Performance of Mid-Treatment Breast Ultrasound and Axillary Ultrasound in Predicting Response to Neoadjuvant Chemotherapy by Breast Cancer Subtype

Background.

The primary objective was to determine whether mid-treatment ultrasound measurements of index breast tumors and index axillary nodes of different cancer subtypes associate with residual cancer burden (RCB).

Methods.

Patients with invasive breast cancer who underwent neoadjuvant chemotherapy and had pre-treatment and mid-treatment breast and axillary ultrasound were included in this single-institution, retrospective cohort study. Linear regression analysis assessed associations between RCB with (a) change in index breast tumor size, (b) change in index node size, and (c) absolute number of abnormal nodes at mid-treatment. Multivariate linear regression was used to calculate best-fit models for RCB.

Results.

One hundred fifty-nine patients (68 triple negative breast cancer [TNBC], 45 hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]–, and 46 HR–/HER2+) were included. Median age at diagnosis was 50 years, range 30–76. Median tumor size was 3.4 cm, range 0.9–10.4. Pathological complete response/RCB-I rates were 36.8% (25/68) for TNBC patients, 24.4% (11/45) for HR+/HER2– patients, and 71.7% (33/46) for HR–/HER2+ patients. Linear regression analyses demonstrated associations between percent change in tumor ultrasound measurements at mid-treatment with RCB index score in TNBC and HR+/HER2– (p < .05) but not in HR–/HER2+ (p > .05) tumors and an association between axillary ultrasound assessment of number of abnormal nodes at mid-treatment with RCB index score across all subtypes (p < .05).

Conclusion.

Performance characteristics of breast ultrasound associated with RCB vary by cancer subtype, whereas the performance characteristics of axillary ultrasound associated with RCB are consistent across cancer subtype. Breast and axillary ultrasound may be valuable in monitoring response to neoadjuvant therapy. The Oncologist 2017;22:1–8

Implications for Practice: The differential performance characteristics of breast ultrasound by molecular subtype and the consistent performance characteristics of axillary ultrasound across molecular subtypes can have clinical utility in monitoring response to neoadjuvant therapy.

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A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer

Lessons Learned.

The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.

Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored.

Background.

Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer. Preclinical data have shown that the two pathways compensate for each other when one is inhibited, and combined inhibition of AR and PI3K signaling may be a viable strategy to prevent or overcome castration resistance.

Methods.

This phase I study evaluated the safety and tolerability of abiraterone acetate and prednisone combined with BEZ235, a dual PI3K and mTORC1/2 inhibitor, in men with progressive metastatic castration resistant prostate cancer (mCRPC) who have not received prior chemotherapy.

Results.

Six patients (n = 6) were treated at the starting dose level of abiraterone acetate 1,000 mg with prednisone 5 mg twice daily and BEZ235 200 mg twice daily in a 3 + 3 dose escalation design. The study was terminated early because three of the six patients (50%) experienced dose-limiting toxicities: grade 3 mucositis, grade 3 hypotension, and grade 4 dyspnea and pneumonitis. All six patients had previously progressed on abiraterone/prednisone. The median treatment duration was 27 days (range: 3–130 days). No prostate-specific antigen (PSA) decline or objective response were observed.

Conclusion.

The combination of standard-dose abiraterone/prednisone with BEZ235 200 mg twice daily was poorly tolerated in patients with mCRPC. The on-target and off-target effects of dual PI3K and mTORC inhibition likely contributed to the unacceptable toxicity profile. The Oncologist 2017;22:1–8

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SAFE-HEaRt: Rationale and Design of a Pilot Study Investigating Cardiac Safety of HER2 Targeted Therapy in Patients with HER2-Positive Breast Cancer and Reduced Left Ventricular Function

Background.

Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. Current U.S. Food and Drug Administration recommendations limit the use of HER2 targeted agents to patients with normal left ventricular (LV) systolic function.

Methods.

The objective of the SAFE-HEaRt study is to evaluate the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and mildly reduced left ventricular ejection fraction (LVEF) with optimized cardiac therapy. Thirty patients with histologically confirmed HER2 positive breast cancer (stage I–IV) and reduced LVEF (40% to 49%) who plan to receive HER2 targeted therapy for ≥3 months will be enrolled. Prior to initiation on study, optimization of heart function with beta-blockers and angiotensin converting enzyme inhibitors will be initiated. Patients will be followed by serial echocardiograms and cardiac visits during and 6 months after completion of HER2 targeted therapy. Myocardial strain and blood biomarkers, including cardiac troponin I and high-sensitivity cardiac troponin T, will be examined at baseline and during the study.

Discussion.

LV dysfunction in patients with breast cancer poses cardiac and oncological challenges and limits the use of HER2 targeted therapies and its oncological benefits. Strategies to prevent cardiac dysfunction associated with HER2 targeted therapy have been limited to patients with normal LVEF, thus excluding patients who may receive the highest benefit from those strategies. SAFE-HEaRt is the first prospective pilot study of HER2 targeted therapies in patients with reduced LV function while on optimized cardiac treatment that can provide the basis for clinical practice changes. The Oncologist 2017;22:1–8

Implications for Practice: Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. To our knowledge, SAFE-HEaRt is the first clinical trial that prospectively tests the hypothesis that HER2 targeted therapies may be safely administered in patients with mildly reduced cardiac function in the setting of ongoing cardiac treatment and monitoring. The results of this study will provide cardiac safety data and inform consideration of clinical practice changes in patients with HER2 positive breast cancer and reduced cardiac function, as well as provide information regarding cardiovascular monitoring and treatment in this population.

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Endocrine Therapy in the Current Management of Postmenopausal Estrogen Receptor-Positive Metastatic Breast Cancer

Metastatic breast cancer (MBC) results in substantial morbidity and mortality for women afflicted with this disease. A majority of MBCs are hormone-responsive and estrogen receptor-positive, making endocrine therapy (ET) an integral component of systemic therapy. With a primary goal of minimizing the effects of estrogen on hormone-responsive MBC, ETs are among the first targeted treatments that aim to inhibit the influence of estrogen receptor activation on tumor proliferation. Several biochemical mechanisms have been the focus of drug development for treatment, including selective estrogen-receptor modulation, aromatase inhibition, and selective estrogen-receptor degradation. Treatments that exploit these mechanisms have improved survival and quality of life for women with MBC. However, in many cases, resistance to ET limits their effectiveness. Elucidation of the complex cellular signal cascades involved in the development of acquired resistance to ET and the interrelationship of growth factor signaling and estrogen responsiveness have characterized components of these pathways as attractive targets for drug development. Based on these insights and with the aim of overcoming hormone resistance, targeted therapies are emerging as useful treatments for MBC. This article reviews current endocrine treatments of MBC as well as recent and ongoing study of combination treatments and targeted therapies that interfere with cellular proliferation pathways as means of overcoming resistance. The Oncologist 2017;22:1–11

Implications for Practice: This review provides medical oncologists and other oncology health care providers with a current understanding of the rationale for endocrine therapy in estrogen receptor-positive metastatic breast cancer and the efficacy and safety profile of available treatment options. Additionally, current concepts regarding the development of treatment resistance and the treatment strategies for overcoming resistance are discussed. Enhancing the current information and the understanding of these topics will assist clinicians in evaluating optimal treatment options for their patients.

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Comprehensive proteomic characterization of stem cell-derived extracellular matrices

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Héloïse Ragelle, Alexandra Naba, Benjamin L. Larson, Fangheng Zhou, Miralem Prijić, Charles A. Whittaker, Amanda Del Rosario, Robert Langer, Richard O. Hynes, Daniel G. Anderson
In the stem-cell niche, the extracellular matrix (ECM) serves as a structural support that additionally provides stem cells with signals that contribute to the regulation of stem-cell function, via reciprocal interactions between cells and components of the ECM. Recently, cell-derived ECMs have emerged as in vitro cell culture substrates to better recapitulate the native stem-cell microenvironment outside the body. Significant changes in cell number, morphology and function have been observed when mesenchymal stem cells (MSC) were cultured on ECM substrates as compared to standard tissue-culture polystyrene (TCPS). As select ECM components are known to regulate specific stem-cell functions, a robust characterization of cell-derived ECM proteomic composition is critical to better comprehend the role of the ECM in directing cellular processes. Here, we characterized and compared the protein composition of ECM produced in vitro by bone marrow-derived MSC, adipose-derived MSC and neonatal fibroblasts from different donors, employing quantitative proteomic methods. Each cell-derived ECM displayed a specific and unique matrisome signature, yet they all shared a common set of proteins. We evaluated the biological response of cells cultured on the different matrices and compared them to cells on standard TCPS. The matrices lead to differential survival and gene-expression profiles among the cell types and as compared to TCPS, indicating that the cell-derived ECMs influence each cell type in a different manner. This general approach to understanding the protein composition of different tissue-specific and cell-derived ECM will inform the rational design of defined systems and biomaterials that recapitulate critical ECM signals for stem-cell culture and tissue engineering.

Graphical abstract

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Supramolecular biofunctional materials

Publication date: June 2017
Source:Biomaterials, Volume 129
Author(s): Jie Zhou, Jie Li, Xuewen Du, Bing Xu
This review discusses supramolecular biofunctional materials, a novel class of biomaterials formed by small molecules that are held together via noncovalent interactions. The complexity of biology and relevant biomedical problems not only inspire, but also demand effective molecular design for functional materials. Supramolecular biofunctional materials offer (almost) unlimited possibilities and opportunities to address challenging biomedical problems. Rational molecular design of supramolecular biofunctional materials exploit powerful and versatile noncovalent interactions, which offer many advantages, such as responsiveness, reversibility, tunability, biomimicry, modularity, predictability, and, most importantly, adaptiveness. In this review, besides elaborating on the merits of supramolecular biofunctional materials (mainly in the form of hydrogels and/or nanoscale assemblies) resulting from noncovalent interactions, we also discuss the advantages of small peptides as a prevalent molecular platform to generate a wide range of supramolecular biofunctional materials for the applications in drug delivery, tissue engineering, immunology, cancer therapy, fluorescent imaging, and stem cell regulation. This review aims to provide a brief synopsis of recent achievements at the intersection of supramolecular chemistry and biomedical science in hope of contributing to the multidisciplinary research on supramolecular biofunctional materials for a wide range of applications. We envision that supramolecular biofunctional materials will contribute to the development of new therapies that will ultimately lead to a paradigm shift for developing next generation biomaterials for medicine.



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Monitoring and visualizing microRNA dynamics during live cell differentiation using microRNA-responsive non-viral reporter vectors

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Hideyuki Nakanishi, Kenji Miki, Kaoru R. Komatsu, Masayuki Umeda, Megumi Mochizuki, Azusa Inagaki, Yoshinori Yoshida, Hirohide Saito
MicroRNA (miRNA) activity differs with cell type, suggesting it can be used as a cell marker. In this study, we developed novel miRNA–responsive non-viral reporter vectors to continuously monitor and visualize miRNA dynamics during differentiation and to efficiently purify target living cells. Each vector codes miRNA-responsive and reference reporter genes in a single mRNA. These two genes are independent modules but transcribed by a single promoter, which enables us to distinguish miRNA-mediated post-transcriptional repression from transcriptional repression. We generated stable, miRNA-responsive vector-containing human induced pluripotent stem cells (hiPSCs) using the piggyBac transposon or episomal vectors. We could continuously monitor the differentiation status of living hiPSCs by detecting the activity of hiPSC-specific miRNA (miR-302a*). In addition, we could selectively sort hiPSC-derived cardiomyocytes using cardiomyocyte-specific miRNA (miR-208a or miR-1)-reporter vectors. Our miRNA reporter system provides a simple way to quantitatively and continuously monitor and visualize changes in the cellular state and should facilitate a broad range of studies that depend on cellular changes including drug discovery and cell-fate conversion.



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A positive feedback strategy for enhanced chemotherapy based on ROS-triggered self-accelerating drug release nanosystem

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Jing-Jing Hu, Qi Lei, Meng-Yun Peng, Di-Wei Zheng, Yi-Xuan Chen, Xian-Zheng Zhang
Here, a positive feedback strategy was utilized to amplify the concentration of intracellular reactive oxygen species (ROS) and a ROS-triggered self-accelerating drug release nanosystem (defined as T/D@RSMSNs) was demonstrated for enhanced tumor chemotherapy. The mesoporous silica nanoparticles (MSNs) based nanocarriers were gated by β-cyclodextrin (β-CD) through the ROS-cleavable thioketal (TK) linker to encapsulate the anticancer drug doxorubicin hydrochloride (DOX) and ROS producing agent α-tocopheryl succinate (α-TOS), whose surface was further anchored with adamantane conjugated poly(ethylene glycol) chain (AD-PEG) via host-guest interaction. It was found that in human breast cancer (MCF-7) cells, T/D@RSMSNs could not only release DOX and α-TOS initiatively, but also lead to increased concentration of intracellular ROS, which could be used as new trigger to cut away TK linkage and then in turn facilitate the further release of DOX for enhanced chemotherapy. Both in vitro and in vivo experiments demonstrated that T/D@RSMSNs exhibited more significant antitumor activity in the human breast cancer than the traditional single-DOX loaded ROS-responsive nanocarrier. This novel ROS-triggered self-accelerating drug release nanosystem with remarkably improved therapeutic effects could provide a general strategy to branch out the applications of existing ROS-responsive drug delivery systems (DDSs).

Graphical abstract

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The Phonological Unit of Japanese Kanji Compounds: A Masked Priming Investigation.

Author: Yoshihara, Masahiro; Nakayama, Mariko; Verdonschot, Rinus G.; Hino, Yasushi

DOI: 10.1037/xhp0000374

Publication Date: POST AUTHOR CORRECTIONS, 16 March 2017

http://ift.tt/2mZ2GAN

The Role of Error Processing in the Contextual Interference Effect During the Training of Perceptual-Cognitive Skills.

Author: Broadbent, David P.; Causer, Joe; Williams, A. Mark; Ford, Paul R.

DOI: 10.1037/xhp0000375

Publication Date: POST AUTHOR CORRECTIONS, 16 March 2017

http://ift.tt/2nBlNiF

Embodied Memory Allows Accurate and Stable Perception of Hidden Objects Despite Orientation Change.

Author: Pan, Jing Samantha; Bingham, Ned; Bingham, Geoffrey P.

DOI: 10.1037/xhp0000392

Publication Date: POST AUTHOR CORRECTIONS, 16 March 2017

http://ift.tt/2mYZSDS

Physical activity alters limb bone structure but not entheseal morphology

Publication date: June 2017
Source:Journal of Human Evolution, Volume 107
Author(s): Ian J. Wallace, Julia M. Winchester, Anne Su, Doug M. Boyer, Nicolai Konow
Studies of ancient human skeletal remains frequently proceed from the assumption that individuals with robust limb bones and/or rugose, hypertrophic entheses can be inferred to have been highly physically active during life. Here, we experimentally test this assumption by measuring the effects of exercise on limb bone structure and entheseal morphology in turkeys. Growing females were either treated with a treadmill-running regimen for 10 weeks or served as controls. After the experiment, femoral cortical and trabecular bone structure were quantified with μCT in the mid-diaphysis and distal epiphysis, respectively, and entheseal morphology was quantified in the lateral epicondyle. The results indicate that elevated levels of physical activity affect limb bone structure but not entheseal morphology. Specifically, animals subjected to exercise displayed enhanced diaphyseal and trabecular bone architecture relative to controls, but no significant difference was detected between experimental groups in entheseal surface topography. These findings suggest that diaphyseal and trabecular structure are more reliable proxies than entheseal morphology for inferring ancient human physical activity levels from skeletal remains.



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Evolutionary anatomy of the Neandertal ulna and radius in the light of the new El Sidrón sample

Publication date: May 2017
Source:Journal of Human Evolution, Volume 106
Author(s): Laura Pérez-Criado, Antonio Rosas
This paper aims to improve our understanding of the phylogenetic trait polarity related to hominin forearm evolution, in particular those traits traditionally defined as "Neandertal features." To this aim, twelve adult and adolescent fragmented forelimb elements (including ulnae and radii) of Homo neanderthalensis recovered from the site of El Sidrón (Asturias, Spain) were examined comparatively using three-dimensional geometric and traditional morphometrics. Mean centroid size and shape comparisons, principal components analysis, and phylogenetic signal analysis were undertaken. Our investigations revealed that the proximal region of the ulna discriminated best between Neandertals and modern humans, with fewer taxonomically-informative features in the distal ulna and radius. Compared to modern humans, the divergent features in the Neandertal ulna are an increase in olecranon breadth (a derived trait), lower coronoid length (primitive), and anterior orientation of the trochlear notch (primitive). In the Neandertal radius, we observe a larger neck length (primitive), medial orientation of the radial tubercle (secondarily primitive), and a curved diaphysis (secondarily primitive). Anatomically, we identified three units of evolutionary change: 1) the olecranon and its fossa, 2) the coronoid–radius neck complex, and 3) the tubercle and radial diaphysis. Based on our data, forearm evolution followed a mosaic pattern in which some features were inherited from a pre-Homo ancestor, others originated in some post-ergaster and pre-antecessor populations, and other characters emerged in the specific Homo sapiens and H. neanderthalensis lineages, sometimes appearing as secondarily primitive. Future investigations might consider the diverse phylogenetic origin of apomorphies while at the same time seeking to elucidate their functional meaning.



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An updated age for the Xujiayao hominin from the Nihewan Basin, North China: Implications for Middle Pleistocene human evolution in East Asia

Publication date: May 2017
Source:Journal of Human Evolution, Volume 106
Author(s): Hong Ao, Chun-Ru Liu, Andrew P. Roberts, Peng Zhang, Xinwen Xu
The Xujiayao site in the Nihewan Basin (North China) is one of the most important Paleolithic sites in East Asia. Twenty Homo fossils, which were previously assigned to an archaic Homo sapiens group, have been excavated along with more than 30,000 lithic artifacts and ∼5000 mammalian fossil specimens. Dating of the Xujiayao hominin has been pursued since its excavation in the 1970s, but its age has remained controversial because of limitations of the dating techniques that have been applied to available materials. Here, we report new ages for the Xujiayao hominin based on combined electron spin resonance (ESR) dating of quartz in the sediments and high-resolution magnetostratigraphy of the fluvio-lacustrine sequence. The magnetostratigraphy suggests that the upper Matuyama and Brunhes polarity chrons are recorded at Xujiayao. The ESR dating results indicate a pooled average age of 260–370 ka for the Homo-bearing layer, which is consistent with its position within the middle Brunhes normal polarity chron indicated by magnetostratigraphy. This age estimate makes the Xujiayao hominin among the oldest mid-Pleistocene hominins with derived Neanderthal traits in East Asia. This age is consistent with the time when early Denisovans, a sister group of Neanderthals, appeared and colonized eastern Eurasia. Our updated age and the Neanderthal-like traits of the Xujiayao Homo fossils, particularly the Denisovan-like molar teeth, make it possible that the Xujiayao hominin could represent an early Denisovan.



http://ift.tt/2mS2cKU

Another look at the foramen magnum in bipedal mammals

Publication date: April 2017
Source:Journal of Human Evolution, Volume 105
Author(s): Gabrielle A. Russo, E. Christopher Kirk
A more anteriorly positioned foramen magnum evolved in concert with bipedalism at least four times within Mammalia: once in macropodid marsupials, once in heteromyid rodents, once in dipodid rodents, and once in hominoid primates. Here, we expand upon previous research on the factors influencing mammalian foramen magnum position (FMP) and angle with four new analyses. First, we quantify FMP using a metric (basioccipital ratio) not previously examined in a broad comparative sample of mammals. Second, we evaluate the potential influence of relative brain size on both FMP and foramen magnum angle (FMA). Third, we assess FMP in an additional rodent clade (Anomaluroidea) containing bipedal springhares (Pedetes spp.) and gliding/quadrupedal anomalures (Anomalurus spp.). Fourth, we determine the relationship between measures of FMP and FMA in extant hominoids and an expanded mammalian sample. Our results indicate that bipedal/orthograde mammals have shorter basioccipitals than their quadrupedal/non-orthograde relatives. Brain size alone has no discernible effect on FMP or FMA. Brain size relative to palate size has a weak influence on FMP in some clades, but effects are not evident in all metrics of FMP and are inconsistent among clades. Among anomaluroids, bipedal Pedetes exhibits a more anterior FMP than gliding/quadrupedal Anomalurus. The relationship between FMA and FMP in hominoids depends on the metric chosen for quantifying FMP, and if modern humans are included in the sample. However, the relationship between FMA and FMP is nonexistent or weak across rodents, marsupials, and, to a lesser extent, strepsirrhine primates. These results provide further evidence that bipedal mammals tend to have more anteriorly positioned foramina magna than their quadrupedal close relatives. Our findings also suggest that the evolution of FMP and FMA in hominins may not be closely coupled.



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A newly discovered galagid fossil from Nakali, an early Late Miocene locality of East Africa

Publication date: Available online 17 March 2017
Source:Journal of Human Evolution
Author(s): Yutaka Kunimatsu, Masato Nakatsukasa, Tetsuya Sakai, Mototaka Saneyoshi, Yoshihiro Sawada, Hideo Nakaya




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Editorial Board

Publication date: March 2017
Source:Journal of Human Evolution, Volume 104





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Molecular defects identified by whole exome sequencing in a child with atypical mucopolysaccharidosis IIIB

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2n7cd9c

Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2mS0ARv

Clinical features of girls with short stature among inv (9), Turner (45, X) and control individuals

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2n7cBoj

Increase of body mass index (BMI) from 1.5 to 3 years of age augments the degree of insulin resistance corresponding to BMI at 12 years of age

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2n7cA3J

A cross-sectional survey of the nature and correlates of sleep disturbance in people with psoriasis

Abstract

Background

Research suggests that sleep disturbance is common in psoriasis. Despite 32 studies conducted in sleep, many demonstrate methodological flaws, often using unvalidated measurement, with no study examining multiple dimensions of sleep-wake functioning. Moreover, research has yet to comprehensively examine the range of physical and psychological factors that may affect sleep in people with psoriasis.

Objective

To characterise sleep disturbance using validated measures and identify physical and psychological predictors of sleep quality in people with psoriasis.

Methods

An online survey was conducted (n=186;M_age=39.2) comprising validated measures assessing sleep (Pittsburgh Sleep Quality Index [PSQI], Berlin Questionnaire, Pre-Sleep Arousal Scale), chronotype (Morningness-Eveningness Questionnaire), mood (Hospital Anxiety and Depression Scale), itch (5-D Itch Scale) and psoriasis severity (Simplified Psoriasis Index). Group comparisons and regression analyses were used to examine predictors of poor sleep.

Results

Mean PSQI score was 9.24 (SD=4.32), with 76.3% scoring above the threshold for poor sleep (≥ 6 on the PSQI) and 32.5% scoring 'positive' for probable obstructive sleep apnoea. Poor sleep and high likelihood of OSA was associated with more severe psoriasis (p<.05; η²=.07; η²=.005). Cognitive arousal (β=.264, p=.001), itch (β=.260, p<.001) and depression (β=.236, p=.001) were the most robust predictors of poor sleep quality which, together with somatic arousal (β=.168, p=.022), accounted for 43% of variance in PSQI scores.

Conclusions

Poor sleep is common in psoriasis and associated with psychological and physical factors. Rates of probable obstructive sleep apnoea are also high. Given the importance of restorative sleep for health, sleep complaints should receive greater clinical attention in the management of psoriasis.

This article is protected by copyright. All rights reserved.

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A chronic recurrent disease course of dermatomyositis is associated with autoantibodies against TIF1γ

Abstract

Dermatomyositis (DM) is a rare autoimmune disease with high clinical variability in terms of cutaneous and muscle involvement as well as disease duration. DM severely impacts the quality of life of the patients and may be life threatening. This is primarily due to lung involvement and the 3.0 to 7.7 fold increased relative risk for cancer compared to the general adult population^1;2.

This article is protected by copyright. All rights reserved.

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Sorption and desorption of silver ions by bentonite clays

Abstract

Anthropogenic activities have increased the concentration of metal species in the environment. The toxicity of silver ions to aquatic and terrestrial organisms has required monitoring by analytical methods, besides actions to promote its control as pollutant. Sorption and desorption processes are directly related to the mobility and availability of metal ions in the environment. In this context, clay minerals can be used for pre-concentration, removal and recovery of silver ions from aqueous solution. Herein, two bentonite clays (BaVC-1 and SWy-2) were characterised and applied to investigate the sorption and desorption of silver ions. Isotherms were fitted to the dual-mode Langmuir-Freundlich model to qualify and quantify sorption sites and evaluate the mobilisation process. The maximum sorption capacity was 743 and 849 meq kg⁻¹ for BaVC-1 and SWy-2, respectively. Hysteresis index (HI) and mobilisation factor (MF) suggest that the desorption of silver ions in BaVC-1 is about four times more conducive compared to that in SWy-2, although both materials have demonstrated a great potential for Ag⁺ pre-concentration from aqueous solutions.

http://ift.tt/2mc1TNY

Dynamics of biochemical properties associated with soil nitrogen mineralization following nitrification inhibitor and fungicide applications

Abstract

Agrochemical applications may have side effects on soil biochemical properties related to soil nitrogen (N) mineralization and thus affect N cycling. The present study aimed to evaluate the effects of nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) and fungicide iprodione on soil neutral protease (NPR), alkaline protease (APR), chitinase (CHI), and their functional genes (nprA, aprA, and chiA) related to soil N mineralization. The following four treatments were included: blank control (CK), single DMPP application (DAA), weekly iprodione applications (IPR), and the combined applications of DMPP and iprodione (DI). Compared with the CK treatment, DMPP application significantly inhibited the CHI activity in the first 14 days of incubation, and iprodione applications, particularly when applied alone, decreased the NPR, APR, and CHI activities. Relative to the IPR treatment, extra DMPP application had the potential to alleviate the inhibitory effects of iprodione on the activities of these enzymes. DMPP application significantly increased aprA gene abundances after 14 days of incubation. However, repeated iprodione applications, alone or with the DMPP, decreased nprA and chiA gene abundances. Relative to the CK treatment, DMPP application generated negligible effects on the positive/negative correlations between soil enzyme activities and the corresponding functional gene abundances. However, the positive correlation between the CHI activity and chiA gene abundance was changed to negative correlation by repeated iprodione applications, alone or together with the DMPP. Our results demonstrated that agrochemical applications, particularly repeated fungicide applications, can have inadvertent effects on enzyme activities and functional gene abundances associated with soil N mineralization.

http://ift.tt/2mEwJuZ

A preliminary investigation of noise impact within metro stations in the urban city of Guangzhou, China

Abstract

The noise in the metro station is synthesized from a variety of different noise sources. Excessive noise exposure will bring serious impacts on humans' health. To alleviate the shortage of the urban land, most metro stations are planning to develop convenience stores and shopping malls. In order to evaluate the potential noise impact on humans' comfort in the metro stations, this study selected four representative stations of Guangzhou Metro Line 1 to carry out a preliminary questionnaire survey of 226 respondents for the perception and perform a noise measurement. Additionally, platform screen doors as a potential method for noise mitigation were examined. The results show that the noise caused by trains was dominant in the metro stations; however, the noise impact by public broadcast and passengers cannot be ignored. The noise levels of the transfer stations were obviously greater than the normal stations, especially during the peak hours. In addition, people in the metro stations have potential exposure to noise that the noise levels exceed the criteria limit of China, which would bring discomfort for humans; however, the normal activities of people would not be impacted. The platform screen doors should be further improved or relevant noise mitigation methods should be taken into account to reduce the noise level within the criteria limit.

http://ift.tt/2mbIzAA

Degradation of n -alkanes and PAHs from the heavy crude oil using salt-tolerant bacterial consortia and analysis of their catabolic genes

Abstract

In the present study, salt-tolerant strains, Dietzia sp. HRJ2, Corynebacterium variabile HRJ4, Dietzia cinnamea HRJ5 and Bacillus tequilensis HRJ6 were isolated from the Dagang oil field, China. These strains degraded n-alkanes and polycyclic aromatic hydrocarbons (PAHs) aerobically from heavy crude oil (HCO) in an experiment at 37 °C and 140 rpm. The GC/MS investigation for degradation of different chain lengths of n-alkanes (C8–C40) by individual strains showed the highest degradation of C8–C19 (HRJ5), C20–C30 (HRJ4) and C31–C40 (HRJ5), respectively. Moreover, degradation of 16 PAHs with individual strains demonstrated that the bicyclic and pentacyclic aromatic hydrocarbons (AHs) were mostly degraded by HRJ5, tricyclic and tetracyclic AHs by HRJ6 and hexacyclic AHs by HRJ2. However, the highest degradation of total petroleum hydrocarbons (TPHs), total saturated hydrocarbons (TSH), total aromatic hydrocarbons (TAH), n-alkanes (C8–C40) and 16 PAHs was achieved by a four-membered consortium (HRJ2 + 4 + 5 + 6) within 12 days, with the predominance of HRJ4 and HRJ6 strains which was confirmed by denaturing gradient gel electrophoresis. The abundance of alkB and nah genes responsible for catabolism of n-alkanes and PAHs was quantified using the qPCR. Maximum copy numbers of genes were observed in HRJ2 + 4 + 5 + 6 consortium (gene copies l⁻¹) 2.53 × 10⁴ (alkB) and 3.47 × 10³ (nah) at 12 days, which corresponded to higher degradation rates of petroleum hydrocarbons. The superoxide dismutase (SOD) (total SOD (T-SOD), Cu²⁺Zn²⁺-SOD), catalase (CAT) and ascorbate peroxidase (APX) activities in Allium sativum and Triticum aestivum were lower in the HRJ2 + 4 + 5 + 6-treated HCO as compared to the plantlets exposed directly to HCO. The present results revealed the effective degradation of HCO-contaminated saline medium using the microbial consortium having greater metabolic diversity.

http://ift.tt/2mEEbGz

Exploiting fruit byproducts for eco-friendly nanosynthesis: Citrus × clementina peel extract mediated fabrication of silver nanoparticles with high efficacy against microbial pathogens and rat glial tumor C6 cells

Abstract

Process byproducts from the fruit industry may represent a cheap and reliable source of green reducing agents to be used in current bio-nanosynthesis. This study reports the use of orange (Citrus × clementina) peel aqueous extract (OPE) for one-pot green synthesis of silver nanoparticles (AgNPs) with high effectiveness against various microbial pathogens as well as rat glial tumor C6 cells. The effects of various operational parameters on the synthesis of AgNPs were systematically investigated. The morphology, particle size, and properties of synthesized AgNPs were characterized using UV–visible spectroscopy, x-ray diffraction, x-ray photoelectron spectroscopy, field emission scanning electron microscopy, energy-dispersive x-ray spectroscopy, and Fourier transform infrared spectroscopy. High-resolution transmission electron microscopy shows that the nanoparticles are mostly spherical in shape and monodispersed, with an average particle size of 15–20 nm. Notably, the OPE-synthesized AgNPs were stable up to 6 months without change in their properties. Low doses of OPE-AgNPs inhibited the growth of human pathogens Escherichia coli, Bacillus cereus, and Staphylococcus aureus. The minimum inhibitory concentration and minimum bactericidal concentration of AgNPs against selected pathogenic bacteria were determined. OPE-AgNPs exhibited strong antioxidant activity in terms of ABTS (2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging (IC₅₀ 49.6 μg/mL) and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging (IC₅₀ 63.4 μg/mL). OPE-AgNPs showed dose-dependent response against rat glial tumor C6 cells (LD₅₀ 60 μg/mL) showing a promising potential as anticancer agents. Overall, the current investigation highlighted a cheap green technology route to synthesize AgNPs using OPE byproducts and could potentially be utilized in biomedical, cosmetic, and pharmaceutical industry.

http://ift.tt/2mbOPZe

Determination of heavy metals in muscle tissue of six fish species with different feeding habits from the Danube River, Belgrade—public health and environmental risk assessment

Abstract

The aim of this study was to investigate the presence of heavy metals/metalloids (Pb, Cd, Hg, Cu, Fe, Zn, As) in the muscle tissue of fish from the Danube River (two locations: Zemun and Grocka). For the purpose of heavy metal determination in fish muscle, 120 samples of six different fish species, Prussian carp, barbel, bream, carp, pike perch, and catfish were collected. For determining heavy metals, we used microwave oven digestion and atomic absorption spectrometer methods. The highest average content of Pb (0.084 ± 0.004 mg kg⁻¹), Cd (0.082 ± 0.003 mg kg⁻¹), Hg (0.466 ± 0.006 mg kg⁻¹), and As (0.333 ± 0.007 mg kg⁻¹) was found in the muscle of carp (an omnivorous fish) from Grocka, while the highest average level of Fe (13.60 ± 0.03 mg kg⁻¹) was deposited in bream (also omnivorous) from Zemun. Also, the average Cu level (1.62 ± 0.13 mg kg⁻¹) was the highest in catfish muscle (a carnivorous fish) from Grocka, while the highest Zn content (11.16 ± 0.17 mg kg⁻¹) was determined in muscle of Prussian carp (an omnivorous fish) from Zemun. The highest content of heavy metals (Cu, Fe, and Zn, respectively) in muscle of the six different types of fish from both locations was symmetrically arranged by species (catfish, barbel, and Prussian carp, respectively). Concentrations of Pb, Hg, and As in the Danube River fish muscle were under the maximum residual levels prescribed by the European Union (EU) and the maximum allowed concentrations (MAC) for Serbia. On the other hand, in all fish muscle from both locations (Zemun and Grocka), higher concentrations of Cd than prescribed (MAC) were found, with the exception of bream and pike perch.

http://ift.tt/2mbRCS1

Spatial distribution, ecological risk assessment, and potential sources of heavy metal(loid)s in surface sediments from the Huai River within the Bengbu section, China

Abstract

The Huai River is one of the major drinking water resources in Bengbu City of China's eastern Anhui Province. The study focused on extracting information for spatial distributions of heavy metal(loid)s (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) based on the contents of pollutants in 20 surface sediments. Geoaccumulation index and Hakanson potential ecological index were used to calculate the ecological risk of sediment environment in this paper. The I _geo results indicated that the sediments were moderately contaminated by Hg and Pb. The potential ecological risk sequence of the metals was Hg > Cd > Pb > Cu > Ni > Cr > Zn > As. Among the metal(loid)s, Hg was the main source of pollution that contributed ∼76% towards the potential ecological risk, followed by Cd. Finally, multivariate statistical analysis methods were conducted to identify the potential causes of pollution and provide basis for environment treatment in Bengbu Reach. The results depicted that Pb may be mainly derived from the traffic emission and manufacturing industry, while Hg may be originated from agricultural emissions.

http://ift.tt/2mEBhBv

Spatiotemporal variability in salinity and hydraulic relationship with salt intrusion in the tidal reaches of the Minjiang River, Fujian Province, China

Abstract

Salinity is one of the most important factors for tidal-affected water bodies including estuaries and tidal river reaches. However, due to the limitations of simultaneous manual monitoring in long-distance areas, studies of estuaries are preferred to tidal reaches. Hence, in this study, we investigated the tidal reach of the Minjiang River and five sets of field observations were used to determine the influence of saltwater intrusion in different seasons. During the dry and wet season with low discharge, the longitudinal salinity profiles showed that a station located about 45 km from the river mouth still suffered from saltwater intrusion especially when the upstream discharge was under 754 m³ s⁻¹, where the periodical fluctuation in the salinity remained the same with the water level, but there was a time lag of approximately 4 h compared with the discharge process. However, during the wet season in April and May 2016, the monitored salinity was approximately at the detectable limit of 0.02–0.04 ppt at the station close to the river mouth, which indicated that there was no saltwater exchange into the river, although dual flow directions were observed in the survey periods. The major differences among five survey periods were mainly related to upstream discharge rather than the seasons, the tidal range, and tidal excursion. The conclusions of this study have strategic importance for protecting water sources by guiding the government to assess the optimal freshwater release time and discharge rate to prevent saltwater entering the important tidal-affected river reaches.

http://ift.tt/2mbTwlF

Nipple reconstruction with complementary triangular flaps

Abstract

Background

Nipple reconstruction is a surgical procedure often performed after total breast reconstruction. The main limitation of all techniques is premature or excessive flattening of the reconstructed nipple. Over the past few years, we have modified the CV flap technique in order to increase the reconstructed nipple size and reduce premature flattening.

Methods

The modified technique proposes the addition of lateral and medial flaps which are drawn as two right triangles disposed symmetrically in a mirror-like fashion along the longitudinal axis. The symmetry between the two triangles allows the use of all the available height during creation of the new nipple. Once raised, flaps are rearranged into the shape of a nipple, trimmed only if necessary, and sutured. Diameter and projection of the reconstructed nipple were measured at 1 and 2 years and compared to immediate postoperative standard measures.

Results

Twenty-two patients underwent nipple reconstruction with this technique. Patients were followed up for 2 years. No complications were reported. Immediate postoperative standard measures of the reconstructed nipple were on average 1.3 cm in projection and 1.3 cm in diameter. After 1-year follow-up, the average projection was 0.61 cm ± 0.14 cm and the diameter was 1.13 ± 0.18 cm. After the 2-year follow-up, the average projection was 0.53 ± 0.16 and the diameter was 1.12 ± 0.18.

Conclusions

The modified nipple reconstruction technique herein presented is easy to perform and provides long-lasting results with a low risk of postoperative complications. Further studies to compare this technique with the traditional CV flap are warranted.

Level of Evidence: Level IV, therapeutic study.

http://ift.tt/2mbQEFn

Effect of acidity of in-office bleaching gels on tooth sensitivity and whitening: a two-center double-blind randomized clinical trial

Abstract

Objectives

The study aimed to compare the tooth sensitivity (TS) and bleaching efficacy of two hydrogen peroxide gels with different pHs (acid pH [Pola Office, SDI] and the neutral pH [Pola Office+, SDI]) used for in-office bleaching.

Materials and methods

Fifty-four patients from Brazil and Chile, with right superior incisor darker than A2, were selected for this double-blind, split-mouth randomized trial. Teeth were bleached in two sessions, with 1-week interval. Each session had three applications of 8 min each, according to the manufacturer's instructions. The color changes were evaluated by subjective (Vita Classical and Vita Bleachedguide) and objective (Easy shade spectrophotometer) methods. Participants recorded TS with 0–10 visual analog scale. Color change in shade guide units (SGU) and ΔE was analyzed by Student's t test (α = 0.05). The absolute risk and intensity of TS were evaluated by McNemar's test and Wilcoxon-paired test, respectively (α = 0.05).

Results

All groups achieved the same level of whitening after 30 days of clinical evaluation. The use of a neutral in-office bleaching gel significantly decreases the absolute risk of TS (28%, 95% CI 18–41) and intensity of TS when compared to the acid bleaching gel (absolute risk of 50%, 95% CI 37–63).

Conclusion

The use of a neutral in-office bleaching agent gel produced the same whitening degree than an acid bleaching gel but with reduced risk and intensity of tooth sensitivity.

Clinical significance

Clinicians should opt to use in-office bleaching with a neutral gel than an acid product because the former causes a significant lower risk and intensity of tooth sensitivity.

http://ift.tt/2mDv3Sh

Fully automated VMAT treatment planning for advanced-stage NSCLC patients

Abstract

Purpose

To develop a fully automated procedure for multicriterial volumetric modulated arc therapy (VMAT) treatment planning (autoVMAT) for stage III/IV non-small cell lung cancer (NSCLC) patients treated with curative intent.

Materials and methods

After configuring the developed autoVMAT system for NSCLC, autoVMAT plans were compared with manually generated clinically delivered intensity-modulated radiotherapy (IMRT) plans for 41 patients. AutoVMAT plans were also compared to manually generated VMAT plans in the absence of time pressure. For 16 patients with reduced planning target volume (PTV) dose prescription in the clinical IMRT plan (to avoid violation of organs at risk tolerances), the potential for dose escalation with autoVMAT was explored.

Results

Two physicians evaluated 35/41 autoVMAT plans (85%) as clinically acceptable. Compared to the manually generated IMRT plans, autoVMAT plans showed statistically significant improved PTV coverage (V_95% increased by 1.1% ± 1.1%), higher dose conformity (R₅₀ reduced by 12.2% ± 12.7%), and reduced mean lung, heart, and esophagus doses (reductions of 0.9 Gy ± 1.0 Gy, 1.5 Gy ± 1.8 Gy, 3.6 Gy ± 2.8 Gy, respectively, all p < 0.001). To render the six remaining autoVMAT plans clinically acceptable, a dosimetrist needed less than 10 min hands-on time for fine-tuning. AutoVMAT plans were also considered equivalent or better than manually optimized VMAT plans. For 6/16 patients, autoVMAT allowed tumor dose escalation of 5–10 Gy.

Conclusion

Clinically deliverable, high-quality autoVMAT plans can be generated fully automatically for the vast majority of advanced-stage NSCLC patients. For a subset of patients, autoVMAT allowed for tumor dose escalation.

http://ift.tt/2mb3m7e

Cooperative inhibitory effects of uremic toxins and other serum components on OATP1B1-mediated transport of SN-38

Abstract

Purpose

Half-life of SN-38, an active metabolite of irinotecan, remarkably increases in patients with end-stage kidney disease (ESKD), even though SN-38 is excreted in bile. Uremic toxins (UTs), which accumulate in the serum of ESKD patients, were reported to inhibit organic anion-transporting polypeptide (OATP) 1B1-mediated uptake of SN-38; however, the relevance of this finding in a clinical setting is unknown. This study focused on cooperative effects of serum components and UTs on OATP1B1-mediated transport of SN-38.

Methods

Uptake of SN-38 by OATP1B1 was evaluated using cells stably expressing OATP1B1. Serum was obtained from > 400 ESKD patients undergoing hemodialysis. Deproteinized serum was combined with human serum albumin (HSA) to explore the effects of albumin-bound and unbound serum compounds.

Results

Uptake clearance of SN-38 in OATP1B1 cells decreased by 40% in the presence of uremic serum residue with albumin compared to that in the presence of normal serum residue. Additional UTs (3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, hippuric acid, indole-3-acetic acid, and 3-indoxyl sulfate) combined with normal serum residue in HSA decreased OATP1B1-mediated SN-38 transport by 32.1% compared to that in the presence of normal serum residue. The inhibitory effect of albumin-unbound fraction with UTs and normal serum residue was comparable to that of uremic serum residue, with an uptake decrease of 17.2% compared to that reported in the presence of normal serum residue.

Conclusions

Hepatic uptake of SN-38 via OATP1B1 decreases in ESKD patients through cooperative inhibitory effects of UTs and serum components.

http://ift.tt/2niuOQ9

Polymeric micelles as mighty nanocarriers for cancer gene therapy: a review

Abstract

Purpose

Gene therapy has shown extensive potential to treat human diseases occurring from the defection of genes like various types of cancers. The cationic polymers, as non-viral gene carriers, offer the ability to engineer carrier systems having customized features that can be adapted to suit any system. Upon polymeric micelle systems' core–shell structure, micelles can create the capacity to load genes/gene-drugs into the different micelle compartments, respectively.

Methods

The search will be managed in Pubmed, Medline, Cochrane library, Embase and Proquest for articles related to polymeric micelle-based gene delivery in order to cancer gene therapy using the accommodative search terms. A database of the first search of all search engines results will be made and repeated articles will be removed. After that, the related articles will be selected, and also the references of selected articles will be searched in order to find any other articles to complete the search database.

Results

This study reviews kinds of polymeric nanomicelles, which have been used in gene therapy, critical parameters for micelle-based gene delivery, challenges and advantages/disadvantages as well as biosafety of nanomicelles in gene delivery systems. Furthermore, the discussion has focused on stimuli-responsive polymers and strategy and mechanisms regarding tumor-selective gene delivery.

Conclusions

This study provides an overview of the advantages/disadvantages of polymeric-based nanocarriers for cancer gene therapy.

http://ift.tt/2nNLX0E

A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Maja de Jonge, Vincent A. de Weger, Mark A. Dickson, Marlies Langenberg, Axel Le Cesne, Andrew J. Wagner, Karl Hsu, Wei Zheng, Sandrine Macé, Gilles Tuffal, Koruth Thomas, Jan H.M. Schellens
PurposeIn tumours with wild-type TP53, the tumour-suppressive function of p53 is frequently inhibited by HDM2. This phase I, dose-escalating study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and pharmacodynamics of SAR405838, an HDM2 inhibitor, in patients with advanced solid tumours (NCT01636479).MethodsIn dose escalation, patients with any locally advanced/metastatic solid tumour with TP53 mutation prevalence below 40%, or documented as TP53 wild-type, were eligible. In the MTD expansion cohort, only patients with de-differentiated liposarcoma were included. Primary end-points were MTD and efficacy in the MTD expansion cohort. Secondary end-points included safety, pharmacokinetics and pharmacodynamics biomarkers.ResultsSeventy-four patients were treated with SAR405838 (50–800 mg once daily [QD], 800–1800 mg weekly and 1800 mg twice weekly). Two patients treated with SAR405838 400 mg QD had thrombocytopaenia as a dose-limiting toxicity (DLT). The MTD for the QD schedule of SAR405838 was 300 mg QD. No DLTs were observed with the weekly schedule; one patient had a DLT of nausea with the 1800 mg twice-weekly dose. Treatment with SAR405838 was associated with increased plasma MIC-1, reflecting p53 pathway activation. In the de-differentiated liposarcoma MTD cohort, 89% of the patients had HDM2 amplification at baseline and no TP53 mutations were observed; best response was stable disease in 56% and progression-free rate at 3 months was 32%.ConclusionSAR405838 had an acceptable safety profile with limited activity in patients with advanced solid tumours. The MTD of SAR405838 was 300 mg QD; MTD was not reached with the weekly schedule.



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Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Jong-chan Lee, Jin Won Kim, Soyeon Ahn, Hyoung Woo Kim, Jongchan Lee, Young Hoon Kim, Kyu-hyun Paik, Jaihwan Kim, Jin-Hyeok Hwang
BackgroundFOLFIRINOX has increased efficacy but also toxicity. Despite various modified FOLFIRINOX regimens, how much reduction is acceptable remains unclear. This study aimed to find the optimal relative dose intensity (RDI, %) of FOLFIRINOX that preserves tumour responses in patients with advanced pancreatic cancer (PC).MethodsWe reviewed 201 patients with PC treated with first-line FOLFIRINOX during 2012–2015. We established a modified Hryniuk model (http://www.rdicalc.com) and defined cumulative RDI (cRDI, %). The optimal cRDI thresholds for response rate (RR) and disease control rate (DCR) were assessed using receiver operating characteristic (ROC) analysis. Relationships between cRDI and haematologic toxicities (neutropenia and febrile neutropenia [FN]) were also analysed according to use of granulocyte colony-stimulating factor (G-CSF).ResultsAmong 156 eligible patients, 133 (48 locally advanced PC and 85 metastatic PC) completed initial treatment plan prior to the first radiological evaluation (median 58 days; 71.8% cRDI). For optimal cRDI thresholds, ROC curves showed a 71.2% cRDI for RR (83.3% sensitivity, 64.7% specificity, and 0.746 area under the curve [AUC]) and a 55.3% cRDI for DCR (93.6% sensitivity, 62.5% specificity and 0.805 AUC). Among 96 patients who did not receive prophylactic G-CSF, cRDI ≥80.1% was a significant predictor for frequent FN (73.7% sensitivity, 72.7% specificity and 0.793 AUC). There was no correlation between cRDI and haematologic toxicities in patients receiving prophylactic G-CSF.ConclusionTo preserve optimal RR and DCR in advanced PC, cRDI values for FOLFIRINOX >70% and >55%, respectively, are recommended. If cRDI is >80%, primary G-CSF prophylaxis is needed.



http://ift.tt/2mEpvHc

Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): For how long?

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): E. Palmerini, N.S. Chawla, S. Ferrari, M. Sudan, P. Picci, E. Marchesi, M. Piccinni Leopardi, I. Syed, K.K. Sankhala, P. Parthasarathy, W.E. Mendanha, M. Pierini, A. Paioli, S.P. Chawla
BackgroundGiant-cell tumours of bone (GCTB) are RANK/RANK-ligand (RANKL) positive, aggressive and progressive osteolytic tumours. Denosumab, a RANKL inhibitor, was FDA-approved for adults and skeletally mature adolescents with unresectable GCTB or when surgical resection is likely to result in severe morbidity. Data on long-term toxicity and activity of denosumab monthly 'GCTB-schedule' (120 mg per 12/year, 1440 mg total dose/year) are lacking.MethodsPatients with GCTB receiving denosumab, 120 mg on days 1, 8, 15, 29 and every 4 weeks thereafter, from 2006 to 2015 treated in two centres were included. Long-term toxicity was evaluated.Results: Ninety-seven patients were identified. 43 patients underwent resection of the tumour with a median time on denosumab treatment of 12 months (range 6–45 months). Fifty-four patients had unresectable GCTB's (male/female 23/31, median age 35 years [range: 13–76 years], 26% presented with lung metastases, 31% had primary tumor located to the spine, 63% were relapsed after previous surgery) with a median time on denosumab of 54 months (9–115 months). In the unresectable GCTB group, tumour control and clinical benefits were observed in all patients undergoing denosumab, whereas 40% of patients discontinuing denosumab had tumour progression after a median of 8 months (range 7–15 months).Adverse eventsOverall, six (6%) patients developed osteonecrosis of jaw (ONJ): 1/43 (2%) in the resectable group, 5/54 (9%) in the unresectable group, with a 5-year ONJ-free survival of 92% (95% CI 84–100). Only patients with prolonged treatment experienced mild peripheral neuropathy (6/54, 11%), skin rash (5/54, 9%), hypophosphataemia (2/54, 4%) and atypical femoral fracture (2/54, 4%).ConclusionsProlonged treatment with denosumab has sustained activity in GCTB, with a mild toxicity profile. The dose-dependent toxicity observed recommends a careful and strict monitoring of patients who need prolonged treatment. Decreased dose-intensity schedules should be further explored in unresectable GCTB.



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Influenza vaccination in adult patients with solid tumours treated with chemotherapy

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Albert Vollaard, Imke Schreuder, Lizzy Slok-Raijmakers, Wim Opstelten, Guus Rimmelzwaan, Hans Gelderblom
Patients with solid tumours receiving chemotherapy are at risk for influenza complications. Yearly influenza vaccination is recommended to patients treated with chemotherapy. However, adherence to vaccination is low, most likely due to lack of data on efficacy, optimal timing and safety of vaccination. There is scarce evidence for the effectiveness of the influenza vaccine in adult patients with solid tumours and chemotherapy on reduction of pneumonia, decreased mortality and fewer interruptions of oncological treatment. A review of 20 non-randomised serological studies in adult patients with different cancer types and chemotherapy provides insight in general trends of response to vaccination. Overall, the magnitude of the antibody response after influenza vaccination (i.e. seroconversion) can be lower than in healthy controls, but the majority of patients with solid tumours is able to mount a timely, protective immunological response (i.e. seroprotection) regardless of chemotherapy schedule, similar to healthy controls. Small sample sizes, patient heterogeneity and lack of comparable study designs limit more specific recommendations related to cancer type and optimal timing of vaccination. The inactivated influenza vaccine is safe to administer to immunosuppressed patients; side-effects are similar to those in healthy individuals. Although vaccination before start of chemotherapy is preferred to ensure optimal protection in adults with solid tumours, also vaccination during chemotherapy can reduce influenza-related complications considering the overall trends in serological response. Given the increased morbidity and mortality of influenza, influenza vaccination should be advocated as an inexpensive and safe preventive measure in patients with solid tumours receiving chemotherapy.



http://ift.tt/2mbBdND

Immune cells and mediators involved in the inflammatory responses induced by a P-I metalloprotease and a phospholipase A2 from Bothrops atrox venom

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Danilo L. Menaldo, Carolina P. Bernardes, Karina F. Zoccal, Anna L. Jacob-Ferreira, Tássia R. Costa, Maria P.F.M. Del Lama, Rose M.Z.G. Naal, Fabiani G. Frantz, Lúcia H. Faccioli, Suely V. Sampaio
Bothrops envenomations can promote severe inflammatory responses by inducing edema, pain, leukocyte recruitment and release of chemical mediators by local cells. In the present study, two toxins from Bothrops atrox venom (the P-I metalloprotease Batroxase and the acidic phospholipase A2 BatroxPLA2) were evaluated in relation to their inflammatory effects induced in vivo and in vitro, mainly focusing on the participation of different immune cells and inflammatory mediators. Both toxins mainly promoted acute inflammatory responses with significant recruitment of neutrophils in the early hours (1–4h) after administration into the peritoneal cavity of C57BL/6 mice, and increased infiltration of mononuclear cells especially after 24h. Among the mediators induced by both toxins are IL-6, IL-10 and PGE2, with Batroxase also inducing the release of L-1β, and BatroxPLA2 of LTB4 and CysLTs. These responses pointed to possible involvement of immune cells such as macrophages and mast cells, which were then evaluated in vitro. Mice peritoneal macrophages stimulated with Batroxase produced significant levels of IL-6, IL-1β, PGE2 and LTB4, whereas stimulus with BatroxPLA2 induced increases of IL-6, PGE2 and LTB4. Furthermore, both toxins were able to stimulate degranulation of RBL-2H3 mast cells, but with distinct concentration-dependent effects. Altogether, these results indicated that Batroxase and BatroxPLA2 promoted local and acute inflammatory responses related to macrophages and mast cells and to the production of several mediators. Our findings should contribute for better understanding the different mechanisms of toxicity induced by P-I metalloproteases and phospholipases A2 after snakebite envenomations.



http://ift.tt/2mEkjTW

JAK inhibitors in dermatology: The promise of a new drug class

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): William Damsky, Brett A. King
New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase–signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.



http://ift.tt/2mRQr7u

Infraorbital cutaneous horn

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Divya Shenoy, Joy King, Julie P. Wyatt, Robert T. Brodell




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Table of Contents

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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Antimalarial therapy for granuloma annulare: Results of a retrospective analysis

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Sungat K. Grewal, Courtney Rubin, Misha Rosenbach




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Information for Readers

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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JAAD Case Reports Article List

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





http://ift.tt/2n70WWH

Can mindfulness-based interventions improve the quality of life of patients with moderate/severe alopecia areata? A prospective pilot study

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Rosella Gallo, Carlo Chiorri, Giulia Gasparini, Alessio Signori, Anna Burroni, Aurora Parodi




http://ift.tt/2mREUVq

Journal Based CME Instructions and Information

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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Beyond JAAD April 2017: Articles of interest to dermatologists from the nondermatologic literature

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Andrew Bronin, Robert Phelps, Robert Sidbury




http://ift.tt/2mRHz1n

The role of imaging in the management of patients with nonmelanoma skin cancer

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Deborah MacFarlane, Komal Shah, Ashley Wysong, Ximena Wortsman, Tatyana R. Humphreys
While uncomplicated cases of nonmelanoma skin cancer can be treated with surgery, destruction, or topical therapy alone, advanced or neglected cases require more complex management decisions. Dermatologists and dermatologic surgeons should be familiar with the imaging techniques relevant to cutaneous oncology and their value in different clinical scenarios. Herein we review imaging modalities used in management of nonmelanoma skin cancer.



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Editorial Board

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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CME examination

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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Clinicopathologic analysis of atypical hand, foot, and mouth disease in adult patients

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Julie Second, Charles Velter, Sophie Calès, François Truchetet, Dan Lipsker, Bernard Cribier
BackgroundHand, foot, and mouth disease is a contagious viral infection usually affecting children. A resurgence of cases in adults, mainly caused by coxsackievirus A6 and with an atypical and more severe presentation, has taken place.ObjectiveThe goal was to examine the clinical, histologic, and immunohistochemical features of this disease in adults.MethodsThis is a retrospective study on documented cases of adult hand, foot, and mouth disease from France's Dermatology Department of Strasbourg University Hospital and Bel-Air Hospital in Thionville.ResultsSix patients with severe and atypical presentation were included, 4 caused by coxsackievirus A6. The histologic features were: spongiosis, neutrophilic exocytosis, massive keratinocyte necrosis, shadow cells in the upper epidermis, vacuolization of basal cells, necrotic cells in follicles and sweat glands, dense superficial dermal infiltrate of CD3⁺ lymphocytes, and strong granulysin expression.LimitationsThis is a retrospective case series.ConclusionIn adult patients presenting with atypical hand, foot, and mouth disease caused by coxsackievirus A6, biopsy specimens show distinctive changes in the epidermis but also in adnexal structures. The inflammatory infiltrate is made of T cells with a cytotoxic profile, with numerous granulysin-positive cells, as observed in severe drug-induced eruption with necrosis of keratinocytes.



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Answers to CME examination

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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Experience with oral tofacitinib in 8 adolescent patients with alopecia universalis

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Leslie Castelo-Soccio




http://ift.tt/2mRz5Yn

The American Board of Dermatology, Inc Future Meeting & Exam Dates

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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Direct immunofluorescence microscopy of skin biopsy samples preserved in honey

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Raghavendra Rao, Anuradha Jindal, Balbir Bhogal, Sathish B. Pai




http://ift.tt/2mRBwKz

The role of imaging in the management of patients with nonmelanoma skin cancer

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Tatyana R. Humphreys, Komal Shah, Ashley Wysong, Frank Lexa, Deborah MacFarlane
When treating aggressive skin cancers, pre- and postoperative imaging provides important information for treatment planning and multidisciplinary cooperation of care. It is important for dermatologists to recognize the clinical scenarios where imaging is indicated in the management of skin cancer. We here address the most common indications for imaging in cutaneous oncology and how to best utilize the modalities available.



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The blind patient and the cosmetic dermatology consultation: Who defines beauty?

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Sailesh Konda, Puja Kathrotiya, Jane M. Grant-Kels




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Answers to CME examination

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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The cancer stem cell phenotype as a determinant factor of the heterotypic nature of breast tumors

Publication date: Available online 16 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Nuno A. Fonseca, Ana Filipa Cruz, Vera Moura, Sérgio Simões, João Nuno Moreira
Gathering evidence supports the existence of a population of cells, with stem-like characteristics, named cancer stem cells (CSC), which is involved not only in tumor recurrence but also in tumorigenicity, metastization and drug resistance. Several markers have been used to identify putative CSC sub-populations in different cancers. Notwithstanding, it has been acknowledged that breast CSC may originate from non-stem cancer cells (non-SCC), interconverting through an epithelial-to-mesenchymal transition-mediated process, and presenting several deregulated canonical and developmental signaling pathways. These support the heterogeneity that, directly or indirectly, influences fundamental biological features supporting breast tumor development. Accordingly, CSC have increasingly become highly relevant cellular targets.In this review, we will address the stemness concept in cancer, setting the perspective on CSC and their origin, by exploring their relation and regulation within the tumor microenvironment, in the context of emerging therapeutic targets. Within this framework, we will discuss nucleolin, a protein that has been associated with angiogenesis and, more recently, with the stemness phenotype, becoming a common denominator between CSC and non-SCC for multicellular targeting.



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RECENT ADVANCES IN GENITOURINARY TUMORS: A REVIEW FOCUSED ON BIOLOGY AND SYSTEMIC TREATMENT

Publication date: Available online 14 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Aránzazu González del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M. Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A. García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2. While sunitinib and pazopanib continue to be the standard first-line treatment in metastatic renal cell carcinoma of clear cell histology, nivolumab and and cabozantinib are now the agents of choice in the second-line setting. In relation to urothelial bladder carcinoma, new potential molecular targets such as FGFR3, PI3K/AKT, RTK/RAS, CDKN2A, ARIDIA, ERBB2 have been identified. Response to adjuvant cisplatin-based chemotherapy appears to be related to basal, luminal, and p53-like intrinsic subtypes. A phase II study with eribulin and a maintenance phase II trial with vinflunine have shown promising results. Similarly, the use of the check point inhibitors in advanced disease is likely to revolutionize the management of patients who have progressed after cisplatin-based chemotherapy. In prostate cancer, seven mutually exclusive molecular subtypes have been identified by the TCGA project. Chemotherapy has been consolidated as a key treatment for castration-sensitive metastatic prostate cancer, and abiraterone, enzalutamide, cabazitaxel, and radium-223 remain standard therapeutic options for men with metastatic castration-resistant prostate cancer. All this progress will undoubtedly contribute to the development of new treatments and therapeutic strategies that will improve the survival and quality of life of our patients.



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Kallistatin Suppresses Cancer Development by Multi-Factorial Actions

Publication date: Available online 14 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Julie Chao, Pengfei Li, Lee Chao
Kallistatin was first identified in human plasma as a tissue kallikrein-binding protein and a serine proteinase inhibitor. Kallistatin via its two structural elements regulates differential signaling cascades, and thus a wide spectrum of biological functions. Kallistatin's active site is essential for: inhibiting tissue kallikrein's activity; stimulating endothelial nitric oxide synthase and sirtuin 1 expression and activation; and modulating the synthesis of the microRNAs, miR-34a, miR-21 and miR-203. Kallistatin's heparin-binding site is crucial for antagonizing the signaling pathways of vascular endothelial growth factor, tumor necrosis factor-α, Wnt, transforming growth factor-β and epidermal growth factor. Circulating kallistatin levels are markedly reduced in patients with prostate and colon cancer. Kallistatin administration attenuates angiogenesis, inflammation, tumor growth and invasion in animal models and cultured cells. Therefore, tumor progression may be substantially suppressed by kallistatin's pleiotropic activities. In this review, we will discuss the role and mechanisms of kallistatin in the regulation of cancer development.



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Stem cell transplantation for immunoglobulin light chain (AL) amyloidosis

Publication date: Available online 16 March 2017
Source:Current Problems in Cancer
Author(s): Taimur Sher, Morie A. Gertz




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Interleukin-6 and prostate cancer: Current developments and unsolved questions

Publication date: Available online 16 March 2017
Source:Molecular and Cellular Endocrinology
Author(s): Zoran Culig, Martin Puhr
Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models. Experimental therapies have been proposed in order to block the IL-6/STAT3 signaling pathway. In this context, the anti-IL-6 antibody siltuximab (CNTO 328) has been demonstrated to inhibit growth of prostate tumors in vitro and in vivo and delays progression towards castration resistance. However, clinically, the anti-IL-6 antibody was not successful as a monotherapy in phase II studies in patients with metastatic PCa. IL-6 is implicated in regulation of cellular stemness by increasing phosphorylation of STAT3. The cytokine has also a role in development of resistance to the non-steroidal anti-androgen enzalutamide. Endogenous inhibitors of IL-6 are suppressors of cytokine signaling and protein inhibitors of activated STAT. Although they inhibit signal transduction through STAT3, they may also exhibit anti-apoptotic effects. On the basis of complexity of IL-6 action in PCa, an individualized approach is needed to identify patients who will benefit from anti-IL-6 therapy in combination with standard treatments.



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Molecular endocrinology of vitamin D on the epigenome level

Publication date: Available online 16 March 2017
Source:Molecular and Cellular Endocrinology
Author(s): Carsten Carlberg
The molecular endocrinology of vitamin D is based on the facts that i) its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is the high affinity ligand of the nuclear receptor vitamin D receptor (VDR) and ii) the transcription factor VDR is the unique target of 1,25(OH)2D3 in the nucleus. Short-term alterations of the epigenome are primarily changes in the post-translational modification status of nucleosome-forming histone proteins, the consequences of which are i) a local increase or decrease in chromatin accessibility and ii) the activation or repression of gene transcription. Vitamin D has via VDR a direct effect on the expression of several hundred primary target genes implying numerous effects on the epigenome. Next-generation sequencing methods, such as ChIP-seq and FAIRE-seq, were applied to cellular model systems of vitamin D signaling, such as THP-1 human monocytes, and provided data for a chromatin model of vitamin D signaling. Key points of this model are that i) in the absence of ligand VDR binds to a limited number of loci within accessible chromatin, ii) a stimulation with ligand increases the number of DNA-bound VDR molecules, iii) VDR's access to genomic DNA is supported by pioneer factors, such as PU.1 in monocytes, iv) VDR binding leads to local opening of chromatin and v) the binding strength of topologically associating domain anchor forming CCCTC-binding factor sites upstream and downstream of prominent VDR binding sites is changing in response to ligand stimulation. This model provides the present basis of the molecular endocrinology of vitamin D and will be in future refined by the integration of vitamin D-sensitive chromatin markers and other genome-wide data, such as the 1,25(OH)2D3-sensitive binding of co-factors, chromatin modifying enzymes and chromatin remodeling proteins.



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YiQiFuMai Powder Injection attenuates coronary artery ligation-induced myocardial remodeling and heart failure through modulating MAPKs signaling pathway

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Li-zhi Pang, Ai-chun Ju, Xian-jie Zheng, Fang Li, Yun-fei Song, Yan Zhao, Yuan-feng Gu, Fei-leng Chen, Chun-Hua Liu, Jin Qi, Zhen Gao, Jun-ping Kou, Bo-yang Yu
Ethnopharmacological relevanceYiQiFuMai Powder Injection (YQFM), a traditional Chinese medicine prescription re-developed based on Sheng-Mai-San, is a classical and traditional therapeutic for clinical heart failure (HF) and angina. However, its potential mechanism against HF remains unclear.Aim of the studyThe present study observes the therapeutic role of YQFM and mechanisms underlying its effects on coronary artery ligation (CAL)-induced myocardial remodeling (MR) and HF.MethodsMR and HF were induced by permanent CAL for 2 weeks in ICR mice. Then mice were treated with YQFM (0.13g/kg, 0.26g/kg and 0.53g/kg) once a day until 2 weeks later. Cardiac structure and function were evaluated by echocardiography. Serum lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) were measured by biochemical kits and cardiomyocyte morphology was assessed by hematoxylin-eosin (HE) staining. Myocardial hydroxyproline (HYP), serum amino-terminal pro-peptide of pro-collagen type III (PIIINP), and Masson's trichrome staining were employed to evaluate cardiac fibrosis. Circulating level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) was tested by ELISA kit to predict prognosis of CAL-induced HF. Effects of YQFM on the mitogen-activated protein kinases (MAPKs) pathway after CAL operation was evaluated by Western blotting and immunohistochemistry assay.ResultsYQFM (0.53g/kg) improved the left ventricular (LV) function and structure impairment after 2 weeks in CAL mice. YQFM administration also decreased LDH and CK activities, circulating levels of MDA, PIIINP, NT-proBNP, and HYP contents. Moreover, YQFM ameliorated cardiac injury and fibrosis. Furthermore, YQFM (0.53g/kg) inhibited the myocardial phosphorylation of MAPKs in HF mice.ConclusionOur findings suggest that YQFM attenuates CAL-induced HF via improving cardiac function, attenuating structure damage, oxidative stress, necrosis, collagen deposition, and fibrosis. In addition, YQFM ameliorates cardiac remodeling and HF, partially through inhibiting the MAPKs signaling pathways. These data provide insights and mechanisms into the widely application of YQFM in patients with HF, MI and other ischemic heart diseases.

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Mechanisms underlying the diuretic effect of Gomphrena celosioides Mart. (Amaranthaceae)

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Paulo César de Paula Vasconcelos, Danilo Ramos Spessotto, Jane Vasconcelos Marinho, Marcos José Salvador, Arquimedes Gasparotto Junior, Candida Aparecida Leite Kassuya
Ethnopharmacological relevanceGomphrena celosioides (Amaranthaceae) is a native medicinal plant found in Mato Grosso do Sul State that is used for treating urinary tract and kidney stones. This study aimed to evaluate the diuretic effects of ethanolic extract from G. celosioides (EEGC) on acute and extended diuresis to provide a pharmacological basis for its use in traditional medicine.Aim of the studyTo evaluate the diuretic and natriuretic activity of EEGC and its mechanism of action in an animal model.Materials and methodsEEGC (30, 100 and 300mg/kg) was orally administered in male Wistar rats, and urinary excretion was measured at intervals of up to 8h after administration. To evaluate participation of the nitric oxide (NO), prostaglandin and bradykinin pathways in its effect, respective inhibitors were also administered together with effectives doses of EEGC and compared with control groups. A 7-day model with daily administration and urine measurement was also carried out.ResultsOral administration of doses of 100 and 300 significantly increased urine output after 8h compared to the control group. It was observed this effect is dependent on the NO, prostaglandin and bradykinin pathways because their inhibitors reduced the diuretic effects of EEGC. Moreover, after 7 days of treatment, the effect was sustained and a decrease in serum aldosterone was observed in the extract group.ConclusionAccording to the results, G. celosioides extract showed diuretic and natriuretic effects associated with more than one mechanism of action. Considering that all diuretic drugs are currently available for the treatment of volume and electrolyte disturbances, especially hypertensive status, the present results may have clinical relevance and open new possibilities for the development of new natural diuretics from G. celosioides.

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Anticonvulsant activity and acute neurotoxic profile of Achyranthes aspera Linn.

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Dinesh Y. Gawande, Dmitry Druzhilovsky, Raghbir Chand Gupta, Vladimir Poroikov, Rajesh Kumar Goel
Ethnopharmacological relevanceRoot powder of Achyranthes aspera Linn. (A. aspera) belongs to family Amaranthaceae is used in Indian traditional medicine for the management of epilepsy and its efficacy is widely acclaimed among the different rural communities.Aim of the studyThe present study was aimed to establish the possible anticonvulsant effect of A. aspera methanolic root extract using acute anticonvulsant models and to evaluate the acute toxicity and neurotoxic potential A. aspera extract.Material and methodsA. aspera methanolic extract was standardized with respect to betaine using HPTLC. The maximal electroshock (MES), pentylenetetrazol (PTZ), picrotoxin and bicuculline induced seizure models were used to evaluate the anticonvulsant potential of standardized A. aspera root extract. The GABA content in cortex and hippocampus of extract treated mice was evaluated using HPLC. Moreover, the animals were also evaluated for acute toxicity study and neurotoxicity test.ResultsA significant enhancement in the seizure threshold was observed by A. aspera extract (5 and 10mg/kg) treated mice in PTZ, picrotoxin and bicuculline models as compared to saline treated mice respectively, whereas the extract failed to show protection in MES induced seizures. Moreover, A. aspera treatment (5 and 10mg/kg) significantly enhances the GABA levels in hippocampus and cortex as compared to saline treated group. A. aspera root extract was devoid of any sign of acute toxicity as well as neurotoxicity.ConclusionsA. aspera root extract exhibits significant anticonvulsant effect by facilitation of GABAergic neurotransmission in the brain.

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Centaurium erythraea methanol extract protects red blood cells from oxidative damage in streptozotocin-induced diabetic rats

Publication date: Available online 16 March 2017
Source:Journal of Ethnopharmacology
Author(s): Miloš Đorđević, Mirjana Mihailović, Jelena Arambašić Jovanović, Nevena Grdović, Aleksandra Uskoković, Anja Tolić, Marija Sinadinović, Jovana Rajić, Danijela Mišić, Branislav Šiler, Goran Poznanović, Melita Vidaković, Svetlana Dinić
Ethnopharmacological relevanceCentaurium erythraea Rafn (CE) is a traditional medicinal herb in Serbia with antidiabetic, digestive, antipyretic and antiflatulent effects.Aim of the studyTo investigate the potential protective effects of the methanol extract of the aerial parts of CE against glyco-oxidative stress in red blood cells (RBCs) in rats with experimentally induced diabetes.Material and MethodsDiabetes was induced in Wistar rats by intraperitoneal (i.p.) injection of multiple low-dose streptozotocin (STZ) (40mg/kg, for five consecutive days), with the 1^st day after the last STZ injection taken as the day of diabetes onset. The methanol extract of CE (100mg/kg) was administered orally and daily, two weeks before the first STZ injection, during the 5-day treatment with STZ, and for four weeks after the STZ injections (pre-treated group) or for four weeks after diabetes onset (post-treated group). The effect of CE extract administration on the redox status of RBCs was evaluated by assessing lipid peroxidation, the ratio of reduced/oxidized glutathione (GSH/GSSG), the level of S-glutathionylated proteins (GSSP) and the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in RBCs four weeks after diabetes onset. The major biochemical parameters of diabetes, protein glycation/glycosylation of erythrocytes and parameters which correlate with their aggregation and deformability were also evaluated.ResultsDaily application of CE extract to STZ-induced diabetic rats provided important antidiabetic effects, observed in both pre-treated and post-treated groups of diabetic rats as elevated serum insulin concentration, reduction of blood glucose and glycated hemoglobin concentrations and an improved lipid profile. Antioxidant effects of CE extract were detected in RBCs of diabetic rats and observed as decreased lipid peroxidation and ameliorated oxidative damage as a result of increased SOD, CAT and GR activities, an improved GSH/GSSG ratio and reduced GSSP levels. Moreover, the CE extract protected RBC proteins from hyperglycemia-induced damage by reducing non-enzymatic glycation and enzymatic glycosylation processes. CE extract was more effective when applied before diabetes induction (pre-treated group).ConclusionsThe results of this study show that the Centaurium erythraea methanol extract protects RBCs in diabetic animals from oxidative damage. They provide additional support for the application of this traditionally used plant in diabetes management.

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Genotoxicity evaluation of Hwanglyeonhaedok-tang, an herbal formula

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Seong Eun Jin, Mee-Young Lee, Chang-Seob Seo, Hyekyung Ha, Ji-Young Kim, Hyeun-Kyoo Shin
Ethnopharmacological relevanceHwanglyeonhaedok-tang (Huanglianjiedu-tang, Orengedoku-to), a traditional herbal formula, is used for the treatment of inflammatory, gastrointestinal and cardiovascular diseases.PurposeThe purpose of this study was to evaluate the genotoxic potential of Hwanglyeonhaedok-tang water extract (HLHDT).MethodsA genotoxicity test was conducted using a bacterial reverse mutation test (Ames test), an in vitro chromosome aberration test using Chinese hamster lung cells, and an in vivo micronucleus test using ICR mouse bone marrow.ResultsIn the Ames test, which used different Salmonella typhimurium (S. typhimurium) and Escherichia coli (E. coli) strains, HLHDT did not increase the number of revertant colonies of S. typhimurium strains TA98, TA100 and TA1535 as well as E. coli strains with or without S9 mix. However, the number of revertant colonies with the S. typhimurium TA1537 strain and S9 mix increased in a dose-dependent manner. The chromosome aberration test showed that HLHDT did not increase the number of structural or numerical chromosome aberrations in a short-period test (6h) with S9 mix. By contrast, HLHDT significantly increased the number of structural chromosome aberrations in a short-period (6h) or continuous (22h) test without S9 mix. In the micronucleus test, no significant increase was observed in micronucleated polychromatic erythrocytes, and no significant decrease was observed in polychromatic to total erythrocytes.ConclusionsThese results indicate that HLHDT might be genotoxic, based on both the Ames and chromosome aberration tests. Therefore, further in vivo studies will be needed to define the mechanism of this genotoxicity.

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The protective effect of the active components of ERPC on diabetic peripheral neuropathy in rats

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Gai-mei Hao, Yong-gang Liu, Yan Wu, Wei Xing, Shu-zhen Guo, Yong Wang, Zheng-lin Wang, Chun Li, Tian-tian Lv, Hong-liang Wang, Tian-jiao Shi, Wei Wang, Jing Han
Ethnopharmacological relevanceEuonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis are popular plants used in traditional Chinese medicine to treat diabetes.Aim of the studyThe aim of the study is to investigate the therapeutic effect of the active components of Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis (cERPC) on diabetic peripheral neuropathy in the rats and explore the underlying mechanism involved.MethodsAfter diabetes was induced in rats for 20 weeks, cERPC or water was administered for 12 weeks. After a hot plate test, motor nerve conduction velocity and sciatic nerve blood flow were determined; the sciatic nerves were isolated for toluidine blue staining; and the fibre area, fibre diameter, axon area, axon diameter and myelin thickness were evaluated. The levels of the myelin basic protein, myelin protein zero, Oct6 and Krox20 were measured by western blot or immunofluorescence.ResultscERPC was efficient in reducing the response latency, increasing motor nerve conduction velocity, enhancing sciatic nerve blood flow and ameliorating the pathological changes in diabetic rats. cERPC also had a role in increasing the levels of myelin basic protein and myelin protein zero and improving the expression of Oct6 and Krox20 in sciatic nerves of diabetic rats.ConclusionscERPC ameliorates diabetic peripheral neuropathy by attenuating electrophysiological, circulatory and morphological alterations, which is mediated by the Oct6-Krox20 pathway.

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Cyperus Rotundus L. extract suppresses RANKL-induced osteoclastogenesis through NFATc1/c-fos downregulation and prevent bone loss in OVX-induced osteoporosis rat

Publication date: Available online 15 March 2017
Source:Journal of Ethnopharmacology
Author(s): Chang-Jun Kum, Eun-Young Kim, Jae-Hyun Kim, Bina Lee, Ju-Hee Min, Jun Heo, Jong-Hyun Kim, Mijung Yeom, Youngjoo Sohn, Hyuk-Sang Jung
Ethnopharmacological relevanceCyperus Rotundus L. (CyR) has been widely used for the treatment of gynecologic disorder. Recent studies have reported that CyR can prevent the formation of cystic follicles and ovarian malfunction. However, the effects of CyR on osteoclastogenesis and postmenopausal osteoporosis remain unknown.Aim of the studyThis study was aimed to investigate the preventive effects of CyR on RANKL-induced osteoclast formation and ovariectomy (OVX)-induced bone loss.Materials and methodsIn this in vitro study, we investigate the anti-osteoporotic effect of CyR on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis, the formation of tartrate-resistant acid phosphatase (TRAP) multinucleated cells, pit formation, transcription factors such as NFATc1 and c-Fos, and mRNA expression of osteoclast-associated genes were investigated. Forty 12-weeks female Sprague-Dawley rats for in vivo effect of CyR were used and OVX rat model was determined. The rats were randomly assigned into sham group and four OVX groups, i.e. OVX with D.W; OVX with estradiol (E2, 100 μg/kg/day), OVX with CyR-L (16mg/kg/day), OVX with CyR-H (160mg/kg/day). The treatment lasted for 8weeks.ResultsCyR inhibited osteoclast differentiation and pit formation in the RANKL-induced osteoclastogenesis of RAW 264.7 cells. Reverse transcription polymerase chain reaction analysis also showed that CyR reduced the mRNA expression of osteoclast-associated genes such as carbonic anhydrase II, TRAP, RANK, cathepsin K, matrix metalloproteinase 9, nuclear factor of activated T cells cytoplasmic 1 (NFATc1), and c-Fos. In addition, CyR decreased protein levels of NFATc1 and c-Fos. CyR inhibited trabecular bone loss in the femur caused by OVX.ConclusionThe results of this study indicate that CyR inhibits the RANKL-induced osteoclast differentiation in RAW 264.7 cells and trabecular bone loss in OVX rats.

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An update of dens invaginatus in the diagnosis and treatment

Abstract

Dens invaginatus is a malformation with varying anatomical features, posing challenges to treatment. Early and accurate diagnosis plays a significant role in selecting the appropriate treatment. The diagnosis of teeth with a complex root canal system including dens invaginatus has made progress with the application of three-dimensional imaging techniques in endodontics. Advanced treatment options provide hope for teeth that could not be saved before. This review discusses diagnostic methods and treatment options for teeth with dens invaginatus, and provides guidelines for the management of dens invaginatus cases in clinic. Current as well as traditional diagnostic techniques are summarised. Treatment options including state-of-the-art alternatives are presented for coronal dens invaginatus and radicular dens invaginatus.

This article is protected by copyright. All rights reserved.

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Non-invasive Liver Ablation Using Histotripsy: Preclinical Safety Study in an in Vivo Porcine Model

Publication date: Available online 17 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Eli Vlaisavljevich, Gabe Owens, Jonathan Lundt, Dejan Teofilovic, Kimberly Ives, Alexander Duryea, Jim Bertolina, Theodore H. Welling, Zhen Xu
This study investigates the safety profile for use of histotripsy, a non-invasive ultrasonic ablation method currently being developed for the treatment of liver cancer, for liver ablation in an in vivo porcine model. Histotripsy treatments were applied to the liver and hepatic veins of 22 porcine subjects, with half of the subjects receiving systemic heparinization. Vital signs (heart rate, blood pressure, temperature, electrocardiogram and SpO2) were monitored throughout the procedure and for 1 h post-treatment. Blood was drawn at six points during the experiment to analyze blood gases, liver function and free hemoglobin levels. All treatments were guided and monitored by real-time ultrasound imaging. After treatment, the tissue was harvested for histological analysis. Results indicated that histotripsy generated well-defined lesions inside the liver and around the treated hepatic veins of all subjects in both treatment groups. Vital signs and blood analysis revealed that animals responded well to histotripsy, with all animals surviving the treatment. One animal in the non-heparinized group had a transient increase in pH and decreases in blood pressure, heart rate and PCO2 during the 15-min vessel treatment, with these changes returning to baseline levels soon after the treatment. Overall, the results indicate that histotripsy can safely be performed on the liver without the need for systemic heparinization, even in regions containing large hepatic vessels, supporting its future use for the treatment of liver cancer.



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Measuring Endotracheal Tube Depth by Bedside Ultrasound in Adult Patients in an Intensive Care Unit: A Pilot Study

Publication date: Available online 17 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Fenglin Dong, Canhong Zhu, Huiwen Xu, Jiajia Wang, Yehan Zhu, Qingmin Fan, Jian'an Huang, Wei Lei
The aim of the study described here was to evaluate the feasibility and accuracy of measuring endotracheal tube (ETT) depth with ultrasound in adult patients in an intensive care unit (ICU). The distance between the upper margin of the cuff and the upper margin of the aortic arch (Duc-ua) of 67 ICU patients was measured by ultrasound, and the time of measurement was recorded. The level of agreement between the distance between the tip of the ETT and the carina (Dtt-c) measured by ultrasound (U-Dtt-c) and Dtt-c measured by bronchoscopy (B-Dtt-c) was assessed using linear regression and a Bland–Altman plot. There was a significant correlation between B-Dtt-c and U-Dtt-c (r = 0.844, p < 0.001). Also, the Bland–Altman plot revealed strong agreement between B-Dtt-c and U-Dtt-c. The time it took to measure ETT depth by ultrasound was 33.91 ± 5.43 s. In conclusion, bedside ultrasound provides a novel and convenient method for measuring the depth of ETT in ICU patients.



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