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Δευτέρα 5 Σεπτεμβρίου 2016

Simulation of Terrigenous Minerogenic Particle Populations in Time and Space in Cayuga Lake, New York, in Response to Runoff Events

Abstract

The important effects of minerogenic particles delivered from watersheds on optical and phosphorus metrics of lacustrine water quality have recently been quantified through measurements of the projected area of these particles per unit volume of water (PAVm), using an individual particle analysis technique. A mass balance type model for PAVm, partitioned according to the contributions of four size classes, is developed and tested for Cayuga Lake, New York, supported by long-term monitoring of PAVm in the lake and its primary tributaries. The model represents the source of PAVm of tributary inputs and three in-lake loss processes: (1) size-dependent settling, (2) enhancement of settling through aggregation, and (3) filter feeding by dreissenid mussels. The central roles of major runoff events and localized external loads of minerogenic sediment at one end of the lake in driving patterns of PAVm in time and space are successfully simulated, including (1) the higher PAVm levels in a shallow area ("shelf") adjoining these inputs, relative to pelagic waters, following runoff events; and (2) the positive dependence of the shelf increases on the magnitude of the event. Analyses conducted with the model establish that settling, with aggregation enhancement, dominates the loss of PAVm from the water column of the shelf, while mussel filtration increases in relative importance in pelagic waters. The utility of PAVm predictions to quantify the effects of these particles on optical and phosphorus concentration metrics of water quality is established.



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Temperature Dependence of Carbon Disulphide Emissions from Rubber

Abstract

This paper has its origin via an inadvertent error wherein a length of rubber hose was added to the sampling line of a sulphur gas analyser at the Australian Baseline Station at Cape Grim. This carbon disulphide (CS2) contamination source was removed after a period of 10 weeks. In the interim, substantial data was collected and is here compared with the record of ambient station temperatures. CS2 was found to vary with ambient temperature over both short and monthly time scales. Comparisons of linear, natural log (ln) and log10 correlations yield the conclusion that log10 and ln CS2 emission vs. temperature (°C) associations provide the best correlations. No significant depletion of CS2 emission from the rubber over a 10-week period was detected. Implications for regional and global emission inventories of CS2 and carbonylsulphide (COS) are discussed.



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Accidente del vuelo 214 de Asiana Airlines (lecciones aprendidas) | Eventos con víctimas múltiples: reconsiderando los recursos necesarios

La planificación adecuada para la atención de los desastres requiere un conocimiento de los recursos necesarios para atender efectivamente a los pacientes en incidentes mayores con múltiples víctimas.

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GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease

Using a mouse model of Kawasaki disease, Stock and collaborators have discovered an essential role for GM-CSF as an instigator of cardiac inflammation.



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Phase I study of NK105, a nanomicellar paclitaxel formulation, administered on a weekly schedule in patients with solid tumors

Abstract

Previous studies have established the rationale for NK105, a nanomicellar formulation of paclitaxel, administered every 3 weeks. The aim of this phase I study was to determine the recommended dose and pharmacokinetics of weekly administered NK105. NK105 was administered by a 30-min infusion once weekly for three consecutive weeks in each 4-week cycle. In the dose-escalation phase, three to seven patients with solid tumors were enrolled to each of the four dose levels (50–100 mg/m2; n = 16). At a dose level of 100 mg/m2, predefined dose-limiting toxicity (DLT) manifested in only one out of six evaluable patients, whereas a dose delay due to neutropenia during the first course occurred two patients. None of the three patients given 80 mg/m2 had a dose reduction, while a dose delay occurred in two. NK105 exhibited linear pharmacokinetics at doses of 50–100 mg/m2, and approximately 5 % of total paclitaxel was released from micelles. Thus, the recommended dose was set at 80 mg/m2, and an additional 10 advanced breast cancer (ABC) patients were given this dose in the dose-expansion phase. DLT manifested in two patients, and grade ≥ 3 neutropenia was found in eight patients. Among the nine patients who completed the first cycle, four had a dose reduction, mostly because of neutropenia. Of the 10 patients, six achieved partial response (PR), and four achieved stable disease (SD) status. Overall, weekly NK105 was well tolerated and had a desirable antitumor activity profile. Further investigations of NK105 in ABC patients are currently underway.



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PEALD YSZ-based bilayer electrolyte for thin film-solid oxide fuel cells

Yttria-stabilized zirconia (YSZ) thin film electrolyte deposited by plasma enhanced atomic layer deposition (PEALD) was investigated. PEALD YSZ-based bi-layered thin film electrolyte was employed for thin film solid oxide fuel cells on nanoporous anodic aluminum oxide substrates, whose electrochemical performance was compared to the cell with sputtered YSZ-based electrolyte. The cell with PEALD YSZ electrolyte showed higher open circuit voltage (OCV) of 1.0 V and peak power density of 182 mW cm −2 at 450 °C compared to the one with sputtered YSZ electrolyte(0.88 V(OCV), 70 mW cm −2 (peak power density)). High OCV and high power density of the cell with PEALD YSZ-based electrolyte is due to the reduction in ohmic and activation losses as well as the gas and electrical current tightness.

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Plasmonic-resonance-based ternary composite complementary enhancement of the performance of dye-sensitized solar cells

Graphene (G), TiO 2 fusiform nanorods (TiO 2 NRs) adsorbed with Au nanoparticles (AuNPs) are prepared and blended as multifunctional materials into TiO 2 nanocrystalline film to form a novel ternary (G-TiO 2 NRs-Au) composite photoanode in dye-sensitized solar cells (DSSCs). The effects of G-TiO 2 NRs-Au on the properties of the photoanode and DSSC are investigated. Results show that, by blending G-TiO 2 NRs-Au, the light absorption and scattering of the photoanode are obviously improved, and the charge transfer resistance R 2 and electron recombination are decreased, resulting in a significant enhancement in the short-circuit current density ( J sc ) and the photoelectric conversion efficiency (PCE) of the DSSCs. The maximum J sc of 17.66 mA cm −2 and PCE of 8.56% are obtained in the optimal G-TiO 2 NRs-Au-based DSSC, about 33.6% and 35.0% higher than that obta...

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Affinity-mediated sorting order reversal of single-walled carbon nanotubes in density gradient ultracentrifugation

Sorted single-walled carbon nanotubes (SWNTs) are of paramount importance for their utilization in high-end optoelectronic applications. Sodium cholate (SC)-based density gradient ultracentrifugation (DGU) has been instrumental in isolating small diameter ( d t ) SWNTs. Here, we show that SWNTs wrapped by flavin mononucleotide (FMN) as a dispersing agent are sorted in DGU, and show sorting order reversal behavior, departing from prototypical SC-SWNT trends. Larger d t SWNTs are sorted in lower density ( ρ ), and buoyant ρ distribution of FMN-SWNT ranges from 1.15–1.25 g cm −3 . Such a nanotube layering pattern originates from both the binding affinity between FMN and SWNT and the less-susceptible hydrated volume of remote phosphate sidechains of FMN according to nanotube d t change.

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Corrigendum: 1D versus 3D quantum confinement in 1–5 nm ZnO nanoparticle agglomerations for application in charge-trapping memory devices (2016 Nanotechnology 27 [http://ift.tt/2cmuHLb] 275205 [http://ift.tt/2cmuHLb] )

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Ultrahigh power factor and enhanced thermoelectric performance of individual Te/TiS 2 nanocables

Here, we present the successful fabrication of Te/TiS 2 heterostructure nanocables with enhanced thermoelectric (TE) performance by a two-step route (a facile solvothermal approach for Te nanowires and then the Te nanowires are used as templates for the controllable growth of the Te/TiS 2 nanocables), which is scalable for practical nanodevice applications. The heterostructure nanocables of different sizes can be prepared by varying the synthetic composition. Measurements of the Seebeck coefficient (S), electrical conductivity ( σ ), and thermal conductivity ( κ ) are carried out on the same nanowires over a temperature range of 2–350 K. The heterostructure nanocables show an ultrahigh power factor (S 2 σ ) with a maximum value of 0.58 Wm −1 K −2 , which comes from a high electrical conductivity and a strongly enhanced Seebeck coefficient. The figure of merit (ZT) can reach 1.91 at room temperature from a single na...

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Dry-powder inhalers in patients with persistent airflow limitation: usability and preference

Inhalation devices represent per sé critical factors because they can affect the therapeutic outcomes independently of the drug used. The role of patients' usability and preference (PUP) for Dry Powder Inhalers (...

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Respiratory Distress, Congenital Hypothyroidism and Hypotonia in a Newborn


Respiration

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Personalized Medicine for Chronic Respiratory Infectious Diseases: Tuberculosis, Nontuberculous Mycobacterial Pulmonary Diseases, and Chronic Pulmonary Aspergillosis

Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections.
Respiration

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Raynaud phenomenon: clinical pearls

- Kenny Lin, MD, MPH

Reversible pallor of the tips of the fingers and/or toes on exposure to cold or emotional stress, known as Raynaud phenomenon, is a common manifestation of systemic lupus erythematosus (SLE) highlighted in the August 15th issue of AFP. As discussed in an earlier Photo Quiz, the differential diagnosis may include acrocyanosis, acute peripheral arterial occlusion, and frostbite. Raynaud phenomenon can be primary (idiopathic) or secondary to / associated with systemic conditions, such as SLE or systemic sclerosis/scleroderma.

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Image from AFP's Photo Quiz. Get the AFP Photo Quiz app.

How can family physicians distinguish primary from secondary Raynaud phenomenon? According to a recent review in the New England Journal of Medicine, patients with primary Raynaud phenomenon typically have a younger age of onset and thumb sparing. Patients with an age of onset over 40 years and severe, frequent events are more likely to develop connective tissue disease. Although most patients with primary Raynaud phenomenon have a normal erythrocyte sedimentation rate (ESR), neither a normal ESR nor a negative antinuclear antibody titer are necessary to make the diagnosis.

If trigger avoidance does not adequately control symptoms, the BMJ Clinical Evidence Handbook and Cochrane for Clinicians concur that an effective drug treatment for primary Raynaud phenomenon is a calcium channel blocker, particularly nifedipine. Although calcium channel blockers (CCBs) reduce average frequency of attacks by 1-2 per week, they do not affect severity or physiologic measurements (e.g., finger systolic pressure or skin temperature), and can be associated with headache, flushing, tachycardia, or edema. Both BMJ and Cochrane conclude that there is a close trade-off between benefits and harms. In their Practice Pointers, Drs. Dean Seehusen and Joseph Huang recommend that "a frank discussion of the benefits and risks should take place before prescribing CCBs to patients with Raynaud phenomenon." Other less well-studied medications for Raynaud phenomenon include phosphodiesterase type 5 inhibitors, topical nitrates, fluoxetine, and losartan.

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Effects of titanium dioxide nanoparticles derived from consumer products on the marine diatom Thalassiosira pseudonana

Abstract

Increased manufacture of TiO2 nanoproducts has caused concern about the potential toxicity of these products to the environment and in public health. Identification and confirmation of the presence of TiO2 nanoparticles derived from consumer products as opposed to industrial TiO2 NPs warrant examination in exploring the significance of their release and resultant impacts on the environment. To this end, we examined the significance of the release of these particles and their toxic effect on the marine diatom algae Thalassiosira pseudonana. Our results indicate that nano-TiO2 sunscreen and toothpaste exhibit more toxicity in comparison to industrial TiO2 and inhibited the growth of the marine diatom T. pseudonana. This inhibition was proportional to the exposure time and concentrations of nano-TiO2. Our findings indicate a significant effect, and therefore, further research is warranted in evaluation and assessment of the toxicity of modified nano-TiO2 derived from consumer products and their physicochemical properties.



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Genomic Instability of iPSCs: Challenges Towards Their Clinical Applications

Abstract

Induced pluripotent stem cells (iPSCs) are a type of pluripotent stem cells generated directly from mature cells through the introduction of key transcription factors. iPSCs can be propagated and differentiated into many cell types in the human body, holding enormous potential in the field of regenerative medicine. However, genomic instability of iPSCs has been reported with the advent of high-throughput technologies such as next-generation sequencing. The presence of genetic variations in iPSCs has raised serious safety concerns, hampering the advancement of iPSC-based novel therapies. Here we summarize our current knowledge on genomic instability of iPSCs, with a particular focus on types of genetic variations and their origins. Importantly, it remains elusive whether genetic variations in iPSCs can be an actual risk factor for adverse effects including malignant outgrowth. Furthermore, we discuss novel approaches to generate iPSCs with fewer genetic variations. Lastly, we outline the safety issues and monitoring strategies of iPSCs in clinical settings.



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IJMS, Vol. 17, Pages 1479: Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy

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Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause–effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy.

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Verbessertes Überleben bei Patienten mit primär metastasiertem Prostatakarzinom



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Prä- oder postoperative Strahlentherapie bei retroperitonealen Sarkomen unverzichtbar



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Quality control of involved field radiotherapy in the HD 13 and HD 14 trials

Abstract

Introduction

As part of the foundation of the German Hodgkin Study Group (GHSG) in 1978, a central radiotherapy (RT) reference centre was established to evaluate and to improve the quality of treatment. During the study generations, the quality assurance programs (QAP) were continued and adapted to the demands of each study. The purpose of this article is to demonstrate the results of the fifth study generation and to compare them to the previous findings.

Methods

With the start of the fourth GHSG study generation (HD10–12), a central prospective review of all diagnostic images was established to create an individual treatment plan for each early stage study patient. The quality of involved field RT was retrospectively evaluated by an expert panel of radiation oncologists. In the fifth study generation (HD13–15), the retrospective review of radiotherapy performed was refined and the results were compared with the findings of the fourth generation.

Results

The expert panel analyzed the RT planning and application of 1037 (28 %) patients (HD13 n = 465, HD14 n = 572). Simulation films were available in 85 % of cases and verification films in 87 %. RT was assessed as major violation in 46 % (HD13 = 38 %, HD14 = 52 %), minor violation in 9 % (HD13 = 9 %, HD14 = 9 %) and according to the protocol in 45 % (HD13 = 52 %, HD14 = 38 %).

Conclusion

The value for QAP of RT within the GHSG trials is well known. Still there were several protocol violations. In the future, the QAP program has to be adapted to the requirements of "modern RT" in malignant lymphoma.



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Therapie des lokalisierten nodulären Lymphozyten-prädominanten Hodgkin-Lymphoms bei Kindern



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Enhanced XOR activity in eNOS-deficient mice: Effects on the nitrate-nitrite-NO pathway and ROS homeostasis

Publication date: Available online 5 September 2016
Source:Free Radical Biology and Medicine
Author(s): Maria Peleli, Christa Zollbrecht, Marcelo F. Montenegro, Michael Hezel, Jianghong Zhong, Erik G. Persson, Rikard Holmdahl, Eddie Weitzberg, Jon O. Lundberg, Mattias Carlström
Xanthine oxidoreductase (XOR) is generally known as the final enzyme in purine metabolism and as a source of reactive oxygen species (ROS). In addition, this enzyme has been suggested to mediate nitric oxide (NO) formation via reduction of inorganic nitrate and nitrite. This NO synthase (NOS)-independent pathway for NO generation is of particular importance during certain conditions when NO bioavailability is diminished due to reduced activity of endothelial NOS (eNOS) or increased oxidative stress, including aging and cardiovascular disease. The exact interplay between NOS- and XOR-derived NO generation is not fully elucidated yet. The aim of the present study was to investigate if eNOS deficiency is associated with changes in XOR expression and activity and the possible impact on nitrite, NO and ROS homeostasis.Plasma levels of nitrate and nitrite were similar between eNOS deficient (eNOS−/−) and wildtype (wt) mice. XOR activity was upregulated in eNOS−/− compared with wt, but not in nNOS−/−, iNOS−/− or wt mice treated with the non-selective NOS inhibitor l-NAME. Following an acute dose of nitrate, plasma nitrite increased more in eNOS−/− compared with wt, and this augmented response was abolished by the selective XOR inhibitor febuxostat. Livers from eNOS−/− displayed higher nitrite reducing capacity compared with wt, and this effect was attenuated by febuxostat. Dietary supplementation with nitrate increased XOR expression and activity, but concomitantly reduced superoxide generation. The latter effect was also seen in vitro after nitrite administration. Treatment with febuxostat elevated blood pressure in eNOS−/−, but not in wt mice. A high dose of dietary nitrate reduced blood pressure in naïve eNOS−/− mice, and again this effect was abolished by febuxostat. In conclusion, eNOS deficiency is associated with an upregulation of XOR facilitating the nitrate-nitrite-NO pathway and decreasing the generation of ROS. This interplay between XOR and eNOS is proposed to play a significant role in NO homeostasis and blood pressure regulation.

Graphical abstract

image


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Long live the liver: immunohistochemical and stereological study of hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells of male and female rats throughout ageing

Abstract

Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.



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The versatility of the mitochondrial presequence processing machinery: cleavage, quality control and turnover

Abstract

Mitochondria play a key role in several metabolic and cell biological pathways and have attracted increasing attention due to their implication in life-span, ageing and human diseases. Mitochondrial proteases have a special role in these multiple biological functions, as they are involved in the regulation of various processes, e.g., mitochondrial protein biogenesis and quality control, mitochondrial dynamics, mitophagy and programmed cell death. The mitochondrial presequence processing machinery serves the particular purpose of maturing the majority of incoming precursor proteins by presequence cleavage, to ensure a stable mature protein by trimming of intermediate N-termini and to remove free toxic targeting peptides.



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Risk factors for active bleeding from colonic angiodysplasia confirmed by colonoscopic observation

Abstract

Purpose

Colonic angiodysplasia is an important cause of lower gastrointestinal bleeding in the elderly. Here, we investigated the risk factors for bleeding from colonic angiodysplasia seen at endoscopy.

Methods

We conducted a retrospective case-control study by reviewing records of 435 patients with angiodysplasia at colonoscopy from November 2006 to November 2015 in our hospital. To identify risk factors for active bleeding, the following were analyzed: age, sex, comorbidities, use of antithrombotic drugs and non-steroidal anti-inflammatory drugs, and the size and location of the lesions.

Results

Among the 435 patients, active bleeding from angiodysplasia was observed at endoscopy in 29 patients (6.7 %). Using multivariate analysis, we identified advanced age (odds ratio 5.15, 95 % confidence interval, 1.61–16.5), comorbidity of heart disease (6.88, 1.04–45.5), use of anticoagulant drug (4.22, 1.21–14.7), multiple lesions (6.67, 1.77–25.2), and small lesions (≤5 mm) (17.7, 4.90–64.0) as independent and significant risk factors for active bleeding. Actively bleeding colonic angiodysplasia lesions were very small in most cases (1–2 mm, 24/29, 83 %) and predominantly located in the right-side colon (26/29, 90 %). All of the 29 patients with active bleeding were successfully and safely treated endoscopically, but re-bleeding occurred in nine patients (31 %, 9/29) during the follow-up period of 2–84 months.

Conclusions

Multiple and small colonic angiodysplasia lesions in patients of advanced age, with heart disease, or receiving anticoagulants have increased risk for bleeding. We should be aware that small colonic angiodysplasia lesions in the right-side colon at colonoscopy in these patients may be a source of bleeding.



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Dry-powder inhalers in patients with persistent airflow limitation: usability and preference

Abstract

Background

Inhalation devices represent per sé critical factors because they can affect the therapeutic outcomes independently of the drug used. The role of patients' usability and preference (PUP) for Dry Powder Inhalers (DPIs) is high indeed because they can influence the extent of the adherence to treatment and the therapeutic outcomes.

Aim of the study was to assess and compare the PUP of three different DPIs in out-patients with persistent airflow limitation due to asthma or COPD.

Methods

The PUP of three different DPIs (Breezhaler; Genuair; Handihaler) were investigated by means of the Handling Questionnaire in out-patients with persistent airflow limitation needing an inhalation therapy. Patients had to report their preference before and after the nurse's instruction on the handling of each device. The nurse had also to note the critical steps during the patient's procedure for actuation; to count the number of attempts needed for actuating the device properly, and to measure the time (in sec.) required for these procedures. Data were collected up to three attempts per device.

Statistics: Welch test was used for normal distributed variables, while the Wilcoxon test for not normal distributed variables. The χ 2 test and the ANOVA test were also used. Univariate and multivariate regressions were also performed in order to investigate the effect of patients' characteristics and of technical differences of each device on their proper use.

Results

Three hundred thirty-three consecutive out-patients (age range 55–58 years, and well matched for gender), with persistent airway limitation of different severity were investigated, suffering from bronchial asthma (n = 175) or from chronic obstructive pulmonary disease (COPD) (n = 158). In particular, 127 patients (38 %) tested the three DPIs, while 110 (33 %) tested Breezhaler and Genuair, and 96 (29 %) Breezhaler and Handihaler. More than 50 % of patients who tested all devices preferred the Genuair and perceived this device as the easiest to use. The nurse's judgement confirmed their opinion. When compared to the other two DPIs, Genuair proved the least problematic either according to the patients' judgement and to the nurse's opinion. Mean number of attempts aimed to achieving the first proper actuation was lower with Genuair than with Breezhaler and Handihaler (1.5 vs 2.5–2.6, p < 0.0001). Finally, Genuair also proved the easiest to use and the least problematic according to the nurse judgement (0.0001), the most easily learned (0.0001), and that one with a successful rate of more than 56 % at the first attempt. Breezhaler and Handihaler needed an average of about one additional attempt to be used properly (p < 0.0001), and their usability proved significantly more difficult (OR of successful rate between 0.15 and 0.17, p < 0.001). In general, older patients needed more attempts to perform their first proper inhalation; their successful rate was lower, and they needed more time to learn how to use devices properly: with Genuair these differences were minimized.

Conclusions

The possibility of grading objectively the performance of different DPIs in terms of their usability and therapeutic convenience in daily life represents a crucial operational opportunity to pursue. To note that a substantial discrepancy exists between the patients' belief "at glance" and the patients' effective usability with can be registered with some devices. From a general point of view, devices requiring less manual actions for their actuation confirmed their better usability and proper handling after less attempts. In particular, Genuair came out as the most preferred DPI also when several different aspects of preference and usability are assessed objectively and compared.



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Fabrication of Biodegradable Synthetic Vascular Networks and Their Use as a Model of Angiogenesis

One of the greatest challenges currently faced in tissue engineering is the incorporation of vascular networks within tissue-engineered constructs. The aim of this study was to develop a technique for producing a perfusable, 3-dimensional, cell-friendly model of vascular structures that could be used to study the factors affecting angiogenesis and vascular biology in engineered systems in more detail. Initially, biodegradable synthetic pseudovascular networks were produced via the combination of robocasting and electrospinning techniques. The internal surfaces of the vascular channels were then recellularized with human dermal microvascular endothelial cells (HDMECs) with and without the presence of human dermal fibroblasts (HDFs) on the outer surface of the scaffold. After 7 days in culture, channels that had been reseeded with HDMECs alone demonstrated irregular cell coverage. However, when using a co-culture of HDMECs inside and HDFs outside the vascular channels, coverage was found to be continuous throughout the internal channel. Using this cell combination, collagen gels loaded with vascular endothelial growth factor were deposited onto the outer surface of the scaffold and cultured for a further 7 days. After this, endothelial cell outgrowth from within the channels into the collagen gel was observed, showing that the engineered vasculature maintains its capacity for angiogenesis. Furthermore, the HDMECs appeared to have formed perfusable tubules within the gel. These results show promising steps towards the development of an in vitro platform for studying angiogenesis and vascular biology in a tissue engineering context.
Cells Tissues Organs

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Angiogenic Effects of Collagen/Mesoporous Nanoparticle Composite Scaffold Delivering VEGF165

Vascularization is a key issue for the success of tissue engineering to repair damaged tissue. In this study, we report a composite scaffold delivering angiogenic factor for this purpose. Vascular endothelial growth factor (VEGF) was loaded on mesoporous silica nanoparticle (MSN), which was then incorporated within a type I collagen sponge, to produce collagen/MSN/VEGF (CMV) scaffold. The CMV composite scaffold could release VEGF sustainably over the test period of 28 days. The release of VEGF improved the cell proliferation. Moreover, the in vivo angiogenesis of the scaffold, as studied by the chick chorioallantoic membrane (CAM) model, showed that the VEGF-releasing scaffold induced significantly increased number of blood vessel complexes when compared with VEGF-free scaffold. The composite scaffold showed good biocompatibility, as examined in rat subcutaneous tissue. These results demonstrate that the CMV scaffold with VEGF-releasing capacity can be potentially used to stimulate angiogenesis and tissue repair.

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Cosmetics, Vol. 3, Pages 32: Packaging Evaluation Approach to Improve Cosmetic Product Safety

In the Regulation 1223/2009, evaluation of packaging has become mandatory to assure cosmetic product safety. In fact, the safety assessment of a cosmetic product can be successfully carried out only if the hazard deriving from the use of the designed packaging for the specific product is correctly evaluated. Despite the law requirement, there is too little information about the chemical-physical characteristics of finished packaging and the possible interactions between formulation and packaging; furthermore, different from food packaging, the cosmetic packaging is not regulated and, to date, appropriate guidelines are still missing. The aim of this work was to propose a practical approach to investigate commercial polymeric containers used in cosmetic field, especially through mechanical properties' evaluation, from a safety point of view. First of all, it is essential to obtain complete information about raw materials. Subsequently, using an appropriate full factorial experimental design, it is possible to investigate the variables, like polymeric density, treatment, or type of formulation involved in changes to packaging properties or in formulation-packaging interaction. The variation of these properties can greatly affect cosmetic safety. In particular, mechanical properties can be used as an indicator of pack performances and safety. As an example, containers made of two types of polyethylene with different density, low-density polyethylene (LDPE) and high-density polyethylene (HDPE), are investigated. Regarding the substances potentially extractable from the packaging, in this work the headspace solid-phase microextraction method (HSSPME) was used because this technique was reported in the literature as suitable to detect extractables from the polymeric material here employed.

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Invasive coronary strategy improves survival after MI, shows UK study

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Issue Information



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FBXO25 promotes cell proliferation, invasion, and migration of NSCLC

Abstract

FBXO25 is a recently discovered protein that belongs to the Fbx class of the F-box family of proteins, and F-box proteins play a crucial role in tumorigenesis. However, the function of FBXO25 in cancer was not revealed so far. As measured by immunohistochemical staining, FBXO25 was highly expressed in the cytoplasm and nucleus of lung cancer samples (64.2 %, 136/212), compared with adjacent normal lung tissues (23.3 %, 7/30, p < 0.01). In addition, its expression was positively correlated with TNM staging (p < 0.001) and lymph node metastasis (p = 0.017). The overall survival of non-small-cell lung cancer (NSCLC) patients with FBXO25-positive expression (40.646 ± 1.745 months) was significantly reduced compared with those with FBXO25-negative expression (46.548 ± 2.176 months, p = 0.023). Consistently, we found that the proliferation, invasion, and migration capacity of A549 cells transfected with FBXO25 were significantly greater than those of control cells, while interference of FBXO25 could significantly inhibit cell proliferation, invasion, and migration in H1299 cells. Furthermore, we demonstrated that FBXO25 could regulate the expression of β-catenin, YAP, some cyclins, and matrix metalloproteinases (MMPs). Collectively, these results indicate that FBXO25 may promote the tumorigenicity of lung cancer cells and might serve as a novel therapeutic target of NSCLC.



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IJMS, Vol. 17, Pages 1476: MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats

ag

As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

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IJMS, Vol. 17, Pages 1482: Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

ag

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.

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Issue Information



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Epstein-Barr virus-positive mucocutaneous ulcer

Publication date: Available online 4 September 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Bo-Jung Chen, Chia-Lang Fang, Shih-Sung Chuang




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Analysis of the diagnostic value of CD138 for chronic endometritis, the risk factors for the pathogenesis of chronic endometritis and the effect of chronic endometritis on pregnancy: a cohort study

Background: To investigate the role of CD138 immunohistochemistry in the diagnosis of chronic endometritis (CE) and the risk factors for assisted conception patients having CE complications. Methods: Ninety-three patients, with normal uterine shape confirmed by examination and who were planning to undergo assisted conception treatments, were selected as research subjects. Endometrial tissue was isolated for routine hematoxylin and eosin (HE) and CD138 immunohistochemical staining. Additionally, the disease histories of patients were collected, and the reproductive prognosis was followed up. Results: ① CE detection rate: The rate of CD138 immunohistochemical staining was greater than that of HE staining (27.96 % vs. 26.89 %, P <0.05); ② Pregnancy rate: the pregnancy rate of CD138-positive patients (7.7 %) was lower than the pregnancy rate of CD138-negative patients (31.3 %) (p = 0.017 < 0.05); ③ The results from univariate analysis showed that a previous history of prolonged menstrual bleeding episodes, an abortion history, and complications of fallopian tube obstruction were associated with CE (P <0.05). The results of logistic regression analysis confirmed that prolonged menstrual bleeding episodes (P = 0.014, OR = 5.394, 95 % CI 1.405-20.699), a previous abortion history (P = 0.029, OR = 3.194, 95 % CI 1.125-9.073), and fallopian tube obstruction (P = 0.028, OR = 3.274, 95 % CI 1.139-9.415) were independent risk factors for positive CD138 results. Conclusions: CD138 immunohistochemistry can improve the CE diagnosis rate. A previous history of prolonged menstrual bleeding episodes, an abortion history, and a history of fallopian tube obstruction are risk factors for chronic endometritis, and a CD138 immunohistochemical examination should be advised among them.

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Comparison of sleep quality based on direction of shift rotation in electronics workers

Background: Previous studies have reported the effects of direction of shift rotation on sleep, however, the findings are inconsistent. In this study, we investigated sleep quality related to direction of shift rotation using large-scale data from shiftwork-specific health examinations of electronics workers. Methods: This study included 4750 electronics workers working in a rotating 3-shift system who completed a medical examination for shift workers survey from January 1 to December 31, 2014, at a general hospital. The subjects were categorized into one of two groups according to direction of shift rotation. We compared sleep quality index between the subjects who worked in forward rotation and backward rotation systems. Results: Backward rotation was positively associated with prevalence of poor sleep quality. In the multivariable-adjusted model, when comparing backward rotation to forward rotation, the odds ratio (OR) with 95 % confidence interval (95 % CI) for poor sleep quality was 1.95 (1.58–2.41). After stratifying by gender, the ORs (95 % CIs) for poor sleep quality in male and female was 1.92 (1.47–2.49) and 2.13 (1.47–3.08), respectively. In subgroup analyses, backward rotation was significantly associated with poor sleep quality in workers ≥30 years of age compared with workers <30 years of age (adjusted OR 2.60 vs. 1.89, respectively; P for interaction <0.001). Conclusions: Our study supports that a backward rotation system is associated with poor sleep quality. Forward rotation systems should be considered to reduce sleep problems.

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Gasterophilus (Diptera, Gasterophilidae) infestation of equids in the Kalamaili Nature Reserve, China

Authors: Heqing Huang, Boru Zhang, Hongjun Chu, Dong Zhang and Kai Li.<br />Parasite Vol. 23 , page 36<br />Published online: 05/09/2016<br /> Keywords: Gasterophilus ; Equids ; Przewalski's horses ; Epidemiology ; Differential analysis.<img src="http://ift.tt/2bYYlFk" height="1" width="1" alt=""/>

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Sandflies in an urban area of transmission of visceral leishmaniasis in midwest Brazil

Authors: Maria Elizabeth Cavalheiros Dorval, Elisa Teruya Oshiro, Andreia Fernandes Brilhante, Vânia Lúcia Brandão Nunes, Geucira Cristaldo, Manoel Sebastião Costa Lima Júnior and Eunice Aparecida Bianchi Galati.<br />Parasite Vol. 23 , page 35<br />Published online: 05/09/2016<br /> Keywords: Bichromomyia flaviscutellata ; Leishmania infantum ; Lutzomyia longipalpis ; Phlebotomine ; Natural infection.<img src="http://ift.tt/2bYYbxQ" height="1" width="1" alt=""/>

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¡Ya está disponible el Vol V Nº 2 de 2016! | IntraMed Journal (investigación científica en medicina)

Un espacio para la investigación científica original en idioma español con revisión por pares. De libre acceso, con indexación en el catálogo de revistas Latindex.

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Retraction Note to: Multifocal multi-organ ischaemia and infarction in a preterm baby due to maternal intravenous cocaine use: a case report



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Successful laparoscopic treatment of a giant solitary fibrous tumor of the mesorectum: A case report and literature review

Abstract

A solitary fibrous tumor is a ubiquitous mesenchymal fibroblastic tumor that was previously considered limited to the pleural cavity. Here, we report a rare case of a large solitary fibrous tumor of the mesorectum, which was successfully resected laparoscopically. A 56-year-old woman was referred to our hospital for a giant pelvic mass. Pelvic MRI showed a well-circumscribed mass, 12 cm in diameter, with heterogeneous signal intensity on T2-weighted images. It was diagnosed as a benign mesorectal tumor of unknown origin. We successfully resected the entire tumor laparoscopically. Histological examination revealed it to be an extrapleural solitary fibrous tumor. For large tumors in the pelvis, the laparoscopic approach is preferable in terms of intraoperative hemorrhage, as long as they do not invade surrounding tissues.



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Methods for Implant Acceptance and Wound Healing: Material Selection and Implant Location Modulate Macrophage and Fibroblast Phenotypes

This review focuses on materials and methods used to induce phenotypic changes in macrophages and fibroblasts. Herein, we give a brief overview on how changes in macrophages and fibroblasts phenotypes are critical biomarkers for identification of implant acceptance, wound healing effectiveness, and are also essential for evaluating the regenerative capabilities of some hybrid strategies that involve the combination of natural and synthetic materials. The different types of cells present during the host response have been extensively studied for evaluating the reaction to different materials and there are varied material approaches towards fabrication of biocompatible substrates. We discuss how natural and synthetic materials have been used to engineer desirable outcomes in lung, heart, liver, skin, and musculoskeletal implants, and how certain properties such as rigidity, surface shape, and porosity play key roles in the progression of the host response. Several fabrication strategies are discussed to control the phenotype of infiltrating macrophages and fibroblasts: decellularization of scaffolds, surface coatings, implant shape, and pore size apart from biochemical signaling pathways that can inhibit or accelerate unfavorable host responses. It is essential to factor all the different design principles and material fabrication criteria for evaluating the choice of implant materials or regenerative therapeutic strategies.

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Tissue engineering is a growing field and its success is determined, in part, by innate host responses to implanted materials. We have reviewed how macrophage and fibroblast phenotypes are altered on the basis of material selection, implant geometry, and implant location. We also discuss the main challenges and future directions for this field.



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Acetalated Dextran Microparticulate Vaccine Formulated via Coaxial Electrospray Preserves Toxin Neutralization and Enhances Murine Survival Following Inhalational Bacillus Anthracis Exposure

Subunit formulations are regarded as the safest type of vaccine, but they often contain a protein-based antigen that can result in significant challenges, such as preserving antigenicity during formulation and administration. Many studies have demonstrated that encapsulation of protein antigens in polymeric microparticles (MPs) via emulsion techniques results in total IgG antibody titers comparable to alum formulations, however, the antibodies themselves are non-neutralizing. To address this issue, a coaxial electrohydrodynamic spraying (electrospray) technique is used to formulate a microparticulate-based subunit anthrax vaccine under conditions that minimize recombinant protective antigen (rPA) exposure to harsh solvents and high shear stress. rPA and the adjuvant resiquimod are encapsulated either in separate or the same acetalated dextran MPs. Using a murine model, the electrospray formulations lead to higher IgG2a subtype titers as well as comparable total IgG antibody titers and toxin neutralization relative to the FDA-approved vaccine (BioThrax). BioThrax provides no protection against a lethal inhalational challenge of the highly virulent Ames Bacillus anthracis anthrax strain, whereas 50% of the mice vaccinated with separately encapsulated electrospray MPs survive. Overall, this study demonstrates the potential use of electrospray for encapsulating protein antigens in polymeric MPs.

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Coaxial electrohydrodynamic spraying (electrospray) is used to encapsulate a protein antigen from Bacillus anthracis in acetalated dextran microparticles under benign processing conditions. Immunizing with this electrospray formulation results in comparable toxin neutralizing activity and substantially enhanced protection relative to the FDA-approved anthrax vaccine. The study establishes electrospray as an effective technique to encapsulate protein antigens in polymeric microparticles.



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The Effect of Advanced Motherhood on Newborn Offspring’s Hippocampal Neural Stem Cell Proliferation

Objective. To investigate the effect of advanced motherhood on rat hippocampal neural stem cell proliferation. Methods. Female parents were subdivided into control and old mother group by age, and neural stem cells were cultured from hippocampal tissues for 24 h newborn offspring. The diameter and numbers of neurospheres were examined by microscopy, and differences in proliferation were examined by EdU immunofluorescence, CCK-8 assay, and cell cycle analysis. Results. The number of neurospheres in the old mother group after culture was lower than the control group. Additionally, neurospheres' diameter was smaller than that of the control group (). The EdU positive rate of the old mother group was lower than that of the control group (). CCK-8 assay results showed that the absorbance values for the old mother group were lower than that of the control group at 48 h and 72 h (). The proportions of cells in the S and G2/M phases of the cell cycle for the older mother group were less than that found for the control group (). Conclusion. The proliferation rates of hippocampal NSCs seen in the older mother group were lower than that seen in the control group.

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Safety of Bronchoscopy in Patients with Echocardiographic Evidence of Pulmonary Hypertension

Background: Bronchoscopy with transbronchial and endobronchial biopsy and transbronchial needle aspiration is an important diagnostic tool in the pulmonologist's armamentarium. Safety in patients with pulmonary hypertension is controversial and many bronchoscopists consider this as a contraindication for the procedure. Objectives: To evaluate safety of bronchoscopy in patients with echocardiographic pulmonary hypertension and to compare with patients without it. Methods: Retrospective analysis of patients who underwent bronchoscopic transbronchial biopsy, endobronchial biopsy and/or endobronchial ultrasound-guided transbronchial needle aspiration. Patients were divided into two groups based on echocardiographic results: control group with systolic pulmonary artery pressure Results: One-hundred and ninety patients met the study criteria. Patients in the control group were younger with a lower incidence of chronic kidney disease. There was no difference in prevalence of congestive heart failure, obstructive airway disease, malignancy, liver disease, coagulopathy, use of antiplatelet agent or anticoagulant drugs. Incidence of minor bleeding due to bronchoscopic biopsies was 4.8% in both groups (p = 1.00). Incidence of major bleeding was similar in the groups (one patient in each group). In the control group, one patient had pneumothorax and another required prolonged mechanical ventilation (>4 h). In the eSPAP group, two patients required prolonged mechanical ventilation. There was no procedure-related mortality or sedation complications in the cohort. Conclusion: Our study provides additional support that in patients with echocardiographic evidence of pulmonary hypertension, transbronchial and endobronchial biopsies and endobronchial ultrasound-guided transbronchial needle aspiration are safe procedures.
Respiration

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Sedation for Bronchoscopy and Complications in Obese Patients

Background: Bronchoscopy is a safe and minimally invasive diagnostic tool, but no studies have reported prospectively on sedation and outcomes in patients with objectively defined obesity. Objectives: The purpose of the study is to determine if obese patients require more sedation or had more procedural complications during bronchoscopy under moderate sedation than non-obese patients. Methods: We evaluated complications and sedation requirements in non-obese versus obese patients, defined by multiple criteria including body mass index (BMI), neck circumference, abdominal height, and Mallampati scores. Results: Data were collected prospectively in 258 patients undergoing bronchoscopy under moderate sedation. By varying criteria, there were the following proportions of obese patients: 30% by BMI >30, 39% by neck circumference >40 cm, and 35% by abdominal height >22 cm in males and >20 cm in females. Sedative and analgesic dosing was not clinically significantly higher in obese patients than in non-obese patients. There was no difference in complications or procedural success based on obesity criteria. Hemoglobin oxygen desaturations occurred more often during bronchoscopy in patients with increasing Mallampati scores (p = 0.04), but this had no effect on bronchoscopy time or successful completion of the procedure. A subset of patients with previous polysomnogram-proven obstructive sleep apnea were more likely to have earlier termination of their procedure (15.8%) than patients with no diagnosed sleep apnea (2.3%; p = 0.002). Conclusion: In this prospective assessment of patients with obesity, we found neither clinically significant differences in sedation needs nor increases in complications in obese versus non-obese patients using a variety of indices of obesity.
Respiration

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High Diagnostic Value of a New Real-Time Pneumocystis PCR from Bronchoalveolar Lavage in a Real-Life Clinical Setting

Background: To diagnose Pneumocystis jirovecii pneumonia (PCP), PCR testing in bronchoalveolar lavage (BAL) fluid has recently become an alternative to immunofluorescence testing (IFT); however, its diagnostic accuracy is less clear. Objective: To analyze the diagnostic value of a new semiquantitative real-time PCR (RT-PCR) in BAL in a real-life clinical setting. Methods: Retrospective analysis of all RT-PCR results [semiquantitative: negative, weakly positive, and strongly positive; measured in cycle thresholds (Ct)] in BAL in the period between 2010 and 2014. The diagnosis of PCP was defined by clinical, radiological, and laboratory signs and by treatment initiation. Any positive PCR was compared with subsequent IFT. Results: Of 128 patient samples, 32 had PCP. There is a relevant correlation of high significance between positive PCR Ct and IFT (r = -0.7781, p Conclusion: A negative RT-PCR (Ct >45) rules out PCP. A strongly positive PCR (Ct Respiration

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Mechanical and microstructural characteristics of Ti6Al4V/AA2519 and Ti6Al4V/AA1050/AA2519 laminates manufactured by explosive welding

Publication date: 5 December 2016
Source:Materials & Design, Volume 111
Author(s): P. Bazarnik, B. Adamczyk-Cieślak, A. Gałka, B. Płonka, L. Snieżek, M. Cantoni, M. Lewandowska
The aim of the work was to produce laminated structures consisting of Ti–6Al–4V alloy and AA2519 plates and to investigate their microstructure and mechanical properties with an emphasis on the role of an additional AA1050 interlayer. Explosive welding was selected as a joining technology. The microstructure and chemical composition of the explosively joined samples were investigated. Mechanical properties were evaluated in the tensile testing and by microhardness analysis.The results demonstrated that explosive welding is an effective way to produce Ti/Al laminates. Both Ti6Al4V/AA2519 and Ti6Al4V/AA1050/AA2519 laminated plates exhibit good quality of bonding without voids and major delamination. The explosive welding produced metallurgical bonding with a nanostructured zone consisting of Al3Ti and Al2Ti phases. This zone is thicker in the joint with additional AA1050 interlayer when compared to direct AA2519/Ti6Al4V bonding. In the latter, SEM and STEM analysis reviled the presence of net-like structure in the collision zone. Advanced EDX analysis shows the enrichment of grain boundaries in copper. The formation of this structure is widely discussed. In addition, the explosive welding introduces large plastic deformation which induces the process of grain refinement in aluminium plates. Tensile testing confirms that joining section is not the weakest element of the cladded plates.

Graphical abstract

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Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome

Background: Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE-mediated food allergy. We recently described a significant increase in fecal eosinophil-derived neurotoxin (EDN) after ingestion of the causative food. However, little is known about the activation status of circulating eosinophils in patients with an acute FPIES reaction. Methods: Surface CD69 expression was assessed by flow cytometry on peripheral eosinophils from 5 patients with FPIES before and after ingestion of the causative food. Fecal EDN was measured by enzyme-linked immunosorbent assay. Results: No eosinophil activation was observed before ingestion; however, a significant increase in CD69 expression on eosinophils after an acute FIPES reaction was demonstrated in all of the patients. There was no significant change in absolute eosinophil counts in the peripheral blood. The levels of fecal EDN increased on the day after ingestion of the causative food in all patients. Conclusion: These results suggest that circulating eosinophils as well as eosinophils in the intestinal mucosal tissue are activated in acute FPIES reactions and might be associated with systemic immune events in FPIES.
Int Arch Allergy Immunol 2016;170:201-205

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Cover Picture: A new fluorescent dye for cell tracing and mitochondrial imaging in vitro and in vivo (J. Biophotonics 9/2016)

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Mitochondria contribute to redox and calcium balance, and apoptosis thus regulating cellular fate. The described dye V07-07059 stains mitochondria effectively due to their membrane potential in vitro and in vivo. It further exhibits superior properties compared to currently used probes such as greater photostability and reduced cell toxicity. Therefore it is a novel tool for longitudinal and functional studies of mitochondria.

Further details can be found in the article by A. T. Press et al. on pp. 888–900.



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Contents: J. Biophotonics 9/2016



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Issue Information: J. Biophotonics 9/2016

No abstract is available for this article.



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IL-33 delivery induces serous cavity macrophage proliferation independent of interleukin-4 receptor alpha

IL-33 plays an important role in the initiation of type-2 immune responses, as well as the enhancement of type 2 effector functions. Engagement of the IL-33 receptor on macrophages facilitates polarization to an alternative activation state by amplifying IL-4 and IL-13 signaling to IL-4Rα. IL-4 and IL-13 also induce macrophage proliferation but IL-33 involvement in this process has not been rigorously evaluated. As expected, in vivo delivery of IL-33 induced IL-4Rα-dependent alternative macrophage activation in the serous cavities. IL-33 delivery also induced macrophages to proliferate but, unexpectedly, this was independent of IL-4Rα signalling. In a filarial nematode infection model in which IL-4Rα-dependent alternative activation and proliferation in the pleural cavity is well described, IL-33R was essential for alternative activation but not macrophage proliferation. Similarly, during Alternaria alternata induced airway inflammation, which provokes strong IL-33 responses, we observed that both IL-4Rα and IL-33R were required for alternative activation, while macrophage proliferation in the pleural cavity was still evident in the absence of either receptor alone. Our data show that IL-33R and IL-4Rα promote macrophage proliferation independently of each other, but both are essential for induction of alternative activation.

This article is protected by copyright. All rights reserved



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Paediatric burns secondary to nail adhesives: a case series

Background: Nail adhesives are widely available beauty products that are used in the cosmetic industry and households to attach false nails. Nail adhesive burns are uncommon, and it is crucial that healthcare providers and the public are aware of its potential to cause chemical burn.Case PresentationCase series of accidental burns secondary to cyanoacrylate nail glue treated at the Welsh Centre for Burns and Plastic Surgery (WCBPS) in Swansea, United Kingdom. Conclusion: All of the burns were observed in children and occurred due to accidental spillage. Therefore, it is important for the public to be aware that nail glue is a chemical agent which should be stored safely away from the reaches of young children. The case series highlights the importance of first aid in reducing the severity of chemical burns secondary to the nail adhesives, and its early recognition and treatment are emphasised.

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Botulinum toxin related research in maxillofacial plastic and reconstructive surgery

No description available

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Effectiveness of Fluticasone Furoate–Vilanterol for COPD in Clinical Practice

New England Journal of Medicine, Ahead of Print.


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The Prognostic Role of Obstructive Sleep Apnea at the Onset of Amyotrophic Lateral Sclerosis

Background/Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of central and peripheral motor neurons. Some studies have found discordant data in the presence of sleep apnea in ALS patients. An obstructive component also occurs with upper airways hypotonia and muscle weakness that may result in an excessive reduction of airway lumen, leading to obstructive sleep apnea (OSA). The aim of this study was to assess the role of obstructive apneic events at disease onset in the ALS prognosis. Methods: A longitudinal retrospective study was conducted on 42 clinically diagnosed ALS patients. The study population was divided into 2 groups according to their obstructive apnea/hypopnea index (AHIo): group 1 consisted of 20 patients with an AHIo ≥5 and group 2 consisted of 22 patients with an AHIo Results: The mean survival in ALS patients with an AHIo ≥5 was significantly shorter than in ALS without OSA (p = 0.0237). The sniff nasal inspiratory pressure test was significantly correlated with AHIo, time of oxyhemoglobin saturation below 90% and the oxyhemoglobin desaturation index (p Conclusions: Our study highlights the importance of an early diagnosis of OSA in ALS patients, allowing the identification of ALS patients with an OSA phenotype (AHIo ≥5), who are characterized by a worse prognosis.
Neurodegener Dis 2017;17:14-21

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Effectiveness of Fluticasone Furoate–Vilanterol for COPD in Clinical Practice

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New England Journal of Medicine, Ahead of Print.


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Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria

Levofloxacin is a synthetic broad-spectrum antibacterial agent for oral or intravenous administration. Chemically, levofloxacin is the levorotatory isomer (L-isomer) of racemate ofloxacin, a fluoroquinolone antibacterial agent. Quinolone derivatives rapidly and specifically inhibit the synthesis of bacterial DNA. Levofloxacin has in vitro activity against a broad range of aerobic and anaerobic Gram-positive and Gram-negative bacteria. However, formulation of combined poloxamers thermoregulated (as Pluronic® F127) and levofloxacin for use in multiresistant bacterial treatment were poorly described in the current literature. Thus, the aim of the present work is to characterize poloxamers for levofloxacin controlled release and their use in the treatment of multidrug bacterial resistance. Micelles were produced in colloidal dispersions, with a diameter between 5 and 100 nm, which form spontaneously from amphiphilic molecules under certain conditions as concentration and temperature. Encapsulation of levofloxacin into nanospheres showed efficiency and enhancement of antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae when compared with only levofloxacin. Furthermore, all formulations were not cytotoxic for NIH/3T3 cell lineage. In conclusion, poloxamers combined with levofloxacin have shown promising results, better than alone, decreasing the minimal inhibitory concentration of the studied bacterial multiresistance strains. In the future, this new formulation will be used after being tested in animal models in patients with resistant bacterial strains.

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Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans

Drug-induced liver injury (DILI) is a major cause of late-stage clinical drug attrition, market withdrawal, black-box warnings, and acute liver failure. Consequently, it has been an area of focus for toxicologists and clinicians for several decades. In spite of considerable efforts, limited improvements in DILI prediction have been made and efforts to improve existing preclinical models or develop new test systems remain a high priority. While prediction of intrinsic DILI has improved, identifying compounds with a risk for idiosyncratic DILI (iDILI) remains extremely challenging because of the lack of a clear mechanistic understanding and the multifactorial pathogenesis of idiosyncratic drug reactions. Well-defined clinical diagnostic criteria and risk factors are also missing. This paper summarizes key data interpretation challenges, practical considerations, model limitations, and the need for an integrated risk assessment. As demonstrated through selected initiatives to address other types of toxicities, opportunities exist however for improvement, especially through better concerted efforts at harmonization of current, emerging and novel in vitro systems or through the establishment of strategies for implementation of preclinical DILI models across the pharmaceutical industry. Perspectives on the incorporation of newer technologies and the value of precompetitive consortia to identify useful practices are also discussed.

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Meta-Analysis of the Association between Vitiligo and Human Leukocyte Antigen-A

Objective. The objective of this study was to systematically evaluate the association between vitiligo and human leukocyte antigen- (HLA-) A. Methods. PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and reference lists were searched for relevant original articles. Results. Nineteen case-control studies comprising 3042 patients and 5614 controls were included, in which 33 HLA-A alleles were reported. Overall, three alleles (HLA-02, 33, and A31) were significantly associated with increased risk of vitiligo, two (HLA-09 and A19) were associated with decreased risk, and the remaining 28 were unassociated. Twelve alleles, seven alleles, and 19 alleles were common to three ethnicities, both types of vitiligo, and both typing methods, respectively. In the subgroup analysis by ethnicity and typing methods, the association of six alleles and five alleles was inconsistent in three populations and both typing methods, respectively. In the subgroup analysis by clinical type, the association of all seven alleles was consistent in both types of vitiligo. Conclusion. The meta-analysis suggests that HLA-02, 33, and A31 are associated with increased risk of vitiligo, while HLA-09 and A19 are associated with decreased risk of vitiligo. The association of some alleles varies in terms of ethnicity and typing methods.

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Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of Human and Mouse

Genetic networks provide new mechanistic insights into the diversity of species morphology. In this study, we have integrated the MGI, GEO, and miRNA database to analyze the genetic regulatory networks under morphology difference of integument of humans and mice. We found that the gene expression network in the skin is highly divergent between human and mouse. The GO term of secretion was highly enriched, and this category was specific in human compared to mouse. These secretion genes might be involved in eccrine system evolution in human. In addition, total 62,637 miRNA binding target sites were predicted in human integument genes (IGs), while 26,280 miRNA binding target sites were predicted in mouse IGs. The interactions between miRNAs and IGs in human are more complex than those in mouse. Furthermore, hsa-miR-548, mmu-miR-466, and mmu-miR-467 have an enormous number of targets on IGs, which both have the role of inhibition of host immunity response. The pattern of distribution on the chromosome of these three miRNAs families is very different. The interaction of miRNA/IGs has added the new dimension in traditional gene regulation networks of skin. Our results are generating new insights into the gene networks basis of skin difference between human and mouse.

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rLj-RGD3, a Novel Three-RGD-Motif-Containing Recombinant Protein from Lampetra japonica, Protects PC12 Cells from Injury Induced by Oxygen-Glucose Deprivation and Reperfusion

rLj-RGD3 is a 14.5 kDa recombinant protein with 3 RGD (Arg-Gly-Asp) motifs from the salivary gland secretions of Lampetra japonica, which is a histidine-rich and arginine-rich protein. Previous reports indicated that rLj-RGD3 has typical functions of RGD-toxin protein, such as platelet aggregation suppression tumour metastasis and angiogenesis inhibition. Because histidine and arginine have cerebral ischemia-reperfusion and neuroprotective functions, we investigated whether rLj-RGD3 has such activities and studied the mechanism. The effects of rLj-RGD3 on neuroprotection and antiapoptosis were determined. The expression level of focal adhesion kinase (FAK), p-FAK, Caspase-3, and Bcl-2 after oxygen-glucose deprivation and reperfusion (OGD-R) was examined. The viability of PC12 cells incubated with rLj-RGD3 at high concentrations (16 μmol/L) increased significantly due to its ability to protect the cells from apoptosis after OGD-R-induced injury. Furthermore, rLj-RGD3 attenuated the damage due to OGD-R. Most of the PC12 cells were apoptotic after OGD-R. In contrast, the number of apoptotic PC12 cells was significantly decreased in the group treated with a high-dose of rLj-RGD3. In addition, rLj-RGD3 activated FAK and p-FAK protein. rLj-RGD3 inhibited Caspase-3 and upregulated Bcl-2 protein expression in PC12 cells after OGD-R. The study provides the first evidence for neuroprotective effects of rLj-RGD3 in ischemic injury that may be partly mediated through inhibition of Caspase-3 and upregulation of Bcl-2, FAK, and p-FAK protein expression.

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Red Marrow Absorbed Dose for non-Hodgkin's Lymphoma Patients treated with the novel anti-CD37 antibody radionuclide conjugate 177Lu-lilotomab satetraxetan.

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Rapidly Progressive Spontaneous Spinal Epidural Abscess

Spinal epidural abscess (SEA) is a rare disease which is often rapidly progressive. Delayed diagnosis of SEA may lead to serious complications and the clinical findings of SEA are generally nonspecific. Paraspinal abscess should be considered in the presence of local low back tenderness, redness, and pain with fever, particularly in children. In case of delayed diagnosis and treatment, SEA may spread to the epidural space and may cause neurological deficits. Magnetic resonance imaging (MRI) remains the method of choice in the diagnosis of SEA. Treatment of SEA often consists of both medical and surgical therapy including drainage with percutaneous entry, corpectomy, and instrumentation.

http://ift.tt/2c5Izf3

Effectiveness of Fluticasone Furoate–Vilanterol for COPD in Clinical Practice

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New England Journal of Medicine, Ahead of Print.


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