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Πέμπτη 26 Απριλίου 2018

Biochemical responses of the Protaetia brevitarsis Lewis larvae to subchronic copper exposure

Abstract

Copper (Cu) is one of the most commonly detected heavy metals in livestock manure pollution. Protaetia brevitarsis Lewis larvae are widely used in the decomposition of livestock manure. During decomposition, heavy metals in livestock manure can accumulate in P. brevitarsis larvae and affect normal growth and reproduction. Therefore, this research focused on characterizing the toxic effects of Cu to P. brevitarsis Lewis larvae. Larvae were exposed to Cu concentrations of 0, 100, 200, 400, and 800 mg kg−1 in edible fungi residue for 7, 14, 21, and 28 days. Results showed that the soluble protein content was markedly increased in 200 and 400 mg kg−1 treatment groups on day 28. Compared to the control group, superoxide dismutase (SOD) and glutathione S-transferase (GST) activities were significantly stimulated on day 7 and then decreased as exposure length was increased (e.g., after 14, 21, and 28 days). Catalase (CAT) activity was also significantly increased after 7 days of exposure. Malondialdehyde (MDA) levels were markedly increased in the 100, 200, and 400 mg kg−1 treatment groups on day 7. However, as time and Cu concentration were increased, MDA levels gradually decreased. These results indicate that Cu has biochemical effects on P. brevitarsis Lewis larvae, and both time and dose affect this biochemical response.



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Synthesis of In2Se3 homojunction photocatalyst with α and γ phases for efficient photocatalytic performance

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): Ruimiao Wang, Jun Wan, Jia Jia, Wenhua Xue, Xiaoyun Hu, Enzhou Liu, Jun Fan
Herein, novel γ-In2Se3 nanoparticle/α-In2Se3 nanosheet (In2Se3 NPS) homojunctions were constructed by a facile solvothermal method and applied to photocatalytic H2 production from water splitting and removel of Cr(VI) pollutant for the first time. The photocatalytic H2 evolution rate and Cr(VI) removal rate can reach 1347.6 μmol/(g·h) and 94.9% in 10 min without any co-catalyst over optimal In2Se3 NPS, which is 4.34 and 4.12 times higher than that of pure γ-phase In2Se3 nanoparticles. The characterizations of valence band X-ray photoelectron spectroscopy and Mott-Schottky measurement prove that the In2Se3 NPS homojunction establishes a staggered band alignment to promote the separation and transfer of photogenerated charge carriers. Meanwhile, the hybrid nanoparticle/ nanosheet structure with appropriate proportion, uniform distribution and intimate contact can boost the light trapping and provide more electron trapping sites, resulting in active photocatalytic performance. This work not only enrich In2Se3-based semiconductor nanomaterials with a simple synthetic route, but also provide a new sight in design homojunction for efficient photocatalytic applications.

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Stress induced martensite variants revealed by in situ high resolution electron backscatter diffraction (HR-EBSD)

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): A. Arabi-Hashemi, Y. Guo, J. Michler, D. Casari, C. Leinenbach, X. Maeder
In situ HR-EBSD during FeMnSi-based micro-pillar compression is used to correlate phase transformations and its underlying stresses. A simple experimental configuration containing two grains, one grain boundary and a uniaxial compression causes complex stress fields. Two out of three differently orientated stress induced martensite variants are expected to form due to high Schmid factors. To reveal the origin of growth of the third variant with a low Schmid factor, we calculate global stress maps and local resolved shear stress maps based on HR-EBSD measurements. Localized shear stresses at the grain boundary are identified to cause the growth of the not expected near grain boundary variant.

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3D-printed biodegradable gyroid scaffolds for tissue engineering applications

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): Loïc Germain, Carlos A. Fuentes, Aart W. van Vuure, Anne des Rieux, Christine Dupont-Gillain
Fused deposition modeling (FDM), a low-cost and easy-to-use additive manufacturing technique, was used to produce poly(lactic acid) (PLA) gyroid scaffolds. Such morphology was selected for its spring shape, high porosity leading to good nutrient and waste diffusion, and favorable mechanical properties. Printing parameters were optimized and the need of a support material to improve printing was evidenced. The gyroid was compared to the common strut-based structure. Scaffold porosity was measured by micro-CT, and mechanical properties were determined by compression tests, taking into account the effect of geometry, printing resolution, and PLA crystallinity. The impact of scaffold geometry and crystallinity on its degradation was studied in vitro. Porosity of the gyroid structure was 71%, as expected from the printing model. The compression tests showed an isotropic behavior for the gyroid, in contrast with the strut-based scaffold. Upon aging in physiological conditions, gyroid scaffolds retained their integrity during 64 weeks, while control scaffolds lost struts starting from week 33, in a way that depended on crystallinity and printing resolution. Based on these results, the gyroid design is proposed as a suitable mesh architecture for tissue engineering scaffolds that can be elaborated using FDM techniques, to produce low-cost and personalized implants.

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Design of Fe3O4@SiO2@mSiO2-organosilane carbon dots nanoparticles: Synthesis and fluorescence red-shift properties with concentration dependence

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): Xiaolei Li, Wei Wang, Qianli Li, Han Lin, Yue Xu, Lin Zhuang
Organosilane-functionalized carbon dots (SiCDs) immobilized silica composite nanoparticles (Fe3O4@SiO2@mSiO2-SiCDs) with dually emissive properties have been prepared by a modified sol-gel method. Such Fe3O4@SiO2@mSiO2-SiCDs nanoparticles solution exhibits blue light emission with a maximum wavelength of 470 nm at lower concentrations, and red-shifts to yellow-green light emission with maximum wavelength of 565 nm at higher concentrations, which is different with traditional carbon dots composite materials displaying strong emission only in the blue-light region. The SiCDs are immobilized in the outer mesoporous silica layer by covalent bonds via proper blending ration, which enables the nanoparticles solution to possess excellent fluorescence stability. The Fe3O4@SiO2@mSiO2-SiCDs nanoparticles show good stability, high surface area (483.19 m2/g), high saturation magnetization (22.1 emu/g) and low remanence (0.217 emu/g). When the concentration of nanoparticles solution is increased, the distance between the nanoparticles decreases and exhibits the concentration-mediated scattering phenomena, which result in the red-shift of fluorescent peaks. The specific structure of the Fe3O4@SiO2@mSiO2-SiCDs nanoparticles and the concentration-mediated scattering phenomena play key roles in the red-shift appearing.

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Calcium phosphate coated 3D printed porous titanium with nanoscale surface modification for orthopedic and dental applications

Publication date: 5 August 2018
Source:Materials & Design, Volume 151
Author(s): Susmita Bose, Dishary Banerjee, Anish Shivaram, Solaiman Tarafder, Amit Bandyopadhyay
This study aims to improve the interfacial bonding between the osseous host tissue and the implant surface through the application of doped calcium phosphate (CaP) coating on 3D printed porous titanium. Porous titanium (Ti) cylinders with 25% volume porosity were fabricated using Laser Engineered Net Shaping (LENS™), a commercial 3D printing technique. The surface of these 3D printed cylinders was modified by growing TiO2 nanotubes first, followed by a coating with Sr2+ and Si4+ doped bioactive CaP ceramic in simulated body fluid (SBF). Doped CaP coated implants were hypothesized to show enhanced early stage bone tissue integration. Biological properties of these implants were investigated in vivo using a rat distal femur model after 4 and 10 weeks. CaP coated porous Ti implants have enhanced tissue ingrowth as was evident from the CT scan analysis, push out test results, and the histological analysis compared to porous implants with or without surface modification via titania nanotubes. Increased osteoid-like new bone formation and accelerated mineralization were revealed inside the CaP coated porous implants. It is envisioned that such an approach of adding a bioactive doped CaP layer on porous Ti surface can reduce healing time by enhancing early stage osseointegration in vivo.

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Development of Fe/Nb-based solar photocatalysts for water treatment: impact of different synthesis routes on materials properties

Abstract

Semiconductors based on Fe/Nb oxides can present both solar sensitivity and high catalytic activity. However, there is still a lack regarding the comparison between different routes to produce Fe/Nb-based solar photocatalysts and the evaluation of the impact of the synthesis operating conditions on the material properties. In this work, Fe/Nb2O5 ratio, type of precipitating agent, presence/absence of washing stage, and temperature of calcination were verified to be the most relevant parameters in the synthesis by the co-precipitation method. These factors led to remarkable differences in the properties and performance of the photocatalysts produced by each distinct synthesis route. Composition, iron species present in the materials, crystallinity characteristics, and pH of the catalysts were affected, leading to different photocatalytic activities under UV-Vis light. Due to their characteristics, the synthesized materials are potential photocatalysts for application in solar processes.

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Clinical and psychological features of children and adolescents diagnosed with avoidant/restrictive food intake disorder in a pediatric tertiary care eating disorder program: a descriptive study

Abstract

Background

Avoidant/Restrictive Food Intake Disorder (ARFID) is an eating disorder first described in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) [American Psychiatric Association, Diagnostic and statistical manual of mental disorders, 2013]. Patients with ARFID do not fear gaining weight or have body image distortions. ARFID involves a persistent disturbance in feeding and eating that results in an inability to meet nutritional and/or energy needs with one of the following: weight loss or failure to achieve appropriate weight gain, nutritional deficiency, dependence on enteral feeding or nutritional supplements and significant interference with psychosocial functioning. To date, studies on patients with ARFID have retrospectively applied the DSM-5 diagnostic criteria for ARFID to reclassify patients diagnosed with DSM-IV eating disorders.

Methods

A descriptive retrospective chart review was completed on patients less than 18-years diagnosed with ARFID after a comprehensive eating disorder assessment between May 2013 and March 2016. The data collected included demographics, anthropometrics, historical information, clinical features, co-morbid diagnoses, need for inpatient hospitalization and psychometric measures.

Results

Three hundred and sixty-nine patients were assessed for an eating disorder between May 2013 and March 2016. Of these, 31 (8.4%) received a DSM-5 diagnosis of ARFID. A full chart review was performed on 28 (90.3%) patients. Weight loss or failure to achieve appropriate weight gain was the reason for diagnosis in 96.4% (27/28). All of our patients had 2 or more physical symptoms at the time of diagnosis and 16 (57.1%) had a co-morbid psychiatric disorder. Twenty (71.4%) reported a specific trigger for their eating disturbance. Admission for inpatient hospitalization occurred in 57.1% (16/28) of patients. Thirteen (46.4%) patients had been previously assessed by another specialist for their eating disturbance. None of the patients had elevated scores on commonly used psychometric tests used to assess eating disorders.

Conclusion

This is the first study to retrospectively determine the incidence of ARFID in children and adolescents using the DSM-5 diagnostic criteria at assessment. The clinical presentation of patients with ARFID is complex with multiple physical symptoms and comorbid psychiatric disorders. Commonly used pediatric eating disorder psychometric measures are not specific for making a diagnosis of ARFID, and may not be sensitive as assessment tools.



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Bulk deposition of base cationic nutrients in China's forests: Annual rates and spatial characteristics

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Enzai Du, Wim de Vries, Steven McNulty, Mark E. Fenn
Base cations, such as potassium (K+), calcium (Ca2+) and magnesium (Mg2+), are essential nutrients for plant growth and their atmospheric inputs can buffer the effect of acid deposition by nitrogen (N) and sulphur (S) compounds. However, the spatial variation in atmospheric deposition of these base cationic nutrients is less understood compared with N and S deposition. By synthesizing bulk deposition data for K+, Ca2+ and Mg2+, we assessed their annual rates and spatial characteristics at 34 forested sites across China. Our synthesis showed relatively high levels of bulk deposition of base cationic nutrients in China's forests, being an order of magnitude higher than in the USA and Europe. On average, K+, Ca2+ and Mg2+ accounted for 13%, 72% and 15% of the bulk deposition of base cationic nutrients, respectively. Surprisingly, base cation deposition was lower at sites near semi-arid regions compared with sites in eastern and southern China, which were far from semi-arid regions. Moreover, elevated base cation deposition was associated with urban hotspots, exhibiting a significant power-law increase with closer distance to the nearest large cities. We estimated that on average base cationic nutrients neutralized a significant proportion (76%) of the potential acid load due to acid deposition. Our findings suggest that in China there is considerable anthropogenic alteration of the regional cycling of base cationic nutrients, which plays an important role in counteracting the risk of soil acidification and base cation depletion in forest ecosystems, especially in the southern regions.

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Artificial neural network model for ozone concentration estimation and Monte Carlo analysis

Publication date: July 2018
Source:Atmospheric Environment, Volume 184
Author(s): Meng Gao, Liting Yin, Jicai Ning
Air pollution in urban atmosphere directly affects public-health; therefore, it is very essential to predict air pollutant concentrations. Air quality is a complex function of emissions, meteorology and topography, and artificial neural networks (ANNs) provide a sound framework for relating these variables. In this study, we investigated the feasibility of using ANN model with meteorological parameters as input variables to predict ozone concentration in the urban area of Jinan, a metropolis in Northern China. We firstly found that the architecture of network of neurons had little effect on the predicting capability of ANN model. A parsimonious ANN model with 6 routinely monitored meteorological parameters and one temporal covariate (the category of day, i.e. working day, legal holiday and regular weekend) as input variables was identified, where the 7 input variables were selected following the forward selection procedure. Compared with the benchmarking ANN model with 9 meteorological and photochemical parameters as input variables, the predicting capability of the parsimonious ANN model was acceptable. Its predicting capability was also verified in term of warming success ratio during the pollution episodes. Finally, uncertainty and sensitivity analysis were also performed based on Monte Carlo simulations (MCS). It was concluded that the ANN could properly predict the ambient ozone level. Maximum temperature, atmospheric pressure, sunshine duration and maximum wind speed were identified as the predominate input variables significantly influencing the prediction of ambient ozone concentrations.

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Cluster analysis of microclimate data to optimize the number of sensors for the assessment of indoor environment within museums

Abstract

For the first time, the cluster analysis (k-means) has been applied on long time series of temperature and relative humidity measurements to identify the thermo-hygrometric features in a museum. Based on ASHRAE (2011) classification, 84% of time all rooms in the Napoleonic Museum in Rome (case study) were found in the class of control B. This result was obtained by analyzing all recorded data in 10 rooms of the museum as well as using the cluster aggregation. The use of objective-oriented methodology allows to achieve an acceptable knowledge of the microclimate in case of multi-room buildings, reducing computations with large amounts of collected data and time-consuming in redundant elaborations. The cluster analysis enables to reduce the number of the sensors in microclimate monitoring programs within museums, provided that the representativeness of the instrument location is known, and professional conservators have assessed that the artifacts are well preserved.



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Editorial Board and Contents

Publication date: May 2018
Source:Trends in Immunology, Volume 39, Issue 5





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Recent advances in phosphorene as a sensing material

Publication date: Available online 26 April 2018
Source:Nano Today
Author(s): Aijun Yang, Dawei Wang, Xiaohua Wang, Dongzhi Zhang, Nikhil Koratkar, Mingzhe Rong
A monolayer of black phosphorus (BP), also called phosphorene, is an emerging member of the family of two-dimensional (2D) materials. It has sparked a surge of research activities in material science since its first preparation by mechanical exfoliation in 2014. Several reviews have focused on the structure and anisotropic properties of phosphorene as well as its applications in transistors, batteries, and solar cells. Compared to graphene and transition metal dichalcogenides (TMDs), phosphorene possesses higher surface to volume ratio due to its "puckered" lattice structure and has presented some unique advantages in sensing applications. This review aims to summarize recent developments in the sensing applications of phosphorene, including gas sensing, humidity sensing, photo-detection, bio-sensing and ion sensing. The article concludes with the current challenges and future prospects for the production and sensing applications of phosphorene.

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What Nurses Do.

Author: Kennedy, Maureen Shawn MA, RN, FAAN
Page: 7


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Adopt Zero Tolerance for Hospital Staff Bullying Nursing Students.

Author: Burkley, John MSN, RN
Page: 11


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Independent Practice by APRNs.

Author: Korbecka, Alicja M. RN
Page: 13


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Saving the Safety Net.

Author: Thompson, Earl nursing student
Page: 13


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Death with Dignity.

Author: V.S., Lisa via Facebook
Page: 13


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Death with Dignity.

Author: S., Jackie via Facebook
Page: 13


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Report: Nursing Homes Are Overmedicating People with Dementia.

Author: Stockwell, Serena
Page: 14


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Fighting Night-Shift Fatigue.

Author: Potera, Carol
Page: 15


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NewsCAP: Updates to adult and child immunization schedules are issued for 2018.

Author:
Page: 15


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Young Single Mothers Benefit from the Affordable Care Act.

Author: Sofer, Dalia
Page: 16


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NewsCAP: New AHA guidelines include extending time to treatment for ischemic stroke.

Author:
Page: 16


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NSAID Users Often Exceed Recommended Dose Limits.

Author: Mechcatie, Elizabeth MA, BSN
Page: 17


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NewsCAP: Asymptomatic women with no known risk of ovarian cancer do not benefit from screening for the disease.

Author:
Page: 17


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NewsCAP: The FDA approves a blood test to aid assessment after head injury.

Author:
Page: 17


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AJN On the Cover.

Author: Szulecki, Diane Editor
Page: 18


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AJN On the Web.

Author:
Page: 18


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Sexual Harassment in Nursing: A Long-Standing, but Rarely Studied Problem.

Author: Nelson, Roxanne BSN
Page: 19-20


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New Treatment for BRCA-Mutated Metastatic Breast Cancer.

Author: Aschenbrenner, Diane S. MS, RN
Page: 21-22


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New Radiopharmaceutical Approved to Treat Rare Digestive Tract Cancer.

Author: Aschenbrenner,, Diane S. MS, RN
Page: 22-23


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Reports of Anaphylaxis with an Antiemetic.

Author: Aschenbrenner,, Diane S. MS, RN
Page: 23


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At What Cost to Clinical Trial Enrollment? A Retrospective Study of Patient Travel Burden in Cancer Clinical Trials

AbstractBackground.Recent literature suggests that living in a rural setting may be associated with adverse cancer outcomes. This study examines the burden of travel from home to cancer center for clinical trial (CT) enrollees.Materials and Methods.Patients from the University of California San Francisco Clinical Trial Management System database who enrolled in a cancer CT for a breast, genitourinary, or gastrointestinal malignancy between 1993 and 2014 were included. Cancer type, household zip code, race/ethnicity, phase of study, study sponsor, and year of signed consent were exported. Distance traveled from home to center was calculated using a GoogleMaps application programming interface. The relationships of distance with phase of CT, household income, and race/ethnicity were examined.Results.A total of 1,600 patients were enrolled in breast (55.8%), genitourinary (29.4%), or gastrointestinal (14.9%) cancer CTs. The overall median unidirectional distance traveled from home to study site was 25.8 miles (interquartile range [IQR] 11.5–75.3). Of the trial sponsors examined, principal investigator (56.4%), industry (22.2%), cooperative group (11.6%), and National Institutes of Health (NIH; 9.8%), the longest distance traveled was for NIH‐sponsored trials, with a median of 39.4 miles (p < .001). Phase I (8.4%) studies had the longest distance traveled, with a median of 41.2 miles (IQR 14.5–101.0 miles; p = .001). White patients (83%) traveled longer compared with black patients (4.4%), with median distances of 29.9 and 13.9 miles, respectively (p < .001). Patients from lower‐income areas (n = 799) traveled longer distances compared with patients from higher‐income areas (n = 773; 58.3 vs. 17.8 miles, respectively; p < .001). A multivariable linear model where log10 (distance) was the outcome and adjusting for the exported variables and income revealed that cancer type, year of consent, race/ethnicity, and income were significantly associated with distance traveled.Conclusion.This study found that the burden of travel is highest among patients enrolled in NIH‐sponsored trials, phase I studies, or living in low‐income areas. These data suggest that travel burden for cancer CT participants may be significant.Implications for Practice.This study is one of the first to measure travel distance for patients in cancer clinical trials using a real‐world GoogleMaps calculator. Out‐of‐pocket expenses such as travel are not typically covered by health care payers; therefore, patients may face considerable cost to attend each study visit. Using a single‐center clinical trials enrollment database, this study found that the burden of travel is highest for patients enrolled in National Institutes of Health‐sponsored trials and phase I studies, as well as for patients living in low‐income areas. Results suggest that a significant proportion of patients enrolled in clinical trials face a substantial travel burden.

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Representation of Minorities and Elderly Patients in Multiple Myeloma Clinical Trials

AbstractMultiple myeloma (MM) occurs in all races, but the incidence in non‐Hispanic black patients (NHBs) is two to three times higher than in non‐Hispanic white patients (NHWs). We determined the representation of minorities and elderly patients in MM clinical trials. Enrollment data from all therapeutic trials reported in ClinicalTrials.gov from 2000 to 2016 were analyzed. Enrollment fraction (EF) was defined as the number of trial enrollees divided by the 2014 MM prevalence. Participation in MM clinical trials varied significantly across racial and ethnic groups; NHWs were more likely to be enrolled in clinical trials (EF 0.18%) than NHBs (EF 0.06%, p < .0001) and Hispanic patients (EF 0.04%, p < .0001). The median age of trial participants was 62 years, with 7,956 participants (66%) being less than 65 years of age. Collaborations between investigators, sponsors, and the community are necessary to increase access to clinical trials to our minority and elderly patients.

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Laboratory‐Based Biomarkers and Liver Metastases in Metastatic Castration‐Resistant Prostate Cancer

AbstractBackground.Metastatic castrate‐resistant prostate cancer (mCRPC) patients with liver metastases have a poor prognosis. No large studies have investigated the clinical and biochemical parameters associated with liver metastases in this population.Materials and Methods.Patient data made available via Project Data Sphere were collected from 1,281 men with mCRPC who were enrolled on to three phase III clinical trials for the treatment of their disease. Multiple logistic regression was performed on eight clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline radiographic imaging. Variables of interest included prior docetaxel exposure, Eastern Cooperative Oncology Group performance status, albumin, alkaline phosphatase, alanine transaminase, aspartate transaminase (AST), hemoglobin (HGB), lactate dehydrogenase (LDH), prostate‐specific antigen, and total bilirubin. Final models were compared when treating the variables as either continuous or categorized.Results.Multiple variable analysis demonstrated that an increasing serum AST or LDH or a decreasing HGB was associated with an increased probability of having documented radiographic liver metastases (p < .0001). The area under the curve for the continuous model was 0.6842 and 0.6890 for the categorical one, with the latter model containing a dichotomized AST and LDH based on the upper limit of normal and tertile ranges of HGB based on the distribution of the outcome.Conclusion.Our analysis demonstrated a significant association between the presence of liver metastases and laboratory levels of AST, LDH, and HGB. These have implications for patient management. More research is needed to validate these biomarkers and prospectively determine their application in the clinical setting.Implications for Practice.The purpose of this study was to evaluate biochemical and clinical biomarkers associated with the presence of liver metastases in men diagnosed with metastatic castrate‐resistant prostate cancer. The results indicate that quantitative assessments of aspartate transaminase, lactate dehydrogenase, and hemoglobin are significantly associated with an increased probability of having documented radiographic liver metastases. Analysis of these simple variables can alert clinicians to those at high risk for prostate cancer that has spread to the liver, a finding of clear importance for clinical management.

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Monoclonal Antibodies and Multiple Myeloma: All in All It's Just Another Brick in the Wall?



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Comprehensive Molecular Characterization of Young Chinese Patients with Lung Adenocarcinoma Identified a Distinctive Genetic Profile

AbstractBackground.Occurrence at a younger age has been demonstrated to be associated with a distinct biology in non‐small cell lung cancer. However, genomics and clinical characteristics among younger patients with lung adenocarcinoma remain to be determined. Here we studied the potentially targetable genetic alterations by next‐generation sequencing (NGS) assay in young Chinese patients with lung adenocarcinoma.Materials and Methods.Seventy‐one surgically resected lung adenocarcinoma tissue samples from patients aged less than 45 years were collected with informed consent from all patients. Targeted NGS assays were used to identify actionable genetic alterations in the cancer tissues. Additionally, the genomic and clinicopathologic characteristics of 106 patients with lung adenocarcinoma who received NGS testing over the same period were analyzed retrospectively.Results.The frequencies of targetable genetic alterations in 177 patients with lung adenocarcinoma were analyzed by defined age categories, which unveiled a distinctive molecular profile in the younger group, aged less than 45 years. Notably, higher frequency of ALK and HER2 genetic alterations were associated with young age. However, a reverse trend was observed for KRAS, STK11 and EGFR exon 20 mutations, which were more frequently identified in the older group, aged more than 46 years. Furthermore, concurrent EGFR/TP53 mutations were much more prevalent in the younger patients (81.6% vs. 46.8%), which might have a poor response to treatment with epidermal growth factor receptor tyrosine kinase inhibitor.Conclusion.In this study, NGS assay revealed a distinctive genetic profile in younger patients with adenocarcinoma. High frequency of concurrent EGFR/TP53 mutations was found in the younger patients, which especially warranted personalized treatment in this population.Implications for Practice.Further investigation is needed to understand the genomics and clinical characteristics of young patients with lung adenocarcinoma. In the present study, hybrid capture‐based next‐generation sequencing assays were used to identify targeted genetic alterations in young lung adenocarcinoma patients. Young patients with lung adenocarcinoma, aged less than 45 years, harbored a higher frequency of ALK and HER2 genetic alterations compared with patients aged more than 46 years. Dramatically, concurrent EGFR/TP53 mutations were much more prevalent in younger patients, which had a poor response to treatment with epidermal growth factor receptor kinase inhibitor. These results reveal a distinctive genetic profile in younger patients with adenocarcinoma, which might improve the treatment of this subpopulation.

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Genomic Profiling of HER2‐Positive Gastric Cancer: PI3K/Akt/mTOR Pathway as Predictor of Outcomes in HER2‐Positive Advanced Gastric Cancer Treated with Trastuzumab

AbstractBackground.HER2‐positive gastric cancer (GC) affects 7%–34% of patients with GC. Trastuzumab‐based first‐line treatment has become the standard of care for HER2‐positive advanced gastric cancer (AGC). However, there are no clinically validated biomarkers for resistance to HER2‐targeted therapies. Upregulation of PI3K pathway and tyrosine kinase receptor (TKR) alterations have been noted as molecular mechanisms of resistance in breast cancer. Our study aimed to perform a molecular characterization of HER2‐positive AGC and investigate the role of PI3K/Akt/mTOR signaling pathway activation and TKR gene copy number (GCN) gains as predictive biomarkers in HER2‐positive AGC treated with trastuzumab.Patients and Methods.Forty‐two HER2‐positive GC samples from patients treated with trastuzumab‐based first‐line chemotherapy were selected. DNA samples were sequenced. PTEN and MET immunohistochemistry were also performed.Results.Concurrent genetic alterations were detected in 97.1% of HER2‐positive AGC. We found activation of PI3K/Akt/mTOR pathway in 52.4% of patients and TKR GCN gains in 38.1%. TKR GCN gains did not correlate with overall survival (OS) or progression‐free survival (PFS). Multivariate Cox models showed that PI3K/Akt/mTOR activation negatively affects the effectiveness of trastuzumab‐based chemotherapy in terms of OS and PFS.Conclusion.Our results provide for the first time a detailed molecular profile of concurrent genetic alterations in HER2‐positive AGC. PI3K pathway activation could be used as a predictive marker of worse outcome in this patient population. In addition, gains in copy number of other TKR genes in this subgroup may also influence the survival benefit obtained with trastuzumab.Implications for Practice.This article reports, for the first time, a detailed molecular profile of genomic alterations in patients with HER2‐positive advanced gastric cancer (AGC). PI3K/Akt/mTOR signaling pathway activation seems to have a differentially negative effect on overall survival and progression‐free survival in AGC treated with trastuzumab‐based chemotherapy. Combining different targeted agents could be a successful therapeutic strategy to improve the prognosis of HER2‐positive AGC.

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Clinical Utility of Analyzing Circulating Tumor DNA in Patients with Metastatic Colorectal Cancer

AbstractMultiple genomic changes caused by clonal evolution induced by therapeutic pressure and corresponding intratumoral heterogeneity have posed great challenges for personalized therapy against metastatic colorectal cancer (mCRC) in the past decade. Liquid biopsy has emerged as an excellent molecular diagnostic tool for assessing predominant spatial and temporal intratumoral heterogeneity with minimal invasiveness.Previous studies have revealed that genomic alterations in RAS, BRAF, ERBB2, and MET, as well as other cancer‐related genes associated with resistance to anti‐epidermal growth factor receptor (EGFR) therapy, can be analyzed with high diagnostic accuracy by circulating tumor DNA (ctDNA) analysis. Furthermore, by longitudinally monitoring ctDNAs during anti‐EGFR therapy, the emergence of genomic alterations can be detected as acquired resistance mechanisms in specific genes, mainly those associated with the mitogen‐activated protein kinase signaling pathway. Analysis of ctDNA can also identify predictive biomarkers to immune checkpoint inhibitors, such as mutations in mismatch repair genes, microsatellite instability‐high phenotype, and tumor mutation burden. Some prospective clinical trials evaluating targeted agents for genomic alterations in ctDNA or exploring resistance biomarkers by monitoring of ctDNA are ongoing.To determine the value of ctDNA analysis for decision‐making by more accurate molecular marker‐based selection of patients and identification of resistance mechanisms to targeted therapies or sensitive biomarkers for immune checkpoint inhibitors, clinical trials must be refined to evaluate the efficacy of study treatment in patients with targetable genomic alterations confirmed by ctDNA analysis, and resistance biomarkers should be explored by monitoring ctDNA in large‐scale clinical trials. In the near future, ctDNA analysis will play an important role in precision medicine for mCRC.Implications for Practice.Treatment strategies for metastatic colorectal cancer (mCRC) are determined according to the molecular profile, which is confirmed by analyzing tumor tissue. Analysis of circulating tumor DNA (ctDNA) may overcome the limitations of tissue‐based analysis by capturing spatial and temporal intratumoral heterogeneity of mCRC. Clinical trials must be refined to test the value of ctDNA analysis in patient selection and identification of biomarkers. This review describes ctDNA analysis, which will have an important role in precision medicine for mCRC.

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Improving the signal detection accuracy of functional Magnetic Resonance Imaging

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Publication date: 1 August 2018
Source:NeuroImage, Volume 176
Author(s): Niels Janssen, Juan A. Hernández-Cabrera, Laura Ezama Foronda
A major drawback of functional Magnetic Resonance Imaging (fMRI) concerns the lack of detection accuracy of the measured signal. Although this limitation stems in part from the neuro-vascular nature of the fMRI signal, it also reflects particular methodological decisions in the fMRI data analysis pathway. Here we show that the signal detection accuracy of fMRI is affected by the specific way in which whole-brain volumes are created from individually acquired brain slices, and by the method of statistically extracting signals from the sampled data. To address these limitations, we propose a new framework for fMRI data analysis. The new framework creates whole-brain volumes from individual brain slices that are all acquired at the same point in time relative to a presented stimulus. These whole-brain volumes contain minimal temporal distortions, and are available at a high temporal resolution. In addition, statistical signal extraction occurred on the basis of a non-standard time point-by-time point approach. We evaluated the detection accuracy of the extracted signal in the standard and new framework with simulated and real-world fMRI data. The new slice-based data-analytic framework yields greatly improved signal detection accuracy of fMRI signals.



https://ift.tt/2HPAyv4

Multi-voxel pattern classification differentiates personally experienced event memories from secondhand event knowledge

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Publication date: 1 August 2018
Source:NeuroImage, Volume 176
Author(s): Tiffany E. Chow, Andrew J. Westphal, Jesse Rissman
Studies of autobiographical memory retrieval often use photographs to probe participants' memories for past events. Recent neuroimaging work has shown that viewing photographs depicting events from one's own life evokes a characteristic pattern of brain activity across a network of frontal, parietal, and medial temporal lobe regions that can be readily distinguished from brain activity associated with viewing photographs from someone else's life (Rissman, Chow, Reggente, and Wagner, 2016). However, it is unclear whether the neural signatures associated with remembering a personally experienced event are distinct from those associated with recognizing previously encountered photographs of an event. The present experiment used a novel functional magnetic resonance imaging (fMRI) paradigm to investigate putative differences in brain activity patterns associated with these distinct expressions of memory retrieval. Eighteen participants wore necklace-mounted digital cameras to capture events from their everyday lives over the course of three weeks. One week later, participants underwent fMRI scanning, where on each trial they viewed a sequence of photographs depicting either an event from their own life or from another participant's life and judged their memory for this event. Importantly, half of the trials featured photographic sequences that had been shown to participants during a laboratory session administered the previous day. Multi-voxel pattern analyses assessed the sensitivity of two brain networks of interest—as identified by a meta-analysis of prior autobiographical and laboratory-based memory retrieval studies—to the original source of the photographs (own life or other's life) and their experiential history as stimuli (previewed or non-previewed). The classification analyses revealed a striking dissociation: activity patterns within the autobiographical memory network were significantly more diagnostic than those within the laboratory-based network as to whether photographs depicted one's own personal experience (regardless of whether they had been previously seen), whereas activity patterns within the laboratory-based memory network were significantly more diagnostic than those within the autobiographical memory network as to whether photographs had been previewed (regardless of whether they were from the participant's own life). These results, also apparent in whole-brain searchlight classifications, provide evidence for dissociable patterns of activation across two putative memory networks as a function of whether real-world photographs trigger the retrieval of firsthand experiences or secondhand event knowledge.



https://ift.tt/2HzGZPs

Correction of eyelid retraction using a half-thickness tarsal flap for lengthening of the eyelid following ptosis surgery

Abstract

Various surgical procedures for correction of upper eyelid retraction have been reported, many of which have had favorable results. However, most of these reports are concerned with the correction of upper eyelid retraction in patients with thyroid ophthalmopathy, and few have focused on upper eyelid retraction caused by overcorrection during ptosis surgery. Corrective surgery for upper eyelid retraction resulting from ptosis surgery is often difficult because of the extensive irregular contracture caused by scar tissue. However, as this is a repeat surgery following ptosis surgery, it is important to ensure good postoperative evaluation indices, particularly favorable symmetry, appropriate palpebral fissure width, appropriate crease height, and natural-looking parabolic eyelid margins. Here, we report the lengthening of the upper eyelids using a half-thickness tarsal flap to address upper eyelid retraction secondary to ptosis surgery. By using a half-thickness tarsal flap, the anatomy of the levator insertion onto the tarsal plate is retained, so that good eyelid contour can be obtained, and the results are quantitatively reproducible. Therefore, this technique can be considered for the treatment of upper eyelid retraction and has a potentially wide range of applications.

Level of Evidence: Level V, therapeutic study.



https://ift.tt/2HySWVG

Antituberculosis drug isoniazid degraded by electro-Fenton and photoelectro-Fenton processes using a boron-doped diamond anode and a carbon-PTFE air-diffusion cathode

Abstract

Solutions with 0.65 mM of the antituberculosis drug isoniazid (INH) in 0.050 M Na2SO4 at pH 3.0 were treated by electro-Fenton (EF) and UVA photoelectro-Fenton (PEF) processes using a cell with a BDD anode and a carbon-PTFE air-diffusion cathode. The influence of current density on degradation, mineralization rate, and current efficiency has been thoroughly evaluated in EF. The effect of the metallic catalyst (Fe2+ or Fe3+) and the formation of products like short-chain linear aliphatic carboxylic acids were assessed in PEF. Two consecutive pseudo-first-order kinetic regions were found using Fe2+ as catalyst. In the first region, at short time, the drug was rapidly oxidized by OH, whereas in the second region, at longer time, a resulting Fe(III)-INH complex was much more slowly removed by oxidants. INH disappeared completely at 300 min by EF, attaining 88 and 94% mineralization at 66.6 and 100 mA cm−2, respectively. Isonicotinamide and its hydroxylated derivative were identified as aromatic products of INH by GC-MS and oxalic, oxamic, and formic acids were quantified by ion-exclusion HPLC. The PEF treatment of a real wastewater polluted with the drug led to slower INH and TOC abatements because of the parallel destruction of its natural organic matter content.



https://ift.tt/2HtSPyI

Dictionary-based monitoring of premature ventricular contractions: An ultra-low-cost point-of-care service

Publication date: Available online 26 April 2018
Source:Artificial Intelligence in Medicine
Author(s): S. Chandra Bollepalli, S. Sastry Challa, Laxminarayana Anumandla, Soumya Jana
While cardiovascular diseases (CVDs) are prevalent across economic strata, the economically disadvantaged population is disproportionately affected due to the high cost of traditional CVD management, involving consultations, testing and monitoring at medical facilities. Accordingly, developing an ultra-low-cost alternative, affordable even to groups at the bottom of the economic pyramid, has emerged as a societal imperative. Against this backdrop, we propose an inexpensive yet accurate home-based electrocardiogram (ECG) monitoring service. Specifically, we seek to provide point-of-care monitoring of premature ventricular contractions (PVCs), high frequency of which could indicate the onset of potentially fatal arrhythmia. Note that the first-generation telecardiology system acquires the ECG, transmits it to a professional diagnostic center without processing, and nearly achieves the diagnostic accuracy of a bedside setup. In the process, such a system incurs high bandwidth cost and requires the physicians to process the entire record for diagnosis. To reduce cost, current telecardiology systems compress data before transmitting. However, the burden on physicians remains undiminished. In this context, we develop a dictionary-based algorithm that reduces not only the overall bandwidth requirement, but also the physicians workload by localizing anomalous beats. Specifically, we detect anomalous beats with high sensitivity and only those beats are then transmitted. In fact, we further compress those beats using class-specific dictionaries subject to suitable reconstruction/diagnostic fidelity. Finally, using Monte Carlo cross validation on MIT/BIH arrhythmia database, we evaluate the performance of the proposed system. In particular, with a sensitivity target of at most one undetected PVC in one hundred beats, and a percentage root mean squared difference less than 9% (a clinically acceptable level of fidelity), we achieved about 99.15% reduction in bandwidth cost, equivalent to 118-fold savings over first-generation telecardiology. In the process, the professional workload is reduced by at least 85.9% for noncritical cases. Our algorithm also outperforms known algorithms under certain measures in the telecardiological context.

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An intelligent algorithm for identification of optimum mix of demographic features for trust in medical centers in Iran

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Publication date: Available online 26 April 2018
Source:Artificial Intelligence in Medicine
Author(s): R. Yazdanparast, S. Abdolhossein Zadeh, D. Dadras, A. Azadeh
Healthcare quality is affected by various factors including trust. Patients' trust to healthcare providers is one of the most important factors for treatment outcomes. The presented study identifies optimum mixture of patient demographic features with respect to trust in three large and busy medical centers in Tehran, Iran. The presented algorithm is composed of adaptive neuro-fuzzy inference system and statistical methods. It is used to deal with data and environmental uncertainty. The required data are collected from three large hospitals using standard questionnaires. The reliability and validity of the collected data is evaluated using Cronbach's Alpha, factor analysis and statistical tests. The results of this study indicate that middle age patients with low level of education and moderate illness severity and young patients with high level of education, moderate illness severity and moderate to weak financial status have the highest trust to the considered medical centers. To the best of our knowledge this the first study that investigates patient demographic features using adaptive neuro-fuzzy inference system in healthcare sector. Second, it is a practical approach for continuous improvement of trust features in medical centers. Third, it deals with the existing uncertainty through the unique neuro-fuzzy approach.



https://ift.tt/2r233vW

MuDeRN: Multi-category classification of breast histopathological image using deep residual networks

Publication date: Available online 26 April 2018
Source:Artificial Intelligence in Medicine
Author(s): Ziba Gandomkar, Patrick C. Brennan, Claudia Mello-Thoms
MotivationIdentifying carcinoma subtype can help to select appropriate treatment options and determining the subtype of benign lesions can be beneficial to estimate the patients' risk of developing cancer in the future. Pathologists' assessment of lesion subtypes is considered as the gold standard, however, sometimes strong disagreements among pathologists for distinction among lesion subtypes have been previously reported in the literature.ObjectiveTo propose a framework for classifying hematoxylin-eosin stained breast digital slides either as benign or cancer, and then categorizing cancer and benign cases into four different subtypes each.Materials and methodsWe used data from a publicly available database (BreakHis) of 81 patients where each patient had images at four magnification factors (×40, ×100, ×200, and ×400) available, for a total of 7786 images. The proposed framework, called MuDeRN (MUlti-category classification of breast histopathological image using DEep Residual Networks) consisted of two stages. In the first stage, for each magnification factor, a deep residual network (ResNet) with 152 layers has been trained for classifying patches from the images as benign or malignant. In the next stage, the images classified as malignant were subdivided into four cancer subcategories and those categorized as benign were classified into four subtypes. Finally, the diagnosis for each patient was made by combining outputs of ResNets' processed images in different magnification factors using a meta-decision tree.ResultsFor the malignant/benign classification of images, MuDeRN's first stage achieved correct classification rates (CCR) of 98.52%, 97.90%, 98.33%, and 97.66% in ×40, ×100, ×200, and ×400 magnification factors respectively. For eight-class categorization of images based on the output of MuDeRN's both stages, CCRs in four magnification factors were 95.40%, 94.90%, 95.70%, and 94.60%. Finally, for making patient-level diagnosis, MuDeRN achieved a CCR of 96.25% for eight-class categorization.ConclusionsMuDeRN can be helpful in the categorization of breast lesions.



https://ift.tt/2vRtEk7

The Battle Ground between Two Giants: Toe Transfer and Hand Allotransplantation

J reconstr Microsurg
DOI: 10.1055/s-0038-1639513

A few severe hand injuries represent a gray zone for the reconstructive surgeon, for which autologous tissue transfer and allotransplantation can yield satisfactory results, but not without downsides or morbidity.This article is written to address the dilemma of application of both techniques in those selected cases.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2I4MuXK

Modeling the oxygen transport process under preferential flow effect in landfill

Abstract

Evaluation of oxygen distribution during aeration in landfill is significantly important to determine the design parameters of an injection well. A coupling model describing gas preferential transport in a landfill was developed, which linked the effect of advection–diffusion and oxidation reaction and mass exchange between the fracture and the matrix system. The quantitative simulation of the variation in gas distribution during vertical well aeration in short term was presented, combined with the typical cases in field site. The parameter sensitivity in the coupling model to gas transport was addressed. Simulation result of the oxygen and methane concentrations by using the dual advective–diffusive (DAD) model, which considered the immobile zone effect, was closer to the monitoring data than that by using single advective–diffusive model. The variation of the AR under aeration was presented with the key parameters to provide the theory evidence for gas well design in landfill. This study provided reference for the design of the gas injection well distribution in aerobic landfill.



https://ift.tt/2FjXDAV

MAGE-A antigens as targets for cancer immunotherapy

Publication date: Available online 26 April 2018
Source:Cancer Treatment Reviews
Author(s): Erik Schooten, Alessia Di Maggio, Paul M.P. van Bergen en Henegouwen, Marta M. Kijanka
Targeted anti-cancer therapies aim at reducing side effects while retaining their anti-cancer efficacy. Immunotherapies e.g. monoclonal antibodies, adoptive T cell therapy and cancer vaccines are used to combat cancer, but the number of available cancer specific targets is limited and new approaches are needed to generate more effective and patient tailored treatments. Unique cancer intracellular epitopes can be presented on the cell surface by MHC class I molecules, which can function as epitopes for targeted therapies. The intracellular MAGE proteins belong to a sub-class of Cancer Testis (CT) antigens which are expressed in germline cells and a wide variety of tumors of different histological origin. Evidence has emerged that their expression is linked to pro-tumorigenic activities like increased cell motility, resisting cell death, and tumor promoting inflammation. Intracellular MAGE proteins are processed by the proteasome and their peptides are presented by MHC class I molecules on the cell surface of cancer cells thereby making them ideal cancer specific antigens. Here we review the previous and ongoing (pre-) clinical studies on the use of surface expressed MAGE antigens for their employment in targeted anti-cancer therapies. We present and analyze study outcomes and discuss possible future directions and improvements for MAGE directed anti-cancer immunotherapies.



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Untying the Gordion Knot of Targeting MET in Cancer

Publication date: Available online 26 April 2018
Source:Cancer Treatment Reviews
Author(s): Kanwal Raghav, Ann Marie Bailey, Jonathan M. Loree, Scott Kopetz, Vijaykumar Holla, Timothy Anthony Yap, Fang Wang, Ken Chen, Ravi Salgia, David Hong
Despite compelling evidence backing the crucial role of a dysregulated MET axis in cancer and a myriad of agents targeting this pathway in active clinical development, the therapeutic value of MET inhibition in cancer oncology remains to be established. Although a series of disappointing clinical trials, at first, lessened fervor for targeting this pathway, investigations continue unabated with a number of novel active compounds entering clinical trials. Suboptimal designs which lacked biomarker selection have been the main reason for these early failures and this has stimulated a more biomarker enriched approach lately. Fresh insights into the mechanics of diverse MET aberrations (amplifications and mutations) have allowed trial enrichment for appropriate patients in appropriate disease settings. Development of MET inhibition as a therapeutic strategy in cancer has been a lesson in itself reflecting the challenging opportunities enclosed in the genetic landscape of cancer. Here, we will review the status of MET targeted therapy in development as it stands today, discuss emerging paradigms in MET inhibition and theorize on concepts for future development. We venture to propose that in spite of early disappointments, the future of this therapeutic strategy is promising with use of appropriate predictive biomarker in the right clinical context.



https://ift.tt/2Flepzw

Selenium and silicon reduce cadmium uptake and mitigate cadmium toxicity in Pfaffia glomerata (Spreng.) Pedersen plants by activation antioxidant enzyme system

Abstract

Cadmium (Cd) is toxic to plants and animals, making it necessary to develop strategies that seek to reduce its introduction into food chains. Thus, the aim of this study was to investigate whether silicon (Si) and selenium (Se) reduce Cd concentrations in Pfaffia glomerata medicinal plant and attenuate the oxidative stress promoted by this metal. These plants were cultivated in hydroponics under the following treatments: control (nutrient solution), 2.5 μM Se, 2.5 mM Si, 50 μM Cd, 50 μM Cd + 2.5 μM Se, 50 μM Cd + 2.5 mM Si. After 14 days of exposure to treatments, leaves and roots were collected for the determination of dry weight of shoot and roots, Cd concentrations, chlorophyll and carotenoids content, and biochemical parameters (lipid peroxidation and guaiacol peroxidase and superoxide dismutase activities). The data were submitted to analysis of variance and means were compared with Scott-Knott test at 5% error probability. Roots of P. glomerata plants showed a significant reduction on dry weight accumulation when exposed to Cd. However, both Se and Si promoted a significant reduction of deleterious effects of Cd. The Cd concentrations in the tissues were reduced in the presence of Se or Si. Plants treated with Cd together with Se or Si presented higher pigment content than those with only Cd, thus showing a reduction in the negative effects caused by this element. In the treatments in which Se and Si were added in the growth medium together with Cd, an activation of superoxide dismutase and guaiacol peroxidase enzymes was observed in the roots and shoot, which may have contributed to lower lipid peroxidation. Thus, Se and Si reduce Cd concentrations and have potential to ameliorate Cd toxicity in P. glomerata plants, which can be used to increase productivity and quality of medicinal plants.



https://ift.tt/2I3dt5E

Changes in the nutritional composition of maize flour due to Tribolium castaneum infestation and application of carbon dioxide to manage this pest

Abstract

Maize flour was infested with fresh emerged Tribolium castaneum adults, and its nutritional composition was evaluated after 0, 45, and 90 days of the infestation. Furthermore, 99% carbon dioxide was applied to different developmental stages of T. castaneum for its management. There were six treatments and five replicates; for each replicate, maize flour (150 g) was taken in a 250-ml plastic jar container, insects were released in the flour, and jars were placed into the incubator at a temperature of 28 ± 1 °C, 60 ± 5% RH. Similarly, the application of 99% CO2 was done with four exposure times of 12, 24, 48, and 72 h, at 35 °C 65 ± 5% RH. Present results showed major fluctuations in the nutritive composition of maize flour. Increase in the moisture, fat, fiber, protein, and ash contents was directly proportional to the increase in infestation level and time, contrary to the depletion of carbohydrates and total weight loss. The results of CO2 treatment indicated that pupa was the most resilient stage as compared with larvae and adult stage. The observed susceptibility order was as follows: adult > larvae > pupae. The maximum mortality of adult, larval, and pupal stages was recorded after 24, 48, and 72 h of CO2 application, respectively. These findings might be helpful to develop an ecofriendly technique to manage this crucial pest.



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Nanocellulose as a natural source for groundbreaking applications in materials science: Today’s state

Publication date: Available online 26 April 2018
Source:Materials Today
Author(s): Dieter Klemm, Emily D. Cranston, Dagmar Fischer, Miguel Gama, Stephanie A. Kedzior, Dana Kralisch, Friederike Kramer, Tetsuo Kondo, Tom Lindström, Sandor Nietzsche, Katrin Petzold-Welcke, Falk Rauchfuß
Nanocelluloses are natural materials with at least one dimension in the nano-scale. They combine important cellulose properties with the features of nanomaterials and open new horizons for materials science and its applications. The field of nanocellulose materials is subdivided into three domains: biotechnologically produced bacterial nanocellulose hydrogels, mechanically delaminated cellulose nanofibers, and hydrolytically extracted cellulose nanocrystals. This review article describes today's state regarding the production, structural details, physicochemical properties, and innovative applications of these nanocelluloses. Promising technical applications including gels/foams, thickeners/stabilizers as well as reinforcing agents have been proposed and research from last five years indicates new potential for groundbreaking innovations in the areas of cosmetic products, wound dressings, drug carriers, medical implants, tissue engineering, food and composites. The current state of worldwide commercialization and the challenge of reducing nanocellulose production costs are also discussed.

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Interface affected zone for optimal strength and ductility in heterogeneous laminate

Publication date: Available online 26 April 2018
Source:Materials Today
Author(s): C.X. Huang, Y.F. Wang, X.L. Ma, S. Yin, H.W. Höppel, M. Göken, X.L. Wu, H.J. Gao, Y.T. Zhu
Interfaces have been reported to significantly strengthen and toughen metallic materials. However, there has been a long-standing question on whether interface-affected-zone (IAZ) exists, and how it might behave. Here we report in situ high-resolution strain mapping near interfaces in a copper–bronze heterogeneous laminate, which revealed the existence of IAZs. Defined as the zone with strain gradient, the IAZ was found to form by the dislocations emitted from the interface. The IAZ width remained largely constant with a magnitude of a few micrometers with increasing applied strain. Interfaces produced both back stress strengthening and work hardening, which led to both higher strength and higher ductility with decreasing interface spacing until adjacent IAZs started to overlap, after which a tradeoff between strength and ductility occurred, indicating the existence of an optimum interface spacing for the best mechanical properties. These findings are expected to help with designing laminates and other heterogeneous metals and alloys for superior mechanical properties.

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Structure and Dynamics of Neurosteroid Binding to the α1β2γ2 GABAA Receptor

Publication date: Available online 26 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Lautaro D. Alvarez, Adali Pecci
Neurosteroids are the principal endogenous modulators of the γ-Aminobutyric acid receptors (GABAARs), pentameric membrane-bound proteins that can be assembled from at least 19 subunits. In the most abundant GABAAR arrangement (α1β2γ2), neurosteroids can potentiate the GABA action as well as produce a direct activation of the channel. The recent crystal structures of neurosteroids bound to α homopentameric GABAAR reveal binding to five equivalent sites. However, these results have been obtained using receptors that are not physiologically relevant, suggesting a need to investigate neurosteroid binding to heteropentameric receptors that exist in the central nervous system. In a previous work, we predicted the neurosteroid binding site by applying molecular modeling methods on the β3 homopentamer. Here we construct a homology model of the transmembrane domain of the heteropentameric α1β2γ2 receptor and then, by combining docking and molecular dynamics simulations, we analyzed neurosteroid binding. Results show that the five neurosteroid cavities are conserved in the α1β2γ2 receptor and all of them are able to bind neurosteroids. Two different binding modes were detected depending on the identity of the residue at position 241 in the transmembrane helix 1. These theoretical findings provide microscopic insights into neurosteroid binding at the heteropentameric GABAAR. The existence of two classes of sites may be associated with how neurosteroids modulate GABAAR. Our finding would represent the essential first step to reach a comprehensive understanding of how these endogenous molecules regulate the central nervous system.

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Towards saving freshwater: halophytes as unconventional feedstuffs in livestock feed: a review

Abstract

Water represents 71% of all earth area and about 97% of this water is salty water. So, only 3% of the overall world water quantity is freshwater. Human can benefit only from 1% of this water and the remaining 2% freeze at both poles of earth. Therefore, it is important to preserve the freshwater through increasing the plants consuming salty water. The future prosperity of feed resources in arid and semi-arid countries depends on economic use of alternative resources that have been marginalized for long periods of time, such as halophytic plants, which are one such potential future resource. Halophyte plants can grow in high salinity water and soil and to some extent during drought. The growth of these plants depends on the contact of the salted water with plant roots as in semi-desert saline water, mangrove swamps, marshes, and seashores. Halophyte plants need high levels of sodium chloride in the soil water for growth, and the soil water must also contain high levels of salts, as sodium hydroxide or magnesium sulfate. There are many uses for halophyte plants, including feed for animals, vegetables, drugs, sand dune stabilizers, wind shelter, soil cover, wetland cultivation, laundry detergents, and paper production. This paper will focus on the use of halophytes as a feed additive for animals. In spite of the good nutritional value of halophytes, some anti-nutritional factors as nitrates, nitrite complexes, tannins, glycosides, phenolic compounds, saponins, oxalates, and alkaloids may be present in some of them. The presence of such anti-nutritional agents makes halophytes unpalatable to animals, which tends to reduce feed intake and nutrient use. Therefore, the negative effects of these plants on animal performance are the only objection against using halophytes in animal feed diets. This review article highlights the beneficial impact of considering halophytes in animal feeding on saving freshwater and illustrates its nutritive value for livestock from different aspects.



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Effective sorption of atrazine by biochar colloids and residues derived from different pyrolysis temperatures

Abstract

Biochar has attracted much attention, which owns many environmental and agronomic benefits, including carbon sequestration, improvement of soil quality, and immobilization of environmental contaminants. Biochar has been also investigated as an effective sorbent in recent publications. Generally, biochar particles can be divided into colloids and residues according to particle sizes, while understanding of adsorption capacities towards organic pollutants in each section is largely unknown, representing a critical knowledge gap in evaluations on the effectiveness of biochar for water treatment application. Scanning electron microscopy (SEM) images, X-ray diffraction (XRD), Raman spectra, Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) method are used to examine the structures and surface properties of biochar colloids and residues derived from corn straws prepared at different pyrolysis temperatures. Also, their roles in atrazine (a typical organic pollutant) removal are investigated by batch adsorption experiments and fitted by different kinetic and thermodynamic models, respectively. The adsorption capacities of biochar colloids are much more than those of residues, resulting from the colloids containing abundant oxygen functional groups and mineral substances, and the adsorption capacities of biochar colloids and residues increase with the increase of pyrolysis temperatures. The highest adsorption performance of 139.33 mg g−1 can be obtained in biochar colloids prepared at 700 °C, suggesting the important functions of biochar colloids in the application of atrazine removal by biochar.



https://ift.tt/2qZZ1Ey

Silibinin exerts antidepressant effects by improving neurogenesis through BDNF/TrkB pathway

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Publication date: 1 August 2018
Source:Behavioural Brain Research, Volume 348
Author(s): Yan-Jiao Li, Yu-Jiao Li, Liu-Di Yang, Kun Zhang, Kai-Yin Zheng, Xin-Miao Wei, Qi Yang, Wen-Min Niu, Ming-Gao Zhao, Yu-Mei Wu
Classic antidepressants benefit depression patients partially by improving neurogenesis and/or brain-derived neurotrophic factor (BDNF)/TrkB pathway which were impaired in depression. In this study, we demonstrated that Silibinin (SLB), a polyphenolic flavanoid from Silybum marianum, ameliorated reserpinized mouse depressant-like behaviors. The antidepressants of SLB administration was associated with increased neural stem cells (NSCs) proliferation and further confirmed in BDNF/TrkB signaling transduction. SLB treatment reversed the decreased expression levels of BDNF and its receptor TrkB, and the reduced activation of downstream target proteins including phosphorylated extracellular-regulated protein kinase (p-ERK) and phosphorylated cAMP-response element binding protein (p-CREB) in depressived hippocampus. Furthermore, intracerebroventricular injection of GNF5837, a TrkB antagonist, abrogated antidepressant-like effects of SLB in mice along with the improved NSC proliferation, as well as enhanced levels of p-ERK and p-CREB in mice hippocampus. Taken together, these results suggest that SLB may exert antidepressant effects through BDNF/TrkB signaling pathway to improve NSC proliferation in acute depression.



https://ift.tt/2HZX6H2

Orexin A in the ventral tegmental area enhances saccharin-induced conditioned flavor preference: The role of D1 receptors in central nucleus of amygdala

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Publication date: 1 August 2018
Source:Behavioural Brain Research, Volume 348
Author(s): Severiano Risco, Cristina Mediavilla
In industrialized societies, food intake is largely determined by its hedonic characteristics, which can be modified by our experience via taste learning. In this learning, the hedonic value of a neutral flavor changes after its association with a motivationally significant stimulus. Experiment 1 analyzes the effect of orexin administration (53 and 107 ng) in the ventral tegmental area (VTA) on hedonic intake through acquisition of a flavor-taste preference and a flavor-taste aversion. Accordingly, animals underwent four one-bottle acquisition sessions with unilateral application of orexin-A or saline in the VTA at 10 min before a 15-min flavor intake period. Preference and aversion were tested by a two-bottle test containing the flavors used for CS+ and CS−. Results indicate that intra-VTA orexin strengthens flavor-taste conditioned flavor preference (CFP) by saccharin but does not facilitate flavor-taste aversion induced by association of a neutral flavor with the unpalatable taste of quinine. Experiment 2 examines the acquisition of a flavor-taste preference after co-administration of an effective dose of orexin-A in the VTA and of D1-like dopamine receptor antagonist SCH23390 (6 and 12 nmol) in the central nucleus of the amygdala (CeA). SCH23390 impedes the CFP strengthening observed after intra-VTA orexin administration, indicating that this effect may be mediated by dopaminergic receptors in the CeA. These data suggest that the simultaneous presentation of a flavor and a hedonically positive taste may be detected by orexinergic neurons that activate dopamine-releasing neurons of the VTA, thereby reinforcing the positive signals required to develop a taste preference.



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Environmental filtering determines patterns of tree species composition in small mountains of Atlantic Central African forests

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Publication date: Available online 26 April 2018
Source:Acta Oecologica
Author(s): Christelle Gonmadje, Charles Doumenge, Terry Sunderland, Doyle McKey
The determinants of patterns of plant species composition on small mountains are poorly known, especially in Central Africa. We aimed here to identify variation in tree species composition throughout the Ngovayang Massif (southern Cameroon) and determine the relative contributions of environmental factors and spatial autocorrelation in shaping tree species composition. Vegetation surveys were conducted in fifteen 1-ha (100 m × 100 m) permanent plots established along a transect from lowland (200 m) to submontane forests (900 m) in which all trees with a diameter (dbh) ≥ 10 cm were inventoried. Data were investigated using ordination methods (Correspondence Analysis and Canonical Correspondence Analysis). At the local scale, the most important variable in determining tree species composition patterns was slope exposure, followed by distance from the ocean and altitude. Together, these environmental variables explained 28% of floristic variation among plots, and the spatial structure almost disappeared when the effects of these variables were removed. Spatial autocorrelation analysis showed that spatial variables (geographic coordinates of the plots) or geographic distance between plots explained only 1% of the total initial variance. Residual spatial variation not explained by the environmental variables probably reflects the history of vegetation and the effects of other climatic variables that were not included in this study. Floristic variation in the Ngovayang Massif is due to strong environmental heterogeneity. The sensitivity of floristic composition to environmental variables such as slope orientation and altitude suggests that tree species composition may shift with expected climate changes, such as changes in the movement of air masses, increase in mean annual temperatures or increasing severity of the dry season. Our study highlights the need for systematic on-the-ground measurements of climate variables in tropical montane areas in order to better understand the current climate regime and serve as a basis for modelling future changes.



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Clinical epidemiology of carbapenem-resistant gram-negative sepsis among hospitalized patients: Shifting burden of disease?

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Publication date: Available online 26 April 2018
Source:American Journal of Infection Control
Author(s): Nicholas S. Britt, David J. Ritchie, Marin H. Kollef, Carey-Ann D. Burnham, Michael J. Durkin, Nicholas B. Hampton, Scott T. Micek
BackgroundInfections caused by carbapenem-resistant gram-negative bacilli are an emerging public health threat. However, there is a paucity of data examining comparative incidence rates, risk factors, and outcomes in this population.MethodsThis single-center retrospective cohort study was conducted at an urban tertiary-care academic medical center. We included patients admitted from 2012 to 2015 who met the following criteria: i) age ≥ 18 years; and ii) culture positive for carbapenem-resistant Enterobacteriaceae (CRE) or carbapenem-resistant non-Enterobacteriaceae (CRNE) from any site. Exclusion criteria were: i) < 2 systemic inflammatory response criteria; ii) cystic fibrosis; and iii) no targeted treatment. We evaluated hospital survival by Cox regression and year-by-year differences in the distribution of cases by the Cochran-Armitage test.Results448 patients were analyzed (CRE, n = 111 [24.8%]; CRNE, n = 337 [75.2%]). CRE sepsis cases increased significantly over the study period (P < .001), driven primarily by increasing incidence of Enterobacter spp. infection (P = .004). No difference was observed in hospital survival between patients with CRE versus CRNE sepsis (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.83-2.02; P = .285), even after adjusting for confounding factors (adjusted HR, 1.08; 95% CI, 0.62-1.87; P = .799).ConclusionsClinical outcomes did not differ between patients with CRE versus CRNE sepsis. Dramatic increases in CRE, particularly Enterobacter spp., appear to be causing a shift in the burden of clinically significant carbapenem-resistant gram-negative infection.



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Multiple Myeloma Among Firefighters Exposed to the World Trade Center Disaster

This case series assesses whether environmental exposures from the World Trade Center disaster site are associated with multiple myeloma and its precursor disease, monoclonal gammopathy of undetermined significance, in New York City firefighters.

https://ift.tt/2KgHq39

When You Hear Hoofbeats, Look for Horses, Not Zebras

To the Editor We read the article by Hung et al with great interest. If anaplastic lymphoma kinase (ALK) rearrangements in peritoneal mesothelioma could be incorporated into the treatment, it would be a godsend for patients. However, we would like to address 1 concern about the diagnosis.

https://ift.tt/2Fk37LH

Some Thoughts on Exposure to the World Trade Center Wreckage and Cancer

The terrorist attacks on September 11, 2001, are still unsettling nearly 17 years later. Time has not healed the pain. In addition to those killed, a number of people were harmed, some irreparably— in particular, the New York Rescue/Recovery workers who were at the World Trade Center (WTC) that day and who worked on the wreckage for months. They were exposed to numerous chemicals, many known to be carcinogens and toxins. These men and women are to be respected for the difficult work they did. They should also be compensated for all the injuries associated with their service and given the best care possible.

https://ift.tt/2KgH5gT

Future Cancer Burden in Rescue and Recovery Workers Exposed to the World Trade Center Disaster

This cohort study projects the future burden of cancer among rescue and recovery workers exposed to multiple carcinogenic agents during the September 11, 2001, World Trade Center attack, by estimating the 20-year cancer incidence.

https://ift.tt/2Jt006J

National Distribution of Cancer Genetic Testing

This cross-sectional study describes the national distribution of genetic testing for hereditary cancer risk, identifies disparities, and assesses whether a gender gap exists

https://ift.tt/2KfU4iQ

When You Hear Hoofbeats, Look for Horses, Not Zebras—Reply

In Reply After the publication of our study identifying anaplastic lymphoma kinase (ALK) rearrangements in peritoneal mesothelioma, we read the Letter by Kataoka et al with skepticism. Because both peritoneal mesothelioma and primary peritoneal carcinoma are rare intra-abdominal tumors, Kataoka et al wonder whether our 3 cases of ALK-rearranged peritoneal mesothelioma may represent misdiagnoses and are instead primary peritoneal carcinomas with ALK rearrangement. We address their concern as follows.

https://ift.tt/2FjlfoY

Costs of Chimeric Antigen Receptor T-Cell Immunotherapy

This study estimates the total costs associated with administering chimeric antigen receptor T-cell treatment.

https://ift.tt/2KiT2CM

Dasatinib and Survival in Patients With Imatinib-Resistant Advanced Gastrointestinal Stromal Tumors

This nonrandomized, noncontrolled clinical trial evaluates the 6-month progression-free survival, tumor objective response, and overall survival rates in patients with gastrointestinal stromal tumors treated with dasatinib.

https://ift.tt/2FhgVXy

The Power of Trust

This article discusses a community support group for patients with neuroendocrine tumors, and learning to build trust as a team.

https://ift.tt/2KigY95

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Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial

Objective

There is increasing recognition that, in men, some biological actions attributed to testosterone (TS) are mediated by estradiol (E2). This study used two low doses of daily transdermal E2 gel to assess the effects on circulating E2 concentrations in men with prostate cancer with suppressed endogenous E2 production arising from androgen deprivation therapy (ADT). Secondarily, we aimed to assess short-term biological effects of E2 add-back without increasing circulating TS.

Design

28-day randomised, placebo-controlled trial.

Methods

37 participants were randomised to either 0.9 or 1.8 mg of 0.1% E2 gel per day or matched placebo gel. Fasting morning serum hormones, quality of life questionnaires, and treatment side effects were evaluated at baseline, days 14 and 28. Hot flush diaries and other biochemical measurements were completed at baseline and study end.

Results

Transdermal E2 significantly raised serum E2 from baseline to day 28 compared to placebo in the 0.9 mg dose group (median: 208 pmol/L; interquartile range: 157–332) and in the 1.8 mg dose group (median: 220 pmol/L; interquartile range: 144–660). E2 treatment reduced hot flush frequency and severity as well as beta carboxyl-terminal type 1 collagen telopeptide.

Conclusion

In men with castrate levels of E2 and TS, daily transdermal E2: 0.9–1.8 mg increased median serum E2 concentrations into the reference range reported for healthy men, but with substantial variability. E2 treatment reduced hot flushes and bone resorption. Larger studies will be required to test whether low-dose E2 treatment can mitigate ADT-associated adverse effects without E2-related toxicity.



https://ift.tt/2vRlW9T

DIAGNOSIS OF ENDOCRINE DISEASE: The role of the desmopressin test in the diagnosis and follow-up of Cushings syndrome

Desmopressin is a vasopressin analogue selective for type 2 vasopressin receptors that mediate renal water retention. In contrast to the native hormone arginine vasopressin, a well-known ACTH secretagogue, desmopressin, exerts minimal or no activity on ACTH excretion. However, in a substantial proportion of patients with ACTH-dependent Cushing's syndrome (CS), desmopressin elicits an ACTH and cortisol response, which contrasts with the minimal responses obtained in healthy subjects. The mechanism underlying this paradoxical response involves upregulation of vasopressin type 3 and/or the aberrant expression of type 2 receptors by neoplastic ACTH-producing cells. This makes desmopressin administration a suitable test enabling the distinction between neoplastic from functional (formerly termed 'pseudo-Cushing syndrome') ACTH-dependent cortisol excess. Several studies have now established an adjunctive role of desmopressin in the initial diagnostic workup of CS. Despite some early data indicating that this test may also have a role in distinguishing between Cushing's disease (CD) and ectopic ACTH secretion, subsequent studies failed to confirm this observation. The ability of the paradoxical response to desmopressin to depict the presence of neoplastic ACTH-secreting cells was also exploited in the follow-up of patients with CD undergoing surgery. Loss of the desmopressin response, performed in the early postoperative period, was a good predictor for a favorable long-term outcome. Moreover, during follow-up, reappearance of desmopressin paradoxical response was an early indicator for recurrence. In conclusion, the desmopressin test is a valid tool in both the diagnosis and follow-up of patients with CD and should be more widely applied in the workup of these patients.



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Continuous subcutaneous insulin infusion vs multiple daily injections in pregnant women with type 1 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials and observational studies

Background

Randomised controlled trials (RCTs) have shown an advantage of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) in the general type 1 diabetes mellitus (T1DM) population. RCT data on T1DM management in pregnancy remain limited.

Objective

We performed a systematic review of both RCTs and non-RCTs evaluating CSII vs MDI in T1DM-complicated pregnancy.

Study design

Electronic databases were searched for studies comparing CSII with MDI in T1DM-complicated pregnancy.

Methods

A meta-analysis provided point estimates with 95% confidence intervals (CI). Continuous outcomes were reported as weighted mean differences (WMD) or standardised mean differences (SMD), and dichotomous data as relative risk (RR).

Results

The search identified 47 studies, including 43 non-RCTs, reporting on 7824 pregnancies. The meta-analysis showed a lower HbA1c level with CSII vs MDI in the first trimester (WMD: –0.45%; 95%CI: –0.62, –0.27). This difference decreased in subsequent trimesters. Compared to MDI, therapy with CSII resulted in higher gestational weight gain (GWG) (WMD: 1.02 kg; 95%CI: 0.41, 1.62), and lower daily insulin dose requirements in the first (SMD: –0.46; 95%CI: –0.68, –0.24) and subsequent trimesters. Moreover, infants from the CSII group were more likely to be large for gestational age (LGA) (RR: 1.16; 95%CI: 1.07, 1.24) and less likely to be small for gestational age (SGA) (RR: 0.66; 95%CI: 0.45; 0.97).

Conclusions

In T1DM-complicated pregnancy, CSII compared to MDI therapy resulted in better first trimester glycaemic control; this difference decreased in subsequent trimesters. CSII therapy was associated with lower insulin requirements, higher GWG and altered risk for infants being LGA and SGA.



https://ift.tt/2vRlOqV

Hepatic safety of ketoconazole in Cushings syndrome: results of a Compassionate Use Programme in France

Objective

Ketoconazole (KTZ) is one of few available treatments for Cushing's syndrome (CS). Although KTZ has been associated with severe hepatotoxicity, little information is available about hepatic safety in CS. The aim of this study was to document changes in liver function in patients with CS treated with KTZ.

Design

An observational prospective French cohort study (Compassionate Use Programme (CUP)).

Methods

Enrolled patients were stratified into a KTZ-naive cohort and a cohort already treated by another formulation of ketoconazole (KTZ-switch cohort). Liver function markers (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, -glutamyltransferase and bilirubin) were monitored at regular intervals. Patients with ALT > 3 x ULN (upper limit of normal), total bilirubin > 2 x ULN or both ALP > 2 x ULN and ALT > ULN were considered to have liver injury.

Results

Overall, 108 patients were analysed (47 KTZ-naïve; 61 KTZ-switch). The median KTZ dose was 600 mg/day. Most abnormalities observed were asymptomatic mild increases of liver enzymes. Four patients in the KTZ-naïve cohort (8.5%) and two in the KTZ-switch cohort (3.3%) developed liver injury, considered related to KTZ in three cases (all KTZ-naïve in the first month of treatment). Five patients had mild liver function abnormalities at baseline and two had proven liver metastases. Two patients recovered on discontinuation of KTZ and the remaining patient died of unrelated causes.

Conclusions

These findings highlight the need for close monitoring of liver enzymes especially during the first six months of treatment. Liver enzyme abnormalities usually occurred within four weeks were asymptomatic and could be reversed on timely discontinuation of KTZ.



https://ift.tt/2qZrqdU

Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial

Objective

Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed.

Design

26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939).

Methods

Male or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n = 61) or once-daily Norditropin (n = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9).

Results

Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin (P = 0.0171).

Conclusions

In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin.



https://ift.tt/2HPeBwl

Longitudinally evaluated the relationship between body fat percentage and the risk for type 2 diabetes mellitus: Korean Genome and Epidemiology Study (KoGES)

Background

Body fat plays the significant role in maintaining glucose homeostasis. However, it is not fully identified how body fat percentage (BF%) has an impact on the development of type 2 diabetes mellitus (T2DM). Thus, this study was to evaluate the incidental risk for T2DM according to BF% level.

Methods

In a community-based Korean cohort, 5972 Korean adults were divided into quintile groups by BF% and followed up for 10 years to monitor the development of T2DM. Cox proportional hazard model was used to evaluate the hazard ratios (HRs) for T2DM according to BF% quintile. Additionally, subgroup analysis was conducted by low and high level of BF% (cut-off: 25 in men and 35 in women) and body mass index (BMI).

Results

In adjusted model, compared to the BF% quintile 1 group, the risk for T2DM significantly increased over BF% of 22.8% in men and 32.9% in women (≥quintile 4). The level of BF% related to the increased risk for T2DM was lower in non-obese men (22.8%) than obese men (28.4%). In subgroup analysis, men with low BMI (<25) and high BF% (≥25) had the highest risk for T2DM than other subgroups (HRs: 1.83 (1.33–2.52)). However, this association did not show the statistical significance in women (HRs: 1.63 (0.98–2.72)).

Conclusion

The incidental risk for T2DM significantly increased over the specific level of BF%, which was lower in non-obese population than obese population. Gender difference was suggested in the incidental relationship between BF% and T2DM.



https://ift.tt/2vOG1gT

Diagnostic accuracy of computed tomography to identify adenomas among adrenal incidentalomas in an endocrinological population

Context

The recent recommendations of the European Endocrine Society states that the performance of computed tomography (CT) to characterize 'true' adrenal incidentalomas (AIs) remains debatable.

Objective

To determine relevant thresholds for usual CT parameters for the diagnosis of benign tumors using robust reference standard among a large series of 'true' AIs recruited in an endocrinological setting.

Design

Retrospective study of 253 AIs in 233 consecutive patients explored in a single university hospital: 183 adenomas, 33 pheochromocytomas, 23 adrenocortical carcinomas, 5 other malignant tumors and 9 other benign tumors. Reference standard was histopathology in 118 AIs, biological diagnosis of pheochromocytoma in 2 AIs and size stability after at least 1 year of follow-up in 133 AIs.

Methods

Sensitivity, specificity and positive and negative predictive values were estimated for various thresholds of size, unenhanced attenuation (UA), relative and absolute wash-out (RPW, APW) of contrast media. 197 scans were reviewed independently in a blinded fashion by two expert radiologists to assess inter-observer reproducibility of measurements.

Results

Criteria associated with a 100% positive predictive value for the diagnosis of benign AI were: a combination of size and UA: 30 mm and 20 HU or 40 mm and 15 HU, respectively; RPW >53%; and APW >78%. Non-adenomatous AIs with rapid contrast wash-out were exclusively benign pseudocysts and pheochromocytomas, suggesting that classical thresholds of 60% and 40% for APW and RPW, respectively, can be safely used for patients with normal metanephrine values. Inter-observer reproducibility of all parameters was excellent (intra-class correlation coefficients: 0.96–0.99).

Conclusions

Our study, the largest conducted in AIs recruited in an endocrinological setting, suggests safe thresholds for quantitative CT parameters to avoid false diagnoses of benignity.



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