Τρίτη 26 Σεπτεμβρίου 2017
Tocotrienol-rich fraction attenuates UV-induced inflammaging: A bench to bedside study
Summary
Background
UV radiation from the sun is the most common environmental stressor to damage the skin. It is now well established that photodamaged skin manifests signs of mild but chronic inflammation, termed as "inflammaging." Thus, there is an urgent need for anti-inflammatory regimes that can limit the damage caused by inflammation.
Objectives
This study aimed to evaluate the possible palliative effects of a new topical nanoemulsion formulation containing tocotrienol-rich fraction (TRF) on UV-induced inflammation (erythema) of human skin.
Methods
An in vitro model was used to demonstrate the ability of TRF to alleviate photodamage via attenuation of UV-induced oxidative stress and inflammation. Two ex vivo models (skin antioxidative potential and radical sun protection factor) were used to determine the efficacy of different formulations of TRF on the skin. A UV-induced erythema protection test in 20 subjects was conducted.
Results
In vitro studies involving HaCaT keratinocytes revealed that TRF possesses marked anti-inflammatory properties, as indicated by the attenuation of UV-induced upregulation of pro-inflammatory cytokines. A 1% TRF formulation was found to be more effective in enhancing the endogenous antioxidative protection of skin compared to 1% TRF in medium chain triglycerides because of its higher penetration kinetic profile. The clinical study showed that formulated TRF was effective in reducing skin redness after UV irradiation as early as after 6 hours of application. A significant depigmentation was also observed in TRF treatment subjects.
Conclusion
TRF may serve as an anti-inflammatory compound that is safe to be applied daily to protect the skin from UV-induced inflammaging.
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Risk prediction tools for keratinocyte carcinoma after solid organ transplantation: a review of the literature
Summary
Long-term iatrogenic immunosuppression increases the risk of cutaneous malignancies in organ transplant recipients (OTRs), particularly the keratinocyte cancers basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC). cSCC is the most common malignancy in OTRs, with the risk increased to over 65-fold in transplanted patients relative to the general population. There have been very few risk prediction tools developed for accurate determination of the risk of developing keratinocyte cancers in the OTR population. This review summarizes the prediction tools developed to date, and outlines future directions for developing more accurate prediction models that are clinically useful for the transplant physician and dermatologist.
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Grounding a natural background level for fluoride in a potentially contaminated crystalline aquifer in south India
Abstract
Fluoride contamination is one of the most alarming issues for those countries that depend on groundwater drinking water supply. A careful examination of the hydrogeochemical conditions and routine monitoring of fluoride level are therefore quintessential. Estimation of natural background level (NBL) of fluoride becomes significant information for assessing the current and future contamination episodes. Vellore District in Tamil Nadu is a hard rock terrain known for its F-rich groundwater. In this study, we attempted to form a benchmark for fluoride using hydrochemical pre-selection (based on TDS and NO3) and cumulative probability plots (CPP). Principle components analysis is (PCA) applied to evaluate the corresponding factor grouping of the total of 68 samples, which is later mapped using geostatistical tool in ArcGIS. From the CPP, we derived the NBL of F as 0.75 mg/L. This value is compared with the observed concentration in each sample and they were spatially plotted based on the NBL. Resultant plot suggests that W-NW part of the study area has exceeded and E-EW regions are below the NBL of F. Spatial variation of the factor scores also supported this observation. Grounding an NBL and extending it to other parts of the potential contaminated aquifers are highly recommended for better understanding and management of the water supply systems.
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Heavy metal pollution in Nanchang City and its health implication on traffic policemen
Abstract
The purpose of this study is to evaluate the health effect of heavy metal pollution in air pollutants on traffic policemen. This study will facilitate the scientific evaluation of health status of traffic policemen. PM10 samples were collected from industrial area, congested traffic area and residential area respectively in Nanchang City, and the concentrations of heavy metals were analyzed. The traffic policemen were examined through chest X-rays. The total of 637 urine samples and 142 blood samples have been collected, and the concentrations of Pb in samples were detected. Vehicle flux data of Nanchang City were collected from the Department of Transport's Traffic Management. Statistic analyses were carried out by statistics software of Excel 2003 and SPSS20.0, and the health effect of heavy metal pollution of PM10 on the traffic policemen was evaluated. The discharge of pollutants from enterprises is an important reason for the high content of heavy metals in urban air pollution. With the rapid growth of urban traffic flow, Bayi Bridge becomes an important transportation hinge in Nanchang City, and the bidirectional traffic flow rate through the bridge at peak hours reached 99 vehicles per minute. The latent hazard of occupational harm on the traffic policemen caused by automobile exhaust is increasing. The concentration of Pb in the urine and blood samples from traffic policemen working in Nanchang City was 268.310 ± 177.031 and 22.873 ± 21.137 μg/L, respectively. Both results (2.04% of Pb in urine and 18.31% of Pb in blood) exceeded the highest limit of observed occupationally outdoor workers. This study provides an initial contribution for the assessment of city air pollution, esp. the health effect of heavy metal (Pb) pollution on traffic policemen.
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In situ remediation of tetrachloroethylene and its intermediates in groundwater using an anaerobic/aerobic permeable reactive barrier
Abstract
Tetrachloroethylene (PCE) is among the most ubiquitous chlorinated compounds found in groundwater contamination. Its chlorinated degradation by-products remain highly toxic. In this study, an anaerobic/aerobic permeable reactive barrier system consisting of four different functional layers was designed to remediate PCE-contaminated groundwater. The first (oxygen capture) layer maintained the dissolved oxygen (DO) concentration at < 1.35 mg/L in influent supplied to the second (anaerobic) layer. The third (oxygen-releasing) layer maintained DO concentration at > 11.3 mg/L within influent supplied to the fourth (aerobic) layer. The results show that 99% of PCE was removed, mostly within the second layer (anaerobic). Furthermore, the toxic by-products trichloroethylene (TCE), dichloroethylene (DCE), and vinyl chloride (VC) were further degraded by 98, 90, and 92%, respectively, in layer 4 (aerobic). Thus, the designed anaerobic/aerobic permeable reactive barrier system could control both PCE and its degradation by-products, showing great potential as an efficient remediation alternative for the in situ treatment of PCE-contaminated groundwater.
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Effects of metal ions on the cultivation of an oleaginous microalga Chlorella sp.
Abstract
A coupling technique to purify wastewater for lipid production based on microalgae is attractive and promising for its potential to clean water and as biofuel feedstocks. Metal ions from wastewater might be involved in microalgal cultivation. In this study, the effects of metal ions on algal growth, lipid-producing potential, and water purifying capability of Chlorella sp. HQ were investigated. The effects of metal ions (Cr6+, Cu2+, Mn2+, Zn2+, Fe3+, Na+, and K+) on alga lipid production combined with water purification showed that Chlorella sp. HQ had strong resistance to metal ions and could efficiently remove them (Fe3+ 85.40~98.73%, Mn2+ 45.63~97.24%, Zn2+ 81.93~100.00%, Cu2+ 81.71~95.19%, Cr6+ 20.07~45.60%). Meanwhile, nutrient removal (total nitrogen (TN) 78.15~94.77%, total phosphorus (TP) 80.52~100%) was not inhibited by metal ions. Besides that, the highest algal biomass, lipid yield, and triacylglycerol (TAG) yield peaked at 350.00 ± 31.50, 87.50 ± 3.54, and 33.39 ± 19.42 mg L−1, respectively, with the addition of Fe3+ (6.6 mg L−1), Na+ (101.81 mg L−1), and K+ (31.9 mg L−1). The lipid/TAG content significantly increased up to 54.17 ± 11.91%/44.92 ± 0.42%, 100%/100%, 32.56 ± 12.40%/37.53 ± 4.58%, and 77.50 ± 1.77%/46.19 ± 1.06%, separately, with the addition of Cr6+(0.50 mg L−1), Cu2+(5.02 mg L−1), Zn2+(5.05 mg L−1), and Mn2+(50.52 mg L−1).
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Marine sedimentary lipidomics of the glacial-interglacial changes during the lower Pleistocene (SW Iberian Margin)
Abstract
Analyses of trimethylsilyl-derivatized neutral lipids by gas chromatography coupled to mass spectrometry afford a wealth of information contained in the marine sediments. This information is useful for unraveling the processes associated with past climate changes such as those from glacial and interglacial periods. Studies of samples from the Iberian Margin deposited about 1,300,000–1,400,000 years ago afforded the qualitative identification and quantification of n-alkanes, n-alkan-1-ols, isoprenoids, triterpenoids, sterols, hopanols, alkenones, alkenols, and polycyclic aromatic hydrocarbons. Using this information, the lipidomic approach has allowed to identifying differences in sea surface temperatures, marine productivity, microbial degradation processes, and inputs from continental plants between these periods. Differences in predominant higher plant species related to climate changes have also been observed.
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Livin’ On The Edge: glia shape nervous system transition zones
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Laura Fontenas, Sarah Kucenas
The vertebrate nervous system is divided into two functional halves; the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system (PNS), which consists of nerves and ganglia. Incoming peripheral stimuli transmitted from the periphery to the CNS and subsequent motor responses created because of this information, require efficient communication between the two halves that make up this organ system. Neurons and glial cells of each half of the nervous system, which are the main actors in this communication, segregate across nervous system transition zones and never mix, allowing for efficient neurotransmission. Studies aimed at understanding the cellular and molecular mechanisms governing the development and maintenance of these transition zones have predominantly focused on mammalian models. However, zebrafish has emerged as a powerful model organism to study these structures and has allowed researchers to identify novel glial cells and mechanisms essential for nervous system assembly. This review will highlight recent advances into the important role that glial cells play in building and maintaining the nervous system and its boundaries.
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Predictors of Venous Thromboembolism and Early Mortality in Lung Cancer: Results from a Global Prospective Study (CANTARISK)
AbstractBackground.Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). Venous thromboembolism is associated with increased risk for early mortality. However, there have been no studies performing a comprehensive assessment of risk factors for VTE or early mortality in lung cancer patients undergoing systemic chemotherapy in a global real‐world setting.Materials and Methods.CANTARISK is a prospective, global, noninterventional cohort study including patients with lung cancer initiating a new cancer therapy. Clinical data were collected until 6‐month follow‐up. The impact of patient‐, disease‐, and treatment‐related factors on the occurrence of VTE and early mortality was evaluated in univariable and multivariable Cox regression analyses. A previously validated VTE risk score (VTE‐RS) was also calculated (also known as Khorana score).Results.Of 1,980 patients with lung cancer who were enrolled from 2011 to 2012, 84% had non‐small cell lung cancer. During the first 6 months, 121 patients developed a VTE (6.1%), of which 47% had pulmonary embolism, 46% deep vein thrombosis, 3% catheter‐associated thrombosis, and 4% visceral thrombosis. Independent predictors for VTE included female sex, North America location, leg immobilization, and presence of a central venous catheter. The VTE‐RS was not significantly associated with VTE in either univariable or multivariable analysis in this population. During the study period, 472 patients died, representing 20%, 24%, 36%, and 25% with VTE‐RS 1, 2, ≥3, or unknown, respectively (p < .0001). Significant independent predictors of early mortality include older age, current/former smoking, chronic obstructive pulmonary disease, Eastern Cooperative Oncology Group performance status ≥2, no prior surgery, and metastatic disease, as well as the VTE‐RS.Conclusion.In this global, prospective, real‐world analysis, several demographic, geographic, and clinical factors are independent risk factors for VTE and early mortality in patients with lung cancer. The VTE‐RS represents a significant independent predictor of early mortality but not for VTE in lung cancer in the era of targeted therapy.Implications for Practice.Multiple risk factors for both venous thromboembolism (VTE) and early mortality in patients with lung cancer receiving systemic chemotherapy should guide best practice by better informing clinical evaluation and treatment decision‐making. The Khorana risk score is of value in assessing the risk of early all‐cause mortality along with other clinical parameters in patients with lung cancer receiving systemic therapy. Further study is needed to fully evaluate the validity of the risk score in predicting the risk of VTE in the modern era of lung cancer therapy.
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A Clinical and Biological Guide for Understanding Chemotherapy‐Induced Alopecia and Its Prevention
AbstractChemotherapy‐induced alopecia (CIA) is the most visibly distressing side effect of commonly administered chemotherapeutic agents. Because psychological health has huge relevance to lifestyle, diet, and self‐esteem, it is important for clinicians to fully appreciate the psychological burden that CIA can place on patients. Here, for the first time to our knowledge, we provide a comprehensive review encompassing the molecular characteristics of the human hair follicle (HF), how different anticancer agents damage the HF to cause CIA, and subsequent HF pathophysiology, and we assess known and emerging prevention modalities that have aimed to reduce or prevent CIA. We argue that, at present, scalp cooling is the only safe and U.S. Food and Drug Administration‐cleared modality available, and we highlight the extensive available clinical and experimental (biological) evidence for its efficacy. The likelihood of a patient that uses scalp cooling during chemotherapy maintaining enough hair to not require a wig is approximately 50%. This is despite different types of chemotherapy regimens, patient‐specific differences, and possible lack of staff experience in effectively delivering scalp cooling. The increased use of scalp cooling and an understanding of how to deliver it most effectively to patients has enormous potential to ease the psychological burden of CIA, until other, more efficacious, equally safe treatments become available.Implications for Practice.Chemotherapy‐induced alopecia (CIA) represents perhaps the most distressing side effect of chemotherapeutic agents and is of huge concern to the majority of patients. Scalp cooling is currently the only safe option to combat CIA. Clinical and biological evidence suggests improvements can be made, including efficacy in delivering adequately‐low temperature to the scalp and patient‐specific cap design. The increased use of scalp cooling, an understanding of how to deliver it most effectively and biological evidence‐based approaches to improve its efficacy have enormous potential to ease the psychological burden of CIA, as this could lead to improvements in treatment and patient quality‐of‐life.
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Transcutaneous aponeurotic repair with small detachment of the levator aponeurosis for aponeurotic blepharoptosis in Japanese patients
To examine the surgical outcomes of a modified transcutaneous aponeurotic repair for aponeurotic blepharoptosis in a Japanese population.
http://ift.tt/2fxXHGk
Reduction mammoplasty in adolescents and elderly a ten year case series analyzing age related outcome with focus on safety and complications
Reduction mammoplasty alleviates symptoms of macromastia in various ways. Current study results mainly identify perioperative risk factors for middle aged patients. We investigated a large series of consecutive breast reductions procedures to study whether patients' age at the time of operation is related to the postoperative outcome.
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FLOTOR Pilot Study
Conditions: Chylothorax; Esophageal Cancer; Thoracic Duct Intra-Operative Injury
Intervention: Drug: Indocyanine Green
Sponsor: Oxford University Hospitals NHS Trust
Not yet recruiting
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Intervention: Drug: Indocyanine Green
Sponsor: Oxford University Hospitals NHS Trust
Not yet recruiting
http://ift.tt/2xAGaC0
Predictors of Normal Tissue Response From the Microenvironment in Radiotherapy for Prostate and Head-and-neck Cancer
Conditions: Prostate Cancer; Head and Neck Cancer
Interventions: Radiation: External beam radiotherapy for prostate cancer; Radiation: External beam radiotherapy for head and neck cancer
Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Recruiting
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Interventions: Radiation: External beam radiotherapy for prostate cancer; Radiation: External beam radiotherapy for head and neck cancer
Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Recruiting
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Assessing toxicity of metal contaminated soil from glassworks sites with a battery of biotests
Publication date: 1 February 2018
Source:Science of The Total Environment, Volumes 613–614
Author(s): M. Hagner, M. Romantschuk, O.-P. Penttinen, A. Egfors, C. Marchand, A. Augustsson
The present study addresses toxicological properties of metal contaminated soils, using glassworks sites in south-eastern Sweden as study objects. Soil from five selected glassworks sites as well as from nearby reference areas were analysed for total and water-soluble metal concentrations and general geochemical parameters. A battery of biotests was then applied to assess the toxicity of the glassworks soil environments: a test of phytotoxicity with garden cress (Lepidium sativum); the BioTox™ test for toxicity to bacteria using Vibrio fischeri; and analyses of abundancies and biomass of nematodes and enchytraeids. The glassworks- and reference areas were comparable with respect to pH and the content of organic matter and nutrients (C, N, P), but total metal concentrations (Pb, As, Ba, Cd and Zn) were significantly higher at the former sites. Higher metal concentrations in the water-soluble fraction were also observed, even though these concentrations were low compared to the total ones. Nevertheless, toxicity of the glassworks soils was not detected by the two ex situ tests; inhibition of light emission by V. fischeri could not be seen, nor was an effect seen on the growth of L. sativum. A decrease in enchytraeid and nematode abundance and biomass was, however, observed for the landfill soils as compared to reference soils, implying in situ toxicity to soil-inhabiting organisms. The confirmation of in situ bioavailability and negative effects motivates additional studies of the risk posed to humans of the glassworks villages.
Graphical abstract
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Zinc oxide nanoparticles in predicted environmentally relevant concentrations leading to behavioral impairments in male swiss mice
Publication date: 1 February 2018
Source:Science of The Total Environment, Volumes 613–614
Author(s): Joyce Moreira de Souza, Bruna de Oliveira Mendes, Abraão Tiago Batista Guimarães, Aline Sueli de Lima Rodrigues, Thales Quintão Chagas, Thiago Lopes Rocha, Guilherme Malafaia
Although the potential neurotoxic effects from the exposure to zinc oxide nanoparticles (ZnO NPs) on humans and on experimental models have been reported in previous studies, the effects from the exposure to environmentally relevant concentrations of them remain unclear. Thus, the aim of the present study is to investigate the effects from the exposure to environmentally relevant concentrations of ZnO NPs on the behavior of male Swiss mice. The animals were daily exposed to environmentally relevant concentrations of ZnO NPs (5.625×10−5mgkg−1) at toxic level (300mgkg−1) through intraperitoneal injection for five days; a control group was set for comparison purposes. Positive control groups (clonazepam and fluoxetine) and a baseline group were included in the experimental design to help analyzing the behavioral tests (open field, elevated plus maze and forced swim tests). Although we did not observe any behavioral change in the animals subjected to the elevated plus maze and forced swim tests, our data evidence the anxiogenic behavior of animals exposed to the two herein tested ZnO NPs concentrations in the open field test. The animals stayed in the central part of the apparatus and presented lower locomotion ratio in the central quadrants/total of locomotion during this test. It indicates that the anxiogenic behavior was induced by ZnO NP exposure, because it leads to Zn accumulation in the brain. Thus, the current study is the first to demonstrate that the predicted environmentally relevant ZnO NPs concentration induces behavioral changes in mammalian experimental models. Our results corroborate previous studies that have indicated the biological risks related to the water surface contamination by metal-based nanomaterials.
Graphical abstract
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Screening of biologically important Zn2+ by a chemosensor with fluorescent turn on-off mechanism
Publication date: 15 January 2018
Source:Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 189
Author(s): Tanveer A. Khan, Monika Sheoran, Venkata Nikhil Raj M., Surbhi Jain, Diksha Gupta, Sunil G. Naik
Reported herein the synthesis, characterization and biologically important zinc ion binding propensity of a weakly fluorescent chemosensor, 4-methyl-2,6-bis((E)-(2-(4-phenylthiazol-2-yl)hydrazono)methyl)phenol (1). 1H NMR spectroscopic titration experiment reveals the binding knack of 1 to the essential Zn2+. The photo-physical studies of 1 exhibit an enhancement in the fluorescence by several folds upon binding with the zinc ions attributed to PET-off process, with a binding constant value of 5.22×103M−1. 1 exhibits an excellent detection range for Zn2+ with lower detection limit value of 2.31×10−8M. The selectivity of 1 was studied with various mono and divalent metal cations and it was observed that most cations either quenches the fluorescence or remains unchanged except for Cd2+, which shows a slight enhancement in fluorescence intensity of 1. The ratiometric displacement of Cd2+ ions by Zn2+ ions shows an excellent selectivity towards in-situ detection of Zn2+ ions. Photo-physical studies also support the reversible binding of 1 to Zn2+ ions having on and off mechanism in presence of EDTA. Such recognition of the biologically important zinc ions finds potential application in live cell imaging.
Graphical abstract
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Scholar : These new articles for Spanish Journal of Finance and Accounting / Revista Española de Financiación y Contabilidad are available online
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NCI-funded TMIST study compares 2-D and 3-D mammography for finding breast cancers
TMIST, the first randomized trial comparing two types of digital mammography for breast cancer screening, is enrolling participants. Developed by ECOG-ACRIN and NCI, the trial is comparing 2-D and 3-D mammography for finding breast cancers.
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Serum 25-hydroxyvitamin D as a predictor of mortality and cardiovascular events: a 20 year study of a community-based cohort
Summary
Objective
Prospective studies, mostly from Europe and North America, suggest that serum 25-hydroxyvitamin D (25(OH)D) is inversely associated with mortality and cardiovascular disease (CVD) risk. Data from other regions are limited, and threshold levels for adverse cardiovascular outcomes uncertain. We examined serum 25(OH)D as a predictor of total mortality and cardiovascular outcomes in an Australian cohort.
Design
A 20-year, community-based cohort study.
Patients
Participants in the 1994/1995 Busselton Health Survey (n=3946, baseline age 25-84 years).
Measurements
Baseline serum 25(OH)D and mortality and cardiovascular outcomes to 2014 obtained by record linkage.
Results
The mean serum 25(OH)D concentration was 60.6±18.0 nmol/L. During 20 years follow-up (excluding the first 2 years), 889 participants died (including 363 from CVD) and 944 experienced a CVD event (including 242 with heart failure). In the full cohort, controlling for Framingham risk score variables, higher baseline 25(OH)D was associated with significantly reduced all-cause mortality (adjusted HR 0.83 per SD increment of 25(OH)D, 95% CI 0.77-0.90), CVD death (HR 0.85, 95% CI 0.74-0.96) and heart failure (HR 0.81, 95% CI 0.69-0.94), but not CVD events (HR 0.99, 0.92-1.07). In restricted cubic spline regression models, serum 25(OH)D below 65 and 55 nmol/L was associated with higher total mortality and higher CVD mortality/heart failure, respectively. In participants without CVD at baseline (n=3220) results were similar, but hazard ratios were attenuated and associations with CVD mortality no longer significant.
Conclusions
In an Australian community-based cohort, baseline vitamin D levels below 55-65 nmol/L are predictive of all-cause mortality, CVD death and heart failure.
This article is protected by copyright. All rights reserved.
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A pseudo-thermodynamic description of dispersion for nanocomposites
Publication date: 27 October 2017
Source:Polymer, Volume 129
Author(s): Yan Jin, Gregory Beaucage, Karsten Vogtt, Hanqiu Jiang, Vikram Kuppa, Jay Kim, Jan Ilavsky, Mindaugas Rackaitis, Andrew Mulderig, Kabir Rishi, Vishak Narayanan
Dispersion in polymer nanocomposites is determined by the kinetics of mixing and chemical affinity. Compounds like reinforcing filler/elastomer blends display some similarity to colloidal solutions in that the filler particles are close to randomly dispersed through processing. It is attractive to apply a pseudo-thermodynamic approach taking advantage of this analogy between the kinetics of mixing for polymer compounds and thermally driven dispersion for colloids. In order to demonstrate this pseudo-thermodynamic approach, two polybutadienes and one polyisoprene were milled with three carbon blacks and two silicas. These samples were examined using small-angle x-ray scattering as a function of filler concentration to determine a pseudo-second order virial coefficient, A2, which is used as an indicator for compatibility of the filler and polymer. It is found that A2 follows the expected behavior with lower values for smaller primary particles indicating that smaller particles are more difficult to mix. A2 is analogous to the excluded volume and long-range interaction potential for non-equilibrated nanocomposites. The measured values of A2 can be used to specify repulsive interaction potentials for coarse grain DPD simulations of filler/elastomer systems. In addition, new methods to quantify the filler percolation threshold and filler mesh size as a function of filler concentration are obtained. The results represent a new approach to understanding and predicting dispersion in polymer nanocomposites based on a thermodynamic analogy.
Graphical abstract
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Scholar : These new articles for Journal of Clinical and Experimental Neuropsychology are available online
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Scholar : These new articles for The Law Teacher are available online
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Scholar : These new articles for CoDesign are available online
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Scholar : Journal of Natural History, Volume 51, Issue 37-38, October 2017 is now available online on Taylor & Francis Online
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Efficacy and safety of the Janus Kinase 1 inhibitor PF-04965842 in patients with moderate to severe psoriasis: phase 2, randomized, double-blind, placebo-controlled study
Abstract
Background
PF-04965842 is an oral Janus Kinase 1 inhibitor being investigated for treatment of plaque psoriasis.
Objectives
To evaluate the efficacy, safety and tolerability of PF-04965842 in patients with moderate to severe plaque psoriasis.
Methods
Patients in this phase 2, placebo-controlled study (NCT02201524) were randomised to receive placebo, 200 mg once-daily (QD), 400 mg QD, or 200 mg twice-daily (BID) PF-04965842 for 4 weeks. The primary endpoint was change from baseline in Psoriasis Area Severity Index (PASI) at Week 4. Study enrolment was discontinued on 25 June 2015 due to changes in the sponsor's development priorities.
Results
Fifty-nine patients were randomised and received at least one dose of PF-04965842 or placebo. The estimated treatment effect (active-placebo PASI change from baseline) and 90% CI at Week 4 was –5·1 (–9·2, –1·0), –5·6 (–9·6, –1·6) and –10·0 (–14·2, –5·8) for the 200 mg QD, 400 mg QD and 200 mg BID groups, respectively. At Week 4, the proportion of patients achieving PASI75 was 17% for the placebo and 200 mg QD groups, 50% for the 400 mg QD group and 60% for the 200 mg BID group. There were more abnormal laboratory test results of clinical interest (low neutrophil, reticulocyte and platelet counts) in the 200 mg BID group vs the QD treatment groups. No serious infections or bleeding events related to neutropenia or thrombocytopenia, respectively, were reported.
Conclusions
These results suggest that treatment with PF-04965842 improves symptoms and is well tolerated in patients with moderate to severe psoriasis.
This article is protected by copyright. All rights reserved.
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A novel approach using metabolomics coupled with hematological and biochemical parameters to explain the enriching-blood effect and mechanism of unprocessed Angelica sinensis and its 4 kinds of processed products
Publication date: Available online 25 September 2017
Source:Journal of Ethnopharmacology
Author(s): Peng Ji, Yanming Wei, Yongli Hua, Xiaosong Zhang, Wanling Yao, Qi Ma, Ziwen Yuan, Yanqiao Wen, Chaoxue Yang
Ethnopharmacological relevanceAngelica sinensis (AS), root of Angelica sinensis (Oliv.) Diels, an important kind of Chinese traditional herbal medicine, has been used for women to enrich the blood for thousands of years. It is mainly distributed in Gansu province of China. According to Traditional Chinese medicine usage, unprocessed AS (UAS) and its 4 kinds of processed products (ASs) are all used to treat different diseases or syndromes. The difference among the enriching-blood effects of ASs is unclear. And their exact mechanisms of enriching the blood are not fully understood.Aim of the studyIn this study, our aim is to compare the enriching-blood effect and explain the related mechanism of ASs, to lay the foundation for the blood deficiency diagnosis and the rational use of ASs in the clinic.Materials and methodsASs were used to intervene the blood deficiency syndrome model mice induced by acetyl phenylhydrazine (APH) and cyclophosphamide (CTX). A novel approach using metabolomics coupled with hematological and biochemical parameters to explain the enriching-blood effect and mechanism of ASs was established. The blood routine examination, ATPase, glucose-6-phosphate dehydrogenase, methemoglobin, glutathion peroxidase, glutathione reductase, and erythropoietin were measured. Two biofluids (plasma and urine) obtained from mice were analyzed with GC-MS. Distinct changes in metabolite patterns of the two biofluids after mice were induced by APH and CTX, and mice were intervened with ASs were analyzed using partial least squares-discriminant analysis. Potential biomarkers were found using a novel method including variable importance in the projection (VIP) >1.0, volcano plot analysis, and significance analysis of microarray.ResultsThe results of hematological, biochemical parameters and the integrated metabolomics all showed the blood deficiency syndrome model was built successfully, ASs exhibited different degree of enriching-blood effect, and AS pached with alcohol (AAS) exhibited the best enriching-blood effect. 16 metabolites in the plasma and 8 metabolites in the urine were considered as the potential biomarkers. These metabolites were involved in 7 metabolic pathways which were concerned with the different enriching-blood effect mechanisms of ASs. The correlation analysis results confirmed L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine) and Cholesterol (urine) were strong positive or negative associated with biochemical indicators.ConclusionsThe enriching-blood effects of ASs are different. The pathological mechanisms of blood deficiency syndrome and the enriching-blood effect mechanism of ASs are involved in 7 metabolic pathways. L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine), Cholesterol (urine) are four important biomarkers being related to the enriching-blood effect of ASs. The combination of VIP, volcano plot analysis and significance analysis of microarray is suitable for screening biomarkers in metabolomics study. They can lay the foundation for clinical practice.
Graphical abstract
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Scholar : AIDS Care, Volume 29, Issue 11, November 2017 is now available online on Taylor & Francis Online
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Engineering two-dimensional electronics by semiconductor defects
Publication date: Available online 25 September 2017
Source:Nano Today
Author(s): Dan Wang, Xian-Bin Li, Dong Han, Wei Quan Tian, Hong-Bo Sun
Two-dimensional (2D) semiconductors have attracted considerable attentions from electronic-engineering community due to their unique electronic properties. Especially, the inherent advantage of scaling semiconductor into atomic thickness has raised the prospect of possible extension of the Moore's law. To achieve 2D electronics, a full comprehension of semiconductor defect physics and chemistry is indispensable due to its controlling electrical performance of 2D materials and functionalizing their devices. In this review, first we explain why 2D semiconductors is important for nanoelectronics and optoelectronics. Second, we elucidate how native defects or intentional impurities affect and control electrical characteristic in 2D semiconductors, such as carrier concentration and their conductive type. In this section, experimental pictures of defects and several updated theoretical methods to evaluate carrier ionization energies of defects and their conductive type are introduced in detail. Third, typical device experiments are shown to demonstrate a direct role of defects to functionalize 2D electronic device. Furthermore, a database of popular defects and their electrical properties in current popular 2D semiconductors is summarized for references. Last, we discuss the challenges and potential prospects of defect engineering for 2D devices. The present paper offers important viewpoints from semiconductor defects to design the emerging 2D electronics.
Graphical abstract
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Assessment of age- and sex-related changes in baggy lower eyelids using a novel objective image analysis method: Orbital gray scale analysis
Summary
Background
Baggy lower eyelids (BLEs) are a common aesthetic problem of aging. Valid and reliable assessment tools for BLEs are required to evaluate the current status and treatment outcome.
Aims
Age- and sex-related changes in BLEs were assessed with the orbital gray scale (OGS), a novel objective image analysis method.
Methods
We gathered frontal-view photographs of the faces of the patients who sought for correction of BLEs. Based on the clinical pattern, we classified the BLEs of the subjects into medial (M), medial and central (MC), and medial to lateral (MCL) types. Severity was evaluated using the OGS, a modified method of the linear gray scale analysis.
Results
The BLEs of 1034 subjects were classified. The most common types were MCL type in the men and MC type in the women, respectively. The M and MC types were common in the young subjects, whereas the MCL type was more common in the old subjects (P < .001). The measurements of OGS in 104 subjects showed positive correlation with age, a higher mean value in the men, and a trend toward higher values in the order of M, MC, and MCL types (P < .001 for central and lateral OGS scores). In a multiple linear regression analysis, central and lateral OGS values were significantly related with age, sex, and M-C-L classification type (P < .001).
Conclusion
The M-C-L classification and OGS were significantly associated with both age and sex, proving that they could be potent objective assessment tools for BLEs.
http://ift.tt/2xwOaDO
Exchange pattern of gaseous elemental mercury in landfill: mercury deposition under vegetation coverage and interactive effects of multiple meteorological conditions
Abstract
Landfill is known as a potential source of atmospheric Hg and an important component of the local or regional atmospheric Hg budget. This study investigated the gaseous elemental Hg surface–air fluxes under differing conditions at a typical municipal solid waste landfill site, highlighting the interactive effects of plant coverage and meteorological conditions. The results indicated that Hg fluxes exhibited a feature represented by diel variation. In particular, Hg deposition was observed under a condition of Kochia sieversiana coverage, whereas emission that occurred after K. sieversiana was removed. Hg emission was the dominant mode under conditions of Setaria viridis coverage and its removal; however, the average Hg emission flux with the S. viridis coverage was nearly four times lower than after its removal. These findings verified that the plant coverage should be a key factor influencing the Hg emission from landfills. In addition, Hg fluxes were correlated positively with solar radiation and air/soil temperature and correlated inversely with relative humidity under all conditions, except K. sieversiana coverage. This suggested that the interactive effects of meteorological conditions and plant coverage played a jointly significant role in the Hg emission from landfills. It was established that K. sieversiana can inhibit Hg emission efficiently, and therefore, it could potentially be suitable for use as a plant-based method to control Hg pollution from landfills.
http://ift.tt/2whm6mE
Heavy metal contamination in surface sediments of representative reservoirs in the hilly area of southern China
Abstract
A study on the characteristics of heavy metals in surface sediments of typical reservoirs in the hilly area of southern China was carried out. The results showed that contents of heavy metals had great temporal and spatial heterogeneity among studied reservoirs. Zn, Pb, and As presented significant enrichment ratio in reservoirs of Dou Shui (DS) and Feng Tang (FT), as well as Ti in reservoirs of DZ and GT. The content of Cd in reservoir of FT reservoirs was characterized with high health risk with the significantly highest value of 52.43 mg/kg. Furthermore, Pb was identified with high health risk in reservoirs of SFM, Ouyang Hai (OYH), FT, and DS, and As was in OYH and ZX. Multivariate statistical analysis suggested high consistency in the variations of Cr, Ni, and Cu; moreover, Cd, Zn, and Pb were characterized with great homogeneity in their sources. In addition, agricultural activities might exert less effect on variations of heavy metals in studied reservoirs, considered that there was a weak relationship between heavy metals and nutrients. These results could improve our understanding of the spatial variations of heavy metals and their potential sources in reservoirs in this ecologically fragile region.
http://ift.tt/2fnDKhF
Parathyroid Hormone: Data Mining for Age-Related Reference Intervals in Adults
Summary
Objective
Age-related changes in parathyroid hormone (PTH) have been previously documented in adults. However, because of the limitations of traditional approaches to establishing reference intervals, age-related reference intervals have not been defined. We sought to use a data mining approach to derive age-related PTH reference intervals.
Design and Participants
Results from patients undergoing PTH testing over a 4 year period were extracted from the database of a private pathology laboratory in New South Wales, Australia. Patients were included in the study if they were 18 years or older and had simultaneous determination of PTH, serum calcium, estimated glomerular filtration rate and 25-hydroxyvitamin D (25-OHD). Patients with abnormalities of serum calcium or renal function were excluded.
Measurements
Bhattacharya analysis of log transformed data was used to derive age-related PTH reference intervals across adulthood.
Results
Results were available for 33,652 subjects. Among patients with optimal 25-OHD status, older age was associated with higher PTH concentrations. Age-related reference intervals were derived and showed a 63% increase in the upper and lower reference limits between the youngest (18 – 29 years of age) and the oldest (80 years of age or older) age partitions. The appropriateness of using a single reference interval for patients of all ages was evaluated against objective criteria and was found to be unsatisfactory.
Conclusions
Data mining was demonstrated to be a useful tool for establishing age-related PTH reference intervals. The technique demonstrated that increasing age is associated with higher PTH concentrations and that age-related reference intervals are important for accurate result interpretation.
This article is protected by copyright. All rights reserved.
http://ift.tt/2wPKsYX
Age-stratified thresholds of anti-Müllerian hormone improve prediction of polycystic ovary syndrome over a population-based threshold
Abstract
In this issue, Quinn et al. reports their experience on the diagnostic value of the anti-mullerian hormone (AMH) assay for the recognition of polycystic ovary syndrome (PCOS). This subject remains very much debated and, in particular, there is no consensus on a specific threshold discriminating PCOS from normal women. One of the reasons, but certainly not the only one, is the heterogeneity of the control groups between the various studies reported to date.
This article is protected by copyright. All rights reserved.
http://ift.tt/2yDxmLE
Developing and validating the CWARTS diagnostic tool, a novel clinical assessment and classification system for cutaneous warts
Abstract
Background
The clinical appearance of cutaneous warts is highly variable and not standardised.
Objectives
The aim of this study was to develop and validate a reproducible clinical tool for the standardised assessment of cutaneous warts to distinguish these lesions accurately.
Methods
Nine morphological characteristics were defined and validated regarding intra- and inter-observer agreement. Based on literature and semi-structured interviews, a systematic dichotomous assessment tool, the Cutaneous WARTS diagnostic tool (CWARTS diagnostic tool) was developed. The validation consisted of two independent parts performed with photographs from the recent WARTS-2 trial. In part A, the CWARTS diagnostic tool was tested by 28 experienced physicians who assessed photographs of 10 different warts to investigate inter-observer concordance. In part B, morphological characteristics were validated by blinded and independent scoring of 299 photographs by 6 different observers. Part B also entailed re-assessment of the photographs after at least 1 week. Primary outcome measurement was the intraclass correlation coefficient (ICC).
Results
Presence of black dots (capillary thrombosis) had the greatest ICC (0.85) for inter-observer agreement in part A, followed by arrangement (0.65), presence of border erythema(0.64) and sharpness of the border (0.60). In part B results were similar for inter-observer agreement with presence of black dots having the highest ICC (0.68), followed by border erythema (0.64), arrangement (0.58) and colour (0.55). For intra-observer agreement, presence of black dots had the highest agreement (0.69), followed by presence of border erythema (0.64) and colour (0.55).
Conclusions
The wart phenotype can be reliably assessed by the CWARTS diagnostic tool.
This article is protected by copyright. All rights reserved.
http://ift.tt/2xHLEg8
Middle East respiratory syndrome coronavirus transmission among health care workers: Implication for infection control
Source:American Journal of Infection Control
Author(s): Sarah H. Alfaraj, Jaffar A. Al-Tawfiq, Talal A. Altuwaijri, Marzouqa Alanazi, Nojoom Alzahrani, Ziad A. Memish
BackgroundMany outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in health care settings and involved health care workers (HCWs). We describe the occurrence of an outbreak among HCWs and attempt to characterize at-risk exposures to improve future infection control interventions.MethodsThis study included an index case and all HCW contacts. All contacts were screened for MERS-CoV using polymerase chain reaction.ResultsDuring the study period in 2015, the index case was a 30-year-old Filipino nurse who had a history of unprotected exposure to a MERS-CoV–positive case on May 15, 2015, and had multiple negative tests for MERS-CoV. Weeks later, she was diagnosed with pulmonary tuberculosis and MERS-CoV infection. A total of 73 staff were quarantined for 14 days, and nasopharyngeal swabs were taken on days 2, 5, and 12 postexposure. Of those contacts, 3 (4%) were confirmed positive for MERS-CoV. An additional 18 staff were quarantined and had MERS-CoV swabs. A fourth case was confirmed positive on day 12. Subsequent contact investigations revealed a fourth-generation transmission. Only 7 (4.5%) of the total 153 contacts were positive for MERS-CoV.ConclusionsThe role of HCWs in MERS-CoV transmission is complex. Although most MERS-CoV–infected HCWs are asymptomatic or have mild disease, fatal infections can occur and HCWs can play a major role in propagating health care facility outbreaks. This investigation highlights the need to continuously review infection control guidance relating to the role of HCWs in MERS-CoV transmission in health care outbreaks, especially as it relates to the complex questions on definition of risky exposures, who to test, and the frequency of MERS-CoV testing; criteria for who to quarantine and for how long; and clearance and return to active duty criteria.
http://ift.tt/2wPM1q1
A pilot survey of the U.S. medical waste industry to determine training needs for safely handling highly infectious waste
Source:American Journal of Infection Control
Author(s): Aurora B. Le, Selin Hoboy, Anne Germain, Hal Miller, Richard Thompson, Jocelyn J. Herstein, Katelyn C. Jelden, Elizabeth L. Beam, Shawn G. Gibbs, John J. Lowe
BackgroundThe recent Ebola outbreak led to the development of Ebola virus disease (EVD) best practices in clinical settings. However, after the care of EVD patients, proper medical waste management and disposal was identified as a crucial component to containing the virus. Category A waste—contaminated with EVD and other highly infectious pathogens—is strictly regulated by governmental agencies, and led to only several facilities willing to accept the waste.MethodsA pilot survey was administered to determine if U.S. medical waste facilities are prepared to handle or transport category A waste, and to determine waste workers' current extent of training to handle highly infectious waste.ResultsSixty-eight percent of survey respondents indicated they had not determined if their facility would accept category A waste. Of those that had acquired a special permit, 67% had yet to modify their permit since the EVD outbreak. This pilot survey underscores gaps in the medical waste industry to handle and respond to category A waste. Furthermore, this study affirms reports a limited number of processing facilities are capable or willing to accept category A waste.ConclusionsDeveloping the proper management of infectious disease materials is essential to close the gaps identified so that states and governmental entities can act accordingly based on the regulations and guidance developed, and to ensure public safety.
http://ift.tt/2yF543A
How are nursing homes cleaned? Results of a survey of 6 nursing homes in Southeast Michigan
Source:American Journal of Infection Control
Author(s): Aya Saeb, Lona Mody, Kristen Gibson
This brief report details 2 surveys that were conducted to better understand current cleaning practices in 6 nursing home facilities in Southeast Michigan. Each facility's environmental services supervisor answered questions regarding cleaning policy and procedures, roles and responsibilities of the staff, and frequency of education and training; one environmental services employee from each facility answered questions addressing education and training, employer evaluation and feedback, and workload. We identify gaps in knowledge and behaviors and note substantial variations in cleaning practices.
http://ift.tt/2wPLYdP
An outbreak of bloodstream infection due to extensively resistant Acinetobacter baumannii among neonates
Source:American Journal of Infection Control
Author(s): Aysegul Ulu-Kilic, Aycan Gundogdu, Fatma Cevahir, Huseyin Kilic, Tamer Gunes, Emine Alp
BackgroundExtensively resistant Acinetobacter baumannii has emerged and spread worldwide as a significant cause of health care-associated infections and outbreaks. It also causes life-threatening infections among neonates, including bacteremia. The aim of this study was to investigate an outbreak of A baumannii bacteremia (ABB) among neonates.Materials and methodsA retrospective, case-control study was conducted from July 2014 to July 2015 in a neonatal intensive care unit (NICU). Risk factors associated with ABB in univariate and multivariate analysis with logistic regression was performed. Molecular typing by pulsed field gel electrophoresis was used to confirm relatedness of bacteremic A baumannii strains.ResultsDuring the 5-year period (2011-2016), 68 patients in our NICU were diagnosed with BSI due to A baumannii. The case-control study included 41 case patients within the outbreak caused by a major epidemic clone and 108 control patients. Risk factors (by univariate analysis) associated with ABB were intubation, 14-day mortality, and use of peritoneal dialysis and an umbilical catheter. Multivariate analysis identified 14-day mortality (odds ratio, 5.75; 95% confidence interval, 2.58-12.79) and umbilical catheter use (odds ratio, 2.44; 95% confidence interval, 1.1-5.4) as independent risk factors for ABB.ConclusionsThis outbreak of bacteremia due to resistant A baumannii affected 41 infants and was associated with 58% mortality. Control of the outbreak was achieved by implementing long-term sustained infection control measures within the unit.
http://ift.tt/2yDEnMm
Interhospital patient transfers between Ontario's academic and large community hospitals increase the risk of Clostridium difficile infection
Source:American Journal of Infection Control
Author(s): Giulio DiDiodato, Leslie McArthur
BackgroundThe objective of this study is to determine the impact of interhospital patient transfers on the risk of Clostridium difficile infection (CDI).MethodsThe number of interhospital patient transfers and CDI cases for 11 academic and 40 large community hospitals (LCHs) were available from 2010-2015. These data were used to compute a CDI score for each sending facility as a measure of CDI pressure on the receiving facility. This CDI score was included as a variable in a multilevel mixed-effect Poisson regression model of CDI cases. Other covariates included year, CDI testing strategy, antimicrobial stewardship program (ASP), and criteria used for patient isolation. Hospital-specific random effects were estimated for the baseline rate of CDI (intercept) and ASP effect (slope).ResultsThe CDI score ranged from 0-103, with a mean score ± SD of 20.4 ± 21.8. Every 10-point increase in the CDI score was associated with a 4.5% increase in the incidence of CDI in the receiving academic hospital (95% confidence interval [CI], 0.9-8.5) and 3.6% increase in the receiving LCHs (95% CI, 0.3-7). The random components of the model varied significantly, with a strong negative correlation of −0.85 (95% CI, −0.94 to −0.65).ConclusionsOur results suggest interhospital patient transfers increase the risk of CDI. ASPs appear to reduce this risk; however, these ASP effects demonstrate significant heterogeneity across hospitals.
http://ift.tt/2wQoS6E
Dynamic transmission models for economic analysis applied to health care-associated infections: A review of the literature
Source:American Journal of Infection Control
Author(s): Richard E. Nelson, Rishi Deka, Karim Khader, Vanessa W. Stevens, Marin L. Schweizer, Michael A. Rubin
BackgroundCost-effectiveness analyses are an important methodology in assessing whether a health care technology is suitable for widespread adoption. Common models used by economists, such as decision trees and Markov models, are appropriate for noninfectious diseases where treatment and exposure are independent. Diseases whose treatment and exposure are dependent require dynamic models to incorporate the nonlinear transmission effect. Two different types of models are often used for dynamic cost-effectiveness analyses: compartmental models and individual models. In this methodology-focused literature review, we describe each model type and summarize the literature associated with each using the example of health care-associated infections (HAIs).MethodsWe conducted a review of the literature to identify dynamic cost-effectiveness analyses that examined interventions to prevent or treat HAIs. To be included in the review, studies needed to have each of 3 necessary components: involve economics, such as cost-effectiveness analysis and evidence of economic theory, use a dynamic transmission model, and examine HAIs.ResultsOf the 9 articles published between 2005 and 2016 that met criteria to be included in our study, 3 used compartmental models and 6 used individual models.ConclusionsVery few published studies exist that use dynamic transmission models to conduct economic analyses related to HAIs and even fewer studies have used these models to perform cost-effectiveness analyses.
http://ift.tt/2yE8bc0
Potential testing of reprocessing procedures by real-time polymerase chain reaction: A multicenter study of colonoscopy devices
Source:American Journal of Infection Control
Author(s): Federica Valeriani, Antonella Agodi, Beatrice Casini, Maria Luisa Cristina, Marcello Mario D'Errico, Gianluca Gianfranceschi, Giorgio Liguori, Renato Liguori, Nicolina Mucci, Ida Mura, Cesira Pasquarella, Andrea Piana, Giovanni Sotgiu, Gaetano Privitera, Carmela Protano, Annalisa Quattrocchi, Giancarlo Ripabelli, Angelo Rossini, Anna Maria Spagnolo, Manuela Tamburro, Stefano Tardivo, Licia Veronesi, Matteo Vitali, Vincenzo Romano Spica
BackgroundReprocessing of endoscopes is key to preventing cross-infection after colonoscopy. Culture-based methods are recommended for monitoring, but alternative and rapid approaches are needed to improve surveillance and reduce turnover times. A molecular strategy based on detection of residual traces from gut microbiota was developed and tested using a multicenter survey.MethodsA simplified sampling and DNA extraction protocol using nylon-tipped flocked swabs was optimized. A multiplex real-time polymerase chain reaction (PCR) test was developed that targeted 6 bacteria genes that were amplified in 3 mixes. The method was validated by interlaboratory tests involving 5 reference laboratories. Colonoscopy devices (n = 111) were sampled in 10 Italian hospitals. Culture-based microbiology and metagenomic tests were performed to verify PCR data.ResultsThe sampling method was easily applied in all 10 endoscopy units and the optimized DNA extraction and amplification protocol was successfully performed by all of the involved laboratories. This PCR-based method allowed identification of both contaminated (n = 59) and fully reprocessed endoscopes (n = 52) with high sensibility (98%) and specificity (98%), within 3-4 hours, in contrast to the 24-72 hours needed for a classic microbiology test. Results were confirmed by next-generation sequencing and classic microbiology.ConclusionsA novel approach for monitoring reprocessing of colonoscopy devices was developed and successfully applied in a multicenter survey. The general principle of tracing biological fluids through microflora DNA amplification was successfully applied and may represent a promising approach for hospital hygiene.
http://ift.tt/2yDlw4d
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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