Biology enters the scene—a new perspective on bilingualism, cognition, and dementia

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Thomas H. Bak, Ian Robertson
The question of whether bilingualism can influence cognitive functions in healthy aging as well as in brain diseases is currently a topic of an intense debate. In a study published in this issue of the "Neurobiology of Ageing", Estanga et al. are breaking new ground by combining cognitive and biological approaches. Based on the data from the Guipuzkoa Alzheimer Project, they report that, compared with monolinguals, early bilinguals are not only characterized by a better cognitive performance in several domains and a lower prevalence of Alzheimer's disease but also by lower levels of t-tau in their cerebrospinal fluid. We suggest that sustained activation of noradrenergic signaling pathways associated with bilingualism could provide a possible mechanism linking results of this study with previous observations of delayed onset of dementia in bilinguals.



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Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Anamika Giri, Kin Y. Mok, Iris Jansen, Manu Sharma, Christelle Tesson, Graziella Mangone, Suzanne Lesage, José M. Bras, Joshua M. Shulman, Una-Marie Sheerin, Mónica Díez-Fairen, Pau Pastor, María José Martí, Mario Ezquerra, Eduardo Tolosa, Leonor Correia-Guedes, Joaquim Ferreira, Najaf Amin, Cornelia M. van Duijn, Jeroen van Rooij, André G. Uitterlinden, Robert Kraaij, Michael Nalls, Javier Simón-Sánchez
Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.



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SNCA mutation p.Ala53Glu is derived from a common founder in the Finnish population

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Petra Pasanen, Eino Palin, Risto Pohjolan-Pirhonen, Minna Pöyhönen, Juha O. Rinne, Markku Päivärinta, Mika H. Martikainen, Valtteri Kaasinen, Marja Hietala, Maria Gardberg, Anna Maija Saukkonen, Johanna Eerola-Rautio, Seppo Kaakkola, Jukka Lyytinen, Pentti J. Tienari, Anders Paetau, Anu Suomalainen, Liisa Myllykangas
Mutations in SNCA are rare causes of familial Parkinson's disease (PD). We have previously described a novel p.Ala53Glu mutation in 2 Finnish families. To assess this mutation's frequency among Finnish PD patients, we screened 110 PD patients (mean age-of-onset 60 years) from Western Finland by Sanger sequencing of the third coding exon of SNCA. In addition, a sample of 47 PD subjects (mean age-of-onset 53 years) originating from Southern and Eastern Finland were studied using next-generation sequencing covering SNCA. Only one new individual with the p.Ala53Glu mutation was identified, confirming that this mutation is a rare cause of PD in the Finnish population. To search for a possible common origin of the p.Ala53Glu mutation, haplotype analysis was conducted in 2 families and in a patient from a third family (6 affected subjects) using both STR markers and a genome-wide SNP array. The results show that patients with the p.Ala53Glu mutation share a haplotype spanning a minimum of 5.7 Mb suggesting a common founder.



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Genetic analysis of CHCHD2 in a southern Spanish population

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Cristina Tejera-Parrado, Silvia Jesús, Ismael Huertas-Fernández, Inmaculada Bernal-Bernal, Marta Bonilla-Toribio, Isabel Córdoba-Tevar, Irene Abreu-Rodríguez, Fátima Carrillo, Maravilla Bernal-Escudero, Laura Vargas-González, Manuel Carballo, Pilar Gómez-Garre, Pablo Mir
Researching genetic factors involved in Parkinson's disease (PD) is crucial to increase our knowledge about the pathophysiology of the disorder. A missense mutation has recently been reported within CHCHD2, a gene newly associated with autosomal dominant PD. Subsequent studies in different ethnic populations have not reached any conclusive result about the role of CHCHD2 in PD. Therefore, the aim of this study was to investigate the implication of this gene for a PD population from southern Spain (including 536 PD patients and 518 unrelated control subjects). We studied all 4 exons of CHCHD2 and their exon-intron boundary regions. Four variants were observed in non-coding regions. No significant differences were observed in the allele frequencies of these variants between patients and controls. Thus, our study suggests that CHCHD2 is probably not involved in the etiopathogenesis of PD in our population.



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Analysis of CHCHD2 gene in familial Parkinson's disease from Calabria

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Monica Gagliardi, Grazia Iannello, Carmela Colica, Grazia Annesi, Aldo Quattrone
Parkinson's disease (PD) is the most common form of degenerative Parkinsonism with a prevalence of 1% of those older than 65 years. PD is characterized by the combination of slowness of movement (bradykinesia), muscular rigidity, resting tremor, and postural instability. Recently, using a genome-wide linkage analysis and exome sequencing, a group identified a candidate gene (CHCHD2) in a large Japanese family with autosomal dominant Parkinson's disease. The aim of this study was to evaluate the presence of CHCHD2 mutations in a cohort of 165 familial patients with clinically diagnosed PD and 200 control subjects from South Italy. No mutations in CHCHD2 were found in our 165 PD patients. This result suggests that CHCHD2 mutations might not be the common cause of PD in South Italy.



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Genetic and functional analysis of TBK1 variants in Korean patients with sporadic amyotrophic lateral sclerosis

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Young-Eun Kim, Ki-Wook Oh, Min-Young Noh, Minyeop Nahm, Jinseok Park, Su Min Lim, Ja-Hyun Jang, Eun-Hae Cho, Chang-Seok Ki, Seungbok Lee, Seung Hyun Kim
The TANK-binding kinase 1 (TBK1) gene has recently been identified as a novel causative gene of amyotrophic lateral sclerosis (ALS). This study aims to determine the frequency and spectrum of TBK1 variants and their functional implications in Korean patients with sporadic ALS (sALS). TBK1 sequences were analyzed in 129 consecutive patients with sALS using either multigene panel or exome sequencing. One frameshift (c.1414delA) and 3 missense variants of uncertain significance in TBK1 were found in 4 patients each. In vitro functional studies revealed that the c.1414delA (p.Ile472Serfs*8) variant was associated with reduced mRNA expression of TBK1. Moreover, protein expression of this variant in patient-derived fibroblasts disrupted binding to autophagy adapter proteins and inhibited the function of TBK1 in HEK293T cells. In contrast, the 3 other missense variants of uncertain significance showed normal mRNA expression and no abnormalities in protein function. Based on these findings, the frequency of pathogenic TBK1 variants in Korean sALS patients was estimated to be 0.8% (1/129). In conclusion, pathogenic variants in TBK1 are rare but could be responsible for sALS in a small number of Korean patients.



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Contents

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50





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Beneficial effect of bilingualism on Alzheimer's disease CSF biomarkers and cognition

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Ainara Estanga, Mirian Ecay-Torres, Almudena Ibañez, Andrea Izagirre, Jorge Villanua, Maite Garcia-Sebastian, M. Teresa Iglesias Gaspar, Ane Otaegui-Arrazola, Ane Iriondo, Monserrat Clerigue, Pablo Martinez-Lage
Bilingualism as a component of cognitive reserve has been claimed to delay the onset of Alzheimer's disease (AD). However, its effect on cerebrospinal fluid (CSF) AD-biomarkers has not been investigated. We assessed cognitive performance and CSF AD-biomarkers, and potential moderation effect of bilingualism on the association between age, CSF AD-biomarkers, and cognition. Cognitively healthy middle-aged participants classified as monolinguals (n = 100, nCSF = 59), early (n = 81, nCSF = 55) and late bilinguals (n = 97, nCSF = 52) were evaluated. Models adjusted for confounders showed that bilinguals performed better than monolinguals on digits backwards (early-bilinguals p = 0.003), Judgment of Line Orientation (JLO) (early-bilinguals p = 0.018; late-bilinguals p = 0.004), and Trail Making Test-B (late-bilinguals p = 0.047). Early bilingualism was associated with lower CSF total-tau (p = 0.019) and lower prevalence of preclinical AD (NIA-AA classification) (p = 0.02). Bilingualism showed a moderation effect on the relationship between age and CSF AD-biomarkers and the relationship between age and executive function. We conclude that bilingualism contributes to cognitive reserve enhancing executive and visual-spatial functions. For the first time, this study reveals that early bilingualism is associated with more favorable CSF AD-biomarker profile.



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Cognitive reserve moderates the association between functional network anti-correlations and memory in MCI

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Nicolai Franzmeier, Katharina Buerger, Stefan Teipel, Yaakov Stern, Martin Dichgans, Michael Ewers
Cognitive reserve (CR) shows protective effects on cognitive function in older adults. Here, we focused on the effects of CR at the functional network level. We assessed in patients with amnestic mild cognitive impairment (aMCI) whether higher CR moderates the association between low internetwork cross-talk on memory performance. In 2 independent aMCI samples (n = 76 and 93) and healthy controls (HC, n = 36), CR was assessed via years of education and intelligence (IQ). We focused on the anti-correlation between the dorsal attention network (DAN) and an anterior and posterior default mode network (DMN), assessed via sliding time window analysis of resting-state functional magnetic resonance imaging (fMRI). The DMN-DAN anti-correlation was numerically but not significantly lower in aMCI compared to HC. However, in aMCI, lower anterior DMN-DAN anti-correlation was associated with lower memory performance. This association was moderated by CR proxies, where the association between the internetwork anti-correlation and memory performance was alleviated at higher levels of education or IQ. In conclusion, lower DAN-DMN cross-talk is associated with lower memory in aMCI, where such effects are buffered by higher CR.



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Emissions of ammonia, carbon dioxide and particulate matter from cage-free layer houses in California

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Xingjun Lin, Ruihong Zhang, Shumei Jiang, Hamed El-Mashad, Hongwei Xin
Cage-free housing systems have attracted considerable attention in the United States recently as they provide more space and other resources (such as litter area, perches, and nest boxes) for hens and are considered to be more favorable from the standpoint of hen welfare. This study was carried out to quantify emissions of aerial ammonia (NH3), carbon dioxide (CO2) and particulate matter (PM10 and PM2.5) from cage-free layer houses in California and compare the values with those for other types of layer houses. Two commercial cage-free houses with 38,000 hens each were monitored from March 1, 2012 to April 1, 2013. Results show that NH3 and CO2 concentrations in the houses were affected by ventilation rate, which was largely influenced by ambient air temperature. The PM10 and PM2.5 concentrations in the houses depended on the activity of birds, ventilation rate and relative humidity of the ambient air. The average emission rates of NH3, CO2, PM10 and PM2.5 were 0.29, 89.9, 0.163 and 0.020 g d⁻¹ hen⁻¹, respectively. The NH3 emission rate determined in this study was higher than those of aviary houses. The PM10 and PM2.5 emission rates were higher than those reported for high-rise layer houses.



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Simultaneous Separation and Determination of 15 Organic UV Filters in Sunscreen Cosmetics by HPLC-ESI-MS/MS

Abstract

Objective

A comprehensive methodology for the simultaneous determination of 15 multiclass organic UV filters in sunscreen cosmetics was developed using high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS).

Methods

Sunscreen cosmetics of various matrices, such as toning lotion, emulsion, cream, and lipstick, were analyzed. Ultrasound-assisted extraction (UAE) was utilized as the extraction technique for sample preparation. The 15 UV filters were chromatographically separated by two groups of mobile phase system on an XBridge C₁₈ analytical column (150 mm × 2.1 mm I.D., 3.5 μm particle size) and quantified using HPLC-ESI-MS/MS. The quantitation was performed using the external calibration method.

Results

The established method was validated in terms of linearity, sensitivity, specificity, accuracy, stability, intra- and inter-day precisions, recovery, and matrix effect. The method was also applied for the determination of UV filters in commercial sunscreen cosmetics.

Conclusion

The experimental results demonstrated that the developed method was accurate, rapid, sensitive, and can be used for the analytical control of sunscreen cosmetics.

This article is protected by copyright. All rights reserved.

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Direct Immunofluorescence Findings in Discoid Lupus Erythematosus and Bullous Pemphigoid

No abstract available

http://ift.tt/2ijGlvE

Coexistence of Adult Onset Eruptive Syringoma and Bilateral Renal Cell Carcinoma: A Case Report

Abstract: Eruptive syringoma is an unusual variant of syringoma, which usually presents before or during puberty. It typically occurs in large numbers as multiple yellow-brown–colored papules, which may show spontaneous regression. Because some authors have proposed that it could present as a reactive process of eccrine ducts to an inflammatory reaction caused by an unknown trigger, the exact pathomechanism is still unclear. There are also reports in the literature on the association of eruptive syringoma in Down syndrome, diabetes, milium, sarcoidosis, and psychiatric disorders. Some reports in the literature highlighted the association of eruptive syringomas and neoplasms. We describe here a case of adult-onset eruptive syringoma in a 53-year-old man and discuss the possibility of its association with renal cell carcinoma as a paraneoplastic phenomenon.

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Superficial Acral Fibromyxoma: Report of 13 Cases With New Immunohistochemical Findings

Background: Superficial acral fibromyxoma (SAF) is a benign, soft tissue neoplasm preferably located on the digits. Methods: We collected 13 cases of SAF and evaluated their clinical, histopathologic, and immunohistochemical features. Results: This study included 9 males and 4 females, median age 54 years. The patients presented with a solitary asymptomatic or tender mass, most of them arising on fingers or toes. Histopathologically all lesions consisted of nonencapsulated dermal nodules, composed of spindled cells with variable myxoid and/or fibrotic stroma. Some lesions were well circumscribed (6/12, 50%), whereas other ones appeared poorly demarcated (6/12, 50%). The stroma was predominantly myxoid (53%), myxoid-collagenous (31%) or mostly collagenous (15%). Neoplastic cells expressed immunoreactivity for CD34 (8/11), CD99 (9/12), and nestin (7/7); whereas MUC4 (0/11) and Bcl-2 (0/7) resulted negative. Conclusions: Nestin is the best immunohistochemical marker for SAF with higher sensitivity than CD34, although nestin is also positive in dermatofibrosarcoma protuberans and therefore is not helpful in differential diagnosis between SAF and dermatofibrosarcoma protuberans. Cellular digital fibromas and acquired reactive digital fibroma probably are neoplasms closely related to SAF. The homogeneous reactivity for CD99, the negativity for Bcl-2 and lack of the honeycomb infiltration of the subcutis help to rule out myxoid dermatofibrosarcoma protuberans, whereas the negativity for MUC4 and Bcl-2 are helpful tools to rule out low-grade fibromyxoid sarcoma and spindled-cell lipoma, respectively.

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Histologic Assessment of Lichenoid Dermatitis Observed in Patients With Advanced Malignancies on Antiprogramed Cell Death–1 (anti–PD-1) Therapy With or Without Ipilimumab

Abstract: Lichenoid drug reaction is a common adverse reaction in patients taking immune-modulatory agents such as antiprogramed cell death (PD-1) and cytotoxic T lymphocyte antigen–4 agents. The authors describe the clinical and histologic features of lichenoid drug reaction in 20 biopsies from 15 patients on anti–PD-1 agents and 9 biopsies from 7 patients on anti–PD-1 plus ipilimumab therapy. Clinically, all except 2 patients presented with discrete, violaceous exanthematous papules to plaques. The lichenoid inflammation in the majority (18 of 29 biopsies) was florid although histology was quite heterogeneous. Nevertheless, there was frequent involvement of the superficial follicular epithelium and acrosyringium, and also a propensity to blister that occurred in approximately 20% of the biopsies. Occasional patients had disease closely resembling lichen planus, although all of these biopsies had some atypical features for lichen planus such as parakeratosis. Dermal eosinophils were common particularly in those with mild inflammation. The lichenoid reaction was responsive to topical steroid or oral systemic treatment in general, and the anti–PD-1 agent had to be ceased in only one patient.

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Nevus Spilus (Speckled Lentiginous Nevus) in the Oral Cavity: Report of a Case and Review of the Literature

Abstract: The congenital melanocytic nevus is a pigmented melanocytic lesion that presents at birth or shortly thereafter. It is commonly described on the skin, usually on the trunk and extremities. Only five intraoral cases of congenital melanocytic nevi have been described in the English literature. A nevus spilus (speckled lentiginous nevus) is a clinical variant of congenital melanocytic nevus. The authors present the case of a 19-year-old male with an intraoral nevus spilus. The anterior mandibular gingiva exhibited multiple speckled, pigmented papules and macules on a thickened, hyperplastic macular background. Microscopic examination revealed characteristic morphologic features of intramucosal nevi extending into the deep portions of the submucosa. Although other authors have reported similar clinical presentation in the oral mucosa, no other case reports were found in the English literature classifying an intraoral congenital nevus as an intraoral nevus spilus. The sixth case of an intraoral congenital melanocytic nevus and the first case subclassified as an intraoral nevus spilus (speckled lentiginous nevus) is reported, with a review of the literature.

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A 64-Year-Old Woman With an Atrophic Plaque on the Thigh—Answer

No abstract available

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An Index Case of Concomitant Tumoral and Ichthyosiform Mycosis Fungoides–Like Presentation of Chronic Adult T-cell Leukemia/Lymphoma Associated With Upregulation of TOX

Abstract: Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities. Histopathologic examination of the hand biopsy revealed coalescing nodules of large atypical noncerebriform lymphocytes with focal areas of epidermotropism. Phenotypically, the infiltrate was positive for β-F1, CD2, CD4, CD5, CD7, Foxp3, and CD25. In both biopsies, there was striking upregulation of TOX (thymocyte selection–associated high mobility group box factor) in the nuclei of neoplastic cells. The second biopsy taken from the ichthyotic patch on the patient's left leg showed a subtle pattern of epidermal infiltration by atypical noncerebriform lymphocytes and a distinct compact scale consistent with the clinical picture of ichthyosis. The histopathologic appearance was that of a yet undescribed ichthyosiform mycosis fungoides–like presentation of chronic ATLL. In addition, the observed upregulation of nuclear TOX may play an oncogenic role in ATLL. The course to date in this patient has been relatively indolent, although the patients believe that large cell transformation could portend more aggressive disease.

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Pemetrexed-Induced Pseudocellulitis Reaction With Eosinophilic Infiltrate on Skin Biopsy

Abstract: Peripheral edema with painful erythema is an increasingly recognized but poorly understood cutaneous adverse reaction to the antifolate agent pemetrexed. It is frequently misdiagnosed as cellulitis, and when it occurs, it is often dose-limiting. The authors report the case of a patient with preexisting lower extremity edema who developed extensive painful, bilateral erythema 5 days after administration of pemetrexed. An eosinophil-rich dermal inflammatory infiltrate was noted histologically. The authors review previously reported cases of pemetrexed-induced pseudocellulitis and discuss possible pathophysiology.

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Differentiating Intralymphatic Histiocytosis, Intravascular Histiocytosis, and Subtypes of Reactive Angioendotheliomatosis: Review of Clinical and Histologic Features of All Cases Reported to Date

Abstract: Reactive angioendotheliomatosis (REA) is a rare benign angioproliferative condition of the skin, which has been noted to occur in patients with a variety of underlying systemic diseases. Histopathologically, this condition is characterized by vascular proliferation, and endothelial cell hyperplasia within the lumina and around dermal vessels, without significant cellular atypia. Since the first case of RAE was reported in 1958, multiple histologic patterns of benign cutaneous vascular proliferations with similar clinical presentations to RAE have been described in the literature and have been proposed as subtypes of the originally described condition. Among these entities are diffuse dermal angiomatosis (DDA), acroangiodermatitis, glomeruloid angioendotheliomatosis, and angiomatosis associated with cryoproteins. It has also been proposed that another entity, characterized by the benign proliferation of histiocytes within the lumina of cutaneous vessels, is a subtype of RAE. Histiocytosis within dermal vessels, in conjunction with skin pathology, was first reported in 1994. Based on the appearance of involved vessels, it was initially believed that the histiocytic proliferations were within the lumina of capillaries. Hence, the term intravascular histiocytosis was introduced to describe this histologic finding. However, subsequent introduction of an immunohistochemical (IHC) marker specific for lymphatic vessels demonstrated that most cases of cutaneous histiocyte proliferation are intralymphatic, rather than truly intravascular. However, there have also been reports of IHC-confirmed cases of true intravascular (intracapillary) histiocytosis. In this study, clinical and histologic data from all of the cases of RAE and IHC-confirmed cases of intravascular histiocytosis and intralymphatic histiocytosis reported in the literature to date are examined. Through comparison of the frequency with which key clinical and histologic features present in cases of each group, the authors provide improved clarity of the similarities and differences between these 3 entities.

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Next-Generation Sequencing Reveals Pathway Activations and New Routes to Targeted Therapies in Cutaneous Metastatic Melanoma

Background: Comprehensive genomic profiling of clinical samples by next-generation sequencing (NGS) can identify one or more therapy targets for the treatment of metastatic melanoma (MM) with a single diagnostic test. Methods: NGS was performed on hybridization-captured, adaptor ligation–based libraries using DNA extracted from 4 formalin-fixed paraffin-embedded sections cut at 10 microns from 30 MM cases. The exons of 182 cancer-related genes were fully sequenced using the Illumina HiSeq 2000 at an average sequencing depth of 1098X and evaluated for genomic alterations (GAs) including point mutations, insertions, deletions, copy number alterations, and select gene fusions/rearrangements. Clinically relevant GAs (CRGAs) were defined as those identifying commercially available targeted therapeutics or therapies in registered clinical trials. Results: The 30 American Joint Committee on Cancer Stage IV MM included 17 (57%) male and 13 (43%) female patients with a mean age of 59.5 years (range 41–83 years). All MM samples had at least 1 GA, and an average of 2.7 GA/sample (range 1–7) was identified. The mean number of GA did not differ based on age or sex; however, on average, significantly more GAs were identified in amelanotic and poorly differentiated MM. GAs were most commonly identified in BRAF (12 cases, 40%), CDKN2A (6 cases, 20%), NF1 (8 cases, 26.7%), and NRAS (6 cases, 20%). CRGAs were identified in all patients, and represented 77% of the GA (64/83) detected. The median and mean CRGAs per tumor were 2 and 2.1, respectively (range 1–7). Conclusion: Comprehensive genomic profiling of MM, using a single diagnostic test, uncovers an unexpectedly high number of CRGA that would not be identified by standard of care testing. Moreover, NGS has the potential to influence therapy selection and can direct patients to enter relevant clinical trials evaluating promising targeted therapies.

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Acquired Localized (Monodactylous) Longitudinal Pachyonychia and Onychocytic Carcinoma In Situ (2 Cases): Part II

Abstract: The authors have recently proposed to use the name pachyonychia as an umbrella term that includes 2 distinctly different entities in the form of congenital pachyonychia and acquired longitudinal pachyonychia. Congenital pachyonychia is defined by a diffuse hyperkeratosis of the nail bed. Acquired longitudinal pachyonychia correspond to the true definition of pachyonychia, that is, a thickened nail plate without subungual keratosis. Acquired (monodactylous) pachyonychia can be diffuse typifying onychomatricoma or localized as a longitudinal band with three etiological possibilities: onychomatricoma, onychocytic matricoma, and onychocytic carcinoma. On histopathological examination, onychomatricoma is a fibroepithelial tumor; conversely, onychocytic matricoma and carcinoma are purely epithelial tumors. The purpose of this study was to present the clinical, pathological, and immunohistochemical profiles of 2 cases of in situ onychocytic carcinoma, to discuss the role of high-risk human papillomavirus in the pathogenesis of this tumor, and to confirm the interest value of nail clipping microscopy in the surgical planning of the acquired (monodactylous) pachyonychia band pattern. Two men were referred for a longitudinal thickening of the lateral part of the nail plate of their fingers. The bands were yellowish with a faint to dominant black coloration. Nail clippings were obtained before excision in one case; the nail plate was thickened with minute holes in a honeycomb pattern. Nail biopsy specimens revealed an onychocytic carcinoma with epithelial projections inducing active production of the nail plate and multiple minute cavitations into the thick nail plate. Hair-related keratins were expressed in all specimens. One tumor expressed p16 in a diffuse pattern, whereas the other showed an unspecific faint patchy staining. p53 was negative. A clinical finding of longitudinal pachyonychia, which by nail clipping microscopy contains small cavities in a honeycomb-like pattern, should be considered an alert to the possibility of a malignant lesions.

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Folliculocentric Lichen Sclerosus et Atrophicus in a 10-Year-Old Girl

Abstract: Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory scarring disease with a predilection for the anogenital area; however, 15%–20% of LSA cases are extragenital. The folliculocentric variant is rarely reported and less well understood. The authors report a rare case of extragenital, folliculocentric LSA in a 10-year-old girl. The patient presented to the dermatology clinic for evaluation of an asymptomatic eruption of the arms and legs, with no vaginal or vulvar involvement. Physical examination revealed the presence of numerous 2–4 mm, mostly perifollicular, hypopigmented, slightly atrophic papules and plaques. Many of the lesions had a central keratotic plug. Cutaneous histopathological examination showed features of LSA. Based on clinical and histological findings, folliculocentric extragenital LSA was diagnosed.

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A 64-Year-Old Woman With an Atrophic Plaque on the Thigh—Question

No abstract available

http://ift.tt/2iQwnPE

Nodules on the Hands

No abstract available

http://ift.tt/2ik0CRN

Nodules on the Hands: Challenge

No abstract available

http://ift.tt/2ijOmks

BRAF Mutational Intertumoral Discrepancies: Think About Technical Limitations Instead of Mutational Heterogeneity

No abstract available

http://ift.tt/2iQGC6e

Reexcision Perineural Invasion and Epithelial Sheath Neuroma Possibly on a Spectrum of Postinjury Reactive Hyperplasia Mediated by IL-6

Abstract: Epithelial sheath neuroma is a rarely recognized but established entity in the medical literature. First described in 2000 by Requena et al, there have only been 7 published cases to date, mostly in female patients and presenting as symptomatic solitary lesions on the back without a known history of trauma. In 2006, Beer et al described and reviewed a dozen cases in which epithelial sheath neuroma-like features were seen in the advent of a surgical procedure, which was termed "re-excision perineural invasion" and attributed to possible eccrine duct implantation during surgery. Our case is a 66-year-old male patient who underwent an excision of a melanocytic neoplasm in which a reactive epithelial sheath neuroma was incidentally discovered in the excision specimen, adjacent to the biopsy site cicatrix. Histologically, there was benign cutaneous nerve hyperplasia with a proliferation of squamous epithelium in intimate apposition to the nerve bundles in the superficial dermis. We postulate that the process active in the formation of re-excision perineural invasion is the same as in epithelial sheath neuroma and that minor trauma not appreciable on histologic examination is responsible in the latter entity. We performed IL-6 staining and documented that IL-6 was upregulated at the interface of the nerve and reactive epithelium, but was absent in nerves distant from the site of surgery, suggesting that IL-6 may be essential to the lesion's development. The recognition of reactive epithelial sheath neuroma including the subcategory of re-excision perineural invasion is crucial for the dermatopathologist to prevent mislabeling this reactive entity as a perineural squamous cell carcinoma, which has clinical consequences for the patient such as wider re-excision and radiation treatment. Additionally, we have identified a potential pathophysiologic basis for this lesion.

http://ift.tt/2ippsh6

Anti-NXP2–Positive Paraneoplastic Dermatomyositis With Histopathologic Changes Confined to the Acrosyringia

Background: Paraneoplastic syndromes consist of a group of disorders that are not related to the extension of the primary tumor or its metastases and that might be the first manifestation of a hidden neoplasm. It is a well-known association between dermatomyositis (DM) and cancer, especially gynecological tumors in women and lung cancer in men. Methods: We describe the case of a 67-year-old male who developed muscular weakness and pruritic skin lesions. Skin biopsies were performed and histologic findings were consistent with DM. Results: Skin biopsy showed interface dermatitis with vacuolar degeneration of the basal layer, dermal mucin deposits, and necrotic keratinocytes in the acrosyringia, a finding that has been previously reported in lupus erythematous but not in DM. Autoimmunity tests showed positivity for antinuclear antibodies and anti-NXP2, a recently described antibody associated with juvenile DM and, more rarely, with paraneoplastic DM. Conclusion: We present the first case in the literature with histopathologic changes of DM affecting the acrosyringia. Besides, our patient autoimmunity results support the utility of the new myositis-specific autoantibodies and its relation with a clinical phenotype.

http://ift.tt/2iQGBzc

Scleromatous Changes in an Abdominal Wall Graft: Graft-Versus-Graft Disease, or Chronic Graft Rejection?

Abstract: Abdominal wall transplants are relatively new procedures that are frequently performed in conjunction with multivisceral transplants. The skin of the abdominal wall transplant is often the first site for graft rejection to manifest itself. Prompt recognition can lead to appropriate treatment before the involvement of the underlying viscera. However, the signs of graft rejection are nonspecific and can overlap with other entities. We present a case of a patient who received a multivisceral and abdominal wall transplant from 2 different donors, who presented with acute and eventually chronic graft rejection of the abdominal wall graft. Serial biopsies performed during the course of her treatment demonstrated progressive sclerotic changes in the dermis. Because these changes were confined to the abdominal wall graft, they could represent either chronic graft rejection or graft-versus-graft disease. To date, graft-versus-graft disease has not been documented in these patients. This case illustrates the possibility that patients with multidonor transplants may be at an increased risk for graft failure secondary to multiple potential etiologies.

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A Case of Trichogerminoma With Pilomatrical Differentiation and a Unique Immunohistochemical Profile

Abstract: Trichogerminomas are rare adnexal neoplasms first described by Sau et al in 1992. Including the initial report, 20 cases have been reported, all with similar histological features, namely tumor nodules composed of basaloid cells that form densely packed, round nests or "cell balls" and which demonstrate variable degrees of pilosebaceous differentiation. In this study, the authors report a case of a trichogerminoma with pilomatrical differentiation and a unique immunohistochemical profile. The patient is a 71-year-old man with a well-delineated nodule on the top of the scalp. Histologically, the lesion measured 16 mm in greatest dimension and was composed of nodules of basaloid cells with central, compact, slightly eosinophilic cells nests. Immunohistochemically, the tumor nodules diffusely expressed cytokeratins 34βE12, AE1/3, and CK5/6. Diffuse expression of β-catenin and nuclear expression of p63 were also evident. The peripheral basaloid cells, but not the cell balls, expressed CD10, Ber-EP4, BCL-2, and CK7, the latter a previously unreported finding. The histological findings and immunohistochemical profile are compatible with a diagnosis of a trichogerminoma.

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Unraveling proteome changes of Holstein beef M. semitendinosus and its relationship to meat discoloration during post-mortem storage analyzed by label-free mass spectrometry

Publication date: 10 February 2017
Source:Journal of Proteomics, Volume 154
Author(s): Qianqian Yu, Wei Wu, Xiaojing Tian, Man Hou, Ruitong Dai, Xingmin Li
Label-free proteomics was applied to characterize the effect of post-mortem storage time (0, 4, and 9days at 4°C±1°C) on the proteome changes of M. semitendinosus (SM) in Holstein cattle, and correlations between differentially abundant proteins and meat color traits were investigated. The redness (a*) value decreased significantly (P<0.05) during post-mortem storage, meanwhile, the relative proportion of metmyoglobin increased significantly (P<0.05) from 16.99% at day 0 to 40.26% at day 9. A total of 118 proteins with significant changes (fold change>1.5, P<0.05) was identified by comparisons of day 4 vs. day 0, day 9 vs. day 0, and day 9 vs. day 4. Principal component and hierarchical cluster analyses of these proteins were performed, and results exhibited clear distinctions among samples from different storage times. Eighteen differentially abundant proteins were correlated closely with the a* value of meat. Bioinformatics analyses revealed that most of these proteins were involved in glycolysis and energy metabolism, electron-transfer processes, and the antioxidation function, which implied an underlying connection between meat discoloration and these biological processes.SignificanceIt is always a challenge for scientists to improve the stability of meat color during post-mortem storage and retail display. However, the mechanism involved in meat discoloration has not been unraveled completely, and the application of label-free proteomics in studying meat discoloration has not been reported. Our work discovers some key proteins in SM muscle of Holstein cattle that were correlated with a* value of meat via label-free proteomics. Bioinformatics analyses revealed that some of these differentially abundant proteins were involved in glycolysis and energy metabolism, electron-transfer processes, and the antioxidation function, which implied an underlying connection between meat discoloration and these biological processes. These results provide the theoretic basis on understanding of complicated biochemical changes and underlying molecular mechanisms responsible for meat discoloration.

Graphical abstract

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Aldehyde dehydrogenase activity plays no functional role in stem cell-like properties in anaplastic thyroid cancer cell lines

Abstract

Recent studies have revealed that aldehyde dehydrogenase (ALDH) is a candidate marker for thyroid cancer stem cells, although its activity is flexible. The goal of this study is to clarify the functional significance of ALDH enzymatic activity on thyroid cancer stem cells properties in anaplastic thyroid cancer cell lines. In vitro sphere formation assay was used to judge the stemness of 4 anaplastic thyroid cancer cell lines (FRO, ACT1, 8505C, and KTC3). Two well-known ALDH inhibitors, N,N-diethylaminobenzaldehyde (DEAB) and disulfiram (DS), were first used. DEAB (50 μM) almost completely suppressed ALDH activity without affecting cell proliferation or spherogenicity. Lack of effect of ALDH suppression on spherogenicity was confirmed using shRNA for ALDH1A3, an ALDH isozyme predominantly expressed in anaplastic thyroid cancer cell lines. In contrast, an ALDH2 inhibitor DS (1 μM) inhibited spherogenicity but did not inhibit ALDH1A3 activity. Based on the recent article from another group reporting the importance of sonic hedgehog (Shh) signaling in ALDH activity and spherogenicity in thyroid cancer, the effects of the Shh inhibitor cyclopamine were also studied. Like DS, cyclopamine (1 μM) decreased spherogenicity but not ALDH activity. Finally, exogenous expression of ALDH1A3 in otherwise ALDH⁻ TPC1 cells (a papillary thyroid cancer cell line) revealed no effect on spherogenicity. In conclusion, we here show no functional role for ALDH activity in thyroid thyroid cancer stem cells properties. That is, ALDH activity and spherogenicity are clearly dissociable. Further understanding of thyroid cancer stem cells biology in thyroid cancers remains necessary for the future development of thyroid thyroid cancer stem cells-targeted therapies.

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Insights into the relationships between diabetes, prediabetes, and cancer

Abstract

Diabetes mellitus and cancer are two growing health problems. They have in common many modifiable risk factors including sex, age, obesity, physical activity, diet, alcohol, and smoking, and have a long latency before overtly manifesting. Patients with diabetes experience a roughly 20–25% higher cancer incidence compared to individuals without diabetes, and it depends on cancer site. Moreover, patients with diabetes who further develop cancer have increased early and late mortality in comparison with cancer patients without diabetes. Prediabetes and metabolic syndrome are also related to an increased risk of developing and die from cancer. Possible mechanisms linking diabetes and prediabetes with cancer include hyperglycemia (endogenous or exogenous), hyperinsulinemia, and alterations of insulin-like growth factor system, chronic subclinical inflammation, abnormalities in sex hormone metabolism, and adipokines. It becomes crucial to define the right orientation of the associations between diabetes and cancer in order to identify the modifiable pathogenic mechanisms. The common soil hypothesis claims that prediabetes and diabetes, as well as metabolic syndrome, may be considered a surrogate sign for dietary risk factors of cancer. The clepsydra of foods may help choose foods associated with healthy benefit while avoiding foods associated with harm, including cancer.

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Environmental risk assessment of pesticides: state of the art and prospective improvement from science

Abstract

Pesticide risk assessment in the European regulatory framework is mandatory performed for active substances (pesticides) and the plant protection products they are constituents of. The aim is to guarantee that safe use can be achieved for the intended use of the product. This paper provides a feedback on the regulatory environmental risk assessment performed for pesticide registration at the EU and member state levels. The different steps of pesticide registration are addressed considering both exposure and hazard. In this paper, we focus on the environmental fate and behaviour in surface water together with the aquatic ecotoxicity of the substances to illustrate pesticide regulatory risk assessment performed for aquatic organisms. Current methodologies are presented along with highlights on potential improvements. For instance, as regards exposure aspects, moving from field based to landscape risk assessments is promising. Regarding ecotoxicology, ecological models may be valuable tools when applied to chemical risk assessment. In addition, interest and further developments to better take into account mitigation measures in risk assessment and management are also presented.

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Data to inform a social media component for professional development and practices: A design-based research study

Publication date: February 2017
Source:Data in Brief, Volume 10
Author(s): Jeanette Novakovich, Steven Shaw, Sophia Miah
This DIB article includes the course artefacts, instruments, survey data, and descriptive statistics, along with in-depth correlational analysis for the first iteration of a design-based research study on designing curriculum for developing online professional identity and social media practices for a multi-major advanced professional writing course. Raw data was entered into SPSS software. For interpretation and discussion, please see the original article entitled, "Designing curriculum to shape professional social media skills and identity in virtual communities of practice" (J. Novakovich, S. Miah, S. Shaw, 2017) [1].



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Disordered cortical connectivity underlies the executive function deficits in children with autism spectrum disorders

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Yvonne M.Y. Han, Agnes S. Chan
The present study examined the executive function and cortical connectivity of children with autism spectrum disorders (ASD) and investigated whether the executive function deficits exhibited by these children were differentially affected and associated with the cortical connectivity. The present study compared high-functioning (HFA) and low-functioning (LFA) children with typically developing children (TDC) on their executive functions as measured by the Hong Kong List Learning Test, D2 Test of Concentration, Five Point Test, Children's Color Trail Test, Tower of California Test, and Go/No-Go task and neural connectivity as measured by theta coherence in the distributed fronto-parietal network. Thirty-eight children with ASD (19 HFA and 19 LFA) and 28 TDC children, aged 8–17 years, participated voluntarily in the study. The results on executive function showed that the LFA group demonstrated the poorest performance as exhibited by their Executive Composite and individual executive function scores, while the TDC group exhibited the highest. These results have extended the findings of previous studies in demonstrating that HFA and LFA children have significant differences in their degree of executive function deficits. The results on neural connectivity also showed that children with ASD demonstrated a different pattern of electroencephalography (EEG) coherence from TDC children, as demonstrated by the significantly elevated theta coherence in the fronto-parietal network, and that the severity of executive dysfunction between high- and low-functioning children with ASD was found to be associated with the disordered neural connectivity in these children.



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“Didn’t I just say that?” Comparing parent report and spontaneous speech as indicators of grammatical development

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Manya Jyotishi, Deborah A. Fein, Letitia R. Naigles
BackgroundThe Vineland Adaptive Behavior Scales use parental report to examine communication and social skills in children with typical and atypical development, and exhibit high reliability when compared against overall direct testing. However, findings are mixed comparing Vineland communication/language scores with experimenter-administered tests of language.MethodsThe current study breaks new ground in comparing Vineland reports with direct observation of children's speech by (a) individual items and (b) level of child functioning, focusing on usage of wh-questions, verb tenses, negation, pronouns and noun-verb combinations. Both 'high-verbal' (HV) and 'middle-verbal' (MV) children with ASD are included, as well as a language-matched TD group.ResultsThe results revealed that parent report on the Vineland varies in accuracy of capturing the production of grammatical items by young children with ASD and TD children. While parents' assessment of their child's production of noun-verb combinations and 'who/why' was highly accurate, children's production of pronouns was under-rated by parents. Additionally, parents of HV children also under-rated their child's production of past regular verbs.ConclusionUnderestimation of these grammatical elements could lead to mistaken conclusions about their development in ASD or in individual children.



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Mathematical learning disabilities and attention deficit and/or hyperactivity disorder: A study of the cognitive processes involved in arithmetic problem solving

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Valentín Iglesias-Sarmiento, Manuel Deaño, Sonia Alfonso, Ángeles Conde
BackgroundThe purpose of this study was to examine the contribution of cognitive functioning to arithmetic problem solving and to explore the cognitive profiles of children with attention deficit and/or hyperactivity disorder (ADHD) and with mathematical learning disabilities (MLD).MethodsThe sample was made up of a total of 90 students of 4th, 5th, and 6th grade organized in three: ADHD (n=30), MLD (n=30) and typically achieving control (TA; n=30) group. Assessment was conducted in two sessions in which the PASS processes and arithmetic problem solving were evaluated.ResultsThe ADHD group's performance in planning and attention was worse than that of the control group. Children with MLD obtained poorer results than the control group in planning and simultaneous and successive processing. Executive processes predicted arithmetic problem solving in the ADHD group whereas simultaneous processing was the unique predictor in the MLD sample.ConclusionsChildren with ADHD and with MLD showed characteristic cognitive profiles. Groups' problem-solving performance can be predicted from their cognitive functioning.



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Pulsed laser deposition of HfO2 thin films on indium zinc oxide: Band offsets measurements

Publication date: 1 April 2017
Source:Applied Surface Science, Volume 400
Author(s): D. Craciun, V. Craciun
One of the most used dielectric films for amorphous indium zinc oxide (IZO) based thin films transistor is HfO2. The estimation of the valence band discontinuity (ΔEV) of HfO2/IZO heterostructure grown using the pulsed laser deposition technique, with In/(In+Zn)=0.79, was obtained from X-ray photoelectron spectroscopy (XPS) measurements. The binding energies of Hf 4d5, Zn 2p3 and In 3d5 core levels and valence band maxima were measured for thick pure films and for a very thin HfO2 film deposited on a thick IZO film. A value of ΔEV=1.75±0.05eV was estimated for the heterostructure. Taking into account the measured HfO2 and IZO optical bandgap values of 5.50eV and 3.10eV, respectively, a conduction band offset ΔEC=0.65±0.05eV in HfO2/IZO heterostructure was then obtained.



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A novel microstructural interpretation for the biomechanics of mouse skin derived from multiscale characterization

Publication date: Available online 30 December 2016
Source:Acta Biomaterialia
Author(s): Barbara Lynch, Stéphane Bancelin, Christelle Bonod-Bidaud, Jean-Baptiste Gueusquin, Florence Ruggiero, Marie-Claire Schanne-Klein, Jean-Marc Allain
Skin is a complex, multi-layered organ, with important functions in the protection of the body. The dermis provides structural support to the epidermal barrier, and thus has attracted a large number of mechanical studies. As the dermis is made of a mixture of stiff fibres embedded in a soft non-fibrillar matrix, it is classically considered that its mechanical response is based on an initial alignment of the fibres, followed by the stretching of the aligned fibres. Using a recently developed setup combining multiphoton microscopy with mechanical assay, we imaged the fibres network evolution during dermis stretching. These observations, combined with a wide set of mechanical tests, allowed us to challenge the classical microstructural interpretation of the mechanical properties of the dermis: we observed a continuous alignment of the collagen fibres along the stretching. All our results can be explained if each fibre contributes by a given stress to the global response. This plastic response is likely due to inner sliding inside each fibre. The non-linear mechanical response is due to structural effects of the fibres network in interaction with the surrounding non-linear matrix. This multiscale interpretation explains our results on genetically-modified mice with a simple alteration of the dermis microstructure.Statement of significanceSoft tissues, as skin, tendon or aorta, are made of extra-cellular matrix, with very few cells embedded inside. The matrix is a mixture of water and biomolecules, which include the collagen fiber network. The role of the collagen is fundamental since the network is supposed to control the tissue mechanical properties and remodeling: the cells attach to the collagen fibers and feel the network deformations. This paper challenges the classical link between fibers organization and mechanical properties. To do so, it uses multiscale observations combined to a large set of mechanical loading. It thus appears that the behavior at low stretches is mostly controlled by the network structural response, while, at large stretches, the fiber inner-sliding dominate.

Graphical abstract

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CDKN2A-p53 mediated antitumor effect of Lupeol in head and neck cancer

Abstract

Purpose

The tumor suppressor protein p53 is known to control cell cycle arrest and apoptosis. Lupeol is a phytochemical that has been found to induce apoptosis in different cancer types through the extrinsic pathway. As yet, however, its role in the induction of cell cycle arrest and apoptosis through the intrinsic pathway in head and neck cancer has not been investigated. Here, we aimed at understanding the mechanism underlying the antitumor effect of Lupeol in head and neck cancer.

Methods

The antitumor effect of Lupeol on oral and laryngeal carcinomas was assessed using two in vitro 2D cell line models (HEp-2, UPCI:SCC-131) and, subsequently, an ex vivo 3D tumor explant culture platform that maintains key features of the native tumor microenvironment. The mechanism underlying Lupeol-mediated antitumor responses was delineated using MTT, colony formation, flow cytometry, immunofluorescence, Western blotting and immunohistochemistry assays.

Results

We found that Lupeol induced an enhanced expression of p53 in both cell line models tested and, subsequently, cell cycle arrest at the G1 phase. In addition we found that, following Lupeol treatment, p53 induced Bax expression and activated the intrinsic apoptotic pathway (as measured by Caspase-3 cleavage). Interestingly, Lupeol was also found to trigger G1 cell cycle arrest through up-regulation of the expression of CDKN2A, but not p21, resulting in inhibition of CyclinD1. In an ex vivo platform Lupeol was found to impart a potent antitumor response as defined by inhibition of Ki67 expression, decreased cell viability and concomitant activation (cleavage) of Caspase-3. Finally, we found that Lupeol can re-sensitize primary head and neck squamous cell carcinoma (HNSCC) tumor samples that had clinically progressed under a Cisplatin treatment regimen.

Conclusion

Together, our data indicate that Lupeol may orchestrate a bifurcated regulation of neoplastic growth and apoptosis in head and neck cancers and may serve as a promising agent for the management of tumors that have progressed on a platinum-based treatment regimen.

http://ift.tt/2hDJ1VL

ELMO3 expression indicates a poor prognosis in head and neck squamous cell carcinoma - a short report

Abstract

Purpose

Previously, the engulfment and cell motility 3 (ELMO3) protein has been reported to be involved in cell migration and cytoskeletal remodeling. As of yet, nothing is known about the role of ELMO3 in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to asses ELMO3 expression in postoperatively irradiated HNSCC patients and to evaluate a possible correlation between this expression and patient survival.

Methods

125 postoperatively irradiated HNSCC patients were included in this study. ELMO3 expression was assessed using immunohistochemistry (IHC). The expression of ELMO3 in the respective HNSCC tumor tissues and its lymph node metastases was correlated with patient survival using Kaplan-Meier curve analyses.

Results

Through IHC, ELMO3 expression was detected in 71.2% of the HNSCC cases tested. We found significantly increased overall and disease-free survival rates and decreased recurrence rates in patients with no detectable ELMO3 expression. In reverse, we found that ELMO3 expression served as an independent marker for a decreased overall and disease-free survival.

Conclusion

Our data indicate that in the surgically treated and postoperatively irradiated patients tested, ELMO3 expression serves as a predictive marker for reduced survival.

http://ift.tt/2hVtexU

HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation

Abstract

Purpose

Hematopoietic PBX interacting protein (HPIP), a scaffold protein, is known to regulate the proliferation, migration and invasion in different cancer cell types. The aim of this study was to assess the role of HPIP in ovarian cancer cell migration, invasion and epithelial-mesenchymal transition (EMT), and to unravel the mechanism by which it regulates these processes.

Methods

HPIP expression was assessed by immunohistochemistry of tissue microarrays containing primary ovarian tumor samples of different grades. OAW42, an ovarian carcinoma-derived cell line exhibiting a high HPIP expression, was used to study the role of HPIP in cell migration, invasion and EMT. HPIP knockdown in these cells was achieved using a small hairpin RNA (shRNA) approach. Cell migration and invasion were assessed using scratch wound and transwell invasion assays, respectively. The extent of EMT was assessed by determining the expression levels of Snail, Vimentin and E-cadherin using Western blotting. The effect of HPIP expression on AKT and MAPK activation was also investigated by Western blotting. Cell viabilities in response to cisplatin treatment were assessed using a MTT assay, whereas apoptosis was assessed by determining caspase-3 and PARP cleavage in ovarian carcinoma-derived SKOV3 cells.

Results

We found that HPIP is highly expressed in high-grade primary ovarian tumors. In addition, we found that HPIP promotes the migration, invasion and EMT in OAW42 cells and induces EMT in these cells via activation of the PI3K/AKT pathway. The latter was found to lead to stabilization of the Snail protein and to repression of E-cadherin expression through inactivation of GSK-3β. We also found that HPIP expression confers cisplatin resistance to SKOV3 cells after prolonged exposure and that its subsequent knockdown decreases the viability of these cells and increases caspase-3 activation and PARP proteolysis in these cells following cisplatin treatment.

Conclusions

From these results we conclude that HPIP expression is associated with high-grade ovarian tumors and may promote their migration, invasion and EMT, a process that is associated with metastasis. In addition, we conclude that HPIP may serve as a potential therapeutic target for cisplatin resistant ovarian tumors.

http://ift.tt/2hDHoaU

New Year's Greetings

Publication date: January 2017
Source:Journal of Dermatological Science, Volume 85, Issue 1
Author(s): Yoshiki Tokura




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Editors Choice

Publication date: January 2017
Source:Journal of Dermatological Science, Volume 85, Issue 1





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Palmoplantar pustular psoriasis (PPPP) is characterized by activation of the IL-17A pathway

Publication date: January 2017
Source:Journal of Dermatological Science, Volume 85, Issue 1
Author(s): Robert Bissonnette, Judilyn Fuentes-Duculan, Shunya Mashiko, Xuan Li, Kathleen M. Bonifacio, Inna Cueto, Mayte Suárez-Fariñas, Catherine Maari, Chantal Bolduc, Simon Nigen, Marika Sarfati, James G. Krueger
BackgroundPalmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied.ObjectiveStudy the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs).MethodsSkin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects. RT-PCR, immunohistochemistry and flow cytometry on cells extracted from skin biopsies were used to compare PPPP to other forms of psoriasis.ResultsThere was a significant (p<0.05) increase in the expression of IL-1β, IL-6, LL-37, IL-19, IL-17A, CXCL1 and CXCL2 in PPPP as compared to NPPPP. However, there was no significant difference in expression of IL-23 in PPPP as compared to NPPPP and other forms of psoriasis. The proportion of IL-22⁺ but not IL-17A⁺ mast cells was higher in PPPP as compared to NPPPP (p<0.05).ConclusionThese results suggest that the IL-17A pathway may play a more important role in PPPP than in NPPPP.



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Editorial board

Publication date: January 2017
Source:Journal of Dermatological Science, Volume 85, Issue 1





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Acknowledgement to Reviewers 2016

Publication date: January 2017
Source:Journal of Dermatological Science, Volume 85, Issue 1





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The host immune enhancing agent Korean red ginseng oil successfully attenuates Brucella abortus infection in a murine model

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Alisha Wehdnesday Bernardo Reyes, Huynh Tan Hop, Lauren Togonon Arayan, Tran Xuan Ngoc Huy, Soo Jong Park, Kwang Dong Kim, WonGi Min, Hu Jang Lee, Man Hee Rhee, Yi-Seong Kwak, Suk Kim
Ethnopharmacological relevancePanax ginseng Meyer (Araliaceae), is one of the most valuable traditional Chinese medicines and is used for the treatment of various human diseases. In this study, we elucidated the protective mechanism of the essential oil from Korean red ginseng (RGO) against Brucella infection.Materials and methodsThe effects of RGO on Brucella abortus viability, NO production, uptake and intracellular growth in macrophages were investigated. Mice were intraperitoneally infected with B. abortus and orally treated with RGO for 14 days. The weights and bacterial numbers from each spleen were monitored, and the sera were evaluated for cytokine production.ResultsB. abortus viability was not affected, whereas NO production, internalization and intracellular replication were inhibited in RGO-treated macrophages. Bacterial adherence, F-actin polymerization and MAPK signaling protein phosphorylation (ERK1/2, JNK and p38α) were reduced and the co-localization of B. abortus-containing phagosomes with LAMP-1 was augmented in RGO-treated cells compared to untreated cells. RGO displayed protective effects against cell damage by inhibiting nitrite production during B. abortus infection in macrophages. Moreover, the spleen weight and bacterial burden were lower in the RGO-treated group than in the control group. The uninfected RGO-treated mice displayed increased TNF-α and IFN-γ production, whereas the B. abortus-infected RGO-treated mice showed reduced IL-10 production compared to the control.ConclusionRGO exhibits protective effects against B. abortus infection in vitro and in vivo, which emphasize the beneficial effects of RGO in the prevention and treatment of brucellosis.

Graphical abstract

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Esculentoside A suppresses lipopolysaccharide-induced pro-inflammatory molecule production partially by casein kinase 2

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Yinghua Li, Yan Cao, Jing Xu, Lei Qiu, Weiheng Xu, Jie Li, Yunlong Song, Bin Lu, Zhenlin Hu, Junping Zhang
Ethnopharmacological relevanceEsculentoside A (EsA) is a saponin isolated from the root of Phytolacca esculenta, an herb which has long been used in Traditional Chinese Medicine for various inflammatory diseases. EsA has been reported to have potent anti-inflammatory properties both in vitro and in vivo.Aim of the studyThe present study focused on the molecular mechanism of EsA for its anti-inflammatory effects in RAW264.7 cells stimulated with lipopolysaccharide (LPS).Methods and resultsEnzyme Linked Immunosorbent Assay (ELISA) showed EsA dose dependently inhibited the production of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide in RAW264.7 cells. Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay further confirmed the suppression of LPS-induced TNF-α, IL-6 and iNOS gene expression by EsA on a transcriptional level. Moreover, EsA treatment markedly suppressed LPS-stimulated IκB phosphorylation and degradation as well as LPS-stimulated luciferase reporter construct driven by κB response elements in RAW264.7 cells. In addition, EsA significantly reduced LPS-induced stimulation of p38 and JNK, but not ERK1/2, phosphorylation. Furthermore, we used a computational method called "reverse docking" to search the possible binding proteins of EsA from the potential drug target database (PDTD), and focused on CK2 as the primary binding protein of EsA. Afterward, we further tested EsA directly interacts with recombinant CK2 using SPR assay. In CK2 kinase activity assay, EsA inhibited recombinant CK2 holoenzyme activity obviously in a dose-dependent manner. In addition, TBB (4, 5, 6, 7-tetrabromo-2-benzotriazole, a pharmacological inhibitor of CK2) blocked IL-6 release in a dose-dependent manner, whereas co-treatment of cells with EsA and TBB did not have an additive effect.ConclusionsTaken together, these results indicate that EsA blocks the LPS-induced pro-inflammatory molecules expression, at least in part, by impediment of LPS-triggered activation of NF-κB and p38/JNK MAPK pathways in macrophages. Furthermore, we discovered for the first time EsA as a ligand for CK2, which was involved in the inhibition of EsA to the expression of inflammatory cytokines. These findings extended our understanding on the cellular and molecular mechanisms responsible for the anti-inflammatory activity of EsA.

Graphical abstract

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REDUCED IMMUNOHISTOCHEMICAL EXPRESSION OF ADHESION MOLECULES IN VITILIGO SKIN BIOPSIES

Publication date: Available online 30 December 2016
Source:Pathology - Research and Practice
Author(s): Adriane Reichert Faria, Juliana Elizabeth Jung, Caio César Silva de Castro, Lucia de Noronha
Because defects in adhesion impairment seem to be involved in the etiopathogenesis of vitiligo, this study aimed to compare the immunohistochemical expression of several adhesion molecules in the epidermis of vitiligo and non lesional vitiligo skin.Sixty-six specimens of lesional and non lesional skin from 33 volunteers with vitiligo were evaluated by immunohistochemistry using anti-beta-catenin, anti-E-cadherin, anti-laminin, anti-beta1 integrin, anti-collagen IV, anti-ICAM-1 and anti-VCAM-1 antibodies. Biopsies of vitiligo skin demonstrated a significant reduction in the expression of laminin and integrin. The average value of the immunohistochemically positive reaction area of the vitiligo specimens was 3053.2μm², compared with the observed value of 3431.8μm² in non vitiligo skin (p=0.003) for laminin. The immuno-positive area was 7174.6μm² (vitiligo) and 8966.7μm² (non lesional skin) for integrin (p=0.042). A reduction in ICAM-1 and VCAM-1 expression in the basal layer of the epidermis in vitiligo samples was also observed (p=0.001 and p<0.001, respectively). However, no significant differences were observed with respect to the expression of beta-catenin, E-cadherin, and collagen IV between vitiligo and non lesional skin.Our results suggest that an impairment in adhesion exists in vitiligo skin, which is supported by the diminished immunohistochemical expression of laminin, beta1 integrin, ICAM-1 and VCAM-1.



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Expression Profiles of Cancer Stem Cell Markers: CD133, CD44, Musashi-1 and EpCAM in the Cardiac Mucosa—Barrett’s Esophagus—Early Esophageal Adenocarcinoma—Advanced Esophageal Adenocarcinoma Sequence

Publication date: Available online 30 December 2016
Source:Pathology - Research and Practice
Author(s): Anna Mokrowiecka, Lothar Veits, Christina Falkeis, Jacek Musial, Radzislaw Kordek, Mariusz Lochowski, Jozef Kozak, Agnieszka Wierzchniewska-Lawska, Michael Vieth, Ewa Malecka-Panas
INTRODUCTIONBarrett's esophagus (BE), which develops as a result of gastroesophageal reflux disease, is a preneoplastic condition for esophageal adenocarcinoma (EAC). A new hypothesis suggests that cancer is a disease of stem cells, however, their expression and pathways in BE − EAC sequence are not fully elucidated yet.AIMSWe used a panel of putative cancer stem cells markers to identify stem cells in consecutive steps of BE-related cancer progression.METHODSImmunohistochemistry was performed on formalin-fixed, paraffin-embedded blocks from 58 patients with normal cardiac mucosa (n=5), BE (n=14), early EAC (pT1) from mucosal resection (n=17) and advanced EAC (pT1-T4) from postoperative specimens (n=22). Expression of the CD133, CD44, Musashi-1 and EpCAM was analyzed using respective monoclonal antibodies.RESULTSAll markers showed a heterogeneous expression pattern, mainly at the base of the crypts of Barrett's epithelium and EAC, with positive stromal cells in metaplastic and dysplastic lesions. Immuno-expression of EpCAM, CD44 and CD133 in cardiac mucosa was significantly lower (mean immunoreactivity score (IRS)=1.2; 0.0; 0.4; respectively) compared to their expression in Barrett's metaplasia (mean IRS=4.3; 0.14; 0.7; respectively), in early adenocarcinoma (mean IRS=4.4; 0.29; 1.3; respectively) and in advanced adenocarcinoma (mean IRS=6.6; 0.7; 2.7; respectively) (p<0.05). On the contrary, Musashi-1 expression was higher in BE and early ADC compared to GM and advanced ADC (NS).CONCLUSIONOur results suggest that the stem cells could be present in premalignant lesions. EpCAM, CD44 and CD133 expression could be candidate markers for BE progression, whereas Musashi-1 may be a marker of the small intestinal features of Barrett's mucosa.



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Preparation of high-quality palladium nanocubes heavily deposited on nitrogen-doped graphene nanocomposites and their application for enhanced electrochemical sensing

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Yu Shen, Dejiang Rao, Wushuang Bai, Qinglin Sheng, Jianbin Zheng
A nanocomposite of high-quality palladium nanocubes (PdNCs) decorated nitrogen-doped graphene (NGE/PdNC) was successfully prepared by using bromide ion as a capping agent and polyvinyl pyrrolidone as a stabilizer. The morphology and composition of NGE/PdNC nanocomposites were characterized by field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), X-ray powder diffraction (XRD) and Raman spectra. To explore the application of NGE/PdNC nanocomposites in electrochemistry, the electrocatalytic response to nitrite at a NGE/PdNC-based electrode was investigated. Thus, a highly sensitive and selective electrochemical sensor for the detection of nitrite was constructed based on a glassy carbon electrode modified with the NGE/PdNC nanocomposites. The electrochemical behavior of this nanocomposites was studied by electrochemical impedance spectroscopy, cyclic voltammetry and chronoamperometry. The electrochemical investigations proved that the NGE/PdNC nanocomposites exhibited good electrocatalytic performance for the oxidation of nitrite, including a wide linear range from 5.0×10⁻⁷ to 1.51×10⁻³molL⁻¹, a high sensitivity of 342.4μAmM⁻¹cm⁻² and a low detection limit of 0.11μmolL⁻¹ at the signal-to-noise ratio of 3 (S/N=3). This non-enzymatic sensor also showed a good reproducibility and stability. The obtained NGE/PdNC nanocomposites may be a potential composite for applying in the field of other electrochemical sensing, catalysis and optics.

Graphical abstract

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An ultrasensitive fluorescent probe for rapid determination of thiophenols

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Lin Lin, Xiangqiong Zeng, Yuning Shen, Hailiang Zhu, Yong Qian
An ultrasensitive fluorescent probe TPP was developed for the highly selective detection of thiophenols based on excited-state intramolecular proton transfer (ESIPT) mechanism, its synthesis through a simple straightforward combination of HBT fluorophore with 2,4-dinitrobenzene functional group. A kinetic study of TPP towards thiophenol displayed a fast response time (~150s) and significant turn-on fluorescence enhancement (~60 fold). Selective and competitive experiments exhibited an excellent selectivity of TPP toward thiophenols over biothiols (Cys, GSH) and other aliphatic thiols or nucleophiles. Using this ultrasensitive probe (LOD, 1.05×10⁻⁸M), we have successfully monitored and quantified highly toxic thiophenols in aqueous media and real-water samples.

Graphical abstract

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In situ fabrication of label-free optical sensing paper strips for the rapid surface-enhanced Raman scattering (SERS) detection of brassinosteroids in plant tissues

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Miao Chen, Zhimin Zhang, Minzhuo Liu, Chen Qiu, Hua Yang, Xiaoqing Chen
A surface-enhanced Raman scattering (SERS)-functionalized, gold nanoparticle (AuNPs)-immobilized paper strip was developed to realize label-free rapid detection of brassinosteroids (BRs) in plant tissues. The AuNPs paper strip was fabricated through utilizing poly(γ-glutamic acid) (γ-PGA) as the linker and concentrator for the directly immobilized AuNPs on paper, which can circumvent many drawbacks of the existing SERS substrates. An enhancement factor of 1.13×10⁸, high reproducibility (relative standard deviation of 4.78%), highly sensitive detection limit with a correlation coefficient of 0.99 (1×10^–11M 4-mercaptophenylboronic acid), and long-term stability for the responses of the SERS-functionalized AuNPs paper strip to Raman intensities were achieved by optimizing reaction conditions including the concentrations of γ-PGA and HAuCl4/NaBH4. Ultimately, this developed paper strip was applied to the determination of BRs in plant tissues, obtaining precisions with RSD values in a range of 3.0–13.8%. The SERS-functionalized AuNPs paper strip featuring label-free rapid analysis, and high sensitivity could serve as an excellent alternative for on-site rapid detections.

Graphical abstract

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Determination of aliphatic amines in food by on-fiber derivatization solid-phase microextraction with a novel zeolitic imidazolate framework 8-coated stainless steel fiber

Publication date: 1 April 2017
Source:Talanta, Volume 165
Author(s): Jie Huang, Changrong Ou, Fangying Lv, Yuting Cao, Haiqing Tang, You Zhou, Ning Gan
Some harmful aliphatic diamines, e.g., putrescine (Put) and cadaverine (Cad), play important roles in food safety evaluation. In this study, we proposed on-fiber derivatization solid-phase microextraction analysis of non-volatile aliphatic diamines in fish using zeolitic imidazolate framework 8 (ZIF-8) as a solid-phase microextraction (SPME) coating. It was employed to encapsulate isobutyl chloroformate (IBCF, 40°C, 15min) for aqueous extraction of Put and Cad. After that, the derivatized aliphatic amines were thermally desorbed in the GC injection port and analyzed by GC-MS. The porous and hydrophobic ZIF-8 with high surface area can increase the IBCF loading amount and prevent it from decomposing, thus increasing the amine extraction effectiveness and sensitivity. In SIM mode and using the molecular ion for quantification, the limits of detection for Put and Cad were 27.1 and 33.2μgL⁻¹, respectively under the optimal conditions. The fiber-to-fiber reproducibility values (RSDs) for three ZIF-8 coated fibers were less than 11.4% for both Put and Cad. The extraction with the new fiber was reproducible for at least 30 cycles without a noticeable decrease of performance (RSD<10%). The new fiber was successfully applied to the detection of putrescine and cadaverine in several fish samples and showed good recoveries (78.6–104%).

Graphical abstract

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Measuring MEG closer to the brain: Performance of on-scalp sensor arrays

Publication date: 15 February 2017
Source:NeuroImage, Volume 147
Author(s): Joonas Iivanainen, Matti Stenroos, Lauri Parkkonen
Optically-pumped magnetometers (OPMs) have recently reached sensitivity levels required for magnetoencephalography (MEG). OPMs do not need cryogenics and can thus be placed within millimetres from the scalp into an array that adapts to the individual head size and shape, thereby reducing the distance from cortical sources to the sensors. Here, we quantified the improvement in recording MEG with hypothetical on-scalp OPM arrays compared to a 306-channel state-of-the-art SQUID array (102 magnetometers and 204 planar gradiometers).We simulated OPM arrays that measured either normal (nOPM; 102 sensors), tangential (tOPM; 204 sensors), or all components (aOPM; 306 sensors) of the magnetic field. We built forward models based on magnetic resonance images of 10 adult heads; we employed a three-compartment boundary element model and distributed current dipoles evenly across the cortical mantle.Compared to the SQUID magnetometers, nOPM and tOPM yielded 7.5 and 5.3 times higher signal power, while the correlations between the field patterns of source dipoles were reduced by factors of 2.8 and 3.6, respectively. Values of the field-pattern correlations were similar across nOPM, tOPM and SQUID gradiometers. Volume currents reduced the signals of primary currents on average by 10%, 72% and 15% in nOPM, tOPM and SQUID magnetometers, respectively. The information capacities of the OPM arrays were clearly higher than that of the SQUID array. The dipole-localization accuracies of the arrays were similar while the minimum-norm-based point-spread functions were on average 2.4 and 2.5 times more spread for the SQUID array compared to nOPM and tOPM arrays, respectively.



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Carl Hermann Lücking, 1938–2016

Publication date: Available online 30 December 2016
Source:Clinical Neurophysiology
Author(s): Reinhard Dengler, Günther Deuschl




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Population pharmacokinetics of lenalidomide in multiple myeloma patients

Abstract

Purpose

Lenalidomide disease-specific toxicity profiles and potentially life-threatening adverse events support the consideration of diversity in starting doses. The aim of this study was to conduct a population pharmacokinetic analysis of lenalidomide in multiple myeloma patients to identify and evaluate non-studied covariates that could be used for dose individualization.

Methods

Blood samples were collected from 15 multiple myeloma patients. Nonlinear mixed-effects modeling was used to develop a population pharmacokinetic model and perform covariate analysis. The developed model was used to simulate dose schedules in order to explore the need of different dosing regimens in patients with different covariate values.

Results

The data were accurately described by a one-compartment model with first-order elimination. Absorption was best described using three transit compartments. Creatinine clearance and body surface area were identified as covariates affecting apparent clearance and apparent volume of distribution, respectively. Simulations revealed that lower starting doses than the standard 25 mg/daily could be used in patients with body surface area below 1.8 m² and even higher doses might be necessary for patients with normal renal function and large body surface area.

Conclusions

This study identified creatinine clearance and body surface area as covariates that have a clinically relevant impact on lenalidomide pharmacokinetics using population pharmacokinetics. In addition, the developed population pharmacokinetic model can be used to individualize lenalidomide dose in multiple myeloma patients, taking into account not only creatinine clearance but also body surface area.

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Three-dimensional graphene network/phenolic resin composites towards tunable and weakly negative permittivity

Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): Haikun Wu, Rui Yin, Lei Qian, Zidong Zhang
Three-dimensional (3D) graphene (GR) network/phenolic resin composites with tunable and weakly negative permittivity were prepared by mechanical mixed method. Dielectric properties including permittivity, dielectric loss tangent and alternating current conductivity (σac), were investigated in detail. When the GR content was increased from 8 to 13vol%, a ladder-shape increase of σac was observed, indicating a percolation phenomenon. It was found that, when the GR content exceeded 13vol% the negative permittivity appeared attributed to the formation of 3D interconnected GR network. Moreover, the negative permittivity was easily adjusted by controlling the GR content. Compared with the metal-ceramics in our previous work, the absolute values of negative permittivity were low, which was in favor of impedance matching. For the GR content of 13vol%, high dielectric loss above 25 over the whole frequency was also observed. Finally, the equivalent circuits were used to analyze the reason of the negative permittivity.

Graphical abstract

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New approach to morphological control for polypropylene/polyethylene blends via magnetic self-organization

Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): Yu-Dong Shi, Kai Zhang, Yi-Fu Chen, Jian-Bing Zeng, Ming Wang
Morphological control has been efficiently used to improve the properties of polymer blends/composites. Here we introduce a non-invasive approach to regulate the morphologies of isotactic polypropylene (iPP)/linear low density polyethylene (LLDPE) blends via magnetic self-organization. First, ferric oxide (Fe3O4) particles are added into LLDPE melts to form an LLDPE+Fe3O4 master batch. Second, the master batch is melt-mixed with iPP to form the iPP/(LLDPE+Fe3O4) composites with a random distribution of LLDPE+Fe3O4 droplets. Finally, the randomly distributed Fe3O4 particles self-organize into particle chains in a magnetic field, which induce LLDPE droplets to coalesce with each other to form a strip morphology. The composites with a parallel strip morphology exhibited mechanical enhancement in comparison to the composites with the droplet morphology. For example, the Young's modulus and storage moduli (at −30°C) of the 80/20–10 composites, where the iPP/(LLDPE+Fe3O4) ratio is 80/20, and the content of Fe3O4 particles in LLDPE is 10wt%, with a parallel strip morphology along the tensile direction being 12 and 36% higher than that of the samples with the droplet morphology, respectively. Complex viscosity of the samples with the strip morphology is lower than that of the samples with the droplet morphology because of interfacial slip.

Graphical abstract

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The loading-rate dependent tensile behavior of CNT film and its bismaleimide composite film

Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): Mengsi Zhang, Min Li, Shaokai Wang, Yanjie Wang, Yongyi Zhang, Yizhuo Gu, Qingwen Li, Zuoguang Zhang
Carbon nanotube (CNT) macroscopic assembly, as a promising candidate for the protective and anti-collision materials, has attracted lots of researchers to explore its mechanical behavior under different loading rates. In this paper, the loading-rate dependent mechanical behavior of CNT film and its composite with bismaleimide (BMI) matrix is investigated. The pristine CNT film shows decreased tensile strength by 33.8% when the loading rate increases from 0.05mm/min to 40mm/min. An obvious necking extending phenomenon is observed in the CNT film during the tensile test under lower tensile rates, e.g. 0.05mm/min and 0.5mm/min. However, the random composite film and the oriented composite film both display increased tensile strength, by 58.2% and 35.7% respectively, with the increasing loading rate from 0.05mm/min to 40mm/min. The different loading-rate dependence of tensile behavior is ascribed to the different tensile-induced motions of CNTs and CNT bundles in composite film. Moreover, strain rate sensitivity coefficients of different film are calculated according to a simplified Johnson-Cook model. The results suggest that the pristine CNT film with the strain rate sensitivity coefficient of −0.0941 has a high loading-rate sensitivity, meanwhile polymer infiltration and oriented alignment can weaken the loading-rate sensitivity of CNT film.

Graphical abstract

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Vertical and lateral distribution of fallout 137Cs and soil properties along representative toposequences of central Rif, Morocco

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Haytam Mesrar, Abdelhamid Sadiki, Ali Faleh, Laura Quijano, Leticia Gaspar, Ana Navas
The purpose of this study is to understand and quantify the relationships between current ¹³⁷Cs inventories and the soil properties and the physiographic characteristics. A total of 36 cores were taken in seven transects with different slopes, lithology and land use. The analysis focused on the ¹³⁷Cs mass activity as well as inventories and its relationship with soil properties as grain size and organic matter.The mass activity of ¹³⁷Cs and the inventories varied between 3.6 and 63.7 Bq kg⁻¹ and between 521.7 and 3304.4 Bq m⁻², respectively. At uncultivated soils, high concentrations of ¹³⁷Cs are located in the top 10 cm and decreased exponentially in depth. Cultivated soils record disturbed and heterogeneous ¹³⁷Cs profiles with values of mass activity and inventories up to 38.7 Bq kg⁻¹ and 2510.8 Bq m⁻², respectively.The ¹³⁷Cs inventories were significantly higher in uncultivated soils (mean: 2086.9 Bq m⁻²) compared to cultivated soils (mean: 1397.1 Bq m⁻²). The ¹³⁷Cs mass activity showed a significant positive correlation with organic matter, silt and clay, but it was negatively correlated with sand and pH respectively. High levels of ¹³⁷Cs were found at altitudes between 500 m and 640 m a.s.l, and at slopes from 8° to 11°, as well as in dense scrub land and Fersialitic soils. A principal component analysis showed that more than 86.7% of the variance in ¹³⁷Cs mass activity was explained by the organic matter content and the land use.The results of this study provide insights into the effects of soil properties and physiographic factors on the behaviour of ¹³⁷Cs in soils of Mediterranean environments of North Africa and strengthen the reliability of this radioisotope as an erosion tracer.



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The Impact of Level of Education on Age-Related Deficits in Associative Memory: Behavioral and Neuropsychological Perspectives

Publication date: Available online 30 December 2016
Source:Cortex
Author(s): Dwight J. Peterson, Sanchita Gargya, Ksenia S. Kopeikin, Moshe Naveh-Benjamin
Older adults have difficulty forming associations and binding distinct item components despite mostly preserved item memory potentially because they rely on more automatic, rather than strategic, processing when attempting to form, store, and retrieve associations from memory. An intriguing possibility is that older adults with greater access to strategic processes (e.g., those with a high level of education) may be less susceptible to age-related associative memory deficits. Two experiments assessed the degree to which a high level of education provides an effective dose of cognitive reserve, potentially preserving associative memory. Standard younger and older adults' item and associative memory performance was compared to older adults who had attained a high level of education (mostly doctoral degrees). In both experiments (Experiment 1: person-action pairs; Experiment 2: unrelated word pairs), consistent evidence was found that older adults, regardless of the level of education, exhibited an age-related associative memory deficit relative to younger adults. Interestingly, neuropsychological assessment of both older adult groups revealed greater frontal lobe, but not enhanced medial temporal lobe, functioning in the highly educated. As such, although the highly educated older adults exhibited greater frontal lobe functioning than the standard older adults, this did not aid in the reduction of the age-related associative memory deficit.



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Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: a systematic review and meta-analysis

Publication date: Available online 30 December 2016
Source:Cancer Treatment Reviews
Author(s): Husam Abdel-Qadir, Josee-Lyne Ethier, Douglas S. Lee, Paaladinesh Thavendiranathan, Eitan Amir
BackgroundThe cardiovascular risk of angiogenesis inhibitors is not well-quantified. We hypothesized that, compared to direct vascular endothelial growth factor (VEGF) inhibitors (anti-VEGF antibodies or decoy receptors), small molecule agents have higher risk due to their less specific mechanism.MethodsWe searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for phase III randomised controlled trials comparing angiogenesis inhibitor-based therapy to other systemic therapy. Outcomes evaluated were hypertension, severe hypertension, cardiac dysfunction, congestive heart failure, cardiac ischemia, arterial thromboembolism, venous thromboembolism, and fatal cardiovascular events. Data were pooled using Mantel-Haenszel random effects method to generate odds ratios (OR).ResultsWe identified 77 studies meeting inclusion criteria. Compared to routine care, angiogenesis inhibitors were associated with a higher risk of hypertension (OR 5.28 [4.53–6.15], number needed to harm [NNH] 6), severe hypertension (OR 5.59 [4.67–6.69], NNH 22), cardiac ischemia (OR 2.83 [1.72–4.65], NNH 84) and cardiac dysfunction (OR 1.35 [1.06–1.70], NNH 139). VEGF inhibitors were associated with an increased risk of arterial thromboembolism (OR 1.52 [1.17,1.98], NNH 140). No significant interaction was observed between the two drug subgroups for any outcomes. We identified no significant increase in the risk of the other outcomes evaluated.ConclusionAngiogenesis inhibitors increase the risk of hypertension, arterial thromboembolism, cardiac ischemia and cardiac dysfunction. There was no significant difference in cardiovascular risk between direct VEGF inhibitors and small molecule agents.



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Strategies to design clinical studies to identify predictive biomarkers in cancer research

Publication date: Available online 30 December 2016
Source:Cancer Treatment Reviews
Author(s): Jose Luis Perez-Gracia, Miguel F. Sanmamed, Ana Bosch, Ana Patiño-Garcia, Kurt A. Schalper, Victor Segura, Joaquim Bellmunt, Josep Tabernero, Christopher J Sweeney, Toni K Choueiri, Miguel Martín, Juan Pablo Fusco, Maria Esperanza Rodriguez-Ruiz, Alfonso Calvo, Celia Prior, Luis Paz-Ares, Ruben Pio, Enrique Gonzalez Billalabeitia, Alvaro Gonzalez Hernandez, David Páez, Jose María Piulats, Alfonso Gurpide, Mapi Andueza, Guillermo de Velasco, Roberto Pazo, Enrique Grande, Pilar Nicolas, Francisco Abad-Santos, Jesus Garcia-Donas, Daniel Castellano, María J. Pajares, Cristina Suarez, Ramon Colomer, Luis M. Montuenga, Ignacio Melero
The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework -the DESIGN guidelines- to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field.



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Front-line treatment of CLL in the era of novel agents

Publication date: Available online 30 December 2016
Source:Cancer Treatment Reviews
Author(s): Tadeusz Robak, Stephan Stilgenbauer, Alessandra Tedeschi
Although chemoimmunotherapy prolongs survival and as such, is the standard of care for treatment-naïve patients, its effectiveness may be reduced by associated toxicity and dose reductions. In addition, it has been associated with the development of myelosuppression and secondary neoplasms; treatments are hence needed which offer greater survival and lowered toxicity. A range of new targeted agents, ibrutinib, idelalisib and venetoclax, have demonstrated such a balance in a second-line setting, offering CLL patients durable remissions and a modest toxicity profile. Ibrutinib has since been given first-line approval,and with news of second-generation targeted agents on the horizon, high-level discussions have taken place concerning their use in elderly or unfit patients; with potential use in younger patients in a first-line setting. This article reviews the potential first-line therapeutic options for treating CLL and their clinical potential and examines whether first-line chemotherapy has a place in the age of targeted agents.



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Leptomeningeal carcinomatosis in non-small cell lung cancer patients: a continuing challenge in the personalized treatment era

Publication date: Available online 30 December 2016
Source:Cancer Treatment Reviews
Author(s): J. Remon, E. Le Rhun, B. Besse
Leptomeningeal metastasis is a fatal manifestation seen in advanced cancer patients. Its incidence is increasing, reaching 3.8% in molecularly unselected non-small cell lung cancer patients and up to 5% and 9% in ALK-rearranged and EGFR-mutant lung cancer patients, respectively. The prognosis remains poor despite systemic treatment, intrathecal chemotherapy, radiation therapy and personalized treatments in molecularly selected patients. However, new therapies with improved cerebral-spinal fluid penetration have been developed for subgroups of molecular selected patients indicating they could be promising therapeutic options for managing leptomeningeal disease. Systemic chemotherapy, which may be combined with intrathecal chemotherapy, remains standard treatment for lung cancer patients with leptomeningeal disease and a good-risk profile. We summarize evidence reported in the literature for managing this complication in lung cancer patients. Based on this, we have selected potential therapeutic strategies that could be used in daily clinical practice.



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Cancer resistance to therapies against the EGFR-RAS-RAF pathway: the role of MEK

Publication date: Available online 30 December 2016
Source:Cancer Treatment Reviews
Author(s): Erika Martinelli, Floriana Morgillo, Teresa Troiani, Fortunato Ciardiello
The mitogen-activated protein kinases (MAPKs) mediate intracellular signals activated by a wide variety of extracellular stimuli. The activation of the RAS-RAF-MEK-MAPK cascade culminates in the regulation of gene transcription promoting cancer cell proliferation, survival, migration and angiogenesis. MEK (mitogen-activated protein kinase kinase-MAPKK) 1/2 is a transducer of the growth factor receptor-RAS-RAF-MAPK signalling cascade and plays a relevant role in development and progression of human cancers, such as colorectal cancer (CRC), non small cell lung cancer (NSCLC). Direct inhibition of MEK is a promising strategy and several inhibitors are currently under evaluation in clinical trials showing initial clinical activity in different tumours. MEK activation, by different genetic mechanisms, has been described for both intrinsic and acquired resistance to drugs targeting the EGFR (Epidermal Growth Factor Receptor)-RAS-RAF pathway in CRC, NSCLC. Combination therapies with chemotherapy and/or with molecular targeted agents are warranted and biomarkers studies are needed to identify those tumours dependent on MEK signalling.



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Functions of the Magnaporthe oryzae Flb3p and Flb4p transcription factors in the regulation of conidiation

Publication date: Available online 30 December 2016
Source:Microbiological Research
Author(s): S. Matheis, A. Yemelin, D. Scheps, K. Andresen, S. Jacob, E. Thines, A.J. Foster
The Magnaporthe oryzae genes FLB3 and FLB4, orthologues of the Aspergillus nidulans regulators of conidiation FlbC and FlbD, were inactivated. These genes encode C2H2 zinc finger and Myb-like transcription factors, respectively, in A. nidulans. Analysis of the resultant mutants demonstrated that FLB4 is essential for spore formation and that strains lacking this gene are fluffy in their colony morphology due to an inability to complete conidiophore formation. Meanwhile, FLB3 is required for normal levels of aerial mycelium formation. We identified genes dependent on both transcription factors using microarray analysis. This analysis revealed that the transcription of several genes encoding proteins implicated in sporulation in Magnaporthe oryzae and other filamentous fungi are affected by FLB3 or FLB4 inactivation. Furthermore, the microarray analysis indicates that Flb3p may effectively reprogramme the cell metabolically by repressing transcription of genes encoding biosynthetic enzymes and inducing transcription of genes encoding catabolic enzymes. Additionally, qRT-PCR was employed and showed that FLB3 and FLB4 transcripts are enriched in synchronously sporulating cultures, as were the transcripts of other genes that are necessary for normal conidiation, consistent with a role for their gene products in this process.



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Genomic and metabolic traits endow Bacillus velezensis CC09 with a potential biocontrol agent in control of wheat powdery mildew disease

Publication date: Available online 30 December 2016
Source:Microbiological Research
Author(s): Xun-Chao Cai, Chang-Hong Liu, Bao-Tong Wang, Ya-Rong Xue
Bacillus velezensis CC09, was isolated from healthy leaves of Cinnamomum camphora and previously identified as Bacillus amyloliquefaciens CC09, shows great potential as a new biocontrol agent, in control of many phytopathogenic diseases. To extend our understanding of the potential antifungal capacities, we did a whole genome sequencing analysis of strain CC09. Result showed that strain CC09 has a relatively large genome size (4.17 Mb) with an average GC content of 46.1%, and 4,021 predicted genes. Thirteen secondary metabolites encoding clusters have been identified within the genome of B. velezensis CC09 using genome mining technique. Data of comparative genomic analysis indicated that 3 of the clusters are conserved by all strains of B. velezensis, B. amyloliquefaciens and B. subtilis 168, 9 by B. velezensis and B. amyloliquefaciens, and 2 by all strains of B. velezensis. Another 2 clusters encoding NRPS (Non-Ribosomal Peptide Synthetases) and NRPS-TransATPKS (NRPS and Trans-AT PolyKetide hybrid Synthetases) respectively are observed only in 15 B. velezensis strains, which might lead to the synthesis of novel bioactive compounds and could be explored as antimicrobial agents in the future. These clusters endow B. velezensis CC09 with strong and broad antimicrobial activities, for example, in control of wheat powdery mildew disease. Moreover, our data further confirmed the taxonomy of strain CC09 is a member of B. velezensis rather than a strain of B. amyloliquefaciens based on core genome sequencing analysis using phylogenomic approach.



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