Head and Neck Diseases by Alexandros G.Sfakianakis: 01/31/18

Τετάρτη 31 Ιανουαρίου 2018

Discussion: The Cost of Contralateral Prophylactic Mastectomy in Women with Unilateral Breast Cancer.

No abstract available

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Radiation therapy will always alter skin in breast cancer treatment

No abstract available

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Principles of Diffusion Kurtosis Imaging and its Role in Early Diagnosis of Neurodegenerative Disorders

Publication date: Available online 31 January 2018
Source:Brain Research Bulletin
Author(s): Anas Arab, Anna Wojna-Pelczar, Amit Khairnar, Nikoletta Szabó, Jana Ruda-Kucerova
Pathology of neurodegenerative diseases can be correlated with intra-neuronal as well as extracellular changes which lead to neuronal degeneration. The central nervous system (CNS) is a complex structure comprising of many biological barriers. These microstructural barriers might be affected by a variety of pathological processes. Specifically, changes in the brain tissue's microstructure affect the diffusion of water which can be assessed non-invasively by diffusion weighted (DW) magnetic resonance imaging (MRI) techniques. Diffusion tensor imaging (DTI) is a diffusion MRI technique that considers diffusivity as a Gaussian process, i.e. does not account for any diffusion hindrance. However, environment of the brain tissues is characterized by a non-Gaussian diffusion. Therefore, diffusion kurtosis imaging (DKI) was developed as an extension of DTI method in order to quantify the non-Gaussian distribution of water diffusion. This technique represents a promising approach for early diagnosis of neurodegenerative diseases when the neurodegenerative process starts. Hence, the purpose of this article is to summarize the ongoing clinical and preclinical research on Parkinson's, Alzheimer's and Huntington diseases, using DKI and to discuss the role of this technique as an early stage biomarker of neurodegenerative conditions.

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Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: reversal by cannabidiol

Publication date: Available online 31 January 2018
Source:Brain Research Bulletin
Author(s): Vanessa Kappel da Silva, Betânia Souza de Freitas, Victória Campos Dornelles, Luiza Wilges Kist, Maurício Reis Bogo, Milena Carvalho Silva, Emílio Luiz Streck, Jaime Eduardo Hallak, Antônio Waldo Zuardi, José Alexandre S. Crippa, Nadja Schröder
Evidence has demonstrated iron accumulation in specific brain regions of patients suffering from neurodegenerative disorders, and this metal has been recognized as a contributing factor for neurodegeneration. Using an experimental model of brain iron accumulation, we have shown that iron induces severe memory deficits that are accompanied by oxidative stress, increased apoptotic markers, and decreased synaptophysin in the hippocampus of rats. The present study aims to characterize iron loading effects as well as to determine the molecular targets of cannabidiol (CBD), the main non-psychomimetic compound of Cannabis sativa, on mitochondria. Rats received iron in the neonatal period and CBD for 14 days in adulthood. Iron induced mitochondrial DNA (mtDNA) deletions, decreased epigenetic modulation of mtDNA, mitochondrial ferritin levels, and succinate dehydrogenase activity. CBD rescued mitochondrial ferritin and epigenetic modulation of mtDNA, and restored succinate dehydrogenase activity in iron-treated rats. These findings provide new insights into molecular targets of iron neurotoxicity and give support for the use of CBD as a disease modifying agent in the treatment of neurodegenerative diseases.

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Confocal calcium imaging analysis of respiratory-related burst activity in the parafacial region

Publication date: Available online 31 January 2018
Source:Brain Research Bulletin
Author(s): Hiroshi Onimaru, Shiro Nakamura, Keiko Ikeda, Kiyoshi Kawakami, Tomio Inoue
The parafacial respiratory group (pFRG) surrounding the ventrolateral part of the facial motor nucleus is one of respiratory rhythm generators that consists of pre-inspiratory (Pre-I) neurons. Previous studies showed that most of the Pre-I neurons locating in the Phox2b cluster of the rostral ventral medulla were also Phox2b positive and intrinsically CO2 sensitive. However, it is not clear what percentage of Phox2b-expressing cells in the pFRG of the ventral medulla are Pre-I neurons. To address this issue, we analyzed the activity of Phox2b-positive cells by calcium imaging using a confocal laser microscope in transgenic rats in which Phox2b-positive cells expressed EYFP. We found that more than 60% of the EYFP/Phox2b-positive cells showed Pre-I neuron-like rhythmic burst activity in the parafacial region of newborn rat.

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Reduction in endogenous cardiac steroids protects the brain from oxidative stress in a mouse model of mania induced by amphetamine

Publication date: Available online 31 January 2018
Source:Brain Research Bulletin
Author(s): Anastasia Hodes, Tzuri Lifschytz, Haim Rosen, Hagit Cohen-Ben Ami, David Lichtstein
ObjectivesBipolar disorder (BD) is a severe mental illness characterized by episodes of mania and depression. Numerous studies have implicated the involvement of endogenous cardiac steroids (CS), and their receptor, Na⁺, K⁺ −ATPase, in BD. The aim of the present study was to examine the role of brain oxidative stress in the CS-induced behavioral effects in mice.MethodsAmphetamine (AMPH)-induced hyperactivity, assessed in the open-field test, served as a model for manic-like behavior in mice. A reduction in brain CS was obtained by specific and sensitive anti-ouabain antibodies. The level of oxidative stress was tested in the hippocampus and frontal cortex by measuring the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the levels of antioxidant non-protein thiols (NPSH) and oxidative damage biomarkers thiobarbituric acid reactive substances (TBARS) and protein carbonyl (PC).ResultsAMPH administration resulted in a marked hyperactivity and increased oxidative stress, as manifested by increased SOD activity, decreased activities of CAT and GPx, reduced levels of NPSH and increased levels of TBARS and PC. The administration of anti-ouabain antibodies, which reduced the AMPH-induced hyperactivity, protected against the concomitant oxidative stress in the brain.ConclusionsOur results demonstrate that oxidative stress participates in the effects of endogenous CS on manic-like behavior induced by AMPH. These finding support the notion that CS and oxidative stress may be associated with the pathophysiology of mania and BD.

Graphical abstract

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Intestinal-type adenocarcinoma of the sinonasal tract: an update

Purpose of review Intestinal-type adenocarcinoma (ITAC) is one of the most frequent sinonasal tumors, especially in European countries. The purpose of this article is to review the most recent literature, with special emphasis on biological and genetic profile and treatment guidelines. Recent findings Results on large series support transnasal endoscopic surgery as the technique of choice in the large majority of patients with ITAC. Adjuvant radiotherapy is recommended in advanced-stage and high-grade lesions. More robust data are required to confirm that early-stage, low-grade lesions can be treated with exclusive surgery. The efficacy of new chemotherapy and biotherapy regimens and the added value of heavy particle radiotherapy are currently under evaluation. With a 5-year overall survival ranging between 53 and 83%, which is mainly impacted by local recurrences, ITAC requires a more detailed understanding of its biology. Genetic and biological studies have identified alterations in the molecular pathways of EGFR, MET, and H-RAS which might be considered as potential targets for biotherapy. Summary Surgery still plays a key role in the treatment of ITAC, but multidisciplinary management is mandatory. Although further validation is needed, the role of nonsurgical treatment strategies is rising, in agreement with the progresses made in the biological profiling of the disease. Correspondence to Piero Nicolai, MD, Unit of Otorhinolaryngology, Spedali Civili of Brescia, University of Brescia, Piazza Spedali Civili, 1, 25123 Brescia, Italy. Tel: +39 0303995319; fax: +39 030395212; e-mail: pieronicolai@virgilio.it Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Lipid metabolism and benzo[a]pyrene degradation by Fusarium solani : an unexplored potential

Abstract

In a search for indigenous soil saprotrophic fungi for bioremediation purposes, Fusarium solani, a saprotrophic fungus belonging to the phylum Ascomycota, was isolated from a fossil carbon contaminated soil. The effect of the carbon source, glucose or olive oil, was investigated in vitro on the biomass produced by F. solani and on the degradation of benzo[a]pyrene (BaP) in mineral medium. After only 12 days of incubation, BaP degradation by F. solani was higher (37.4%) with olive oil used as the carbon source than the one obtained with glucose (4.2%). Catalase activity increased in the presence of olive oil (3.4 μkat mg⁻¹ protein) in comparison with glucose (2.1 μkat mg⁻¹ protein). When olive oil was used as the carbon source, BaP degradation increased up to 76.0% in the presence of a specific catalase inhibitor, 3-Amino-1,2,4-triazole (2 mM). This metabolic engineering strategy based both on the use of olive oil as carbon source (cultivation strategy) and on the blocking of the catalase activity could be an innovative and promising approach for fungal biodegradation of BaP and consequently for bioremediation of soil contaminated with polycyclic aromatic hydrocarbons.

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The liver X receptors and sterol regulatory element binding proteins alter progesterone secretion and are regulated by human chorionic gonadotropin in human luteinized granulosa cells

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Yafei Xu, José J. Hernández-Ledezma, Scot M. Hutchison, Randy L. Bogan
There is increased expression of liver x receptor (LXR) target genes and reduced low density lipoprotein receptor (LDLR) during spontaneous luteolysis in primates. The LXRs are nuclear receptors that increase cholesterol efflux by inducing transcription of their target genes. Transcription of LDLR is regulated by sterol regulatory element binding proteins (SREBPs). Human chorionic gonadotropin (hCG) prevents luteolysis and stimulates progesterone synthesis via protein kinase A (PKA). Thus, our primary objectives are: 1) Determine the effects of LXR activation and SREBP inhibition on progesterone secretion and cholesterol metabolism, and 2) Determine whether hCG signaling via PKA regulates transcription of LXR and SREBP target genes in human luteinized granulosa cells. Basal and hCG-stimulated progesterone secretion was significantly decreased by the combined actions of the LXR agonist T0901317 and the SREBP inhibitor fatostatin, which was associated with reduced intracellular cholesterol storage. Expression of LXR target genes in the presence of T0901317 was significantly reduced by hCG, while hCG promoted transcriptional changes that favor LDL uptake. These effects of hCG were reversed by a specific PKA inhibitor. A third objective was to resolve a dilemma concerning LXR regulation of steroidogenic acute regulatory protein (STAR) expression in primate and non-primate steroidogenic cells. T0901317 induced STAR expression and progesterone synthesis in ovine, but not human cells, revealing a key difference between species in LXR regulation of luteal function. Collectively, these data support the hypothesis that LXR-induced cholesterol efflux and reduced LDL uptake via SREBP inhibition mediates luteolysis in primates, which is prevented by hCG.

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Effect of hypoxia on caveolae-related protein expression and insulin signaling in adipocytes

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): M. Varela-Guruceaga, F.I. Milagro, J.A. Martínez, C. de Miguel
Obesity is characterized by hypertrophy and hyperplasia of adipose tissue, which have been related to the development of hypoxia and insulin resistance. On the other hand, caveolin-1 (Cav-1), one of the main proteins of caveolae, promotes insulin receptor (IR) phosphorylation and the subsequent activation of insulin signaling. In this work we investigated the effect of hypoxia on Cav-1 regulation and the status of insulin signaling in 3T3-L1 adipocytes. Our results showed that hypoxia inhibited adipogenesis and insulin signaling in adipocytes. Furthermore, 48 h of hypoxia reduced insulin-induced glucose uptake while increased basal glucose uptake. This result was consistent with the upregulation of glucose transporter GLUT1 and the downregulation of GLUT4, which also showed defective translocation to plasma membrane when adipocytes were stimulated with insulin. In addition, the expression of caveolae-related proteins was reduced by hypoxia and chromatin immunoprecipitation assay demonstrated that Cav-1 transcription was directly regulated by HIF-1. These results strengthen the role of caveolae in insulin signaling and help to explain adipocyte response to hypoxia.

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Activation of bombesin receptor Subtype-3 by [D-Tyr6,β-Ala11,Phe13,Nle14]bombesin6-14 increased glucose uptake and lipogenesis in human and rat adipocytes

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Zaida Moreno-Villegas, Antonio Martín-Duce, César Aparicio, Sergio Portal-Núñez, Raúl Sanz, Samuel A. Mantey, Robert T. Jensen, Oscar Lorenzo, Jesús Egido, Nieves González
BRS-3 has an important role in glucose homeostasis. Its expression was reduced in skeletal muscle from obese and/or diabetic patients, and BRS-3 KO-mice developed obesity. In this work, focused on rat/human adipose tissue, BRS-3 gene-expression was lower than normal-levels in hyperlipidemic, type-2-diabetic (T2D), and type-1-diabetic rats and also in obese (OB) and T2D patients. Moreover, BRS-3 protein levels were decreased in diabetic rat and in obese and diabetic human fat pieces; but neither mutation nor even polymorphism in the BRS-3-gene was found in OB or T2D patients. Interestingly, in rat and human adipocytes, without metabolic alterations, [D-Tyr⁶,β-Ala¹¹,Phe¹³,Nle¹⁴]bombesin6-14 ―BRS-3-agonist―, as insulin, enhanced BRS-3 gene/protein expression, increased, PKB, p70s6K, MAPKs and p90RSK1 phosphorylation-levels, and induced a concentration-related stimulation of glucose transport, GLUT-4 membrane translocation and lipogenesis, exclusively mediated by BRS-3, and abolished by wortmannin, PD98059 or rapamacyn. These results confirm that BRS-3 and/or its agonist are a potential therapeutic tool for obesity/diabetes.

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Adrenergic receptor stimulation suppresses oxidative metabolism in isolated rat islets and Min6 cells

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Amy C. Kelly, Leticia E. Camacho, Ken Pendarvis, Hailey M. Davenport, Nathan R. Steffens, Kate E. Smith, Craig S. Weber, Ronald M. Lynch, Klearchos K. Papas, Sean W. Limesand
Insulin secretion is stimulated by glucose metabolism and inhibited by catecholamines through adrenergic receptor stimulation. We determined whether catecholamines suppress oxidative metabolism in β-cells through adrenergic receptors. In Min6 cells and isolated rat islets, epinephrine decreased oxygen consumption rates compared to vehicle control or co-administration of epinephrine with α2-adrenergic receptor antagonist yohimbine. Epinephrine also decreased forskolin-stimulated oxygen consumption rates, indicating cAMP dependent and independent actions. Furthermore, glucose oxidation rates were decreased with epinephrine, independent of the exocytosis of insulin, which was blocked with yohimbine. We evaluated metabolic targets through proteomic analysis after 4 h epinephrine exposure that revealed 466 differentially expressed proteins that were significantly enriched for processes including oxidative metabolism, protein turnover, exocytosis, and cell proliferation. These results demonstrate that acute α2-adrenergic stimulation suppresses glucose oxidation in β-cells independent of nutrient availability and insulin exocytosis, while cAMP concentrations are elevated. Proteomics and immunoblots revealed changes in electron transport chain proteins that were correlated with lower metabolic reducing equivalents, intracellular ATP concentrations, and altered mitochondrial membrane potential implicating a new role for adrenergic control of mitochondrial function and ultimately insulin secretion.

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Determination of EPAC2 function using EPAC2 null Min6 sublines generated through CRISPR-Cas9 technology

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Haiyan Xu, Yi Yang, Yiping Chen, Uwe Muller, Sharanya Iyer, Jeremy Presland, Ruojing Yang, Ilona Kariv
Min6 cells, a mouse β cell line derived from transgenic mouse expressing the large T-antigen of SV40 in pancreatic beta cells, are commonly utilized as an in vitro cellular model for investigating targets involved in insulin secretion. Epac2, an exchange protein that can be directly activated by cyclic AMP (cAMP), is critical for pharmacologic stimuli-induced insulin secretion and has been hypothesized to be a direct target of sulfonylurea. Previous loss of function studies only specifically knocked out EPAC2 isoform A, leaving the other two isoforms intact. In this study, we investigated the function of EPAC2 in Min6 cells by generating EPAC2 knock-out sublines using CRISPR-Cas9 technology, by removing all three isoforms of EPAC2. Our results indicate that Min6 cells can be successfully cloned from a single cell after electroporation with plasmids expressing EPAC2 specific guide RNA, Cas9 and GFP, followed by sorting for GFP expressing single cells. Two clones were found to have a single nucleotide deletion in targeted site of EPAC2 gene by sequencing, therefore creating a frame shift in exon 13. The EPAC2 null clones unexpectedly have increased secretion of insulin at basal level and elevated total intracellular insulin content. However, EPAC2 deficiency impaired glucose and sulfonylurea induced insulin secretion without affecting sulfonylurea binding to cells. Potassium chloride induced insulin secretion remains intact. Interestingly, cAMP levels remained unchanged in EPAC2 null cells during these processes. To understand the global function of EPAC2, RNA Seq study was performed, which reveals that EPAC2 deficiency affects expression of multiple previously unrecognized genes, suggesting that EPAC2 can function through multiple pathways in addition to being a cAMP sensor.

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Single cell transcriptome sequencing: A new approach for the study of mammalian sex determination

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Isabelle Stévant, Serge Nef
Mammalian sex determination is a highly complex developmental process that is particularly difficult to study due to the limited number of gonadal cells present at the bipotential stage, the large cellular heterogeneity in both testis and ovaries and the rapid sex-dependent differentiation processes. Single-cell RNA-sequencing (scRNA-seq) circumvents the averaging artifacts associated with methods traditionally used to profile bulk populations of cells. It is a powerful tool that allows the identification and classification of cell populations in a comprehensive and unbiased manner. In particular, scRNA-seq enables the tracing of cells along developmental trajectories and characterization of the transcriptional dynamics controlling their differentiation. In this review, we describe the current state-of-the-art experimental methods used for scRNA-seq and discuss their strengths and limitations. Additionally, we summarize the multiple key insights that scRNA-seq has provided to the understanding of mammalian sex determination. Finally, we briefly discuss the future of this technology, as well as complementary applications in single cell -omics in the context of mammalian sex determination.

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Icariin modulates mitochondrial function and apoptosis in high glucose-induced glomerular podocytes through G protein-coupled estrogen receptors

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Chen Qiao, Wenjuan Ye, Sai Li, Hui Wang, Xuansheng Ding
Podocyte apoptosis in glomerular lesions has been found to have a dominant role in the progression of diabetic nephropathy. The present research aimed to explore the beneficial effect of icariin on diabetic podocytes by interfering in the process of apoptosis. Podocyte apoptosis was significantly exacerbated after high glucose treatment, with the level of reactive oxygen species (ROS) increasing simultaneously. Here, we demonstrated that icariin, which is a G protein-coupled estrogen receptor 1 (GPER) agonist, inhibited podocyte apoptosis by reducing ROS, maintaining the integrity of mitochondrial membranes. Moreover, the stabilization of mitochondria by icariin was reversed when GPER was knocked down in podocytes. Meanwhile, icariin inhibited the caspase cascade in podocyte apoptosis by promoting Bcl-2 expression and mitochondrial translocation. The above findings at least partly elucidated the mechanism by which icariin stabilized podocytes by inducing the mitochondrial Bcl-2 translocation and therefore preventing downstream apoptosis.

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Alpha 1 adrenergic receptor-mediated inflammatory responses in human testicular peritubular cells

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Soledad Paola Rossi, Lena Walenta, Verónica Rey-Ares, Frank-Michael Köhn, J. Ullrich Schwarzer, Harald Welter, Ricardo Saúl Calandra, Mónica Beatriz Frungieri, Artur Mayerhofer
Stress activates the sympathetic nervous system and is linked to impaired fertility in man. We hypothesized that catecholamines by acting on testicular cells have a role in these events, possibly by fostering an inflammatory environment. The cells of the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), express adrenergic receptors (ADRs) α1B, α1D, β1 and β2. A selective α1-ADR agonist, phenylephrine, increased intracellular Ca²⁺-levels in cultured HTPCs and induced COX-2, IL-6 and MCP-1 mRNA expression without affecting IL-1β mRNA. These changes were paralleled by a significant increase in the secretion of IL-6 and MCP-1. Epinephrine was also effective, but salbutamol, a selective β2-ADR agonist was not. Our results suggest that stress-associated elevation of catecholamines may be able to promote inflammatory events by targeting peritubular cells in the human testis. Blockage of α1-ADRs may therefore be a novel way to interfere with stress-related impairment of male reproductive functions.

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Epidermal growth factor receptor / extracellular signal-regulated kinase pathway enhances mineralocorticoid receptor transcriptional activity through protein stabilization

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Yuko Mitsuishi, Hirotaka Shibata, Isao Kurihara, Sakiko Kobayashi, Kenichi Yokota, Ayano Murai-Takeda, Takeshi Hayashi, Rie Jo, Toshifumi Nakamura, Mitsuha Morisaki, Hiroshi Itoh
Activation of mineralocorticoid receptor (MR) is evoked by aldosterone, and it induces hypertension and cardiovascular disease when it's concomitant with excessive salt loading. We have proposed the notion of "MR-associated hypertension", in which add-on therapy of MR blockers is effective even though serum aldosterone level is within normal range. To elucidate its underlying molecular mechanism, we focused on the effect of epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) activation on MR activity. Epidermal growth factor (EGF) administration increased MR transcriptional activity through EGFR/ERK pathway and increased protein level by counteracting MR ubiquitylation in vitro. EGF administration in vivo also increased MR protein level and target gene expression in kidney, which were decreased by EGFR inhibitor. In addition, the administration of EGFR inhibitor lowered systolic blood pressure and MR activity in DOCA/salt-treated mice. In conclusion, EGFR/ERK pathway activation is considered as one of the underlying mechanisms of aberrant MR activation and EGFR/ERK pathway blockade could be an alternative approach for the prevention of MR-related cardiovascular events.

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Postprandial regulation of natriuretic peptides in vivo and of their receptors by fatty acids in adipocytes in vitro

Publication date: Available online 31 January 2018
Source:Molecular and Cellular Endocrinology
Author(s): Andreas Schmid, Jens Albrecht, Judith Brock, Maria Koukou, Efthymia Arapogianni, Andreas Schäffler, Thomas Karrasch
Background and aimNatriuretic peptides (NPs) and their receptors gain attention regarding adipocyte function. It was the aim to investigate the expression of natriuretic peptide receptors NPR-A, NPR-B, NPR-C during adipocyte differentiation (AD), upon stimulation with fatty acids (FA), and in murine and human adipose tissue depots (AT) of patients undergoing bariatric surgery (n = 44).Patients, material and methodsThe postprandial regulation of NT-proANP and NT-proBNP levels was measured by ELISA and was studied in two cohorts of healthy individuals undergoing an oral glucose tolerance test (OGTT) (n = 100) and an oral lipid tolerance test (OLTT) (n = 100). mRNA expression was investigated by quantitative real-time PCR.ResultsDuring AD, an early expression pattern could be described for NPR-C, a bimodal expression for NPR-B and a late expression pattern for NPR-A. NPR-A and NPR-B expression was high in epididymal and subcutaneous AT but low in peri-renal AT of mice. NPR-C showed a differential expression profile. FA stimulation caused a significant and differential regulation of NPRs in adipocytes. Serum NT-proANP and NT-proBNP concentrations did not change during OGTT, whereas NT-pro-ANP significantly declined during OLTT. Basal NT-proANP and NT-proBNP concentrations were positively correlated with each other and with FGF-19 and FGF-21 levels.ConclusionAdipocytes and AT show a characteristic expression of NPRs. FA are able to regulate NPR expression differentially. There exists a postprandial and negative regulation of serum NT-proANP concentrations after OLTT and of NPR-A after FA stimulation. Both effects could represent a novel hypothetical negative feedback mechanism on adipocytic lipolysis.

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Real world data on the efficacy and safety of apremilast in patients with moderate to severe plaque psoriasis

Abstract

Background

Psoriasis is a chronic inflammatory skin disease, which requires long term, safe and effective treatment. Apremilast, a small-molecule PDE4 inhibitor, has been introduced as psoriasis (and psoriatic arthritis) treatment in Europe in 2015.

Objective

We analysed and report the efficacy and safety of apremilast in the first 51 patients with psoriasis that have undergone treatment with this novel small molecule in our outpatient clinic.

Method

Our primary endpoint was the evaluation of clinical response to apremilast according to the percentage of PASI reduction (ΔPASI) at 16 weeks after treatment initiation. Secondary endpoints were the evaluation at week 16 of: (i) Psoriasis Area Severity Index (PASI); (ii) Dermatology Life Quality Index (DLQI); (iii) Physician Global Assessment (PGA); (iv) Psoriasis Scalp Severity Index (PSSI); and (v) the percentage of patients who achieved ΔPASI50, ΔPASI75, ΔPASI90 and ΔPASI100; (vi) adverse events (AE); (vii) reasons for drug discontinuation; and (viii) drug survival.

Results

59.3% of the patients who remained on apremilast achieved at least ΔPASI75 at week 16, while 11.1% achieved combined 50%≤PASI<75% and DLQI≤5 (satisfactory response) adequate enough to maintain treatment. Five patients (18.5%) also achieved ΔPASI100. Patients discontinued apremilast (28%), mostly during the first four weeks due to adverse events (12%) with gastrointestinal symptoms being the most common, and later due to lack of efficacy (16%). A statistically significant improvement of PASI, DLQI, PGA and PSSI scores was observed after 4 and 16 weeks of treatment relative to pre-treatment measurements.

Conclusion

Apremilast is a safe and efficacious treatment for psoriasis patients as it produces ΔPASI75 and ΔPASI50 responses combined with DLQI≤5 in 16 weeks in 70.4% of the patients. These results, from a real-world setting, confirm the efficacy and safety of apremilast which has been demonstrated in large phase III clinical trials.

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Outcomes of Donation After Cardiac Death Liver Grafts from Donors ≥ 50 years of Age: A Multi-center Analysis

ABSTRACTIntroductionAs the population in the United States continues to age, an increase in the number of potential DCD donors with advanced chronological age can be expected. The aim of this study was to analyze a multi-institutional experience in liver transplantation using DCD donor age ≥50 years.MethodsAll DCD LT performed at Mayo Clinic Florida, Mayo Clinic Rochester and Mayo Clinic Arizona from 2002-2016 were included. Recipients of DCD LT were divided into 2 groups: those with donor age ≥50 years(N=155) and those with donor age

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Inequalities in zoster disease burden: a population-based cohort study to identify social determinants using linked data from the UK Clinical Practice Research Datalink

Abstract

Background

Zoster vaccination was introduced in England in 2013, where tackling health inequalities is a statutory requirement. However, specific population groups with higher zoster burden remain largely unidentified.

Objective

To evaluate health inequalities in zoster disease burden prior to zoster vaccine introduction in England.

Methods

This population-based cohort study utilised anonymised UK primary care data linked to hospitalisation and deprivation data. Individuals aged ≥65 years without prior zoster history (N=862,470) were followed from 01/09/2003-31/08/2013. Poisson regression was used to obtain adjusted rate ratios (ARR) for the association of socio-demographic factors (ethnicity, immigration status, individuals' area-level deprivation, care home residence, living arrangements) with first zoster episode. Possible mediation by co-morbidities and immunosuppressive medications was also assessed.

Results

There were 37,014 first zoster episodes, with incidence of 8.79 (95% confidence interval (CI):8.70-8.88) per 1,000 person-years at risk. In multivariable analyses, factors associated with higher zoster rates included care home residence (10% higher versus those not in care homes), being female (16% higher versus males), non-immigrants (~30% higher than immigrants) and White ethnicity (for example, twice the rate compared to those of Black ethnicity). Zoster incidence decreased slightly with increasing deprivation (ARR most versus least deprived=0.96 (95%CI:0.92-0.99) and among those living alone (ARR 0.96 (95%CI:0.94-0.98). Mediating variables made little difference to the ARR of social factors but were themselves associated with increased zoster burden (ARR varied from 1.11-3.84).

Conclusions

The burden of zoster was higher in specific socio-demographic groups. Further study is needed to ascertain whether these individuals are attending for zoster vaccination.

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The PARACELSUS score: A novel diagnostic tool for pyoderma gangrenosum

Abstract

Background

The lack of objective diagnostic criteria renders pyoderma gangrenosum (PG) a diagnosis of exclusion. The diagnostic approaches proposed to date have not been systematically evaluated. Thus, PG remains a challenging and frequently misdiagnosed disorder.

Objectives

To develop and assess a comprehensive yet clinically practicable as well as sensitive diagnostic scoring system for PG.

Methods

Clinical history and images of a total of 60 subjects with previously confirmed PG located on the lower extremity as well as a control cohort of 50 patients with venous leg ulcers were retrospectively evaluated by expert teams at two tertiary dermatological centres specializing in wound care using a newly developed diagnostic scoring system composed of ten criteria.

Results

The three major diagnostic criteria are rapidly progressing disease, assessment (absence) of relevant differential diagnoses and reddish-violaceous wound border (prevalent in 98.3% of PG patients, respectively). Minor criteria (evident in 61-95% of PG cases) include amelioration (alleviation) by immunosuppressant drugs, characteristically irregular shape of ulceration, extreme pain >4/10 on visual analogue scale, and localization of lesion at site of trauma. Three additional criteria (observed in up to 60% of PG subjects) encompass suppurative inflammation in histopathology, undermined wound margins as well as concomitant systemic disease. A total score value of ten points or higher indicates a high likelihood of PG and differentiates PG from venous leg ulcers. The initial letters of the above-listed criteria form the acronym PARACELSUS.

Conclusion

The PARACELSUS score represents a novel, easily implementable, effective and sensitive diagnostic tool for PG.

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Sirolimus for treatment of Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon: A retrospective cohort study

Abstract

Kaposiform hemangioendothelima (KHE) is a locally aggressive vascular tumor that mainly occurs during childhood and invades adjacent tissue and organ. It is commonly complicated by Kasabach-Merritt phenomenon (KMP) in about 50%-70% of the cases. KMP is most often associated with a rapidly growing, large solitary tumor that may result in severe hemorrhage and directly responsible for high mortality and morbidity.

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Inequalities in zoster disease burden: a population-based cohort study to identify social determinants using linked data from the UK Clinical Practice Research Datalink

Abstract

Background

Objective

To evaluate health inequalities in zoster disease burden prior to zoster vaccine introduction in England.

Methods

Results

Conclusions

The burden of zoster was higher in specific socio-demographic groups. Further study is needed to ascertain whether these individuals are attending for zoster vaccination.

http://ift.tt/2DRWkco

The PARACELSUS score: A novel diagnostic tool for pyoderma gangrenosum

Abstract

Background

Objectives

To develop and assess a comprehensive yet clinically practicable as well as sensitive diagnostic scoring system for PG.

Methods

Results

Conclusion

The PARACELSUS score represents a novel, easily implementable, effective and sensitive diagnostic tool for PG.

http://ift.tt/2EtSQ0Z

Sirolimus for treatment of Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon: A retrospective cohort study

Abstract

http://ift.tt/2DPizQ5

Combining Behavior and EEG Analysis for Exploration of Dynamic Effects of ADHD Treatment in Animal Models

Publication date: Available online 31 January 2018
Source:Journal of Neuroscience Methods
Author(s): Peter Jurica, Zbigniew R. Struzik, Junhua Li, Masahito Horiuchi, Shuichi Hiroyama, Yuji Takahara, Kohei Nishitomi, Koichi Ogawa, Andrzej Cichocki
BackgroundWe analyze the dynamics of rodent EEG amplitude in an experiment accompanied by video recordings. Brain activity of animals is commonly acquired together with a video of behavior, but recordings are rarely combined in analysis. The data acquired is most commonly analyzed separately. To our knowledge, no study has used behavior to improve the analysis of EEG waveforms, specifically for artifact removal - other than through manual editing.Comparison with Existing Method(s)We explore two approaches: a traditional approach that relies on data preprocessing and artifact rejection by an expert; and an alternative approach that combines analysis of EEG with behavior extracted from video recordings.New MethodWe use the level of activity extracted from the behavioral video as a measure of confidence in the acquired EEG waveform, and as a weighting factor in averaging and statistical comparisons.ResultsWe find in analysis of the EEG that the two approaches lead to similar conclusions, but the analysis leveraging behavioral data achieves this while avoiding many subjective choices often required for artifact rejection and data preprocessing.ConclusionsThe methods we describe allow for the inclusion of all recorded data in the analysis, thereby making statistical tests more friendly to interpretation, and making the data processing transparent and reproducible.

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Utility of Radionuclide Bone Scintigraphy in Complex Regional Pain Syndrome

Abstract

Purpose of Review

To describe the current understanding of the role of three-phase bone scintigraphy (TPBS) in the diagnosis and management of complex regional pain syndrome (CRPS), discuss its advantages and limitations, and present three examples of TPBS patterns typically seen in CRPS patients.

Recent Findings

CRPS is a debilitating disorder frequently presenting with pain to ordinarily non-painful stimuli, redness, swelling, following fractures, stroke, myocardial infarction, surgery, or even minor trauma, and its diagnosis, based on clinical criteria and supportive imaging findings, is difficult. Of the available adjunctive diagnostic imaging modalities, radionuclide bone scintigraphy using a TPBS protocol is the most sensitive and specific for detecting abnormalities commonly seen with this condition—classically, increased periarticular uptake on delayed phase of TPBS, with variable increased uptake on perfusion phases, depending on chronicity. Recent studies have (1) demonstrated a more heterogeneous correlation of TPBS findings with CRPS diagnosis using the current Budapest criteria than in studies using older criteria, (2) pointed to the utility of novel quantitative scintigraphic techniques, and (3) highlighted the value of the early perfusion phases of TPBS in predicting treatment response.

Summary

TPBS remains a valuable imaging adjunct to clinical diagnosis of CRPS. In combination with a multi-modal analgesic approach, TPBS can be used to follow disease course and potentially treatment response, although prospective trials are needed to further delineate its role.

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Medical Cannabis for Neuropathic Pain

Abstract

Purpose of Review

Many cultures throughout history have used cannabis to treat a variety of painful ailments. Neuropathic pain is a complicated condition that is challenging to treat with our current medications. Recent scientific discovery has elucidated the intricate role of the endocannabinoid system in the pathophysiology of neuropathic pain. As societal perceptions change, and legislation on medical cannabis relaxes, there is growing interest in the use of medical cannabis for neuropathic pain.

Recent Findings

We examined current basic scientific research and data from recent randomized controlled trials (RCTs) evaluating medical cannabis for the treatment of neuropathic pain. These studies involved patients with diverse etiologies of neuropathic pain and included medical cannabis with different THC concentrations and routes of administration. Multiple RCTs demonstrated efficacy of medical cannabis for treating neuropathic pain, with number needed to treat (NNT) values similar to current pharmacotherapies.

Summary

Although limited by small sample sizes and short duration of study, the evidence appears to support the safety and efficacy of short-term, low-dose cannabis vaporization and oral mucosal delivery for the treatment of neuropathic pain. The results suggest medical cannabis may be as tolerable and effective as current neuropathic agents; however, more studies are needed to determine the long-term effects of medical cannabis use. Furthermore, continued research to optimize dosing, cannabinoid ratios, and alternate routes of administration may help to refine the therapeutic role of medical cannabis for neuropathic pain.

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High Dose of A Conjugated Linoleic Acid Mixture Increases Insulin Resistance in Rats Fed Either A Low Fat or A High Fat Diet

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-118348

Obesity and related diseases are becoming more prevalent. Conjugated linoleic acid (CLA) might be a useful coadjutant treatment helping to decrease fat mass. However, the precise impact of CLA is unclear because the decreased body fat mass is followed by an increase in insulin resistance. This study aimed to evaluate some of the consequences of a high dose of CLA in rats fed a normal low fat or a high fat diet for 30 days. Male Wistar rats were separated into 4 groups (each n = 10): Control group receiving 7% fat (soybean oil); CLA group receiving 4% soybean oil and 3% CLA mixture; animal fat (AF) group, receiving 45% fat (lard); and animal fat plus CLA (AF+CLA) group, receiving 42% lard and 3% CLA mixture. The CLA mixture contained 39.32 mole% c9,t11-CLA and 40.50 mole% t10,c12-CLA. After 30 days, both CLA groups (CLA and AF+CLA groups) developed insulin resistance, with an increase in glucose in the fasting state and in an insulin tolerance test. The CLA group had increased liver weight and percentage of saturated fatty acids in liver and adipose tissue. Feeding the high fat diet resulted in increased hepatic triacylglycerol accumulation and this was exacerbated by dietary CLA. It is concluded that a high dose of CLA mixture increases insulin resistance and exacerbates hepatic steatosis when combined with a high fat diet.
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Antral Follicle Diameter Variance Within Each Ovary May Be A Predictor For Poor Response In Cases With Normal Ovarian Reserve

10-2017-0393-endo_10-1055-s-0043-125404-

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-125404

Objectives To determine the predictive value of antral follicle diameter variance within each ovary for ovarian response in cases with normal ovarian reserve tests. Methods This is a prospective observational study. One hundred and thirty nine infertile women who underwent ART in IVF-ICSI unit of Zeynep Kamil women and children's Health Training and research hospital between January 2017 to June 2017 were recruited. Blood samples were collected on day 2/day 3 for assessment of serum FSH and estradiol. Trans-vaginal sonography was done for antral follicle count. During antral follicle count, in order to determine antral follicle diameter variance, diameters of the largest and smallest follicles were recorded. Variance was calculated by subtracting the smallest diameter from the largest one. Following ovarian stimulation with antagonist protocol, poor response was determined in cases with total oocyte number≤3. Ovarian reserve tests and antral follicle diameter variance were utilized to predict cases with poor response in women with normal ovarian reserve. Results Antral follicle diameter variance both in right (AUC=0.737, P<0.001) and left (AUC=0.651, P<0.05) ovaries significantly predicted poor ovarian response. Variance>3.5 mm was found to have 75% sensitivity to predict poor response. Basal serum FSH with estradiol levels and AFC failed to predict poor response (P>0.05). Other significant predictors for poor response were day 5 estradiol level and estradiol level at trigger day (P<0.05). In multivariate regression analysis, both AFC and antral follicle diameter variance in the right ovary were found to be significantly associated with clinical pregnancy, on the other hand peak estradiol concentration and antral follicle diameter variance in the right ovary were significantly associated with poor response. Conclusion Antral follicle diameter variance may be utilized to predict poor ovarian response in cases with normal ovarian reserve.
[...]

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Early Stage Graves’ Disease is Uniformly Accompanied by Orbital Immune Activity even in Patients who Fail to Develop Orbithopathy during Follow-up

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-125065

Purpose Graves' orbitopathy (GO) is a complication of Graves' disease (GD), the development of which cannot be predicted at the time of diagnosis of GD. Our aims were (i) to test if orbital 99mTc-labelled diethylenetriamine pentaacetic acid single-photon emission computer tomography (DTPA SPECT) can predict development of GO later during the course of the disease and (ii) to study whether orbital immune activity can be detected in GD patients who do not develop GO during follow-up. Methods Fifty-four orbits of 27 patients with newly diagnosed GD were entered into the case-control study. Individuals showing signs of GO at enrolment were excluded. During the two-year follow-up, eye signs were recorded every 3 months. Orbital DTPA uptakes on SPECT images were measured when entering the study and at the end of the follow-up period, or when clinical signs of GO developed, whichever occurred first. Results During the follow-up, 6 patients (22%) were diagnosed with GO. There was no significant difference between the initial DTPA uptakes of the patients with or without later developing GO (10.45±1.72 MBq/cm3 vs. 9.18±1.18 MBq/cm3 respectively). However, the DTPA uptakes of both GD groups (ie. with and without GO) were higher than that of the control group (7.45±1.36 MBq/cm3, p<0.05). Conclusions We have shown that GD is accompanied by moderate orbital immune activity in GD patients without GO, irrespective of later development of GO. Why this orbital autoimmunity remains subclinical in the majority of the cases, and progresses into clinically detectable GO in others, remains unclear.
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Tanshinone IIA Improves Painful Diabetic Neuropathy by Suppressing the Expression and Activity of Voltage-Gated Sodium Channel in Rat Dorsal Root Ganglia

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0044-100722

Painful diabetic neuropathy (PDN) is one of the intractable complications of diabetes mellitus, which manifest as exaggerated pain perception. Previous studies showed that Tanshinone IIA (TIIA), one of the major bioactive extracts of Salvia miltiorrhiza Bunge, have obvious analgesic effect on different types of pain process, and the underlying analgesic mechanisms are not fully understood. The present study combined the behavioral, electrophysiological and biochemical methods to elucidate the analgesic mechanism of TIIA, using streptozotocin (STZ)-induced PDN rat models. Intraperitoneal injection (i.p.) of TIIA for 3 weeks in PDN rats significantly improved mechanical allodynia and thermal hyperalgesia. Patch clamp recordings showed that the excitability of dorsal root ganglion (DRG) nociceptive neuron was increased in diabetic state, and TIIA treatment effectively recovered the subnormality, which was achieved by preventing augments of both Tetrodotoxin-sensitive (TTX-resistant) and Tetrodotoxin-sensitive (TTX-S) sodium currents. Further, the protein expressions of voltage-gated sodium channels (VGSCs) α-subunits Nav1.3, Nav1.7 and Nav1.9 increased in DRG of diabetic rats and were normalized by TIIA application. In conclusion, this study provides evidence that the TIIA attenuated PDN by effecting VGSCs activities and expressions, indicating that the TIIA could be a promising agent for PDN treatment.
[...]

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The PCOS Patients differ in Lipid Profile According to their Phenotypes

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-121264

Polycystic ovary syndrome (PCOS) affects 4–18% of women of reproductive age. The number of reports exploring the lipid profiles among PCOS patients and number of studied patients are limited. The aim of our study was to assess the lipid profile separately in lean and non-lean women with polycystic ovary syndrome divided according to hyperandrogenemia, defined as free androgen index (FAI)≥5. The second aim was to compare the lipid profiles among lean and non-lean PCOS patients with respect to hyperandrogenemia and regularity of menstruation cycles. We evaluated 232 patients from Department of Endocrinological Gynecology, Jagiellonian University Medical College in Krakow diagnosed with PCOS. The population consisted of 166 lean and 66 non-lean women. We observed higher levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C) in lean patients with FAI<5 than in lean patients with FAI≥5. There were no differences in lipid profile between non-lean patients with FAI≥5 and non-lean patients with FAI<5. Among lean patients higher total cholesterol levels were observed in those with irregular menstruation cycles and FAI<5 than in patients with FAI≥5 and regular cycles. There were no differences in lipid profiles between four phenotypes among non-lean PCOS patients. Conclusions The results of our study showed differences in lipid profile between lean PCOS patients according to their phenotype based on androgens' level. This effect was abandoned by fat tissue mass in non-lean ones. Further studies should be conducted to explore these associations.
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New findings in non-invasive imaging of cutaneous endometriosis: Dermoscopy, high-frequency ultrasound and reflectance confocal microscopy

Abstract

Background

Cutaneous endometriosis (CE) is rare and its dermoscopic features were reported only in 3 patients. The aim of this study was to examine a case of pigmented CE with multiple non-invasive imaging techniques, to compare the obtained images with histopathology and to define their utility in an early diagnosis of the disease.

Case report

We performed dermoscopy, high-frequency ultrasound (HFUS), in vivo and ex vivo reflectance confocal microscopy (RCM) of a pigmented CE arising on the caesarean scar of a phototype IV patient, along with histologic studies. Dermoscopy showed a greyish background and a brownish pigmentation. HFUS shows well-demarcated anechoic areas corresponding to ectopic endometrial tissue at histopathologic examination. RCM and OCT only showed the alterations of the epidermis.

Conclusion

High-frequency ultrasound could represent a very useful tool for an early diagnosis of CE and its usefulness could be tested in patients with unusual cyclical pain, even before skin lesion appearance. RCM allowed the visualization of skin surface modification due to underlying endometriosic tissue. Dermoscopy showed a new aspect that was probably related to the mix of blood extravasation (ie, greyish background) and epidermal pigmentation (ie, brown pigmentation).

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Benign and malignant collision tumors of melanocytic skin lesions with hemangioma: Dermoscopic and reflectance confocal microscopy features

Abstract

Background

Though the combination/collision of nevi or lentigo simplex and hemangiomas is frequent, the malignant collision tumor melanoma-hemangioma is exceptional and can sometime clinically simulate a benign collision. To date, a series of collision tumors of hemangiomas associated with either benign or malignant melanocytic skin lesions (MSL) has yet to be studied by non-invasive imaging and clinico-pathologic correlates.

Methods

We present 10 cases of patients with collision tumors of hemangioma with different MSL including: 2 in situ lentigo-maligna melanoma, 1 invasive melanoma, 5 melanocytic nevi, and 2 lentigo simplex. The clinical aspect along with the dermoscopic and reflectance confocal microscopy (RCM) features is described and compared with histopathologic findings.

Results

Dermoscopic examination allows to recognize a dark ring in malignant collision melanoma-hemangioma and a jelly ring sign in benign collision of nevi/lentigo simplex-hemangioma. These peculiar features were confirmed by RCM and histopathologic findings.

Conclusion

Two simple dermoscopic clues confirmed by RCM features can be proposed to help distinguish between benign and malignant collisions tumors.

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Liponeurofibroma: Clinicopathological features and histogenesis

Abstract

A neurofibroma is a common cutaneous benign tumor of neural origin. Various histological variants have been reported. Recently, sporadic reports of fatty variants have been reported but their clinicopathological features have not been well studied. The purpose of this study was to examine liponeurofibroma, and to report the distinctive clinicopathological features and histogenesis in comparison with the classic form. A retrospective study was performed on 130 cases. Immunohistochemical staining was performed for S100, factor VIIIa, perilipin and vascular endothelial growth factor. Masson's trichrome stain was also used. Intratumoral adipocytes were examined with transmission electron microscopy. Thirty-two (24.6%) cases were classified as liponeurofibroma on microscopic examination. This variant was more common in patients with neurofibromatosis type 1, older age and female sex. The most prevalent location was the head and neck. Intratumoral fat deposits showed differences in morphology and size compared with subcutaneous fat on light microscopy. Neurofibromatosis type 1 had the highest odds of fatty change in liponeurofibroma. In sporadic cases, fatty change can be caused by senescence, chronic injury, or tissue hypoxia secondary to internal or external stimuli. Further investigation is needed to identify the pathomechanism of fatty change in various cutaneous neoplasms, including neurofibroma.

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Posterior reversible encephalopathy syndrome secondary to asymptomatic poststreptococcal glomerulonephritis in a child with sickle cell anemia: a case report

Posterior reversible encephalopathy syndrome is a neurotoxic condition that occurs as a result of the failure of posterior circulatory autoregulation in response to acute changes in blood pressure. Overperfusi...

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Correction to: An exotic abscess within the United Kingdom from The Gambia: a case report

In the publication of this article [1], there is an error in an authors name.

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Carcinoid heart disease revealed by cyanosis with both right and left valvular involvement: a case report

Carcinoid heart disease is a frequent complication of carcinoid syndrome. It is related to the release by the carcinoid tumor and/or its metastases of bioactive substances such as serotonin. It is characterize...

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Burden of atopic dermatitis in Japanese adults: Analysis of data from the 2013 National Health and Wellness Survey

Abstract

Atopic dermatitis is a chronic inflammatory skin disease. The objective of this study was to characterize the burden of atopic dermatitis in Japanese adult patients relative to the general population. Japanese adults (≥18 years) with a self-reported diagnosis of atopic dermatitis and adult controls without atopic dermatitis/eczema/dermatitis were identified from the 2013 Japan National Health and Wellness Survey. Atopic dermatitis patients were propensity-score matched with non-atopic dermatitis controls (1:2 ratio) on demographic variables. Patient-reported outcome data on comorbidities, mood and sleep disorders, health-related quality of life, work productivity and activity impairment, and health-care resource utilization were analyzed in atopic dermatitis patients and matched controls. A total of 638 Japanese adult patients with atopic dermatitis were identified, of whom 290 (45.5%) rated their disease as "moderate/severe" and 348 (54.5%) as "mild". The analysis cohort comprised 634 atopic dermatitis patients and 1268 matched controls. Atopic dermatitis patients reported a significantly higher prevalence of arthritis, asthma, nasal allergies/hay fever, anxiety, depression and sleep disorders compared with controls (all P < 0.001). Atopic dermatitis patients also reported a significantly poorer health-related quality of life, higher overall work and activity impairment, and higher health-care resource utilization (all P < 0.001). Self-rated disease severity was not associated with disease burden, except for a significantly higher overall work and activity impairment. In conclusion, Japanese adult patients with atopic dermatitis reported a substantial disease burden relative to adults without atopic dermatitis, suggesting an unmet need for effective strategies targeting disease management.

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Case of psoriatic patient who maintains long-term remission after anti-hepatitis C virus agents and ustekinumab treatment

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Immunohistochemical evaluation of H3K27 trimethylation in malignant peripheral nerve sheath tumors

Publication date: Available online 31 January 2018
Source:Pathology - Research and Practice
Author(s): Hiroshi Otsuka, Kenichi Kohashi, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yuichi Yamada, Hidetaka Yamamoto, Yasuharu Nakashima, Yoshinao Oda
The histological definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is quite difficult because the morphological features are not specific and no useful immunohistochemical marker has been identified. Loss-of-function mutations in EED or SUZ12, which encode the core subunit of polycomb repressive complex 2 (PRC2), were reported in MPNSTs, and the mutations were shown to cause inactivation of PRC2, leading to loss of trimethylation of histone H3 at lysine 27 (H3K27me3). Immunohistochemistry of H3K27me3 is expected to be a specific marker for MPNSTs. We evaluated immunohistochemical expression of H3K27me3 in MPNSTs with heterologous components and metachronous cases of MPNSTs. Among 145 MPNST samples, 50 (34.5%) showed complete loss of staining, and 45 (31.0%) showed partial loss of staining. Regarding the backgrounds of MPNSTs, 74 samples of neurofibromatosis type 1 (NF-1)-associated MPNST demonstrated 26 (35.1%) complete and 26 (35.1%) partial loss of H3K27me3. Among MPNSTs with heterologous component, almost all of MPNSTs with epithelioid differentiation (8/9 samples, 88.9%) retained H3K27me3, and malignant Triton tumors without epithelioid component lacked H3K27me3 at high rate (91.7%). Five of 20 metachronous MPNST cases showed significantly reduced expression of H3K27me3 between primary and later-occurring tumors, but in some cases increased expression of H3K27me3 in the clinical course (such as complete loss to partial loss) was observed. If the tumors are recurrent or metastatic, H3K27me3 expression should be reduced or at least maintained because loss of H3K27me3 is due to genetic mutation of EED or SUZ12. MPNSTs, especially those associated with NF-1, can occur in heterochronous and multiple patterns, and the identification of increased expression of H3K27me3 during a patient's clinical course can be helpful for determining whether the tumors are heterochronous, multiple or not. As heterochronous and multiple tumors may show lower malignancy compared to recurrent or metastatic tumors, favorable prognosis may be expected when H3K27me3 expression is increased.

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Downregulation of SETD8 by MiR-382 is involved in glioma progression

Publication date: Available online 31 January 2018
Source:Pathology - Research and Practice
Author(s): Zhiming Ma
BackgroundSETD8 (named PR-SET7 or KMT5a) has been reported to regulate various biological processes including carcinogenesis. However, the role of SETD8 in glioma progression has not been investigated.MethodqPCR and western blot were used to detect the expression levels of miR-382 and SETD8. MTT and wound healing assay used to detect the cell proliferation and migratory capability. A predicted target of miR-382 (SETD8) was first validated using a luciferase assay.ResultsIn this study, we found that SETD8 expression was evidently upregulated in glioma tissues and glioma cells, compared with the adjacent normal tissues and normal human astrocytes (NHA). Next, we showed that SETD8 evidently induced cell proliferation and migration in vitro and in vivo. In addition,dual-luciferase assays revealed that miR-382 directly regulates oncogenic SETD8 expression in U87 and U251 cells. Finally a statistically significant inverse correlation of miR-382 and SETD8 expression was observed in 30 glioma patients.ConclusionThese data indicated that oncogenic SETD8 was regulated by miR-382 and involved glioma progression, .revealing new therapeutic targets for glioma cancer.

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Knowledge of resting heart rate mediates the relationship between intelligence and the heartbeat counting task

Publication date: Available online 31 January 2018
Source:Biological Psychology
Author(s): Jennifer Murphy, Edward Millgate, Hayley Geary, Eri Ichijo, Michel-Pierre Coll, Rebecca Brewer, Caroline Catmur, Geoffrey Bird
Evidence suggests that intelligence is positively associated with performance on the heartbeat counting task (HCT). The HCT is often employed as measure of interoception – the ability to perceive the internal state of one's body – however it's use remains controversial as performance on the HCT is strongly influenced by knowledge of resting heart rate. This raises the possibility that heart rate knowledge may mediate the previously-observed association between intelligence and HCT performance. Study One demonstrates an association between intelligence and HCT performance (N = 94), and Study Two demonstrates that this relationship is mediated by knowledge of the average resting heart rate (N = 134). These data underscore the need to account for the influence of prior knowledge and beliefs when examining individual differences in cardiac interoceptive accuracy using the HCT.

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Electrophysiological individual face adaptation effects with fast periodic visual stimulation resist long interruptions in adaptation

Publication date: Available online 31 January 2018
Source:Biological Psychology
Author(s): Segolene Lithfous, Bruno Rossion
This study used fast periodic visual stimulation (FPVS) and electroencephalography (EEG) to investigate whether the reduction of face adaptation effects over time is due to the introduction of a novel stimulus. In adapting sequences, one individual face was presented at a rate of 6 Hz over 60 sec. In testing sequences this adapted face was alternated with a novel individual face at the same rate for 20 sec, so that face identity was repeated at a frequency of 3 Hz (i.e. 6 Hz/2). Testing sequences started immediately or 9–15 sec after adapting sequences. Identity adaptation produced a selective response at 3 Hz over the right occipito-temporal cortex both with and without delay after adapting sequences. These results suggest that the adaptation effect persists for several seconds, and that the decay of the adaptation effect is due to the introduction of a novel face stimulus.

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The Late Posterior Negativity in Episodic Memory: A Correlate of Stimulus Retrieval?

Publication date: Available online 31 January 2018
Source:Biological Psychology
Author(s): Kathrin Sommer, Salvatore Vita, Vilfredo De Pascalis
We investigated whether the late posterior negativity (LPN) is a component linked to stimulus retrieval or rather to complex, higher-order stimulus evaluation processes or response preparation processes. Participants performed three separate tasks across separate sessions: an encoding task, a memory recognition task, and a visual discrimination task. In the visual discrimination task, the difficulty of stimulus evaluation was manipulated via stimuli varying in complexity (easy vs. moderately difficult) and duration of stimulus presentation (short vs. long). Three indices of the LPN peak were examined: amplitude, latency, and width. The LPN was present in all three tasks, with maximum amplitudes at occipital sites. Results of the visual discrimination task showed that the LPN amplitude is modulated by task difficulty. No latency differences were observed between short and long presentations, suggesting that the LPN is not related to response preparation. Consequently, we compared the LPN associated with short presentations of easy and difficult stimuli with the LPN of the encoding and memory task. The LPN amplitude was more negative in the memory task compared to the other tasks. Latency and width of the LPN were modulated by stimulus complexity, with increased latency and width in the encoding and memory task relative to the visual discrimination task. Overall, these findings suggest that the LPN is not a component linked to stimulus retrieval and response preparation, but rather to complex, higher-order stimulus evaluation processes, which are modulated by task difficulty.

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Haptic recognition memory following short-terrm visual deprivation: Behavioral and neural correlates from ERPs and alpha band oscillations

Publication date: Available online 31 January 2018
Source:Biological Psychology
Author(s): Gerardo Santaniello, Manuel Sebastián, Luis Carretié, Uxia Fernández-Folgueiras, José Antonio Hinojosa
In the current study, we investigated the effects of short-term visual deprivation (2 hours) on a haptic recognition memory task with familiar objects. Behavioral data, as well as event-related potentials (ERPs) and induced event-related oscillations (EROs) were analyzed. At the behavioral level, deprived participants showed speeded reaction times to new stimuli. Analyses of ERPs indicated that starting from 1000 ms the recognition of old objects elicited enhanced positive amplitudes only for the visually deprived group. Visual deprivation also influenced EROs. In this sense, we observed reduced power in the lower-1 alpha band for the processing of new compared to old stimuli between 500 and 750 ms. Overall, our data showed improved haptic recognition memory after a short period of visual deprivation. These effects were thought to reflect a compensatory mechanism that might have developed as an adaptive strategy for dealing with the environment when visual information is not available.

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Coupling and Segregation of Large-scale Brain Networks Predict Individual Differences in Delay Discounting

Publication date: Available online 31 January 2018
Source:Biological Psychology
Author(s): Zhiyi Chen, Yiqun Guo, Tingyong Feng
Decision-making about rewards, which requires us to choose between different time points, generally refers to intertemporal choice. Converging evidence suggests that some of the brain networks recruited in the delay discounting task have been well characterized for intertemporal choice. However, little is known about how the connectivity patterns of these large-scale brain networks are associated with delay discounting. Here, we use a resting-state functional connectivity MRI (rs-fcMRI) and a graph theoretical analysis to address this question. We found that the delay discounting rates showed a positive correlation with the functional network connectivity (FNC) between the cingulo-opercular network (CON) and the default mode network (DMN), while they showed a negative correlation with the FNC of both the CON-SAN (salience network) and the SAN-FPN (fronto-parietal network). Our results showed the association of both coupling and segregating processes with large-scale brain networks in delay discounting. Thus, the present study highlights the pivotal role of the functional connectivity patterns of intrinsic large-scale brain networks in delay discounting and extends our perspective on the neural mechanism of delay discounting.

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Measurement of attentional reserve and mental effort for cognitive workload assessment under various task demands during dual-task walking

Publication date: Available online 31 January 2018
Source:Biological Psychology
Author(s): Emma P. Shaw, Jeremy C. Rietschel, Brad D. Hendershot, Alison L. Pruziner, Matthew W. Miller, Bradley D. Hatfield, Rodolphe J. Gentili
Previous work focused on assessing cognitive workload has suggested EEG spectral content and component amplitudes of the event-related potential (ERP) waveform may index mental effort and attentional reserve, respectively. Although few studies have assessed attentional reserve and mental effort during upper-extremity performance, none employed a combined approach to measure cognitive workload during locomotion. Therefore, by systematically considering ERPs, spectral content, and importantly, their combinations this study aimed to examine whether concurrent changes in spectral content and ERPs could collectively index cognitive workload during locomotion. Specifically, ERP and EEG markers were assessed as participants performed a cognitive task under two levels of difficulty (easy or hard) and two conditions (seated or walking). Changes in attentional reserve and mental effort appeared to collectively index cognitive workload under varying demands due to changes in task difficulty or performance conditions. This work can inform cognitive workload assessment in patient populations with gait deficiencies for future applications.

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The Power to Choose

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Benefit‐Risk Summary of Regorafenib for the Treatment of Patients with Advanced Hepatocellular Carcinoma That Has Progressed on Sorafenib

AbstractOn April 27, 2017, the U.S. Food and Drug Administration approved regorafenib for the treatment of patients with advanced hepatocellular carcinoma (HCC) who had previously been treated with sorafenib. Approval was based on the results of a single, randomized, placebo‐controlled trial (RESORCE) that demonstrated an improvement in overall survival (OS). Patients were randomly allocated to receive regorafenib160 mg orally once daily or matching placebo for the first 21 days of each 28‐day cycle. The trial demonstrated a significant improvement in OS (hazard ratio [HR] = 0.63; 95% confidence interval [CI], 0.50–0.79, p < .0001) with an estimated median OS of 10.6 months in the regorafenib arm and 7.8 months in the placebo arm. A statistically significant improvement in progression‐free survival (PFS) based on modified RECIST for HCC [Semin Liver Dis 2010;30:52–60] (HR = 0.46; 95% CI, 0.37–0.56, p < .0001) was also demonstrated; the estimated median PFS was 3.1 and 1.5 months in the regorafenib and placebo arms, respectively. The overall response rate, based on modified RECIST for HCC, was 11% in the regorafenib arm and 4% in the placebo arm. The toxicity profile was consistent with that observed in other indications; the most clinically significant adverse reactions were palmar‐plantar erythrodysesthesia, diarrhea, and hypertension. Based on the improvement in survival and acceptable toxicity, a favorable benefit‐to‐risk evaluation led to approval for treatment of patients with advanced HCC.Implications for Practice.Regorafenib is the first drug approved by the U.S. Food and Drug Administration for the treatment of hepatocellular carcinoma that has progressed on sorafenib and is expected to become a standard of care for these patients.

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Tumor Mutational Burden Guides Therapy in a Treatment Refractory POLE‐Mutant Uterine Carcinosarcoma

AbstractGynecologic carcinosarcomas, previously known as malignant mixed Müllerian tumors, are uncommon malignancies that demonstrate an aggressive biology and lack a standard therapeutic approach. Molecular analyses have revealed recurrent alterations in chromatin remodeling genes, but clinical support for therapeutic significance is lacking. We prospectively identified a patient with refractory uterine carcinosarcoma whose tumor was subject to molecular profiling at diagnosis and again at radiographic progression. Initial molecular testing did not assess tumor mutational burden, DNA polymerase ɛ (POLE), or microsatellite status. After the failure of several lines of chemotherapy, comprehensive genomic profiling of a repeat biopsy identified two missense mutations of the exonuclease domain of POLE (P286R and T323A). Tumor mutational burden was elevated (169 mutations per DNA megabase), consistent with an ultramutator phenotype. As seen in previously reported POLE‐endometrioid cases, our patient harbored alterations in PIK3CA, ARID1A, and PTEN and was microsatellite stable, with appreciable tumor‐infiltrating lymphocytes. She achieved an ongoing durable response with pembrolizumab. This is the first report of programmed cell death protein 1 response in uterine carcinosarcoma.Key Points. Uterine carcinosarcoma is an uncommon and aggressive histologic variant of endometrial carcinoma with a poor prognosis. Inactivating DNA polymerase ɛ (POLE) mutations have been associated with high tumor mutational burden (TMB) and response to immune checkpoint inhibition. To the authors' knowledge, this is the first report of response to immune checkpoint inhibitor therapy in a patient with uterine carcinosarcoma. This case further supports expanding genomic profiling to include assessment of tumor mutational burden across tumor types, given the potential for immune checkpoint inhibitor therapy in TMB‐high tumors.

http://ift.tt/2DTEFko

Early Gastric Cancer: Clinical Behavior and Treatment Options. Results of an Italian Multicenter Study on Behalf of the Italian Gastric Cancer Research Group (GIRCG)

AbstractBackground.Early gastric cancer (EGC) generally has a good prognosis. However, the current definition of EGC includes various subgroups of patients with different pathological characteristics and different prognoses, some of whom have aggressive disease with a biological behavior similar to that of advanced carcinoma.Materials and Methods.We retrospectively evaluated 1,074 patients with EGC who had undergone surgery between 1982 and 2009. The cumulative incidence function of cancer‐specific mortality and competing mortality were estimated using the Fine and Gray method.Results.The median follow‐up period was 193 months (range 1–324). Five hundred and sixty‐two (52.3%) patients died, 96 (8.9%) from EGC. The 5‐, 10‐, and 15‐year cumulative incidence rates for mortality of all causes were 20.5% (95% confidence interval [CI] 18.0–22.9), 37.1% (95% CI 34.7–40.7), and 52.6% (95% CI 49.1–56.0), respectively; for cancer‐specific mortality, 6.0% (95% CI 4.5–7.6), 9.9% (95% CI 7.9–11.9), and 11.1% (95% CI 8.8–13.3), respectively; and for mortality of other causes, 14.4% (95% CI 12.1–16.6), 27.2% (95% CI 24.2–30.2), and 41.5% (95% CI 38.1–43.3), respectively. A significant increase in the risk of cancer‐specific mortality was observed for lesions >2 cm (adjusted hazard ratio [HR] = 1.44, 95% CI 1.07–1.94), Pen A‐type disease (adjusted HR = 1.73, 95% CI 1.15–2.61), and node‐positive cancers (adjusted HR = 2.28, 95% CI 1.61–3.21).Conclusion.Patients with EGC with tumors >2 cm, Pen A‐type disease according to Kodama, or lymph node metastases show a poorer prognosis and an increased risk of cancer‐specific mortality.Implications for Practice.Early gastric cancer generally has a good prognosis, and some patients can be treated radically by endoscopic resection. However, the current definition of early gastric cancer includes subgroups of patients with an aggressive disease. In particular, patients with lymph node metastases and Pen A‐type tumors according to Kodama's classification need a more invasive treatment, such as subtotal or total gastrectomy with an extended D2 lymphadenectomy, plus eventual adjuvant chemotherapy.

http://ift.tt/2EucVnQ

Comparison of manipulation and stabilization exercises in patients with sacroiliac joint dysfunction patients: A randomized clinical trial

Publication date: Available online 31 January 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Fahimeh Kamali, Mehdi Zamanlou, Ali Ghanbari, Abbass Alipour, Soha Bervis
BackgroundManual therapy and exercise therapy are two common treatments for low back pain. Although their effects have been discussed in several studies, the superiority of one over the other for patients with sacroiliac joint dysfunction is still unclear.ObjectivesThe aim of this study was to compare the effects of manipulation (M) and stabilization exercises (S) in patients with subacute or chronic sacroiliac joint dysfunction.MethodsThe participants in this randomized controlled trial study were patients with subacute or chronic sacroiliac joint dysfunction for more than 4 weeks and less than 1 year. A total of 40 patients were randomized with a minimization method to the M (n = 20) or S (n = 20) group; 15 patients in each group received treatment. The treatment program lasted 2 week in group M and 4 weeks in group S. Pain and the Oswestry Disability Index (ODI) were recorded before and immediately after the treatment period.ResultsBoth groups showed significant improvement in assessed pain and ODI (P < 0.05). There were no statistically significant differences between groups in post-intervention assessed pain or ODI (P > 0.05).ConclusionsDespite the improvements seen after both manipulation and stabilization exercise therapies in patients with sacroiliac joint dysfunction, there was no significant between-group difference in the treatment effects. This result suggests that neither manual therapy nor stabilization exercise therapy is superior for treating subacute or chronic sacroiliac joint dysfunction.

http://ift.tt/2DRxDNg

The effect of traditional dysphagia therapy on the swallowing function in patients with Multiple Sclerosis: A pilot double-blinded randomized controlled trial

Publication date: Available online 31 January 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Maryam Tarameshlu, Leila Ghelichi, Amir Reza Azimi, Noureddin Nakhostin Ansari, Ahmad Reza Khatoonabadi
BackgroundDysphagia is common following Multiple Sclerosis (MS) and is associated with significant morbidity and mortality. The current rehabilitation program to swallowing therapy is Traditional Dysphagia Therapy (TDT), but there is a dearth of evidence about its effectiveness in MS patients.ObjectivesThis study was aimed to determine the effects of the TDT on the swallowing function in MS patients with dysphagia.MethodsA pilot double blind randomized clinical trial was carried out on 20 patients with MS. Patients were randomly divided into experimental group (TDT) comprising sensorimotor exercises and swallowing maneuvers, and Usual Care (UC) comprising diet prescription and postural changes. Patients in both groups received treatments for 6 weeks, 18 treatment sessions, 3 times per week, every other day. The Mann Assessment of Swallowing Ability (MASA) was the main outcome measure. The swallowing ability was assessed before treatment (T0), after the end of 9th session (T1), after the end of 18th session (T2), and after 6 weeks follow-up (T3). Penetration–Aspiration Scale (PAS) and Pharyngeal Residue Rating Scale (PRRS) as secondary outcome measures were applied at T0 and T2.ResultsBoth groups had improved regarding MASA, PAS and PRRS scores over the time (P < 0.001). The improvements achieved in all outcomes were significantly greater in the TDT group than those of the UC group. The Main effect of the Time × Group interaction was significant for MASA score (P < 0.001). The large effect sizes were found for MASA score in both the TDT (d = 3.91) and the UC (d = 1.11) groups.ConclusionsThis pilot randomized controlled trial showed that the TDT significantly improved the swallowing function of the MS patients with dysphagia.

http://ift.tt/2EsIe2j

Dry needling versus friction massage to treat tension type headache: A randomized clinical trial

Publication date: Available online 31 January 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Fahimeh Kamali, Marzieh Mohamadi, Leila Fakheri, Fatemeh Mohammadnejad
Tension type headache (TTH), the most common type of headache, is known to be associated with myofascial pain syndrome and the existence of myofascial trigger points. There are several treatment options for myofascial trigger points. In this study we compared the effectiveness of dry needling and friction massage to treat patients with TTH.A convenience sample of 44 patients with TTH participated in this randomized clinical trial. The frequency and intensity of headache, pressure pain threshold at the trigger point site, and cervical range of motion were recorded. Then the participants were randomly assigned to one of two treatment groups for dry needling or friction massage, delivered in 3 sessions during 1 week. The participants were evaluated 48 h after the last treatment session. Analysis of covariance, paired t-test and Wilcoxon's test were used for statistical analysis.The results showed that both treatment methods significantly reduced headache frequency and intensity, and increased pain threshold at the trigger points. However, neither treatment had any effect on cervical range of motion except for extension, which increased in the dry needling group. Between-group comparisons showed that dry needling increased pain threshold significantly more than friction massage. There were no significant differences between groups in any other outcome variables.Dry needling and friction massage were equally effective in improving symptoms in patients with TTH. The decreases in frequency and intensity of headache were similar after both dry needing and friction massage.

http://ift.tt/2DSjY8y

Evaluating the effect of rain on the fate of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) accumulated in polluted trees in Amman, Jordan

Abstract

Open combustion of solid waste is one of the main sources of the emission of dioxin and dioxin-like compounds (DLCs). Ambient dioxin will eventually undergo depositions on soils and tree leaves. Pine trees have shown an ability to store dioxin in their needles allowing biomonitoring of dioxin atmospheric concentrations. Infiltration can transport dioxin to greater depths into the ground, on one hand, while vaporization can allow dioxin to return back to the atmosphere on the other. Several studies evaluated the migration of dioxin between two compartments; however, few studies have attempted to understand the fate of non-conservative PCDDs and PCDFs in an unsteady state system of more than two mediums. This study focused on the transportation of dioxin between polluted trees and the underlying soil through the effect of rain water. For approximately 10 years, pine trees in this study have been exposed to emissions generated by the open combustion of municipal solid waste (MSW) from a fixed location. Soil samples located further from the point source had generally lower dioxin concentrations. Dioxin concentrations were correlated to distance from the source using least square regression. Soil samples below contaminated trees had dioxin concentrations 10–35% greater than the calculated measurements for the same spots using the regression model. By detecting these spikes in concentrations, it was possible to identify pools of dioxin found directly under the contaminated trees—indicating a rinsing effect of rain water on the stored dioxin on the trees' needles.

http://ift.tt/2FxI9d0

Inverse association between MDM2 and HUWE1 protein expression levels in human breast cancer and liposarcoma.

Inverse association between MDM2 and HUWE1 protein expression levels in human breast cancer and liposarcoma.

Int J Clin Exp Pathol. 2016;9(6):6342-6349

Authors: Canfeld K, Wells W, Geradts J, Kinlaw WB, Cheng C, Kurokawa M

Abstract
The ubiquitin E3 ligase MDM2 is best known for its ability to suppress the tumor suppressor p53. However, MDM2 also targets other proteins for proteasomal degradation and accumulating evidence strongly suggests p53-independent roles of MDM2 in cancer. We previously reported that MDM2 promotes degradation of another ubiquitin E3 ligase HUWE1 by ubiquitination, particularly, which confers HER2+ breast cancer cells resistance to the HER2 inhibitor lapatinib. However, it remains unclear whether such a mechanism can operate in other cell types, independently of HER2 inhibitors. Moreover, in vivo evidence that supports HUWE1 degradation by MDM2 is missing. In the current study, we performed immunohistochemistry (IHC) to analyze expression levels of MDM2 and HUWE1 in normal organs, two breast cancer cohorts (A, n = 137 and B, n = 27), and a liposarcoma cohort (n = 45). Our results show that HUWE1 is ubiquitously expressed in healthy organs, where the oncoprotein MDM2 is undetectable. Likewise, in the majority of breast cancers regardless of their subtypes, MDM2 is below detectable levels, while HUWE1 is highly expressed. In contrast, in a subset of liposarcoma that is characterized by MDM2 overexpression, only 40% of these showed detectable HUWE1 protein. Importantly, despite the inverse association between MDM2 and HUWE1 protein levels, gene expression analysis in independent datasets revealed no such correlation at the mRNA level. Our results demonstrate the first in vivo evidence to support the hypothesis of MDM2-mediated HUWE1 degradation, which may help to understand the regulation of HUWE1 as well as p53-independent roles of MDM2.

PMID: 29375730 [PubMed]

http://ift.tt/2rWS0XF

Unexpected potential protective associations between outdoor air pollution and cataracts

Abstract

Air pollution is one of the biggest public health issues, and the eye is continuously exposed to multiple outdoor air pollution. However, to date, no large-scale study has assessed the relationship between air pollutants and cataracts. We investigated associations between outdoor air pollution and cataracts in the Korean population. A population-based cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey, including 18,622 adults more than 40 years of age. The presence of cataracts and their subtypes were evaluated by ophthalmologists. Air pollution data (levels of particulate matter, ozone, nitrogen dioxide, and sulfur dioxide) for the 2 years prior to the ocular examinations were collected from national monitoring stations. The associations of multiple air pollutants with cataracts were assessed by multivariate logistic regression analyses. Sociodemographic factors and previously known risk factors for cataracts were controlled as covariates (model 1 included sociodemographic factors, sun exposure, and behavioral factors, while model 2 further included clinical factors). Higher ozone concentrations were protectively associated with overall cataract which included all subtypes [single pollutant model: 0.003 ppm increase—model 1 (OR 0.89, p = 0.014), model 2 (OR 0.87, p = 0.011); multi-pollutant model: 0.003 ppm increase—model 1 (OR 0.80, p = 0.002), model 2 (OR 0.87, p = 0.002)]. Especially, higher ozone concentrations showed deeply protective association with nuclear cataract subtype [0.003 ppm increase—single pollutant model: model 2 (OR 0.84, p = 0.006), multi-pollutant model: model 2 (OR 0.73, p < 0.001)]. Higher tropospheric ozone concentrations showed protective associations with overall cataract and nuclear cataract subtype in the Korean population.

http://ift.tt/2Fz5sDc

Use of balloon catheter dilation vs. traditional endoscopic sinus surgery in management of light and severe chronic rhinosinusitis of the frontal sinus: a multicenter prospective randomized study

OBJECTIVE: Chronic rhinosinusitis (CRS) of the frontal sinus is a complex pathological condition and many surgical techniques were described to treat this area endoscopically, like traditional endoscopic sinus surgery (ESS) and balloon catheter dilation (BCD).

PATIENTS AND METHODS: We designed a multicenter prospective randomized study to assess the validity and safety of BCD vs. ESS in symptomatological chronic rhinosinusitis of the frontal sinus enrolling a population of 102 adult patients (64 men and 38 women; overall 148 frontal sinuses studied) with non-polypoid CRS. For a better evaluation of the disease, in our study we decided to analyze both radiological (Lund-McKay CT scoring modified by Zinreich) and symptomatological results (SNOT-20 questionnaire). We divided the population affected in two groups, one with light/mild frontal CRS and the other with moderate/severe frontal CRS, basing on radiological findings at Lund-MacKay modified by Zinreich score. Every group was divided in two subgroups, in one we used BCD and in the other we used traditional ESS.

RESULTS: The current literature does not support the suggestion that indications for BCD and ESS are identical, and additional research is needed to determine the role for BCD in specific patient populations. The results showed a not statistically significative difference between BCD and conventional ESS of the frontal sinus in patients with light/mild CRS and in patients with moderate/severe CRS at Lund-Mackay modified by Zinreich score. The same not statistically significative difference was observed comparing the results of SNOT-20 questionnaire in the group of light/mild frontal chronic rhinosinusitis. However, we noticed a statistically significant better outcome of SNOT-20 score in patients with moderate/severe chronic rhinosinusitis that underwent BCD of frontal sinus compared to ESS.

CONCLUSIONS: BCD and ESS are two alternative weapons in the baggage of every endoscopic surgeon, even because they present similar outcomes, safeness and effectiveness both in light/mild and moderate/severe chronic rhinosinusitis of the frontal sinus. An interesting result of our study was the statistically significant better outcome of SNOT-20 score in patients that underwent BCD of frontal sinus for a moderate/severe CRS, compared to those that underwent a traditional ESS.

L'articolo Use of balloon catheter dilation vs. traditional endoscopic sinus surgery in management of light and severe chronic rhinosinusitis of the frontal sinus: a multicenter prospective randomized study sembra essere il primo su European Review.

http://ift.tt/2nzcvoe

The Effects of Pressure Biofeedback Training on Infraspinatus Muscle Activity and Muscle Thickness

Publication date: Available online 31 January 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Il-young Yu, Yeon-ki Choo, Moon-hwan Kim, Jae-seop Oh
The aim of this study was to investigate muscle activity in the infraspinatus and posterior deltoid and infraspinatus muscle thickness during a prone external rotation (PER) exercise using pressure biofeedback. Fifteen healthy men participated in this study, performing PER exercise with pressure biofeedback under four conditions (comfortable, 2 mm Hg, 4 mm Hg, and 8 mm Hg). Surface electromyography (EMG) was used to monitor infraspinatus and posterior deltoid muscle activity, and ultrasonography was used to collect infraspinatus muscle thickness data. Infraspinatus activity and muscle thickness were greatest at 2 mm Hg pressure feedback, and both measures were significantly different from those under other pressure feedback conditions (p < 0.05). In contrast, posterior deltoid activity was lower at 2 mm Hg. However, there was no significant difference between any of the four pressure feedback conditions. These findings suggest that PER exercise with pressure biofeedback, particularly at 2 mm Hg, is effective in selectively activating the infraspinatus muscle.

http://ift.tt/2s2iXJV

A prospective study of the safety and efficacy of liver stereotactic body radiotherapy in patients with and without prior liver-directed therapy

Publication date: Available online 30 January 2018
Source:Radiotherapy and Oncology
Author(s): Dominic H. Moon, Andrew Z. Wang, Joel E. Tepper
Background and purposeTo evaluate the safety and efficacy of liver stereotactic body radiotherapy (SBRT), and examine potential factors impacting outcomes including prior liver-directed therapy.Materials and methodsPatients with ECOG 0–1, Child-Pugh Class A or B, and primary hepatocellular carcinoma (HCC) or liver metastases unsuitable for surgical resection or ablation were eligible for a prospective single arm trial. SBRT was delivered with a CyberKnife system to 45 Gy in 3 fractions with a predetermined dose de-escalation scheme. Adverse events, local control, and survival were assessed.ResultsA total of 30 patients were enrolled. Eleven patients (37%) had HCC and 19 (63%) patients had liver metastases. Fourteen patients (47%) had prior liver-directed therapies including nine with liver resection, seven with trans-arterial chemoembolization, and six with radiofrequency ablation. Cumulative grade 2 and 3 acute toxicity occurred in 47% and 7% of patients, respectively. Similar rates of ≥grade 2 acute toxicity were observed between patients who had prior liver-directed treatments and those who did not. At a median follow-up of 12.7 months, 1-year local control and overall survival were 81% and 62%, respectively. Prior liver-directed therapy did not affect local control or survival.ConclusionsLiver SBRT is a safe and effective treatment even in the setting of prior liver-directed surgical and ablative therapies.

http://ift.tt/2ErJNNO

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! # Ola via Alexandros G.Sfakianakis on Inoreader

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Τετάρτη 31 Ιανουαρίου 2018

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