizability, added value, and ethics with 11 scored, supporting statements. Although 73 out of 111 papers (66%) scored below 70%, a sizeable portion (34%) scored higher.

Conclusion

Our theoretical framework presents, for debate and further validation, a method of assessing the quality of non-traditional studies and thus supporting the best available evidence approach to disaster response. (Disaster Med Public Health Preparedness. 2019;13:147–151)
A low-frequency variational model for energetic particle effects in the pressure-coupling scheme
Authors: Close Alexander R. D. , Burby Joshua W. , Tronci Cesare
Published: July 2018

Energetic particle effects in magnetic confinement fusion devices are commonly studied by hybrid kinetic-fluid simulation codes whose underlying continuum evolution equations often lack the correct energy balance. While two different kinetic-fluid coupling options are available (current coupling and pressure coupling), this paper applies the Euler–Poincaré variational approach to formulate a new conservative hybrid model in the pressure-coupling scheme. In our case the kinetics of the energetic particles are described by guiding center theory. The interplay between the Lagrangian fluid paths and phase space particle trajectories reflects an intricate variational structure which can be approached by letting the four-dimensional guiding center trajectories evolve in the full six-dimensional phase space. Then, the redundant perpendicular velocity is integrated out to recover a four-dimensional description. A second equivalent variational approach is also reported, which involves the use of phase space Lagrangians. Not only do these variational structures confer on the new model a correct energy balance, but also they produce a cross-helicity invariant which is lost in the other pressure-coupling schemes reported in the literature.
Hémodissection Pariétale Oblitérante des Vaisseaux Intracrâniens, une Forme Particulière d’Anévrysme Disséquant
Authors: Gagne F. , Lemay M. , Verret S.
Published: July 2018

A six year old girl complained of sudden severe headache, became hemiplegic and unconscious. A right carotid arteriogram revealed an obstruction of the right anterior cerebral artery and many sylvian branches. Death occurred four days later. At autopsy, a recent softening of nearly all the right middle cerebral arterial territory was found. Thrombus filled the sylvian artery and its main branches. Histologic examination of the vessel walls showed a dissecting infiltration of blood between the internal elastic lamina and the media. This particular form of dissecting aneurysm, occurring in young subjects, in the absence of atherosclerosis, high blood pressure and idiopathic medial necrosis, represents a distinct nosologic entity that has been called “Obstructive parietal hemodissection of intracranial vessels.” The pathogenesis of the disease is unknown: trauma has been mentioned, also congenital defects in the elastic lamina or other morphologic abnormalities ofthat lamina.
Enhanced temporal binding of audiovisual information in the bilingual brain
Authors: BIDELMAN GAVIN M. , HEATH SHELLEY T.
Published: July 2018

We asked whether bilinguals’ benefits reach beyond the auditory modality to benefit multisensory processing. We measured audiovisual integration of auditory and visual cues in monolinguals and bilinguals via the double-flash illusion where the presentation of multiple auditory stimuli concurrent with a single visual flash induces an illusory perception of multiple flashes. We varied stimulus onset asynchrony (SOA) between auditory and visual cues to measure the “temporal binding window” where listeners fuse a single percept. Bilinguals showed faster responses and were less susceptible to the double-flash illusion than monolinguals. Moreover, monolinguals showed poorer sensitivity in AV processing compared to bilinguals. The width of bilinguals’ AV temporal integration window was narrower than monolinguals’ for both leading and lagging SOAs (Biling.: -65–112 ms; Mono.: -193 – 112 ms). Our results suggest the plasticity afforded by speaking multiple languages enhances multisensory integration and audiovisual binding in the bilingual brain.
Leveraging Spatial and Temporal Variability to Probabilistically Characterize Nutrient Sources and Export Rates in a Developing Watershed
Authors: Strickling H. L. , Obenour D. R.
Published: July 2018

Hybrid watershed models based on nonlinear regression are useful tools for estimating the magnitude of loading rates (i.e., export coefficients) for various pollutant sources within large‐scale river basins. Few such models, however, have incorporated temporal variability in either source distributions or climate, despite evidence that precipitation is the primary driver in interannual variability in loading rates. The model developed here includes changes in precipitation, land use, point source discharge, and livestock operations to capture temporal variability in nitrogen loads. Precipitation is incorporated directly in the formulation of export rates using coefficients that vary by source type. Instream and reservoir retention of nitrogen is included to account for nitrogen sinks within the watershed. A Bayesian hierarchical approach is employed to integrate uncertainty in loading estimates, include prior knowledge of parameters, address intrawatershed correlation, and estimate export coefficients probabilistically. We apply this method to three North Carolina river basins that have experienced substantial growth in urban development and livestock operations in the past few decades, and where eutrophication‐related water quality problems are common. Accounting for temporal variability constrains uncertainties in nonpoint source export coefficients by nearly 50%, relative to a spatial‐only model. Results indicate that livestock operations are a significant contributor of nitrogen throughout much of the study area. Precipitation is shown to have a larger influence on export rates for agricultural than for developed lands, creating a system dominated by agricultural total nitrogen during high precipitation years and by developed (urban) regions during low precipitation years.
Pollen Rupture and Its Impact on Precipitation in Clean Continental Conditions
Authors: Wozniak M. C. , Solmon F. , Steiner A. L.
Published: July 2018

Pollen grains emitted from vegetation can rupture, releasing subpollen particles (SPPs) as fine atmospheric particulates. Previous laboratory research demonstrates potential for SPPs as efficient cloud condensation nuclei (CCN). We develop the first model of atmospheric pollen grain rupture and implement the mechanism in regional climate model simulations over spring pollen season in the United States with a CCN‐dependent moisture scheme. The source of SPPs (surface or in‐atmosphere) depends on region and sometimes season, due to the distribution of relative humidity and rain. Simulated concentrations of SPPs are approximately 1–10 or 1–1,000 cm−3, depending on the number of SPPs produced per pollen grain (nspg). Lower nspg (103) produces a negligible effect on precipitation, but high nspg (106) in clean continental CCN background concentrations (100 CCN per cubic centimeter) shows that SPPs suppress average seasonal precipitation by 32% and shift rates from heavy to light while increasing dry days. This effect is smaller (2% reduction) for polluted air.
Variations in the H2O Content and H2O/Ce Ratio of Mantle Pyroxenites: Implications for Enriched Components in the Mantle
Authors: Hao Yan‐Tao , Li Pei , Coltorti Massimo , Xia Qun‐Ke
Published: July 2018

Mantle pyroxenite xenoliths were collected from Hannuoba, East China, and investigated for their H2O content and trace element contents, with particular regard to the H2O/Ce ratio. The pyroxenites were divided into three groups: Cr‐pyroxenites, Al‐pyroxenites, and garnet pyroxenites. The H2O contents and H2O/Ce ratios of the pyroxenites in this study showed much wider ranges than those previously reported for the whole rock pyroxenites. The Cr‐pyroxenites had an H2O content ranging from 23 to 339 ppm and an H2O/Ce ratio between 32 and 212; the Al‐pyroxenites had an H2O content ranging from 42 to 106 ppm and an H2O/Ce ratio between 1 and 22, and the garnet pyroxenites had an H2O content ranging from 37 to 69 ppm and an H2O/Ce ratio between 5 and 54. These systematic variations in the H2O contents and H2O/Ce ratios for the Hannuoba pyroxenites are associated with their origins. Both the H2O content and H2O/Ce ratio of the Al‐pyroxenites were low compared to those of Hawaiian pyroxenite, enriched mantle, and depleted MORB mantle sources. The high H2O content and H2O/Ce ratio of the melt equilibrated with the Cr‐pyroxenites indicate that a water‐rich component was involved in its formation. Their large variations in the H2O contents and H2O/Ce ratios may indicate that pyroxenites are essential enriched components in the sources of continental basalts.
Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms
Authors: Heath Alesha , Lindberg Daniel R. , Makowiecki Kalina , Gray Avalon , Asp Anders J. , Rodger Jennifer , Choi Doo-Sup , Croarkin Paul E.
Published: July 2018

Definitive data are lacking on the mechanism of action and biomarkers of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression. Low-intensity rTMS (LI-rTMS) has demonstrated utility in preclinical models of rTMS treatments but the effects of LI-rTMS in murine models of depression are unknown. We examined the behavioral and neurobiologic changes in olfactory bulbectomy (OB) mice with medium-intensity rTMS (MI-rTMS) treatment and fluoxetine hydrochloride. We then compared 10-Hz rTMS sessions for 3 min at intensities (measured at the cortical surface) of 4 mT (LI-rTMS), 50 mT (medium-intensity rTMS [MI-rTMS]), or 1 T (high-intensity rTMS [HI-rTMS]) 5 days per week over 4 weeks in an OB model of agitated depression. Behavioral effects were assessed with forced swim test; neurobiologic effects were assessed with brain levels of 5-hydroxytryptamine, brain-derived neurotrophic factor (BDNF), and neurogenesis. Peripheral metabolomic changes induced by OB and rTMS were monitored through enzyme-linked immunosorbent assay and ultrapressure liquid chromatography-driven targeted metabolomics evaluated with ingenuity pathway analysis (IPA). MI-rTMS and HI-rTMS attenuated psychomotor agitation but only MI-rTMS increased BDNF and neurogenesis levels. HI-rTMS normalized the plasma concentration of α-amino-n-butyric acid and 3-methylhistidine. IPA revealed significant changes in glutamine processing and glutamate signaling in the OB model and following MI-rTMS and HI-rTMS treatment. The present findings suggest that MI-rTMS and HI-rTMS induce differential neurobiologic changes in a mouse model of agitated depression. Further, α-amino-n-butyric acid and 3-methylhistidine may have utility as biomarkers to objectively monitor the response to rTMS treatment of depression.
Proprotein convertase furin inhibits matrix metalloproteinase 13 in a TGFβ-dependent manner and limits osteoarthritis in mice
Authors: Lin Hilène , Hay Eric , Latourte Augustin , Funck-Brentano Thomas , Bouaziz Wafa , Ea Hang-Korng , Khatib Abdel-Majid , Richette Pascal , Cohen-Solal Martine
Published: July 2018

Cartilage loss in osteoarthritis (OA) results from altered local production of growth factors and metalloproteases (MMPs). Furin, an enzyme involved in the protein maturation of MMPs, might regulate chondrocyte function. Here, we tested the effect of furin on chondrocyte catabolism and the development of OA. In primary chondrocytes, furin reduced the expression of MMP-13, which was reversed by treatment with the furin inhibitor α1-PDX. Furin also promoted the activation of Smad3 signaling, whereas activin receptor-like kinase 5 (ALK5) knockdown mitigated the effects of furin on MMP-13 expression. Mice underwent destabilization of the medial meniscus (DMM) to induce OA, then received furin (1 U/mice), α1-PDX (14 µg/mice) or vehicle. In mice with DMM, the OA score was lower with furin than vehicle treatment (6.42 ± 0.75 vs 9.16 ± 0.6, p < 0.01), and the number of MMP-13(+) chondrocytes was lower (4.96 ± 0.60% vs 20.96 ± 8.49%, p < 0.05). Moreover, furin prevented the increase in ALK1/ALK5 ratio in cartilage induced by OA. Conversely, α1-PDX had no effect on OA cartilage structure. These results support a protective role for furin in OA by maintaining ALK5 receptor levels and reducing MMP-13 expression. Therefore, furin might be a potential target mediating the development of OA.
Dietary non-fermentable fiber prevents autoimmune neurological disease by changing gut metabolic and immune status
Authors: Berer Kerstin , Martínez Inés , Walker Alesia , Kunkel Birgit , Schmitt-Kopplin Philippe , Walter Jens , Krishnamoorthy Gurumoorthy
Published: July 2018

The autoimmune neurological disease, Multiple Sclerosis (MS), have increased at alarming rates in the Western society over the last few decades. While there are numerous efforts to develop novel treatment approaches, there is an unmet need to identify preventive strategies. We explored whether central nervous system (CNS) autoimmunity can be prevented through dietary manipulation using a spontaneous autoimmune encephalomyelitis mouse model. We report that the nutritional supplementation of non-fermentable fiber, common components of a vegetarian diet, in early adult life, prevents autoimmune disease. Dietary non-fermentable fiber alters the composition of the gut microbiota and metabolic profile with an increase in the abundance of long-chain fatty acids. Immune assays revealed that cecal extracts and a long chain fatty acid but not cecal lysates promoted autoimmune suppressive TH2 immune responses, demonstrating that non-fermentable fiber-induced metabolic changes account for the beneficial effects. Overall, these findings identify a non-invasive dietary strategy to prevent CNS autoimmunity and warrants a focus on nutritional approaches in human MS.
A novel sample cell for reducing the “Position Effect” in laser ablation MC-ICP-MS isotopic measurements
Authors: Xie Lie-Wen , Xu Lei , Yin Qing-Zhu , Yang Yue-Heng , Huang Chao , Yang Jin-Hui
Published: July 2018

A novel laser ablation cell geometry significantly reduces the so-calledposition effecton high precision and accuracy isotopic measurements by Laser Ablation-Multiple Collector-Inductively Coupled Plasma-Mass Spectrometry (LA-MC-ICP-MS).
miR-15b reduces amyloid-β accumulation in SH-SY5Y cell line through targetting NF-κB signaling and BACE1
Authors: Li Juan , Wang Haitao
Published: July 2018

Alzheimer’s disease (AD) is the multifactorial neurodegenerative disorder causing progressive memory loss and cognitive impairment. The aberrant accumulation of amyloid-β (Aβ) and neuroinflammation are two major events in AD. BACE1 is required for the cleavage of amyloid precursor protein (APP) to generate Aβ, which stimulates the nuclear transcription factor κB (NF-κB) signaling, leading to the secretion of inflammatory cytokines. And NF-κB can up-regulate the expression of BACE1. miRNAs are small non-coding RNAs that regulate gene transcription. miR-15b down-regulates BACE1 expression while it is unclear whether miR-15b can regulate Aβ in human neuronal cells, and if so, whether it is by targetting NF-κB. SH-SY5Y cell line was transfected with Swedish APP mutant (APPswe) as an in vitro AD model. Quantitative PCR (qPCR), WB, and ELISA were used to detected related gene expression intracellularly or in supernatant. Dual luciferase assay was used to validate miRNA and targets binding. miR-15b inhibits expression of BACE1and APP. Moreover, the reduced level of Aβ was observed in response to miR-15b mimics in SH-SH5Y/APPswe cells. miR-15b directly targetted the conserved Bace1 3′UTR to regulate its expression. In addition, the inhibition of APPswe-induced secretion of inflammatory cytokines and the suppression of NF-κB activation by miR-15b were validated. And miR-15b directly targetted the 3′UTRs of NF-κB1 and inhibitor of NF-κB (IκB) kinase α (IKK-α), encoding NF-κB1 and IKK-α, respectively. Our study suggests that miR-15b inhibits Aβ accumulation through targetting NF-κB signaling and BACE1 and serves as a potential molecular target for AD therapy.
The diagnostic values of circulating miRNAs for hypertension and bioinformatics analysis
Authors: Zhang Xiaoyi , Wang Xiaoyan , Wu Jian , Peng Juan , Deng Xin , Shen Yi , Yang Chunjie , Yuan Jie , Zou Yunzeng
Published: July 2018

Few studies have compared the performances of those reported miRNAs as biomarkers for hypertension in a same cohort, we aimed to comprehensively examine the performances of those reported miRNAs as biomarkers for hypertension and identify the genes and pathways targetted by these miRNAs. Serum samples were collected from patients hospitalized for hypertension in Zhongshan Hospital. Gene expressions of 25 miRNAs were compared between hypertension and normal groups. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of those miRNAs as biomarkers for hypertension. miRWALK2.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to predict the target genes and pathways of selected miRNAs. A total of 164 participants were enrolled, amongst which 53 were patients with hypertension, 111 were normal population. MiR-122-5p (area under curve (AUC): 0.750), miR-199a-3p (AUC: 0.744), miR-208a-3p (AUC: 0.743), miR-423-5p (AUC: 0.740), and miR-223-5p (AUC: 0.718) showed better performance than others, and the best performance was the combination of miR-199a-3p, miR-208a-3p, miR-122-5p, and miR-223-3p (AUC: 0.80). Pathway analysis revealed that 94 pathways enriched with genes targetted by miR-199a-3p, miR-208a-3p, miR-122-5p, miR-223-5p. FoxO signaling was enriched with genes targetted by all the three miRNAs (miR-199a-3p, miR-208a-3p, miR-122-5p). The combination of miR-199a-3p, miR-208a-3p, miR-122-5p, and miR-223-3p has a good diagnostic performance for hypertension, and multitudes of possible mechanisms/pathways through which dysregulation of these miRNAs may impact risk of hypertension.
Atherosclerosis in subjects newly diagnosed with human immunodeficiency virus infection
Authors: Kirichenko Tatiana V. , Myasoedova Veronika A. , Shimonova Tatiana E. , Melnichenko Alexandra A. , Sviridov Dmitri , Sobenin Igor A. , Mazus Alexey I. , Orekhov Alexander N. , Bukrinsky Michael I.
Published: July 2018

HIV infection is associated with the increased risk of cardiovascular disease (CVD), even in patients successfully treated with the combination antiretroviral therapy (cART). However, the relationship between HIV, cART, and pathogenesis of CVD remains controversial. In the present study, we evaluated the carotid intima–media thickness (CIMT), a surrogate marker of atherosclerosis, in HIV-infected subjects receiving or not receiving cART. One hundred nine newly diagnosed HIV-infected subjects and one hundred nine uninfected age-matched controls (all males) without the history of CVD, hypertension, or diabetes were recruited into the present study. Cross-sectional analysis at baseline (BL) showed significantly increased levels of triglycerides (TG) and decreased levels of high-density lipoprotein (HDL) in HIV-infected subjects, indicating that these risk factors for CVD appeared during the undiagnosed period of HIV infection. Nevertheless, no differences in CIMT were detected between the groups, suggesting that these risk factors were yet to be translated into the clinical disease. The prospective arm of the study, which included 37 HIV-infected and 23 uninfected subjects, showed higher CIMT increase in HIV-infected group than in control group (P=0.0063). This difference was significant for both cART-treated (P=0.0066) and untreated (P=0.0246) subgroups relative to the uninfected subjects, but no difference was found between the HIV-infected subgroups. These results suggest that cART does not reverse the HIV-induced increase of CIMT. The present study demonstrates that the progression of atherosclerosis is accelerated in HIV-infected subjects regardless of treatment.
Multi-zone non-thermal radiative model for stellar bowshocks
Authors: del Palacio S. , Bosch-Ramon V. , Müller A. L. , Romero G. E.
Published: July 2018

Context. Runaway stars produce bowshocks that are usually observed at infrared (IR) wavelengths. Non-thermal radio emission has been detected so far only from the bowshock of BD+43°3654, whereas the detection of non-thermal radiation from these bowshocks at high energies remains elusive.

Aims. We aim at characterising in detail the radio, X-ray, and γ-ray emission from stellar bowshocks accounting for the structure of the region of interaction between the stellar wind and its environment.

Methods. We develop a broadband-radiative, multi-zone model for stellar bowshocks that takes into account the spatial structure of the emitting region and the observational constraints. The model predicts the evolution and the emission of the relativistic particles accelerated and streaming together with the shocked flow.

Results. We present broadband non-thermal spectral energy distributions for different scenarios, synthetic radio-cm synchrotron maps that reproduce the morphology of BD+43°3654, and updated predictions in X-ray and γ-ray energy ranges. We also compare the results of the multi-zone model applied in this work with those of a refined one-zone model.

Conclusions. A multi-zone model provides better constraints than a one-zone model on the relevant parameters, namely the magnetic field intensity and the amount of energy deposited in non-thermal particles. However, one-zone models can be improved by carefully characterising the intensity of the IR dust photon field and the escape rate of the plasma from the shocked region. Finally, comparing observed radio maps with those obtained from a multi-zone model enables constraints to be obtained on the direction of stellar motion with respect to the observer.
Surgically-Treated Locoregionally Advanced Hypopharyngeal Cancer: Outcomes
Authors: Rodrigues Jorge , Breda Eduardo , Monteiro Eurico
Published: July 2018

Introduction Hypopharyngeal tumors are head and neck malignancies associated with a great mortality rate, and the treatment of advanced lesions constitutes a challenging problem. Pharyngolaryngectomy continues to be the gold standard treatment modality for locally-advanced diseases, and it is currently used as the primary treatment or in cases of relapse after an organ preservation strategy.

Objective This study aims to compare the survival rates of patients with advanced hypopharyngeal tumors treated with pharyngolaryngectomy as a primary or salvage option, and identify possible prognostic factors.

Methods All patients with advanced hypopharyngeal squamous cell carcinomas who performed pharyngolaryngectomy between 2007 and 2014 were reviewed retrospectively.

Results A total of 87 patients fulfilled the aforementioned criteria, and the sample had a mean age of 57.2 years and a male predominance of 43:1. The tumors were located in the pyriform sinus walls (81 tumors), in the posterior pharyngeal wall (4 tumors) and in the postcricoid region (2 tumors). A total of 60 patients underwent surgery as the primary treatment option, and 27 were submitted to salvage pharyngolaryngectomy after a previous treatment with chemoradiotherapy or radiotherapy. The 5-year overall survival was of 25.9%, the 5-year disease-free survival was of 24.2%, and the disease-specific survival was of 29.5%.

Conclusion The patients treated with pharyngolaryngectomy as the primary option revealed a better 5-year-disease free survival than the patients who underwent the salvage surgery (35.8% versus 11.7% respectively; p < 0.05). The histopathological criteria of capsular rupture of the lymph nodes (30.1% versus 19.8% respectively for the primary and salvage groups; p < 0.05) and vascular invasion (30.5% versus 22.5% respectively; p < 0.05) reduced the 5-year disease-free survival. Pharyngolaryngectomy as the primary intent revealed a lower local recurrence rate than the salvage surgery (40.6% versus 83.3% respectively; p < 0.05).
The Additive Effect of Low Molecular Weight Heparins on Thrombin Inhibition by Dermatan Sulfate
Authors: Cosmi Benilde , Agnelli Giancarlo , Young Edward , Hirsh Jack , Weitz Jeffrey
Published: July 2018

The aim of this study was to investigate the mechanism by which the anticoagulant activity of dermatan sulfate (DS) is increased by low molecular weight heparin (LMWH). In platelet poor plasma, LMWH enhances the effect of DS on thrombin (IIa) inhibition as determined by thrombin clotting times and with a chromogenic substrate assay. Analysis of the results of the chromogenic assays using either the algebraic fractional or the graphic isobole method suggests that LMWH has an additive effect on the anti-IIa activity of DS. This additive effect was lost when the experiments were repeated in plasma immunodepleted of antithrombin III (ATIII), indicating that the anti-IIa activity of LMWH is ATIII-dependent. To further explore the mechanism of the interaction between LMWH and DS, 125I-labeled IIa was added to plasma in the presence or absence of DS and/or LMWH and the formation of IIa-inhibitor complexes was assessed using SDS-PAGE followed by autoradiography. DS addition selectively increases the formation of heparin cofactor II (HCII)-IIa complexes, whereas LMWH enhances ATIII-IIa complex generation. Compared to plasma containing DS alone, the formation of ATIII-IIa complexes also is increased when the combination of DS and LMWH is added. These findings suggest that the additive effect of LMWH on the anti-IIa activity of DS reflects their different modes of IIa inhibition; DS potentiates IIa inhibition by HCII, while LMWH catalyses ATIII-dependent IIa inactivation. The potential clinical significance of these findings requires further investigation.
The Significance of TFPI in Clotting Assays – Gomparison and Combination with other Anticoagulants
Authors: Nordfang Ole , Kristensen Hanne I , Valentin Sanne , Østergaard Per , Wadt Johnny
Published: July 2018

The anticoagulant activities of Tissue Factor Pathway Inhibitor (TFPI), heparin and hirudin were compared in intrinsic (APTT) and extrinsic (PT) activated clotting assays. In contrast to the thrombin inhibitor hirudin, heparin was 10 fold more potent in the APTT assay than in the PT assay, indicating that inhibition of intrinsic activation is important for the anticoagulant activity of heparin as measured in an APTT assay. TFPI was most potent in the PT assay and the effect of TFPI was most pronounced in the presence of other anticoagulants (heparin and hirudin). The activities of the two natural anticoagulants antithrombin III (ATIII) and TFPI were compared in a PT assay with very dilute tissue factor. In this assay system TFPI in normal plasma affected the clotting time more than ATIII in the plasma. However, when heparin was added ATIII was the major anticoagulant, but profound Prolongation of the clotting time was only seen when TFPI was also added. In an ATIII deficient plasma heparin did not augment the effect of TFPI, showing that the increased effect of TFPI in the presence of heparin is dependent on the anticoagulant activity of ATIII/heparin. The effect of TFPI at prolonged clotting times was also illustrated by the significant effect of blocking TFPI in the plasma from warfarin-treated patients. Thus TFPI is a major anticoagulant in normal plasma and the effect of TFPI is especially seen at prolonged clotting times.
Comparison of the In Vitro Fibrinolytic Activities of Low and High Molecular Weight Single-Chain Urokinase-Type Plasminogen Activator
Authors: de Munk Gerard A W , Groeneveld Eleonore , Rijken Dingeman C
Published: July 2018

The fibrinolytic activity of low molecular weight (LMW) single-chain urokinase-type plasminogen activator (scu-PA) lacking the epidermal growth factor domain and the kringle domain was compared with the activity of high molecular weight (HMW) scu-PA. LMW scu-PA was 1-5 times less active than HMW scu-PA in a fibrin plate method, in a purified fibrin clot lysis assay and in a plasma clot lysis assay. Time course experiments in a chromogenic plasminogen activator assay suggested that LMW scu-PA was less sensitive to activation by plasmin than HMW scu-PA. This was confirmed in a scu-PA activation test, which showed that at a concentration of 40 IU/ml LMW scu-PA required a three-fold higher plasmin concentration for 50% activation in 20 min than did HMW scu-PA. Kinetic experiments in the presence of 0.1 M NaCl showed non-standard Michaelis-Menten kinetics for the activation by plasmin of both HMW and LMW scu-PA. In contrast, standard kinetics was observed at 0.15 M NaCl, showing a 2.6-fold lower catalytic efficiency for LMW scu-PA than for HMW scu-PA. It is concluded that the plasmin activation of LMW scu-PA is about three times slower than the activation of HMW scu-PA. This explains, at least partially, the lower fibrinolytic activity of LMW scu-PA in comparison with HMW scu-PA.
The Platelet-Stimulating Effect of Adrenaline Through α2-Adrenergic Receptors Requires Simultaneous Activation by a True Stimulatory Platelet Agonist
Authors: Steen Vidar M , Holmsen Holm , Aarbakke Grethe
Published: July 2018

The stimulating effect of adrenaline on human platelet phospholipase C (PLC) activation and responses in vitro (shape change, aggregation and dense granule secretion) was investigated with respect to its dependence on exogenously added agonists. All experiments were performed with human gel-filtered platelets pretreated with acetylsalicylic acid to prevent endogenous stimulation by the arachidonate pathway. (1) Preliminary experiments demonstrated the presence of trace amounts of extracellular ADP (0.05-0.58 μM) in non-stimulated platelet suspensions; ADP was effectively converted to ATP by the enzyme system creatine phosphate (CP)/creatine phosphokinase (CPK). (2) The adrenaline-induced optical aggregation and single particle (platelet) disappearance in the presence of trace amounts of ADP were almost abolished by the ADP-scavanger system CP/ CPK. (3) The response of CP/CPK-treated thrombin- or platelet-activating factor (PAF)-stimulated platelets was markedly increased by a subsequent addition of adrenaline. When hirudin or BN 50726 was added just prior to adrenaline to terminate the activation by thrombin or PAF, respectively, the stimulating effect of adrenaline was also abolished. (4) CP/CPK-treated, PAF-stimulated platelets rapidly developed decreased responsiveness to a subsequent addition of PAF. When adrenaline was added instead of a second addition of PAF, the stimulating effect of adrenaline was gradually decreased and prevented in parallel with the homologous desensitization of PAF. (5) The weak platelet agonist serotonin by itself induced only shape change in CP/CPK-treated platelets. Adrenaline failed to enhance the extent of this serotonin-induced platelet activation. (6) These results strongly suggest that adrenaline per se is not a platelet agonist in vitro but acts to enhance the stimulation induced by true agonists.
Antiphospholipid Antibodies: Prevalence, Clinical Significance and Correlation to Cytokine Levels in Acute Myeloid Leukemia and Non-Hodgkin’s Lymphoma
Authors: Stasi Roberto , Stipa Elisa , Masi Mario , Oliva Felicia , Sciarra Alessandro , Perrotti Alessio , Zaccari Giuseppe , Papa Giuseppe
Published: July 2018

This study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and highgrade non-Hodgkin’s lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p <0.0001). APA titres became normal in all patients responding to treatment, whereas nonresponders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from Controls, and concordance between ACA and LA results reached just 30%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and sIL-2r in NHL were found significantly elevated compared to Controls (p = 0.003, p = 0.009 and p = 0.024 respectively). In addition, the levels of these cytokines correlated with IgG-ACA at the different times of laboratory investigations. These results demonstrate that APA may have a role as markers of disease activity and progression in some haematological malignancies.
Inhibition of Endothelial Cell Expression of Plasminogen Activator Inhibitor Type-1 by Gemfibrozil
Authors: Fujii Satoshi , Sawa Hirofumi , Sobel Burton E
Published: July 2018

Increased concentrations of plasminogen activator inhibitor type-1 (PAI-1) in plasma are associated with impaired fibrinolysis and venous and arterial thrombo-embolic disease. In pilot studies designed to identify pharmacologic approaches capable of diminishing such increases, we found that gemfibrozil attenuated the Stimulation of synthesis of PAI-1 in a human, immortal, hepatoma cell line (Hep G2) induced by platelets. The present study was performed to determine whether it exerts analogous effects in non-immortal endothelial cells and whether it may therefore facilitate fibrinolysis locally in vivo. Human umbilical vein endothelial cells were incubated with pharmacologic concentrations of gemfibrozil. Gemfibrozil, 100 μM, suppressed basal PAI-1 production by 15% and attenuated the augmentation of synthesis of PAI-1 induced by lysates from platelets (4 × 107/ml) by 36% over 24 h without inhibiting overall protein synthesis. In addition, the increases in PAI-1 mRNA otherwise induced by platelet lysates over 6 h were suppressed by 49% (Northern blots) without any demonstrable change in the intracellular half-life of PAI-1 mRNA. Pulse-chase experiments demonstrated diminution of PAI-1 protein synthesis in parallel with the changes observed in PAI-1 mRNA. To determine whether these effects of gemfibrozil on endothelial cells in vitro were paralleled by consistent changes in the concentrations of PAI-1 in plasma in vivo, we studied rabbits with induced carotid artery thrombosis and thrombolysis. The increases in plasma PAI-1 induced by thrombosis and thrombolysis were inhibited by gemfibrozil (8.75 mg/kg i.v.), by 14% and 75%, respectively, Increases in endothelial cell PAI-1 gene expression in aorta, liver, and heart (4–6 fold over control) induced by thrombolysis were attenuated by gemfibrozil as well. Thus, gemfibrozil can attenuate shut down of the fibrinolytic system that is known to accompany thrombosis and thrombolysis and may therefore diminish the likelihood of early, thrombotic coronary artery reocclusion following revascularization with fibrinolytic agents.