Τετάρτη 28 Φεβρουαρίου 2018
First evidence of anticoagulant rodenticides in fish and suspended particulate matter: spatial and temporal distribution in German freshwater aquatic systems
Abstract
Anticoagulant rodenticides (ARs) have been used for decades for rodent control worldwide. Research on the exposure of the environment and accumulation of these active substances in biota has been focused on terrestrial food webs, but few data are available on the impact of ARs on aquatic systems and water organisms. To fill this gap, we analyzed liver samples of bream (Abramis brama) and co-located suspended particulate matter (SPM) from the German Environmental Specimen Bank (ESB). An appropriate method was developed for the determination of eight different ARs, including first- and second-generation ARs, in fish liver and SPM. Applying this method to bream liver samples from 17 and 18 sampling locations of the years 2011 and 2015, respectively, five ARs were found at levels above limits of quantifications (LOQs, 0.2 to 2 μg kg−1). For 2015, brodifacoum was detected in 88% of the samples with a maximum concentration of 12.5 μg kg−1. Moreover, difenacoum, bromadiolone, difethialone, and flocoumafen were detected in some samples above LOQ. In contrast, no first generation AR was detected in the ESB samples. In SPM, only bromadiolone could be detected in 56% of the samples at levels up to 9.24 μg kg−1. A temporal trend analysis of bream liver from two sampling locations over a period of up to 23 years revealed a significant trend for brodifacoum at one of the sampling locations.
http://ift.tt/2HTUOc1
Ecotoxicological assessment of oil-based paint using three-dimensional multi-species bio-testing model: pre- and post-bioremediation analysis
Abstract
The present study validates the oil-based paint bioremediation potential of Bacillus subtilis NAP1 for ecotoxicological assessment using a three-dimensional multi-species bio-testing model. The model included bioassays to determine phytotoxic effect, cytotoxic effect, and antimicrobial effect of oil-based paint. Additionally, the antioxidant activity of pre- and post-bioremediation samples was also detected to confirm its detoxification. Although, the pre-bioremediation samples of oil-based paint displayed significant toxicity against all the life forms. However, post-bioremediation, the cytotoxic effect against Artemia salina revealed substantial detoxification of oil-based paint with LD50 of 121 μl ml−1 (without glucose) and > 400 μl ml−1 (with glucose). Similarly, the reduction in toxicity against Raphanus raphanistrum seeds germination (%FG = 98 to 100%) was also evident of successful detoxification under experimental conditions. Moreover, the toxicity against test bacterial strains and fungal strains was completely removed after bioremediation. In addition, the post-bioremediation samples showed reduced antioxidant activities (% scavenging = 23.5 ± 0.35 and 28.9 ± 2.7) without and with glucose, respectively. Convincingly, the present multi-species bio-testing model in addition to antioxidant studies could be suggested as a validation tool for bioremediation experiments, especially for middle and low-income countries.
Graphical abstract
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http://ift.tt/2HTUN7X
Correction to: Effects-based spatial assessment of contaminated estuarine sediments from Bear Creek, Baltimore Harbor, MD, USA
Abstract
The authors of the article have informed the Journal that an author, Dr. Sacoby Wilson of the University of Maryland School of Public Health, was inadvertently omitted from the published version of their manuscript due to a miscommunication regarding authorship criteria.
http://ift.tt/2oGLoI6
Are oral mucosal nevi potential precursors for oral mucosal melanoma?
Source:Oral Oncology
Author(s): A. Thirumal Raj, Shankargouda Patil, Chandini Rajkumar
http://ift.tt/2t7CF7v
Multiple Imputation for Incomplete Data in Epidemiologic Studies
Abstract
Epidemiologic studies are frequently susceptible to missing information. Omitting observations with missing variables remains a common strategy in epidemiologic studies, yet this simple approach can often severely bias parameter estimates of interest if the values are not missing completely at random. Even when missingness is completely random, complete-case analysis can reduce the efficiency of estimated parameters, because large amounts of available data are simply tossed out with the incomplete observations. Alternative methods for mitigating the influence of missing information, such as multiple imputation, are becoming an increasing popular strategy in order to retain all available information, reduce potential bias, and improve efficiency in parameter estimation. In this paper, we describe the theoretical underpinnings of multiple imputation, and we illustrate application of this method as part of a collaborative challenge to assess the performance of various techniques for dealing with missing data (Am J Epidemiol. 2018;187(3):568–575). We detail the steps necessary to perform multiple imputation on a subset of data from the Collaborative Perinatal Project (1959–1974), where the goal is to estimate the odds of spontaneous abortion associated with smoking during pregnancy.http://ift.tt/2FdyaNf
Invited Commentary: Sex and Race Differences in Diabetes and Cardiovascular Disease—Achieving the Promise of Sex and Race Subgroup Analyses in Epidemiologic Research
Abstract
Diabetes confers a higher risk of cardiovascular disease on women than on men. The reasons for these sex differences, such as poorer cardiovascular risk factor profiles, have received considerable attention. However, a recent report on sex × diabetes interactions on cardiovascular disease identified that few if any prior studies have confirmed these sex differences in black individuals, despite known diabetes-related disparities. In this issue of the Journal, George et al. (Am J Epidemiol. 2018;187(3):403–410.) found marginally significant multiplicative sex × diabetes interactions in black but not white study participants after adjustments for traditional and behavioral risk factors, competing risk, and change in diabetes status over time. This study is notable for its attempt to fill an important literature gap, and it elegantly addressed multiple statistical considerations in assessing sex × diabetes interactions according to race strata. The findings also highlighted several important considerations for conducting race and sex subgroup analyses.http://ift.tt/2F5Ucyw
Breast Cancer Incidence and Exposure to Metalworking Fluid in a Cohort of Female Autoworkers
Abstract
Breast cancer is the leading cancer diagnosed among women, and environmental studies have produced few leads on modifiable risk factors for breast cancer. Following an Institute of Medicine recommendation for occupational studies of women highly exposed to potential breast cancer risk factors, we took advantage of an existing cohort of 4,503 female autoworkers in Michigan exposed to metalworking fluid (MWF), complex mixtures of oils and chemicals widely used in metal manufacturing worldwide. Cox proportional hazards models were fit to estimate hazard ratios for incident breast cancer (follow-up, 1985–2013) and cumulative exposure (20-year lag) to straight mineral oils (a known human carcinogen) and water-based soluble and synthetic MWF. Because the state cancer registry began decades after the cohort was defined, we restricted our analyses to subcohorts of women hired closer to the start of follow-up. Among those hired after 1969, the hazard ratio associated with a 1 interquartile-range increase in straight MWF exposure was 1.13 (95% confidence interval: 1.03, 1.23). In separate analyses of premenopausal breast cancer, defined by age at diagnosis, the hazard ratio was elevated for exposure to synthetic MWF (chemical lubricants with no oil content), possibly suggesting a different mechanism in the younger women with breast cancer. This study adds to the limited literature regarding quantitative chemical exposures and breast cancer risk.http://ift.tt/2FcCMDl
Association of DNA Methylation-Based Biological Age With Health Risk Factors and Overall and Cause-Specific Mortality
Abstract
Measures of biological age based on blood DNA methylation, referred to as age acceleration (AA), have been developed. We examined whether AA was associated with health risk factors and overall and cause-specific mortality. At baseline (1990–1994), blood samples were drawn from 2,818 participants in the Melbourne Collaborative Cohort Study (Melbourne, Victoria, Australia). DNA methylation was determined using the Infinium HumanMethylation450 BeadChip array (Illumina Inc., San Diego, California). Mixed-effects models were used to examine the association of AA with health risk factors. Cox models were used to assess the association of AA with mortality. A total of 831 deaths were observed during a median 10.7 years of follow-up. Associations of AA were observed with male sex, Greek nationality (country of birth), smoking, obesity, diabetes, lower education, and meat intake. AA measures were associated with increased mortality, and this was only partly accounted for by known determinants of health (hazard ratios were attenuated by 20%–40%). Weak evidence of heterogeneity in the association was observed by sex (P = 0.06) and cause of death (P = 0.07) but not by other factors. DNA-methylation-based AA measures are associated with several major health risk factors, but these do not fully explain the association between AA and mortality. Future research should investigate what genetic and environmental factors determine AA.http://ift.tt/2GR0lPs
Possible Mediation by Methylation in Acute Inflammation Following Personal Exposure to Fine Particulate Air Pollution
Abstract
Air pollution may increase cardiovascular and respiratory risk through inflammatory pathways, but evidence for acute effects has been weak and indirect. Between December 2014 and July 2015, we enrolled 36 healthy, nonsmoking college students for a panel study in Shanghai, China, a city with highly variable levels of air pollution. We measured personal exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5) continuously for 72 hours preceding each of 4 clinical visits that included phlebotomy. We measured 4 inflammation proteins and DNA methylation at nearby regulatory cytosine-phosphate-guanine (CpG) loci. We applied linear mixed-effect models to examine associations over various lag times. When results suggested mediation, we evaluated methylation as mediator. Increased PM2.5 concentration was positively associated with all 4 inflammation proteins and negatively associated with DNA methylation at regulatory loci for tumor necrosis factor alpha (TNF-α) and soluble intercellular adhesion molecule-1. A 10-μg/m3 increase in average PM2.5 during the 24 hours preceding blood draw corresponded to a 4.4% increase in TNF-α and a statistically significant decrease in methylation at one of the two studied candidate CpG loci for TNF-α. Epigenetics may play an important role in mediating effects of PM2.5 on inflammatory pathways.http://ift.tt/2Ffbdt6
Sickle Cell Trait and Heat Injury Among US Army Soldiers
Abstract
There is concern that sickle cell trait (SCT) increases risk of exertional collapse, a primary cause of which is heat injury. However, to our knowledge, no population-based studies among active individuals have addressed this, representing a critical evidence gap. We conducted a retrospective cohort study of SCT-tested African-American soldiers who were on active duty in the US Army anytime between January 2011 and December 2014. Using Cox proportional hazards models and adjusting for demographic and medical factors, we observed no significant associations between SCT and either mild heat injury (hazard ratio (HR) = 1.15, 95% confidence interval (CI): 0.84, 1.56; n = 45,999) or heat stroke (HR = 1.11, 95% CI: 0.44, 2.79; n = 46,183). Risk of mild heat injury was substantially higher among soldiers with recent prescriptions for antipsychotic agents (HR = 3.25, 95% CI: 1.33, 7.90). Risk of heat stroke was elevated among those with a prior mild heat injury (HR = 17.7, 95% CI: 8.50, 36.7) and among overweight and obese individuals (HR = 2.91 (95% CI: 1.38, 6.17) and HR = 4.04 (95% CI: 1.72, 9.45), respectively). In a setting where universal precautions are utilized to mitigate risk of exertion-related illnesses, SCT is not associated with either mild heat injury or heat stroke.http://ift.tt/2F4eAQv
Understanding Causal Distributional and Subgroup Effects With the Instrumental Propensity Score
Abstract
To address issues with measured and unmeasured confounding in observational studies, we developed a unified approach to using an instrumental variable in more flexible ways to evaluate treatment effects. The approach is based on an instrumental propensity score conditional on baseline variables, which can then be incorporated in matching, regression, subclassification, or weighting along with various parametric, semiparametric, or nonparametric methods for the assessment of treatment effects. Therefore, the application of the instrumental propensity score allows different methods for outcome effect evaluations in addition to standard 2-stage least square models while controlling for unmeasured confounders. Several properties of the instrumental propensity score are discussed. The approach is then illustrated using subclassification along with a semiparametric density ratio model and empirical likelihood. This method allows us to evaluate distributional and subgroup treatment effects in addition to the overall average treatment effect. Simulation studies showed that the method works well. We applied our method to a study of the effects of attending a Catholic school versus a public school and found that attending a Catholic school had significant beneficial effects on subsequent wages among a subgroup of subjects.http://ift.tt/2GRmX27
The Mental Health Benefits of Acquiring a Home in Older Age: A Fixed-Effects Analysis of Older US Adults
Abstract
Homeownership is consistently associated with better mental health, but whether becoming a homeowner in later in life has positive psychological benefits has not, to our knowledge, been examined. We assessed whether acquiring a home after age 50 years was associated with depression in a representative sample of older US adults. We used individual fixed-effects models based on data from 20,524 respondents aged ≥50 years from the Health and Retirement Study, who were interviewed biennially during 1993–2010. Depressive symptoms were measured using the 8-item Center for Epidemiologic Studies Depression Scale. Controlling for confounders, becoming a homeowner in later life predicted a decline in depressive symptoms in the same year (β = −0.0768, 95% confidence interval (CI): −0.152, −0.007). The association remained significant after 2 years (β = −0.0556, 95% CI: −0.134, −0.001) but weakened afterward. Buying a home for reasons associated with positive characteristics of the new house or neighborhood drove this association (β = −0.426, 95% CI: −0.786, −0.066), while acquiring a home for reasons associated with characteristics of the previous home or neighborhood, the desire to be closer to relatives, downsizing, or upsizing did not predict mental health improvements. Findings suggest that there are small but significant benefits for mental health associated with acquiring a home in older age.http://ift.tt/2oxFNod
When to Censor?
Abstract
Loss to follow-up is an endemic feature of time-to-event analyses that precludes observation of the event of interest. To our knowledge, in typical cohort studies with encounters occurring at regular or irregular intervals, there is no consensus on how to handle person-time between participants' last study encounter and the point at which they meet a definition of loss to follow-up. We demonstrate, using simulation and an example, that when the event of interest is captured outside of a study encounter (e.g., in a registry), person-time should be censored when the study-defined criterion for loss to follow-up is met (e.g., 1 year after last encounter), rather than at the last study encounter. Conversely, when the event of interest must be measured within the context of a study encounter (e.g., a biomarker value), person-time should be censored at the last study encounter. An inappropriate censoring scheme has the potential to result in substantial bias that may not be easily corrected.http://ift.tt/2F3j2Pv
Invited Commentary: “Bedroom Light Exposure at Night and the Incidence of Depressive Symptoms: A Longitudinal Study of the HEIJO-KYO Cohort”
Abstract
In modern society, we are increasingly disconnected from natural light/dark cycles and beset by round-the-clock exposure to artificial light. Light has powerful effects on physical and mental health, in part via the circadian system, and thus the timing of light exposure dictates whether it is helpful or harmful. In their compelling paper, Obayashi et al. (Am J Epidemiol. 2018;187(3):427–434.) offer evidence that light at night can prospectively predict an elevated incidence of depressive symptoms in older adults. Strengths of the study include the longitudinal design and direct, objective assessment of light levels, as well as accounting for multiple plausible confounders during analyses. Follow-up studies should address the study's limitations, including reliance on a global self-report of sleep quality and a 2-night assessment of light exposure that may not reliably represent typical light exposure. In addition, experimental studies including physiological circadian measures will be necessary to determine whether the light effects on depression are mediated through the circadian system or are so-called "direct" effects of light. In any case, these exciting findings could inform novel approaches to preventing depressive disorders in older adults.http://ift.tt/2FaIJAO
Bedroom Light Exposure at Night and the Incidence of Depressive Symptoms: A Longitudinal Study of the HEIJO-KYO Cohort
Abstract
Previous studies have indicated that minimal exposure to light at night (LAN) increases depression risk, even at 5 lux, in nocturnal and diurnal mammals. Although such low-level LAN may affect human circadian physiology, the association between exposure to LAN and depressive symptoms remains uncertain. In the present study, bedroom light intensity was measured objectively, and depressive symptoms were assessed, during 2010–2014 in Nara, Japan. Of 863 participants (mean age = 71.5 years) who did not have depressive symptoms at baseline, 73 participants reported development of depressive symptoms during follow-up (median, 24 months). Compared with the "dark" group (average of <5 lux; n = 710), the LAN group (average of ≥5 lux; n = 153) exhibited a significantly higher depression risk (hazard ratio = 1.89; 95% CI: 1.13, 3.14), according to a Cox proportional hazards model adjusting for age, sex, body mass index, and economic status. Further, the significance remained in a multivariable model adjusting for hypertension, diabetes, and sleep parameters (hazard ratio = 1.72; 95% CI: 1.03, 2.89). Sensitivity analyses using bedroom light data with a cutoff value of ≥10 lux suggested consistent results. In conclusion, these results indicated that exposure to LAN in home settings was independently associated with subsequent depression risk in an elderly general population.http://ift.tt/2FfaZ5e
Fractional CO 2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects
Abstract
The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 7% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO2 laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects.
http://ift.tt/2oxX6pc
Cumulative effects of cascade hydropower stations on total dissolved gas supersaturation
Abstract
Elevated levels of total dissolved gas (TDG) may occur downstream of dams during the spill process. These high levels would increase the incidence of gas bubble disease in fish and cause severe environmental impacts. With increasing numbers of cascade hydropower stations being built or planned, the cumulative effects of TDG supersaturation are becoming increasingly prominent. The TDG saturation distribution in the downstream reaches of the Jinsha River was studied to investigate the cumulative effects of TDG supersaturation resulting from the cascade hydropower stations. A comparison of the effects of the joint operation and the single operation of two hydropower stations (XLD and XJB) was performed to analyze the risk degree to fish posed by TDG supersaturation. The results showed that water with supersaturated TDG generated at the upstream cascade can be transported to the downstream power station, leading to cumulative TDG supersaturation effects. Compared with the single operation of XJB, the joint operation of both stations produced a much higher TDG saturation downstream of XJB, especially during the non-flood discharge period. Moreover, the duration of high TDG saturation and the lengths of the lethal and sub-lethal areas were much higher in the joint operation scenario, posing a greater threat to fish and severely damaging the environment. This work provides a scientific basis for strategies to reduce TDG supersaturation to the permissible level and minimize the potential risk of supersaturated TDG.
http://ift.tt/2oGExOP
Fabrication and characterization of β-cypermethrin-loaded PLA microcapsules prepared by emulsion-solvent evaporation: loading and release properties
Abstract
Microcapsulses can be designed to effectively encapsulate, protect, and control the release of pesticides. In this study, emulsion-solvent evaporation method was used to fabricate microcapsules using dichloromethane as the solvent, polylactic acid (PLA) as the carrier materials, poly(vinyl alcohol) as the emulsifier, and β-cypermethrin as the entrapped pesticide. The effects of process parameters on the microcapsules characteristics (size, loading content, and encapsulation efficiency) were investigated. Also, the release behavior of the β-cypermethrin was measured experimentally and modeled mathematically. Kinetic analysis indicated that release mechanism of β-cypermethrin was compatible to Fickian diffusion. By optimizing the process parameters, β-cypermethrin-loaded microcapsules were successfully produced with spherical shape, smooth surface, high encapsulation efficiency (> 80%), and a range of pesticide contents. These parameters could be adjusted to achieve delivery systems with desirable release profiles. The results are beneficial to develop delivery systems for rational and effective usage of pesticides.
http://ift.tt/2HSV1ML
Experimental investigation on emission reduction in neem oil biodiesel using selective catalytic reduction and catalytic converter techniques
Abstract
In the present study, non-edible seed oil namely raw neem oil was converted into biodiesel using transesterification process. In the experimentation, two biodiesel blends were prepared namely B25 (25% neem oil methyl ester with 75% of diesel) and B50 (50% neem oil methyl ester with 50% diesel). Urea-based selective catalytic reduction (SCR) technique with catalytic converter (CC) was fixed in the exhaust tail pipe of the engine for the reduction of engine exhaust emissions. Initially, the engine was operated with diesel as a working fluid and followed by refilling of biodiesel blends B25 and B50 to obtain the baseline readings without SCR and CC. Then, the same procedure was repeated with SCR and CC technique for emission reduction measurement in diesel, B25 and B50 sample. The experimental results revealed that the B25 blend showed higher break thermal efficiency (BTE) and exhaust gas temperature (EGT) with lower break-specific fuel consumption (BSFC) than B50 blend at all loads. On comparing with biodiesel blends, diesel experiences increased BTE of 31.9% with reduced BSFC of 0.29 kg/kWh at full load. A notable emission reduction was noticed for all test fuels in SCR and CC setup. At full load, B25 showed lower carbon monoxide (CO) of 0.09% volume, hydrocarbon (HC) of 24 ppm, and smoke of 14 HSU and oxides of nitrogen (NOx) of 735 ppm than diesel and B50 in SCR and CC setup. On the whole, the engine with SCR and CC setup showed better performance and emission characteristics than standard engine operation.
http://ift.tt/2oG78nH
Impact of military on biofuels consumption and GHG emissions: the evidence from G7 countries
Abstract
It was aimed to test the relation among the greenhouse gases emissions, economic growth, biofuels consumption, and militarization in G7 countries during the 1985–2015 period by Pedroni 1995 and panel Johansen tests and two long-run estimators—dynamic OLS and fully modified OLS. Long-run estimators found that economic growth and militarization have statistically significant positive impact on CO2 emission of G7 countries. Furthermore, the panel causality tests were applied: Dumitrescu and Hurlin (Econ Model 29(4):1450–1460, 2012) and panel Granger causality. These tests determined the causal relationship between the variables. The results of this paper implied that economic growth and biofuels consumption depend on militarization, and economic growth and militarization are granger causes of the greenhouse gases emissions.
http://ift.tt/2HULRiX
Anodal transcranial direct current stimulation (tDCS) boosts dominant brain oscillations
Source:Brain Stimulation
Author(s): Caroline Di Bernardi Luft, Ioanna Zioga, Joydeep Bhattacharya
http://ift.tt/2EYbAZM
Long-lasting effects of transcranial static magnetic field stimulation on motor cortex excitability
Source:Brain Stimulation
Author(s): Michele Dileone, Laura Mordillo-Mateos, Antonio Oliviero, Guglielmo Foffani
BackgroundTranscranial static magnetic field stimulation (tSMS) was recently added to the family of inhibitory non-invasive brain stimulation techniques. However, the application of tSMS for 10–20 min over the motor cortex (M1) induces only short-lasting effects that revert within few minutes.ObjectiveWe examined whether increasing the duration of tSMS to 30 min leads to long-lasting changes in cortical excitability, which is critical for translating tSMS toward clinical applications.MethodsThe study comprised 5 experiments in 45 healthy subjects. We assessed the impact of 30-min-tSMS over M1 on corticospinal excitability, as measured by the amplitude of motor evoked potentials (MEPs) and resting motor thresholds (RMTs) to single-pulse transcranial magnetic stimulation (TMS) (experiments 1–2). We then assessed the impact of 30-min-tSMS on intracortical excitability, as measured by short-interval intracortical facilitation (SICF) and short-interval intracortical inhibition (SICI) using paired-pulse TMS protocols (experiments 2–4). We finally assessed the impact of 10-min-tSMS on SICF and SICI (experiment 5).Results30-min-tSMS decreased MEP amplitude compared to sham for at least 30 min after the end of the stimulation. This long-lasting effect was associated with increased SICF and reduced SICI. 10-min-tSMS –previously reported to induce a short-lasting decrease in MEP amplitude– produced the opposite changes in intracortical excitability, decreasing SICF while increasing SICI.ConclusionsThese results suggest a dissociation of intracortical changes in the consolidation from short-lasting to long-lasting decrease of corticospinal excitability induced by tSMS. The long-lasting effects of 30-min-tSMS open the way to the translation of this simple, portable and low-cost technique toward clinical trials.
http://ift.tt/2FcCZXi
Simplified Preparation of αvβ3 Integrin-Targeted Microbubbles Based on a Clinically Available Ultrasound Contrast Agent: Validation in a Tumor-Bearing Mouse Model
Source:Ultrasound in Medicine & Biology
Author(s): Kentaro Otani, Hirohito Nishimura, Atsunori Kamiya, Mariko Harada-Shiba
The usefulness of ultrasound molecular imaging with αvβ3 integrin-targeted microbubbles for detecting tumor angiogenesis has been demonstrated. Recently, we developed αvβ3 integrin-targeted microbubbles by modifying clinically available microbubbles (Sonazoid, Daiichi-Sankyo Pharmaceuticals, Tokyo, Japan) with a secreted glycoprotein (lactadherin). The aims of our present study were to simplify the preparation of lactadherin-bearing Sonazoid and to examine the diagnostic utility of lactadherin-bearing Sonazoid for αvβ3 integrin-expressing tumor vessels by using SK-OV-3-tumor–bearing mice. By incubating 1.2 × 107 Sonazoid microbubbles with 1.0 µg lactadherin, the complicated washing and centrifugation steps during the microbubble preparation could be omitted with no significant reduction in labeling ratio of lactadherin-bearing Sonazoid. In addition, the number of Sonazoid microbubbles accumulated in the SK-OV-3 tumor was significantly increased by modifying Sonazoid with lactadherin. Our data suggest that the lactadherin-bearing Sonazoid is an easily prepared and potentially clinically translatable targeted microbubble for αvβ3 integrin-expressing vessels.
http://ift.tt/2FgbeNL
Removing polycyclic aromatic hydrocarbons from water using granular activated carbon: kinetic and equilibrium adsorption studies
Abstract
Polycyclic aromatic hydrocarbons (PAHs) constitute a group of highly persistent, toxic and widespread environmental micropollutants that are increasingly found in water. A study was conducted in removing five PAHs, specifically naphthalene, acenaphthylene, acenaphthene, fluorene and phenanthrene, from water by adsorption onto granular activated carbon (GAC). The pseudo-first-order (PFO) model satisfactorily described the kinetics of adsorption of the PAHs. The Weber and Morris diffusion model's fit to the data showed that there were faster and slower rates of intra-particle diffusion probably into the mesopores and micropores of the GAC, respectively. These rates were negatively related to the molar volumes of the PAHs. Batch equilibrium adsorption data fitted well to the Langmuir, Freundlich and Dubinin–Radushkevich models, of which the Freundlich model exhibited the best fit. The adsorption affinities were related to the hydrophobicity of the PAHs as determined by the log Kow values. Free energies of adsorption calculated from the Dubinin–Radushkevich model and the satisfactory kinetic data fitting to the PFO model suggested physical adsorption of the PAHs. Adsorption of naphthalene, acenaphthylene and acenaphthene in fixed-bed columns containing a mixture of GAC (0.5 g) + sand (24.5 g) was satisfactorily simulated by the Thomas model.
http://ift.tt/2ouWpNB
Editorial Board
Source:Acta Oecologica, Volume 87
http://ift.tt/2oxFKJb
Pathogenesis of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) or ‘idiopathic retinal arteriolar aneurysms (IRAA)’ with macular star
Source:Medical Hypotheses, Volume 112
Author(s): Koushik Tripathy
http://ift.tt/2F1WN06
Splenectomy may have more complications than currently proven
Source:Medical Hypotheses, Volume 112
Author(s): Somayeh Zakeri, Narjes Gorji, Marjan Akhtari, Reihaneh Moeini
The spleen has been one of the least understood major organs for centuries. Its significance is relatively well-known today but it seems that all aspects of its activities are not fully understood. Persian medicine (PM) has special views on the function of spleen; many side effects were reported in PM due to spleen dysfunction. On the other hand nowadays splenectomy as a treatment strategy is recommended for some disorders and increasing risk of infections is considered as the most important long term side effect of that. In this study, we hypothesize that splenectomy may have more side effects than currently proven.According to PM, spleen is in close connection with liver, cardiovascular system, stomach, bone, brain and skin, and that is why any kind of spleen dysfunction leads to change in blood viscosity, appetite and bone strength, liver dysfunction, mood and skin disorders, cancer formation and fever. Considering this viewpoint it can be hypothesized such side effects may also occur after splenectomy.Proven complications of splenectomy include hypercoagulated state, cardiovascular events and infectious diseases but there is also some evidence about increased risk of cancer, skin disease like systemic lupus erythematosus, mood disorder such as depression, defective bone formation and impairment of immunity which can be considered as different levels of evidence to confirm the hypothesis.But for some others such as changes in appetite, there are no studies let alone convincing evidence. Future research about theses possible complications may lead to novel results.
http://ift.tt/2CPu5K3
Editorial Board
Source:Medical Hypotheses, Volume 112
http://ift.tt/2ox1mWi
Editorial Board
Publication date: April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 178
http://ift.tt/2F3Qkhp
Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy
AbstractBackground.Several breast cancer (BC) trials have adopted pathological complete response (pCR) as a surrogate marker of long‐term treatment efficacy. In patients with luminal subtype, pCR seems less important for outcome prediction. BC is a heterogeneous disease, which is evident in residual tumors after neoadjuvant‐chemotherapy (NAC). This study evaluates changes in Ki67 in relation to disease‐free survival (DFS) and overall survival (OS) in patients without pCR.Subjects, Materials, and Methods.Four hundred thirty‐five patients with stage IIA–IIIC BC without pCR after standard NAC with anthracycline and paclitaxel were analyzed. We analyzed the decrease or lack of decrease in the percentage of Ki67‐positive cells between core biopsy samples and surgical specimens and correlated this value with outcome.Results.Twenty‐five percent of patients presented with luminal A‐like tumors, 45% had luminal B‐like tumors, 14% had triple‐negative BC, 5% had HER2‐positive BC, and 11% had triple‐positive BC. Patients were predominantly diagnosed with stage III disease (52%) and high‐grade tumors (46%). Median Ki67 level was 20% before NAC, which decreased to a median of 10% after NAC. Fifty‐seven percent of patients had a decrease in Ki67 percentage. Ki67 decrease significantly correlated with better DFS and OS compared with no decrease, particularly in the luminal B subgroup. Multivariate analysis showed that nonreduction of Ki67 significantly increased the hazard ratio of recurrence and death by 3.39 (95% confidence interval [CI] 1.8–6.37) and 7.03 (95% CI 2.6–18.7), respectively.Conclusion.Patients without a decrease in Ki67 in residual tumors after NAC have poor prognosis. This warrants the introduction of new therapeutic strategies in this setting.Implications for Practice.This study evaluates the change in Ki67 percentage before and after neoadjuvant chemotherapy (NAC) and its relationship with survival outcomes in patients with breast cancer who did not achieve complete pathological response (pCR). These patients, a heterogeneous group with diverse prognoses that cannot be treated using a single algorithm, pose a challenge to clinicians. This study identified a subgroup of these patients with a poor prognosis, those with luminal B‐like tumors without a Ki67 decrease after NAC, thus justifying the introduction of new therapeutic strategies for patients who already present a favorable prognosis (luminal B‐like with Ki67 decrease).
http://ift.tt/2oFQSTH
Daily maternal separations during stress hyporesponsive period decrease the thresholds of panic-like behaviors to electrical stimulation of the dorsal periaqueductal gray of the adult rat
Source:Behavioural Brain Research, Volume 344
Author(s): Ana Cristina Borges-Aguiar, Luana Zanoni Schauffer, Edo Ronald de Kloet, Luiz Carlos Schenberg
The present study examined whether early life maternal separation (MS), a model of childhood separation anxiety, predisposes to panic at adulthood. For this purpose, male pups were submitted to 3-h daily maternal separations along postnatal (PN) days of either the 'stress hyporesponsive period' (SHRP) from PN4 to PN14 (MS11) or throughout lactation from PN2 to PN21 (MS20). Pups were further reunited to conscious (CM) or anesthetized (AM) mothers to assess the effect of mother-pup interaction upon reunion. Controls were subjected to brief handling (15 s) once a day throughout lactation (BH20). As adults (PN60), rats were tested for the thresholds to evoke panic-like behaviors upon electrical stimulation of dorsal periaqueductal gray matter and exposed to an elevated plus-maze, an open-field, a forced swim and a sucrose preference test. A factor analysis was also performed to gain insight into the meaning of behavioral tests. MS11-CM rather than MS20-CM rats showed enhanced panic responses and reductions in both swimming and sucrose preference. Panic facilitations were less intense in mother-neglected rats. Although MS did not affect anxiety, MS11-AM showed robust reductions of defecation in an open-field. Factor analysis singled out anxiety, hedonia, exploration, coping and gut activity. Although sucrose preference and coping loaded on separate factors, appetite (adult weight) correlated with active coping in both forced swim and open-field (central area exploration). Concluding, whereas 3h-daily maternal separations during SHRP increased rat's susceptibility to experimental panic attacks, separations throughout lactation had no effects on panic and enhanced active coping.
http://ift.tt/2GOhI3a
Molecular classification as prognostic factor and guide for treatment decision of pancreatic cancer
Publication date: Available online 28 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): David J. Birnbaum, François Bertucci, Pascal Finetti, Daniel Birnbaum, Emilie Mamessier
Clinico-pathological factors fail to consistently predict the outcome after pancreatic resection for oancreatic ductal adenocarcinoma (PDAC). PDACs show a high level of inter and intra tumor genetic heterogeneity. A molecular classification should help reduce heterogeneity among patients, with the consequences of better predicting evolution and better orienting the treatment. This review summarizes the information that should be retained in clinical practice from all the molecular analyses. PDAC can be classified based on mutational subtypes and gene alterations. Whole-genome sequencing identified mutational signatures, mutational burden and hyper-mutated tumors with specific DNA repair defects. Different molecular classifications have been established by using gene expression analyses to reduce PDAC heterogeneity. Their overlap/similarities allow the definition of molecular subtypes. DNA and RNA classifications can be used in prognosis assessment. They are useful in therapeutic choice for they allow the design of approaches that can predict the respective drug sensitivity of each molecular subtype. This review provides a comprehensive analysis of available molecular classifications in PDAC and how this can help guide clinical decisions.
http://ift.tt/2F4iMzC
Protein Disaggregation in Multicellular Organisms
Publication date: Available online 28 February 2018
Source:Trends in Biochemical Sciences
Author(s): Nadinath B. Nillegoda, Anne S. Wentink, Bernd Bukau
Protein aggregates are formed in cells with profoundly perturbed proteostasis, where the generation of misfolded proteins exceeds the cellular refolding and degradative capacity. They are a hallmark of protein conformational disorders and aged and/or environmentally stressed cells. Protein aggregation is a reversible process in vivo, which counteracts proteotoxicities derived from aggregate persistence, but the chaperone machineries involved in protein disaggregation in Metazoa were uncovered only recently. Here we highlight recent advances in the mechanistic understanding of the major protein disaggregation machinery mediated by the Hsp70 chaperone system and discuss emerging alternative disaggregation activities in multicellular organisms.
http://ift.tt/2F25lEu
GR-regulating Serine/Threonine Kinases: New Physiologic and Pathologic Implications
Publication date: Available online 28 February 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Tomoshige Kino
Glucocorticoid hormones, end products of the hypothalamic–pituitary–adrenal axis, virtually influence all human functions both in a basal homeostatic condition and under stress. The glucocorticoid receptor (GR), a nuclear hormone receptor superfamily protein, mediates these actions of glucocorticoids by acting as a ligand-dependent transcription factor. Because glucocorticoid actions are diverse and strong, many biological pathways adjust them in local tissues by targeting the GR signaling pathway as part of the regulatory loop coordinating complex human functions. Phosphorylation of GR protein by serine/threonine kinases is one of the major regulatory mechanisms for this communication. In this review, recent progress in research investigating GR phosphorylation by these kinases is discussed, along with the possible physiologic and pathophysiologic implications.
http://ift.tt/2oE1tyk
Mitochondria and Hypoxia: Metabolic Crosstalk in Cell-Fate Decisions
Publication date: Available online 28 February 2018
Source:Trends in Endocrinology & Metabolism
Author(s): David Bargiela, Stephen P. Burr, Patrick F. Chinnery
Alterations in mitochondrial metabolism influence cell differentiation and growth. This process is regulated by the activity of 2-oxoglutarate (2OG)-dependent dioxygenases (2OGDDs) – a diverse superfamily of oxygen-consuming enzymes – through modulation of the epigenetic landscape and transcriptional responses. Recent reports have described the role of mitochondrial metabolites in directing 2OGDD-driven cell-fate switches in stem cells (SCs), immune cells, and cancer cells. An understanding of the metabolic mechanisms underlying 2OGDD autoregulation is required for therapeutic targeting of this system. We propose a model dependent on oxygen and metabolite availability and discuss how this integrates 2OGDD metabolic signalling, the hypoxic transcriptional response, and fate-determining epigenetic changes.
http://ift.tt/2HUrpib
Stereotactic Body Radiation Therapy for Patients with Early-stage Prostate Cancer
Aim: Stereotactic body radiation therapy (SBRT) is emerging as a new treatment option for early-stage prostate cancer, theoretically providing clinical and economic benefits compared to conventionally fractionated external-beam radiation therapy (CF-EBRT). This review aimed to evaluate available published data to determine if the proposed theoretical benefits translate clinically. Materials and Methods: A systematic search strategy was employed across three databases using predefined search terms, inclusion and exclusion criteria to identify relevant articles. Results: Sixteen articles were included. Biochemical progression-free survival rates of 77.1-100% were reported in SBRT studies compared to 55-98% in CF-EBRT studies. Incidence of acute grade 1, 2, and 3 genitourinary toxicities were reported in the range of 13.3-71%, 12-25% and 0-3%, respectively, in the SBRT cohort in comparison to 28.7-51.9%, 15.6-41.4%. and 1.1-8.1%, respectively, in the CF-EBRT cohort. Incidence of acute grade 1, 2, and 3 gastrointestinal toxicities were reported in the range of 13-67%, 1-27% and 0-9%, respectively, of the SBRT cohort compared to 16.1- 51.1%, 6.3-20.7% and 0-3%, respectively, of the CF-EBRT cohort. Mean treatment costs estimates associated with SBRT ranged from $22,152 to $24,873 and $33,068 to $35,431 for CF-EBRT. Conclusion: Available data support the hypothesis of lower rates of acute toxicity and reduced economic burden associated with SBRT compared to CF-EBRT, however, randomised data with longer follow-up are needed to determine whether SBRT is clinically more effective than CF-EBRT.
http://ift.tt/2oF58Mw
Safety of Simultaneous Bilateral Pulmonary Resection for Metastatic Lung Tumors
Aim: We investigated the safety of simultaneous bilateral lung resection for lung metastases. Patients and Methods: We retrospectively analyzed 185 patients with pulmonary metastases who underwent unilateral or bilateral pulmonary resection from August 2009 to December 2016 at a single institution. Results: Single-stage bilateral lung resection was undertaken in 19 patients, and the other 166 patients underwent unilateral pulmonary resection, including 20 patients who underwent repeated resections for synchronous or metachronous metastases. Operative time and drainage days in the bilateral group were significantly longer than those in the unilateral group (220±20 vs. 152±6.9 min: p<0.01, and 2.79±0.3 vs. 2.08±0.1 days: p<0.01). Incidence of postoperative complications and postoperative in-hospital days did not differ between the two groups (p=0.33 and 0.66, respectively). The bilateral group was further divided into two groups, namely, those who underwent wedge resection on both sides (WW) and those who underwent wedge resection on one side and segmentectomy or lobectomy on an opposite side (WSL). Operative time in the WSL group was significantly longer than that in the WW group (260±19 vs. 201±18 min: p=0.03). However, there was no significant difference in duration of chest tube use and postoperative hospital days between the two groups (p=0.26 and p=0.89). No severe postoperative complications occurred in either group. Conclusion: One-stage bilateral pulmonary metastasectomy appears to be safe as long as only wedge resection is performed on at least one side.
http://ift.tt/2HTzmnD
Radiation Therapy for Angiosarcoma of the Scalp: Total Scalp Irradiation and Local Irradiation
Angiosarcoma, a rare cutaneous malignancy, frequently arises in the scalp of older individuals. Because it characteristically initially mimics benign disease, such as a bruise, definitive diagnosis in the early stages is difficult. Angiosarcoma of the scalp is highly malignant and often accompanied by lung metastases that cause hemopneumothorax. Although surgery has been the standard and most reliable curative treatment for angiosarcoma of the scalp, there is a high probability of local recurrence, even after wide surgical excision. Therefore, postoperative radiation therapy has been administered in an attempt to minimize local recurrence. However, surgery is contraindicated in many older patients because of severe comorbidities or age. Definitive radiation therapy has been administered to such patients and has achieved good local control. In particular, total scalp irradiation may be a promising option for curative treatment of angiosarcoma of the scalp. Recent reports suggest that chemotherapy, particularly with taxanes, can prolong survival by reducing the rate of distant failure after radiation therapy. Thus, radiation therapy along with chemotherapy is now recommended for curative treatment of patients with inoperable disease and even some patients with operable disease. Technological developments in radiation therapy, such as intensity-modulated radiation therapy, will contribute to enhanced efficacy and reduced toxicities in the treatment of patients with angiosarcoma of the scalp.
http://ift.tt/2HQv3cK
Gastric Cancer Cells in Peritoneal Lavage Fluid: A Systematic Review Comparing Cytological with Molecular Detection for Diagnosis of Peritoneal Metastases and Prediction of Peritoneal Recurrences
Background/Aim: Detecting free tumor cells in the peritoneal lavage fluid of gastric cancer patients permits to assess a more accurate prognosis, predict peritoneal recurrence and select cases for a more aggressive treatment. Currently, cytology and molecular biology comprise the two most popular methods of detection that are under constant study by researchers. Materials and Methods: We burrowed into the available literature comparing cytological with molecular detection of free intraperitoneal gastric cancer cells. PubMed, Science Direct, Scopus and Google Scholar were the search engines investigated. Results: As of 2017, 51 dedicated studies have been published. Messenger RNA of carcinoembryonic antigen was the genetic target most frequently described. The genetic technique is usually superior to cytology in sensitivity (38-100% vs. 12.3-67% respectively), whereas cytological examination tends to show a slight pre-eminence in specificity (approximately 100%). Conclusion: So far, given the imperfection of each method, employment of both cytology and molecular examination seem to be mandatory.
http://ift.tt/2HTzjrX
Clinicopathological Characteristics of High-grade Squamous Intraepithelial Lesions Involving Condyloma Acuminatum
Background/Aim: Severe nuclear atypia can be associated with condyloma acuminatum. In this study, we investigated nine cases of perianal condyloma acuminatum with severe nuclear atypia and determined whether severe nuclear atypia is sufficient for the diagnosis of high-grade squamous intraepithelial lesion (HSIL). Materials and Methods: The clinical data and pathological features of the nine patients were collected. p16 Immunostaining and human papillomavirus genotyping were also performed. Results: The resected specimens of six men infected with human immunodeficiency virus showed features suggestive of HSIL, including the expansion of basaloid cells, severe nuclear pleomorphism in the lower one-third, bizarre nuclei, mitotic figure in the upper two-thirds, atypical mitosis, block positivity for p16, and high-risk human papillomavirus infection. In contrast, the resected specimens of the remaining three patients did not show any of those HSIL features, even though there were several microscopic foci showing severe nuclear atypia in the upper two-thirds of the papillomatous epithelium. Conclusion: Our observation regarding the occurrence of HSIL involving perianal condyloma acuminatum in human immunodeficiency virus-infected patients suggests that active, complete surgical excision of perianal condyloma acuminatum and a thorough histopathological examination are necessary. The diagnosis of severe nuclear atypia involving the upper two-thirds of the epithelium should be made with great caution.
http://ift.tt/2oHwKjR
Number of Resected Lymph Nodes and Survival of Patients with Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Preoperative Chemoradiotherapy
Background: The association of extended lymph node (LN) dissection with improved outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received preoperative chemoradiotherapy (CRT) followed by surgery is debatable. Patients and Methods: We reviewed data from patients with esophageal cancer enrolled in three phase II clinical trials of preoperative paclitaxel and cisplatin-based CRT during 2000-2012. Patients with ESCC who underwent planned esophagectomy were enrolled. The number of resected LNs and other clinicopathological factors were analyzed regarding their impact on progression-free (PFS) and overall (OS) survival using Cox proportional hazards model. Results: In total, 139 patients were included. The median PFS and OS were 24.4 and 31.8 months, respectively. The median number of resected and positive LNs were 19 (range=2-96) and 0 (range=0-9), respectively. The mean number of positive LNs did not differ significantly among quartile groups of total resected LNs (quartile 1: 2-12, 2: 13-19, 3: 20-29, and 4: 30-96). The resected LN number analyzed as dichotomies divided by the median or as continuous variables was not associated with PFS or OS. However, in an exploratory analysis, patients of quartiles 2 and 3 had longer PFS and OS than those with quartiles of 1 and 4 in multivariate analysis (p=0.019 and 0.005, respectively). Conclusion: Although extensive LN dissection was not associated with improved survival, resection of 13-29 LNs was associated with improved survival in patients with locally advanced ESCC receiving preoperative paclitaxel and cisplatin-based CRT.
http://ift.tt/2oGe6c8
Update on Surgical Management of Small Bowel Neuroendocrine Tumors
The widespread use of endoscopy and imaging in combination with the continuous update of the staging systems for neuroendocrine tumors has led to an increase in the incidence of small intestinal neuroendocrine tumors (si-NENs) globally. Despite high survival rates, severe complications may occur even in early stages due to the anatomic location of the primary site and the desmoplastic reaction. Surgery plays a central role in the management of patients with si-NENs. Excision of locoregional disease along with extensive lymph node dissection should be performed in fit patients, even in the presence of metastases. Multimodality treatment of liver metastases includes hepatectomy, ablative techniques and liver transplantation. Hormone therapy with somatostatine analogs is of high importance for symptomatic control; special caution should be exercised both pre- and intra-operatively. A multidisciplinary approach is essential in order to provide personalized therapeutics for patients with si-NENs. Clinical research and specialization in this field should be further encouraged.
http://ift.tt/2HTzfZf
Detection of Distinct Changes in Gene-expression Profiles in Specimens of Tumors and Transition Zones of Tenascin-positive/-negative Head and Neck Squamous Cell Carcinoma
Background/Aim: Having previously initiated genome-wide expression profiling in head and neck squamous cell carcinoma (HNSCC) for regions of the tumor, the margin of surgical resecate (MSR) and normal mucosa (NM), we here proceed with respective analysis of cases after stratification according to the expression status of tenascin (Ten). Materials and Methods: Tissue specimens of each anatomical site were analyzed by immunofluorescent detection of Ten, fibronectin (Fn) and galectin-1 (Gal-1) as well as by microarrays. Results: Histopathological examination demonstrated that Ten+Fn+Gal-1+ co-expression occurs more frequently in samples of HNSCC (55%) than in NM (9%; p<0.01). Contrary, the Ten–Fn+Gal-1– (45%) and Ten–Fn–Gal-1– (39%) status occurred with significantly (p<0.01) higher frequency than in HNSCC (3% and 4%, respectively). In MSRs, different immunophenotypes were distributed rather equally (Ten+Fn+Gal-1+=24%; Ten–Fn+Gal-1–=36%; Ten–Fn–Gal-1–=33%), differing to the results in tumors (p<0.05). Absence/presence of Ten was used for stratification of patients into cohorts without a difference in prognosis, to comparatively examine gene-activity signatures. Microarray analysis revealed i) expression of several tumor progression-associated genes in Ten+ HNSCC tumors and ii) a strong up-regulation of gene expression assigned to lipid metabolism in MSRs of Ten– tumors, while NM profiles remained similar. Conclusion: The presented data reveal marked and specific changes in tumors and MSR specimens of HNSCC without a separation based on prognosis.
http://ift.tt/2HTzcN3
Prognostic Significance of High EphA1-4 Expression Levels in Locally Advanced Gastric Cancer
Background/Aim: Erythropoietin-producing hepatocellular carcinoma receptor A (EphA) is associated with angiogenesis and invasive tumor progression. In this study, we evaluated the EphA1-4 expression levels in advanced gastric cancer. Patients and Methods: Tumor tissues obtained from 114 patients with advanced gastric adenocarcinoma who underwent gastrectomy were analyzed. In addition, the impact of EPHA 1-4 mRNA expression on survival was analyzed using the Kaplan-Meier plotter database on the website. Results: High EphA 1, 2, and 4 expression levels were significantly related to recurrence (p<0.01, p=0.04, and p<0.01). Both high EphA 1 and 4 expression levels were independent predictors of relapse-free interval (hazard ratio [HR]=2.0, p=0.03; HR=2.4, p=0.03) and disease-specific survival (HR=2.0, 95% p=0.03; HR=2.5, p=0.02) on multivariate analysis. In the Kaplan-Meier plotter database, high EPHA2 mRNA expression was significantly associated with poor survival in patients with gastric cancer (p=0.0098), and high expression levels of EPHA1 and 4 tended to be associated with poor survival (p=0.050, p=0.052). Conclusion: EphA 1, 2, and 4 may play key roles in recurrence and survival in patients with advanced gastric cancer.
http://ift.tt/2oF4P4k
Modulation of Tumor Cell Metabolism by Laser Photochemotherapy with Cisplatin or Zoledronic Acid In Vitro
Background/Aim: Laser photochemotherapy is a new approach in cancer treatment using low-level laser therapy (LLLT) to enhance the effect of chemotherapy. Materials and Methods: In order to evaluate the effect of LLLT on tumor cells, HeLa cells were treated with cisplatin or zoledronic acid (ZA) followed by LLLT. Cell viability was evaluated with 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Oxidative phosphorylation and glycolysis were measured using extracellular flux analysis. Immunocytochemistry of heat-shock protein 70 (HSP70) and western blot analysis were performed. Results: LLLT alone increased viability and was associated with lower oxidative phosphorylation but higher glycolysis rates. Cisplatin and ZA alone lowered cell viability, glycolysis and oxidative phosphorylation. This effect was significantly enhanced in conjunction with LLLT and was accompanied by reduced oxidative phosphorylation and collapse of glycolysis. Conclusion: Our observations indicate that LLLT may raise the cytotoxicity of cisplatin and ZA by modulating cellular metabolism, pointing to a possible application in cancer treatment.
http://ift.tt/2HT6bkF
A Feasibility Study of Capecitabine and Oxaliplatin for Patients with Stage II/III Colon Cancer -ACTOR Study-
Background/Aim: Past studies have suggested that adjuvant capecitabine and oxaliplatin (CAPOX) provides decreased tumor relapse and longer survival in patients with curatively resected colon cancer. We report the first evidence of the feasibility of adjuvant CAPOX in Japanese patients with early colon cancer. Patients and Methods: Eligible patients had histologically-confirmed stage II/III colon cancer and received curative resection. The primary endpoint was completion rate of treatment after 8 cycles of adjuvant CAPOX. Results: Thirty-six patients were enrolled in this study. The completion rate of CAPOX and oxaliplatin were 77.8% and 61.1%, respectively. The incidence of grade ≥3 adverse events was neutropenia (n=6), thrombocytopenia (n=3), nausea (n=5), hand-foot syndrome (n=1) and peripheral sensory neuropathy (n=1). Three-year disease-free survival for stage II patients and stage III patients were 100% and 79.3%, respectively. Conclusion: Adjuvant CAPOX can be safely administered to Japanese patients with stage II/III colon cancer.
http://ift.tt/2oF4O0g
Combination Treatment of Polo-Like Kinase 1 and Tankyrase-1 Inhibitors Enhances Anticancer Effect in Triple-negative Breast Cancer Cells
Background/Aim: Breast cancer is the most common malignant cancer type in women, and triple-negative breast cancer (TNBC) is an extremely aggressive subtype of breast cancer with poor prognosis rates. The present study investigated the antitumor effect of polo-like kinase 1 (PLK1) inhibitor in combination with the tankyrase-1 (TNKS1) inhibitor on TNBC cells. Materials and Methods: We evaluated the antitumor effects of combination therapy with PLK1 and TNKS1 inhibitor using cell viability analysis, apoptosis assay and transwell assay for cell invasion and migration in TNBC cells. Results: Combination treatment with PLK1 and TNKS1 inhibitors not only inhibited the invasion and migration capacity of TNBC cells, but also increased the apoptosis and cell death of TNBC cells. The viability of TNBC cells with low expression of β-catenin and high expression of PLK1 was not affected by treatment with PLK1 inhibitor. However, the combination treatment with the TNKS1 inhibitor significantly decreased cell invasion and migration and increased apoptosis. Conclusion: Combination therapy of PLK1 and TNKS1 inhibitors may improve the therapeutic efficacy of the current treatment for TNBC.
http://ift.tt/2HUZ0II
Dental and skeletal changes associated with long-term oral appliance use for obstructive sleep apnea: A systematic review and meta-analysis
An oral appliance (OA) is an effective treatment option for patients with obstructive sleep apnea (OSA), but dental and skeletal changes have been detected by many studies after long-term OA use. Better understanding of the long-term side effects may decrease discontinuation of OA use and assist clinicians to make informed decisions. Accordingly, a systematic review and meta-analysis were performed to evaluate the dental and skeletal changes associated with OAs designed to advance the mandible. The quality of the studies was determined by using the risk of bias assessment tool for non-randomized studies (RoBANS), and 12 studies were included in the meta-analysis.
http://ift.tt/2ouIw1V
Asthma exacerbation prediction: recent insights
Purpose of review Asthma attacks are frequent in children with asthma and can lead to significant adverse outcomes including time off school, hospital admission and death. Identifying children at risk of an asthma attack affords the opportunity to prevent attacks and improve outcomes. Recent findings Clinical features, patient behaviours and characteristics, physiological factors, environmental data and biomarkers are all associated with asthma attacks and can be used in asthma exacerbation prediction models. Recent studies have better characterized children at risk of an attack: history of a severe exacerbation in the previous 12 months, poor adherence and current poor control are important features which should alert healthcare professionals to the need for remedial action. There is increasing interest in the use of biomarkers. A number of novel biomarkers, including patterns of volatile organic compounds in exhaled breath, show promise. Biomarkers are likely to be of greatest utility if measured frequently and combined with other measures. To date, most prediction models are based on epidemiological data and population-based risk. The use of digital technology affords the opportunity to collect large amounts of real-time data, including clinical and physiological measurements and combine these with environmental data to develop personal risk scores. These developments need to be matched by changes in clinical guidelines away from a focus on current asthma control and stepwise escalation in drug therapy towards inclusion of personal risk scores and tailored management strategies including nonpharmacological approaches. Summary There have been significant steps towards personalized prediction models of asthma attacks. The utility of such models needs to be tested in the ability not only to predict attacks but also to reduce them.http://ift.tt/2HSvfIv
‘Hidden’ occupational allergens such as additives
Purpose of review With the development of innovative technologies, new agents are continually introduced to the workplace. Some of these agents can act as hidden allergens whenever they are not declared in the product labels or whenever their health hazards are unknown. This review article focuses on the identification and description of unusual and/or hidden allergens recently incriminated in occupational diseases. Recent findings Occupational exposure is an important global health issue that can induce respiratory and cutaneous disorders, as well as life-threatening anaphylaxis. Apart from the classic forms of occupational exposure, reports have emerged from nonconventional or newly identified allergens or additives. These compounds are substances added to another in order to alter or improve the general quality or to counteract undesirable properties, and some of them may behave as potent and frequently hidden allergens. These highly uncommon and/or hidden allergens belong to several categories: foods, spices, cosmetics, insects, enzymes, chemicals, drugs, preservatives, and coloring agents, among others. Summary A high level of suspicion and awareness about the potential hidden allergens is necessary to ascertain the allergens implicated. It is of utmost importance to identify the specific eliciting agents of the occupational diseases in order to avoid strictly further exposure to them.http://ift.tt/2oFQnZA
Evidence establishing a link between prenatal and early-life stress and asthma development
Purpose of review The objective of this review is to provide an update on our evolving understanding of the effects of stress in pregnancy and during early development on the onset of asthma-related phenotypes across childhood, adolescence, and into early adulthood. Recent findings Accumulating evidence over the past 2 decades has established that prenatal and early-life psychological stress and stress correlates (e.g., maternal anxiety or depression) increase the risk for childhood respiratory disorders. Recent systematic reviews and meta-analyses including numerous prospective epidemiological and case–control studies substantiate a significant effect of prenatal stress and stress in early childhood on the development of wheeze, asthma, and other atopic-related disorders (eczema and allergic rhinitis), with many studies showing an exposure–response relationship. Offspring of both sexes are susceptible to perinatal stress, but effects differ. The impact of stress on child wheeze/asthma can also be modified by exposure timing. Moreover, coexposure to prenatal stress can enhance the effect of chemical stressors, such as prenatal traffic-related air pollution, on childhood respiratory disease risk. Understanding complex interactions among exposure dose, timing, child sex, and concurrent environmental exposures promises to more fully characterize stress effects and identify susceptible subgroups. Although the link between perinatal stress and childhood asthma-related phenotypes is now well established, pathways by which stress predisposes children to chronic respiratory disorders are not as well delineated. Mechanisms central to the pathophysiology of wheeze/asthma and lung growth and development overlap and involve a cascade of events that include disrupted immune, neuroendocrine, and autonomic function as well as oxidative stress. Altered homeostatic functioning of these integrated systems during development can enhance vulnerability to asthma and altered lung development. Summary Mechanistic studies that more comprehensively assess biomarkers reflecting alterations across interrelated stress response systems and associated regulatory processes, in both pregnant women and young children, could be highly informative. Leveraging high-throughput systems-wide technologies to include epigenomics (e.g., DNA methylation, microRNAs), transcriptomics, and microbiomics as well as integrated multiomics are needed to advance this field of science. Understanding stress-induced physiological changes occurring during vulnerable life periods that contribute to chronic respiratory disease risk could lead to the development of preventive strategies and novel therapeutic interventions.http://ift.tt/2HSaqNi
Role of epigenetics in the development of childhood asthma
Purpose of review Epigenetic marks are emerging as mediators of genetics and the environment on complex disease phenotypes, including childhood asthma and allergy. Recent findings Epigenome-wide association studies over the past year have added to the growing body of evidence supporting significant associations of epigenetic regulation of gene expression and asthma and allergy. Studies in children have identified signatures of eosinophils in peripheral blood, Th2 cell transcription factors and cytokines in peripheral blood mononuclear cells, and epithelial dysfunction in the respiratory epithelium. Importantly, studies at birth have begun to decipher the contribution of epigenetic marks to asthma inception. Few studies have also begun to address the contribution of genetics and the environment to these associations. Summary Next generation of epigenome-wide association studies that will deal with confounders, study the influence of the genetics and environment, and incorporate multiple datasets to provide better interpretation of the findings are on the horizon. Identification of key epigenetic marks that are shaped by genetics and the environment, and impact transcription of specific genes will help us have a better understanding of etiology, heterogeneity and severity of asthma, and will also empower us to develop biologically driven therapeutics and biomarkers for secondary prevention of this disease.http://ift.tt/2HTyKyz
Health surveillance for occupational asthma
Purpose of review The outcome for workers with occupational asthma is improved for those with an earlier diagnosis. Health surveillance at work is in principle designed to identify such cases, so that the risks to the individual worker, and coworkers, can be reduced. There is recent evidence to suggest that the uptake and quality of such surveillance could be improved. This review has assessed current approaches to health surveillance for occupational asthma. Recent findings The article covers a review of the utility of questionnaires, lung function testing, immunological investigations, and other tests, including exhaled nitric oxide, sputum eosinophilia, and exhaled breath condensate specifically in the context of workplace-based health surveillance. Summary Questionnaires remain a key component of respiratory health surveillance, although maybe limited by both sensitivity and specificity for early occupational asthma. The role of lung function testing is debated, although is recommended for higher level health surveillance. Various examples of immunological testing in health surveillance are discussed, but more evidence is needed in many specific areas before more general recommendations can be made. Evidence is discussed in relation to the utility of newer approaches such as exhaled nitric oxide, sputum eosinophilia, and exhaled breath condensate.http://ift.tt/2oEWkpP
The emerging spectrum of exposure-related bronchiolitis
Purpose of review Exposure-related bronchiolitis is increasingly recognized as an important but challenging clinical diagnosis. Acute and chronic inhalational exposures are associated with variable clinical presentations and a spectrum of histopathologic abnormalities affecting the small airways. This review provides an overview of the histologic patterns and occupational settings for exposure-related bronchiolitis, along with recent advances in disease diagnosis and management. Recent findings The entire histopathologic spectrum of bronchiolitis (constrictive, obliterative, proliferative, lymphocytic, respiratory) has been reported in exposure-related bronchiolitis. Recent studies have shown that lung clearance index testing and impulse oscillometry are more sensitive than spirometry in detecting small airways abnormalities and may augment the diagnosis of occupational bronchiolitis. Prognosis in indolent occupational bronchiolitis appears more favorable than some other types of bronchiolitis but is variable depending on the extent of bronchiolar inflammation and the stage of disease at which exposure removal occurs. Summary No specific histopathologic pattern of bronchiolitis is pathognomonic for occupational bronchiolitis as one or more histologic patterns may be present. A high index of suspicion is needed for exposure and disease recognition. Recent advances that may aid in diagnosis include transbronchial cryobiopsy, lung clearance index testing, and impulse oscillometry, although further research is needed.http://ift.tt/2oC0nmK
Assessing the impact of air pollution on childhood asthma morbidity: how, when, and what to do
Purpose of review Exposure to air pollutants is linked with poor asthma control in children and represents a potentially modifiable risk factor for impaired lung function, rescue medication use, and increased asthma-related healthcare utilization. Identification of the most relevant pollutants to asthma as well as susceptibility factors and strategies to reduce exposure are needed to improve child health. Recent findings The current available literature supports the association between pollutants and negative asthma outcomes. Ethnicity, socioeconomic status, and presence of certain gene polymorphisms may impact susceptibility to the negative health effects of air pollution. Improved air quality standards were associated with better asthma outcomes. Summary The link between air pollution and pediatric asthma morbidity is supported by the recent relevant literature. Continued efforts are needed to identify the most vulnerable populations and develop strategies to reduce exposures and improve air quality.http://ift.tt/2HSanRC
Biomarkers and asthma management: analysis and potential applications
Purpose of review Asthma features a high degree of heterogeneity in both pathophysiology and therapeutic response, resulting in many asthma patients being treated inadequately. Biomarkers indicative of underlying pathological processes could be used to identify disease subtypes, determine prognosis and to predict or monitor treatment response. However, the newly identified as well as more established biomarkers have different applications and limitations. Recent findings Conventional markers for type 2-high asthma, such as blood eosinophils, fraction of exhaled nitric oxide, serum IgE and periostin, feature limited sensitivity and specificity despite their significant correlations. More distinctive models have been developed by combining biomarkers and/or using omics techniques. Recently, a model with a positive predictive value of 100% for identification of type 2-high asthma based on a combination of minimally invasive biomarkers was developed. Summary Individualisation of asthma treatment regimens on the basis of biomarkers is necessary to improve asthma control. However, the suboptimal properties of currently available conventional biomarkers limit its clinical utility. Newly identified biomarkers and models based on combinations and/or omics analysis must be validated and standardised before they can be routinely applied in clinical practice. The development of robust biomarkers will allow development of more efficacious precision medicine-based treatment approaches for asthma.http://ift.tt/2oJPH5N
Asthma in inner city children: recent insights United States
Purpose of review Children living in US inner cities experience disparate burdens of asthma, especially in severity, impairment, exacerbations, and morbidity. Investigations seeking to better understand the factors and mechanisms underlying asthma prevalence, severity, and exacerbation in children living in these communities can lead to interventions that can narrow asthma disparities and potentially benefit all children with asthma. This update will focus on recent (i.e. late 2016–2017) advances in the understanding of asthma in US inner city children. Recent findings Studies published in the past year expand understanding of asthma prevalence, severity, exacerbation, and the outcomes of guidelines-based management of these at-risk children, including: asthma phenotypes in US inner city children that are severe and difficult-to-control; key environmental determinants and mechanisms underlying asthma severity and exacerbations (e.g. allergy-mediated exacerbation susceptibility to rhinovirus); the importance of schools as a place for provocative exposures (e.g. mouse allergen, nitrogen dioxide) as well as a place where asthma care and outcomes can be improved; and the development and validation of clinically useful indices for gauging asthma severity and predicting exacerbations. Summary These recent studies provide a trove of actionable findings that can improve asthma care and outcomes for these at-risk children.http://ift.tt/2HVBE5Q
Development of allergic sensitization and its relevance to paediatric asthma
Purpose of review The purpose of this review is to summarize the recent evidence on the distinct atopic phenotypes and their relationship with childhood asthma. We start by considering definitions and phenotypic classification of atopy and then review evidence on its association with asthma in children. Recent findings It is now well recognized that both asthma and atopy are complex entities encompassing various different sub-groups that also differ in the way they interconnect. The lack of gold standards for diagnostic markers of atopy and asthma further adds to the existing complexity over diagnostic accuracy and definitions. Although recent statistical phenotyping studies contributed significantly to our understanding of these heterogeneous disorders, translating these findings into meaningful information and effective therapies requires further work on understanding underpinning biological mechanisms. Summary The disaggregation of allergic sensitization may help predict how the allergic disease is likely to progress. One of the important questions is how best to incorporate tests for the assessment of allergic sensitization into diagnostic algorithms for asthma, both in terms of confirming asthma diagnosis, and the assessment of future risk.http://ift.tt/2oJPwaD
Precision medicine in the treatment of primary immunodeficiency diseases
Purpose of the review Since the 1990s with the advances in molecular biology, a number of genetic defects have been described. The International Union of Immunological Sciences has recently updated the classification of genetic defects associated with primary immune deficiencies that now number 354. With the ever-expanding list of new monogenic disorders and a better understanding of the immunobiology and function of these defective genes, new therapies have emerged particularly aimed at the autoimmune and inflammatory conditions that plague these patients. Recent findings Immune deficiencies associated with gain-of-function (GOF) mutations are a potential category for targeted therapies to control the GOF activities of the mutated gene. In addition to the increased susceptibility to infections these patients have autoimmune and inflammatory diseases that are difficult to control with conventional therapies. The dysregulated immune functions of the activated phospholipase-3-kinase δ syndrome, cytotoxic T lymphocyte-associated antigen-4 haploinsufficiency, lipopolysaccharide-responsive beige-like anchor deficiency, the GOF mutations of signal transducer and activator of transcription 1 and 3 immune deficiencies will be reviewed. The targeted therapies for each of these immune deficiencies using small molecule kinase inhibitors and fusion protein biologic modifiers will be described. Summary In this review, we explore the recent advances in precision medicine treatment of several primary immunodeficiency syndromes in which immune dysregulation is a key feature. Understanding the immunobiology associated with these GOF mutations has led to the use of biologic therapies to better control the associated autoimmune and inflammatory manifestations.http://ift.tt/2HV1Ygc
Hypereosinophilic syndrome presenting acutely with neurologic signs
A 70-year-old white male with a longstanding history of allergic rhinitis and nasal polyposis, and relatively recent onset of chronic cough one year prior, presented to the hospital for one-week duration of neurologic complaints including chronic and worsening neck pain, bilateral upper extremity weakness, difficulty gripping objects, blurry vision, confusion, change in gait, and difficulty with initiation of urination. His medical history also included essential hypertension, dyslipidemia, gastroesophageal reflux, and shingles.
http://ift.tt/2oDTrFG
Displacement of the Recurrent Laryngeal Nerve in Patients with Recurrent Goiter Undergoing Redo Thyroid Surgery
Thyroid reoperations are surgically challenging because of scarring and disturbances in the anatomy of the recurrent laryngeal nerve (RLN). This study was conducted on 49 patients who underwent redo surgery. 61 RLNs were identified and completely exposed. Their functional integrity was evaluated using intraoperative nerve monitoring (IONM). Indications for secondary surgery, anatomical changes secondary to recurrent goiter mass and prior surgery, and results of IONM were studied. Frequent indications for redo surgery were multinodular goiter (MNG) in 19 (38.8%) and results of cytology in 14 (28.5%) patients. The mean time interval between primary and redo thyroid surgery was 23.4 years. We laterally approached 41 (67.2%) thyroid lobes between the sternocleidomastoid and sternohyoid muscles. 16 (26.2%) RLNs were found to be adherent to the lateral surface of the corresponding thyroid lobe. The functional integrity of all RLNs was confirmed by IONM. The remnant thyroid tissue can then lead to goiter recurrence requiring secondary surgery after a long period of time. The indications for redo surgery were similar to primary cases. Lateral displacement of the RLN which is adherent to the lateral surface of recurrent goiter mass is common anatomic variation. Thyroid reoperations based on awareness of anatomical disturbances can be performed safely by an experienced surgeon with support of ancillary electrophysiological technology.
http://ift.tt/2EZUgng
Editorial board
Publication date: March 2018
Source:Journal of Dermatological Science, Volume 89, Issue 3
http://ift.tt/2ovL0Ns
Lymph stasis promotes tumor growth
Publication date: Available online 15 February 2018
Source:Journal of Dermatological Science
Author(s): Valerio De Vita, Eleonora Ruocco
http://ift.tt/2oykfrB
Editor's Choice
Publication date: February 2018
Source:Journal of Dermatological Science, Volume 89, Issue 2
http://ift.tt/2GUhNmf
The role of the OVOL1–OVOL2 axis in normal and diseased human skin
Publication date: Available online 12 February 2018
Source:Journal of Dermatological Science
Author(s): Gaku Tsuji, Takamichi Ito, Takahito Chiba, Chikage Mitoma, Takeshi Nakahara, Hiroshi Uchi, Masutaka Furue
OVOLs (OVO-like proteins) are ubiquitously conserved genes encoding a C2H2 zinc finger transcription factor in mammals. Functional studies on OVOL1 and OVOL2 using knockout mice have suggested that these genes play a pivotal role in the development of epithelial tissues arising from germ cells; however, the role of the OVOL1–OVOL2 axis in normal and diseased tissues remains unclear. This review highlights recent advances in understanding how the OVOL1–OVOL2 axis modulates cell differentiation and proliferation in human keratinocytes, hair follicles, and benign or malignant skin tumors including squamous cell carcinoma and malignant melanoma. Furthermore, OVOL1 has been shown to be involved in the expression of skin barrier proteins including filaggrin (FLG), and its mutation or dysfunction leads to the development of atopic dermatitis (AD). OVOL1 has also been identified as a susceptibility gene for AD by genome-wide association studies, in addition to FLG. Therefore, we discuss the relationship between OVOL1 and FLG in the development of AD.
http://ift.tt/2t5CbP1
Heat shock protein 90 inhibitor enhances apoptosis by inhibiting the AKT pathway in thermal-stimulated SK-MEL-2 human melanoma cell line
Publication date: Available online 8 February 2018
Source:Journal of Dermatological Science
Author(s): Min Kyung Shin, Ki-Heon Jeong, Hyeongwon Choi, Hye-Jin Ahn, Mu-Hyoung Lee
BackgroundHeat shock proteins (Hsps) are chaperone proteins, which are upregulated after various stresses. Hsp90 inhibitors have been investigated as adjuvant therapies for the treatment of melanoma. Thermal ablation could be a treatment option for surgically unresectable melanoma or congenital nevomelanocytic nevi, however, there is a limitation such as the possibility of recurrence.ObjectiveWe evaluated apoptosis in a melanoma cell line treated with the Hsp90 inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in hyperthermic conditions.MethodsSK-MEL-2 cells were stimulated at 43 °C for 1 h and treated with 0, 0.1 and 1 μM 17-DMAG. We evaluated the cell viability using MTT and apoptosis with HSP 90 inhibitor. We studied the protein expression of AKT, phospho-AKT, ERK, phospho-ERK, MAPK, and phospho-MAPK, caspase 3,7,9, and anti-poly (ADP-ribose) polymerase.Results17-DMAG significantly inhibited the proliferation of the SK-MEL-2 cells at 37 °C (0.1 μM: 44.47% and 1 μM: 61.23%) and 43 °C (0.1 μM: 49.21% and 1 μM: 63.60%), suggesting synergism between thermal stimulation and 17-DMAG. 17-DMAG treatment increased the frequency of apoptotic cell populations to 2.17% (0.1 μM) and 3.05% (1 μM) in 37 °C controls, and 4.40% (0.1 μM) and 4.97% (1 μM) in the group stimulated at 43 °C. AKT phosphorylation were activated by thermal stimulation and inhibited by 17-DMAG.ConclusionHsp90 inhibitor treatment may be clinically applicable to enhance the apoptosis of melanoma cells in hyperthermic condition.
http://ift.tt/2F2CRdT
Reduced-HMGB1 suppresses poly(I:C)-induced inflammation in keratinocytes
Publication date: Available online 2 February 2018
Source:Journal of Dermatological Science
Author(s): Hideki Mori, Masamoto Murakami, Teruko Tsuda, Kenji Kameda, Ryo Utsunomiya, Kana Masuda, Ken Shiraishi, Xiuju Dai, Mikiko Tohyama, Hiroki Nakaoka, Koji Sayama
BackgroundHigh mobility group box 1 (HMGB1) is a nuclear protein that stabilizes DNA and facilitates gene transcription. Additionally, cell stress or death induces the release of HMGB1 outside the cell membrane, where HMGB1 functions as an alarmin, causing an inflammatory response in combination with other cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs).ObjectiveTo evaluate the effect of reduced-HMGB1 (previously termed chemoattractive-HMGB1) on polyinosine-polycytidylic acid [poly(I:C)]-induced inflammation in normal human keratinocytes (NHKs).MethodsWe focused on downstream components of the poly(I:C)-Toll-like receptor 3 (TLR3), retinoic acid-inducible gene-I (RIG-I), and melanoma differentiation-associated protein 5 (MDA5) pathways, including IκBα, nuclear factor (NF)-κB p65, mitogen-activated protein kinase (MAPK), and interferon regulatory factor 3 (IRF3), and assessed whether these pathways are involved in the suppression of poly(I:C)-induced inflammation in NHKs by HMGB1. An immunoprecipitation was performed to know whether HMGB1 could bind to poly(I:C), and immunofluorescence staining and flow cytometric analysis were performed to check whether reduced-HMGB interferes with cellular uptake of poly(I:C) translocation (possibly by endocytosis).ResultsApplication of exogenous HMGB1 before, but not after, exerted a suppressive effect on poly(I:C)-induced inflammation in NHKs. In addition, reduced-HMGB1, but not disulfide-HMGB1, exerted a suppressive effect on poly(I:C)-induced inflammation in NHKs, suggesting the importance of the redox status of exogenous HMGB1. Pre-treatment with reduced-HMGB1 inhibited the phosphorylation of IκBα, NF-κB p65, and IRF3 induced by poly(I:C) stimulation in NHKs; however, phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) was unaffected. Disulfide-HMGB1 formed a complex with poly(I:C), as did reduced- and oxidized-HMGB1, albeit to a lesser extent. Immunofluorescence staining and flow cytometric analysis indicated that reduced-HMGB interferes with cellular uptake of poly(I:C) translocation (possibly by endocytosis).ConclusionThese findings suggest that pre-treatment with reduced-HMGB1 ameliorates poly(I:C)-mediated inflammation in NHKs.
http://ift.tt/2oyIhCZ
Localization of collagen type 5 in the papillary dermis and its role in maintaining stem cell functions
Publication date: February 2018
Source:Journal of Dermatological Science, Volume 89, Issue 2
Author(s): Yuichi Hasebe, Seiji Hasegawa, Yasushi Date, Satoru Nakata, Akiko Yagami, Yohei Iwata, Kazumitsu Sugiura, Hirohiko Akamatsu
http://ift.tt/2GRufTv
Proteins involved in the antioxidant and inflammatory response in rutin-treated human skin fibroblasts exposed to UVA or UVB irradiation
Publication date: Available online 15 February 2018
Source:Journal of Dermatological Science
Author(s): Agnieszka Gęgotek, Pedro Domingues, Elżbieta Skrzydlewska
BackgroundRutin, due to its polyphenolic structure, has antioxidant properties and can be used as a cytoprotective compound against UV-induced effects on skin cells.ObjectiveThe aim of this study was to examine the effect of rutin on proteomic profile in human skin fibroblasts irradiated with UV dose that induces apoptosis.MethodsProteome analysis based on the results obtained by the QExactive OrbiTrap mass spectrometer.ResultsResults show that rutin treatment more strongly protects against UVA-induced rather than UVB-induced increases in the total expression of proteins involved in antioxidant (such as SOD, TrxR, and Prxs 1/2) and inflammatory response (e.g., IL-17F, PAK2, and YWHAZ). However, in the case of UVB-irradiated cells, rutin additionally enhances the levels of disulfide-isomerase − an enzyme that is responsible for the formation and breakage of disulfide bonds. Moreover, UVB radiation promotes rutin-Keap1 adduct formation, which leads to the activation of Nrf2, a factor that is responsible for the synthesis of cytoprotective proteins. Furthermore, rutin partially prevents UV-induced apoptosis by restoring the physiological levels of p53, cytochrome c, and cell cycle and apoptosis regulator protein 2 that were increased following irradiation.ConclusionIn conclusion, our results show that rutin effectively prevents UV-induced damages associated with proinflammatory and prooxidative activity and protects cells against apoptosis.
http://ift.tt/2oyjX3Z
Reply: lymph stasis promotes tumor growth
Publication date: Available online 15 February 2018
Source:Journal of Dermatological Science
Author(s): Yoshiyuki Nakamura, Yasuhiro Fujisawa, Naoko Okiyama, Rei Watanabe, Ryota Tanaka, Yosuke Ishitsuka, Hideaki Tahara, Manabu Fujimoto
http://ift.tt/2t5BWDB
Protective role of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous ligand for arylhydrocarbon receptor, in chronic mite-induced dermatitis
Publication date: Available online 21 February 2018
Source:Journal of Dermatological Science
Author(s): Mari Kiyomatsu-Oda, Hiroshi Uchi, Saori Morino-Koga, Masutaka Furue
BackgroundChronic eczema such as atopic dermatitis imposes significant socio-econo-psychologic burdens on the affected individuals. In addition to conventional topical treatments, phototherapy is recommended for patients with extensive lesions. Although immunosuppression is believed to explain its primary effectiveness, the underlying mechanisms of phototherapy remain unsolved. Ultraviolet irradiation generates various tryptophan photoproducts including 6-formylindolo[3,2-b]-carbazole (FICZ). FICZ is known to be a potent endogenous agonist for aryl hydrocarbon receptor (AHR); however, the biological role of FICZ in chronic eczema is unknown.ObjectiveTo investigate the effect of FICZ on chronic eczema such as atopic dermatitis.MethodsWe stimulated HaCaT cells and normal human epidermal keratinocytes (NHEKs) with or without FICZ and then performed quantitative reverse transcriptase polymerase chain reaction, immunofluorescence, and siRNA treatment. We used the atopic dermatitis-like NC/Nga murine model and treated the mice for 2 weeks with either Vaseline® as a control, FICZ ointment, or betamethasone 17-valerate ointment. The dermatitis score, transepidermal water loss, histology, and expression of skin barrier genes and proteins were evaluated.ResultsFICZ significantly upregulated the gene expression of filaggrin in both HaCaT cells and NHEKs in an AHR-dependent manner, but did not affect the gene expression of other barrier-related proteins. In addition, FICZ improved the atopic dermatitis-like skin inflammation, clinical scores, and transepidermal water loss in NC/Nga mice compared with those of control mice. On histology, FICZ significantly reduced the epidermal and dermal thickness as well as the number of mast cells. Topical FICZ also significantly reduced the gene expression of Il22.ConclusionThese findings highlight the beneficial role of FICZ-AHR and provide a new strategic basis for developing new drugs for chronic eczema.
http://ift.tt/2oyjLBN
Introduction of the TERT and BMI1 Genes into Murine Dermal Papilla Cells Ameliorates Hair Inductive Activity
Publication date: Available online 21 February 2018
Source:Journal of Dermatological Science
Author(s): Masahiro Kiso, Shigeharu Yabe, Munenari Itoh, Hidemi Nakagawa, Hitoshi Okochi
http://ift.tt/2F2CAYp
The UVA-induced long non-coding RNA GS1-600G8.5 regulates the expression of IL-8
Publication date: Available online 21 February 2018
Source:Journal of Dermatological Science
Author(s): Kazuyuki Yo, Thomas M. Rünger
http://ift.tt/2t4GdHr
A heterozygous mutation in the SAM domain of p63 underlies a mild form of ectodermal dysplasia
Publication date: Available online 21 February 2018
Source:Journal of Dermatological Science
Author(s): Toru Kawai, Ryota Hayashi, Hiroyuki Nakai, Yutaka Shimomura, Mazen Kurban, Lamiaa Hamie, Hiroki Fujikawa, Atsushi Fujimoto, Riichiro Abe
http://ift.tt/2GRtHgp
Dupilumab treatment in moderate-to-severe atopic dermatitis: A systematic review and meta-analysis
Publication date: Available online 20 February 2018
Source:Journal of Dermatological Science
Author(s): Fa-Ping Wang, Xiao-Ju Tang, Chuan-Qi Wei, Lin-Rui Xu, Hui Mao, Feng-Ming Luo
BackgroundDupilumab, a fully human monoclonal antibody against the interleukin-4-receptor α subunit, has been developed and used in clinical trials to treat atopic dermatitis (AD).ObjectiveWe aimed to assess the overall efficacy and safety of dupilumab treatment in AD.MethodsPubMed, Embase, Cochrane library databases, and the Chinese Biological Medicine (CBM) published up to September 2017 were searched. All randomized controlled trials (RCTs) of dupilumab treatment on adult patients with AD were included. Fixed- or random-effects models were used to calculate pooled standard mean differences or relative risks (SMD or RR, respectively).ResultsSix trials involving 2447 patients were identified. Pooled analysis revealed significant improvements in Eczema Area and Severity Index (EASI) score (SMD = −0.89, 95% CI: −1.0 to −0.78), percentage of body surface area (BSA) (SMD = −0.83, 95% CI: −0.90 to −0.75), pruritus numeric rating scale (NRS) scores (SMD = −0.81, 95% CI: −0.96 to −0.66), and Dermatology Life Quality Index (DLQI) scores (SMD = −0.78, 95% CI: −0.89 to −0.66). Dupilumab treatment was also associated with a significant increase in the proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.82; 95% CI: 3.23 to 4.51) and a similar incidence of adverse events (RR = 1.0; 95% CI: 0.96 to 1.04).ConclusionsOur analysis provided evidence that dupilumab had an acceptable safety profile and resulted in clinically relevant improvements in signs and symptoms of AD. Dose regimens of 300 mg qw and q2 w seemed to have similar benefits. Further long-term trials are required for confirmation.
http://ift.tt/2EY6ixz
Whole Exome Sequencing allows the identification of two novel groups of Xeroderma pigmentosum in Tunisia, XP-D and XP-E: Impact on molecular diagnosis
Publication date: February 2018
Source:Journal of Dermatological Science, Volume 89, Issue 2
Author(s): Mariem Ben Rekaya, Chokri Naouali, Olfa Messaoud, Meriem Jones, Yosra Bouyacoub, Majdi Nagara, Tommaso Pippucci, Haifa Jmel, Mariem Chargui, Manel Jerbi, Mohamed Alibi, Hamza Dallali, Anu Bashamboo, Kenneth McElreavey, Giovanni Romeo, Abdelhamid Barakat, Mohamed Zghal, Houda Yacoub-Youssef, Sonia Abdelhak
BackgroundSkin cancers (SC) are complex diseases that develop from complex combinations of genetic and environmental risk factors. One of the most severe and rare genetic diseases predisposing to SC is the Xeroderma pigmentosum (XP) syndrome.ObjectivesFirst, to identify the genetic etiology of XP and to better classify affected patients. Second, to provide early molecular diagnosis for pre-symptomatic patient and finally to offer genetic counseling for related individuals.MethodsWhole Exome Sequencing (WES) and Run Of Homozygosity (ROH) were performed for two patients belonging to two different multiplex consanguineous families. The identified mutations were confirmed by Sanger sequencing and researched in ten Tunisian families including a total of 25 affected individuals previously suspected as having XP group V (XP-V) form. All patients had mild dermatological manifestations, absence of neurological abnormalities and late onset of skin tumors.ResultsScreening for functional variations showed the presence of the ERCC2 p.Arg683Gln in XP14KA-2 patient and a novel mutation, DDB2 p. (Lys381Argfs*2), in XP51-MAH-1 patient. Sanger sequencing and familial segregation showed that the ERCC2 mutation is present at a homozygous state in 10 affected patients belonging to 3 families. The second mutation in DDB2, is present at a homozygous state in 5 affected cases belonging to the same family. These two mutations are absent in the remaining 10 affected patients. The ERCC2 c.2048G > A mutation is present in a medium ROH region (class B) suggesting that it mostly arises from ancient relatedness within individuals. However, the c.1138delG DDB2 mutation is present in a large ROH region (class C) suggesting that it arises from recent relatedness.ConclusionTo our knowledge, this is the first study that identifies XP-D and XP-E complementation groups in Tunisia. These two groups are very rare and under-diagnosed in the world and were not reported in North Africa.
http://ift.tt/2t4FMgh
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