http://ift.tt/2E6v39t
Τετάρτη 31 Ιανουαρίου 2018
Principles of Diffusion Kurtosis Imaging and its Role in Early Diagnosis of Neurodegenerative Disorders
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.
http://ift.tt/2GzZO55
Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: reversal by cannabidiol
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.
http://ift.tt/2rXiCrM
Confocal calcium imaging analysis of respiratory-related burst activity in the parafacial region
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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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.
http://ift.tt/2GDheOm
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
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
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.
http://ift.tt/2GA0tDz
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
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
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
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.
http://ift.tt/2rWAL9c
Single cell transcriptome sequencing: A new approach for the study of mammalian sex determination
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.
http://ift.tt/2GxxAI5
Icariin modulates mitochondrial function and apoptosis in high glucose-induced glomerular podocytes through G protein-coupled estrogen receptors
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.
http://ift.tt/2rXFDe8
Alpha 1 adrenergic receptor-mediated inflammatory responses in human testicular peritubular cells
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.
http://ift.tt/2GAxxex
Epidermal growth factor receptor / extracellular signal-regulated kinase pathway enhances mineralocorticoid receptor transcriptional activity through protein stabilization
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
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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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.
This article is protected by copyright. All rights reserved.
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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.
This article is protected by copyright. All rights reserved.
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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.
This article is protected by copyright. All rights reserved.
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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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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.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Antral Follicle Diameter Variance Within Each Ovary May Be A Predictor For Poor Response In Cases With Normal Ovarian Reserve
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.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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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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© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
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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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© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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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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© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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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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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
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?
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.
http://ift.tt/2EvGntm
Haptic recognition memory following short-terrm visual deprivation: Behavioral and neural correlates from ERPs and alpha band oscillations
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.
http://ift.tt/2DRDD8K
Coupling and Segregation of Large-scale Brain Networks Predict Individual Differences in Delay Discounting
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.
http://ift.tt/2ErWOaa
The role of emotions and physiological arousal in modulating impulsive behaviour
Publication date: Available online 31 January 2018
Source:Biological Psychology
Author(s): Aleksandra M. Herman, Hugo D. Critchley, Theodora Duka
Impulsivity received considerable attention in the context of drug misuse and certain neuropsychiatric conditions. Because of its great health and well-being importance, it is crucial to understand factors which modulate impulsive behaviour. As a growing body of literature indicates the role of emotional and physiological states in guiding our actions and decisions, we argue that current affective state and physiological arousal exert a significant influence on behavioural impulsivity. As 'impulsivity' is a heterogeneous concept, in this paper, we review key theories of the topic and summarise information about distinct impulsivity subtypes and their methods of assessment, pointing out to the differences between the various components of the construct. Moreover, we review existing literature on the relationship between emotional states, arousal and impulsive behaviour and suggest directions for future research.
Graphical abstract
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Measurement of attentional reserve and mental effort for cognitive workload assessment under various task demands during dual-task walking
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.
http://ift.tt/2EufJkY
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.
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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.
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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.
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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.
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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
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
Muscle activity and kinetics of lower limbs during walking in pronated feet individuals with and without low back pain
Source:Journal of Electromyography and Kinesiology
Author(s): Nader Farahpour, AmirAli Jafarnezhadgero, Paul Allard, Mahdi Majlesi
The objectives of this study were to investigate whether excessive feet pronation alters the joints' kinematics, kinetics and the activity of involved muscles during gait in low back pain patients. Methods: The lower limb joints' motion, moment and power, as well as the activity of involved muscles during walking were measured in a control group, and two experimental groups including a group with excessive feet pronation only, and another group of low back pain patients with excessive feet pronation. Results: In both experimental groups, ankle inversion, knee flexion and internal rotation, hip internal rotation, plantar flexors' moment, hip flexors' moment, and peak positive ankle power were lower than those in control group (p<0.05). Besides, in patients, higher activity of gastrocnemius medialis, gluteus medius, erector spinae, and internal oblique muscles, and lower negative power at the ankle and peak positive power at the knee were observed (p < 0.05). In conclusion, pronated feet with low back pain was associated with less ankle inversion and knee flexion, higher knee and hip internal rotation, higher muscle activity, less energy absorption at the ankle, and reduced positive power at the knee. This study reveals that strengthening of the muscles especially knee extensors are of great importance in low back pain patients with feet pronation.
http://ift.tt/2GBxlvM
The Effects of Pressure Biofeedback Training on Infraspinatus Muscle Activity and Muscle Thickness
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
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
Development and validation of an MRI-based model to predict response to chemoradiotherapy for rectal cancer
Source:Radiotherapy and Oncology
Author(s): Philippe Bulens, Alice Couwenberg, Karin Haustermans, Annelies Debucquoy, Vincent Vandecaveye, Marielle Philippens, Mu Zhou, Olivier Gevaert, Martijn Intven
Background and purposeTo safely implement organ preserving treatment strategies for patients with rectal cancer, well-considered selection of patients with favourable response is needed. In this study, we develop and validate an MRI-based response predicting model.MethodsA multivariate model using T2-volumetric and DWI parameters before and 6 weeks after chemoradiation (CRT) was developed using a cohort of 85 rectal cancer patients and validated in an external cohort of 55 patients that underwent preoperative CRT.ResultsTwenty-two patients (26%) achieved ypT0-1N0 response in the development cohort versus 13 patients (24%) in the validation cohort. Two T2-volumetric parameters (ΔVolume% and Sphere_post) and two DWI parameters (ADC_avg_post and ADCratio_avg) were retained in a model predicting (near-)complete response (ypT0-1N0). In the development cohort, this model had a good predictive performance (AUC = 0.89; 95% CI 0.80–0.98). Validation of the model in an external cohort resulted in a similar performance (AUC = 0.88 95% CI 0.79–0.98).ConclusionAn MRI-based prediction model of (near-)complete pathological response following CRT in rectal cancer patients, shows a high predictive performance in an external validation cohort. The clinically relevant features in the model make it an interesting tool for implementation of organ-preserving strategies in rectal cancer.
http://ift.tt/2DQQfwZ
Palliative radiotherapy for locally advanced non-metastatic head and neck cancer: A survey of UK national practice
Source:Radiotherapy and Oncology
Author(s): Muhammad Shahid Iqbal, Charles Kelly, Josef Kovarik, Bojidar Goranov, Ghazia Shaikh, David Morgan, Werner Dobrowsky, Vinidh Paleri
http://ift.tt/2DTk9kg
Clinical significance of soluble programmed cell death ligand-1 (sPD-L1) in hepatocellular carcinoma patients treated with radiotherapy
Source:Radiotherapy and Oncology
Author(s): Hyun Ju Kim, Sangjoon Park, Kyoung-Jin Kim, Jinsil Seong
PurposeTo investigate the clinical implications of the soluble programmed cell death-ligand 1 (sPD-L1) level in hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT).Materials/methodsHCC patients treated with RT between June 2011 and March 2015 were prospectively recruited and sPD-L1 levels were measured using an enzyme-linked immunosorbent assay. Blood samples were obtained at the RT start, RT end, and 1-month follow-up. The associations of the sPD-L1 level with the clinical features and outcomes were analyzed.ResultsFifty-three patients with HCC were included. Thirty-four patients received conventional fractionated RT with hepatic arterial infusional chemotherapy, while 19 patients received stereotactic body radiotherapy (SBRT). The initial sPD-L1 level was significantly associated with stage, tumor size, portal vein tumor thrombosis, and venous invasion. The overall-survival was significantly poorer in patients with a higher level of initial sPD-L1 (≥1.315 pg/mL). A higher level of sPD-L1 at 1 month (≥12.9 pg/mL) was significantly related to early lung metastasis. The sPD-L1 level was significantly increased after RT and the change pattern of sPD-L1 was different between two RT schemes.ConclusionsThe level of sPD-L1 was associated with tumor aggressiveness and outcomes, suggesting its role as a possible predictive biomarker. The increases in sPD-L1 after RT suggests that combined treatment with RT and immune checkpoint inhibitors may be a promising therapeutic strategy in HCC.
http://ift.tt/2Es5nBN
Review of the patient positioning reproducibility in head-and-neck radiotherapy using Statistical Process Control
Source:Radiotherapy and Oncology
Author(s): Sarah J. Moore, Patries M. Herst, Robert J.W. Louwe
Background and purposeA remarkable improvement in patient positioning was observed after the implementation of various process changes aiming to increase the consistency of patient positioning throughout the radiotherapy treatment chain. However, no tool was available to describe these changes over time in a standardised way. This study reports on the feasibility of Statistical Process Control (SPC) to highlight changes in patient positioning accuracy and facilitate correlation of these changes with the underlying process changes.Materials and methodsMetrics were designed to quantify the systematic and random patient deformation as input for the SPC charts. These metrics were based on data obtained from multiple local ROI matches for 191 patients who were treated for head-and-neck cancer during the period 2011–2016.ResultsSPC highlighted a significant improvement in patient positioning that coincided with multiple intentional process changes. The observed improvements could be described as a combination of a reduction in outliers and a systematic improvement in the patient positioning accuracy of all patients.ConclusionSPC is able to track changes in the reproducibility of patient positioning in head-and-neck radiation oncology, and distinguish between systematic and random process changes. Identification of process changes underlying these trends requires additional statistical analysis and seems only possible when the changes do not overlap in time.
http://ift.tt/2EtRBii
Biological hydrogen peroxide detection with aryl boronate and benzil BODIPY-based fluorescent probes
Publication date: Available online 31 January 2018
Source:Sensors and Actuators B: Chemical
Author(s): Malcolm S. Purdey, Hanna J. McLennan, Melanie L. Sutton-McDowall, Daniel W. Drumm, Xiaozhou Zhang, Patrick K. Capon, Sabrina Heng, Jeremy G. Thompson, Andrew D. Abell
The detection of hydrogen peroxide (H2O2) using fluorescent probes is critical to the study of oxidative stress in biological environments. Two important sensing architectures for detecting H2O2, aryl boronates and benzils, are compared here using novel boron-dipyrromethene (BODIPY) fluorescent probes. The aryl boronate PeroxyBODIPY-1 (PB1) and benzil-based nitrobenzoylBODIPY (NbzB) were synthesised from a common BODIPY intermediate in order to compare sensitivity and selectivity to H2O2. The aryl boronate PB1 gives the highest change in fluorescence on reaction with H2O2 while the benzil NbzB exhibits exclusive selectivity for H2O2 over other reactive oxygen species (ROS). Both proved to be cell-permeable, with PB1 being able to detect H2O2 in denuded bovine oocytes. The strengths of these aryl boronate and benzil probes can now be exploited concurrently to elucidate biological mechanisms of H2O2 production and oxidative stress.
http://ift.tt/2E3JLy1
Influence of surface composition on the colloidal stability of ultra-small detonation nanodiamonds in biological media
Publication date: Available online 31 January 2018
Source:Diamond and Related Materials
Author(s): Carlo Bradac, Ishan Das Rastogi, Nicole M. Cordina, Alfonso Garcia-Bennett, Louise J. Brown
Fluorescent nanodiamonds (NDs) are strong contenders as bio-labels for life science imaging, diagnostics and therapeutics. Ultimately, for their use in biomedical applications, their size should ideally be <10 nm. Yet, even more critical for their specificity and efficient uptake in cellular systems, is their resilience to aggregation, which is dictated by their colloidal stability in complex, physiological environments. To this end, we characterize small detonation NDs (~5 nm) by examining their surface chemical profiles and stability in solutions of varying ionic strength and pH. Using dynamic light scattering measurements, we demonstrate that small monodisperse ND particles with chemically homogeneous and negatively charged surface profiles are more stable than positive particles under a broad range of simulated biological environments. We show that the colloidal stability of small clusters of both positive and negative detonation NDs is improved by functionalization with bovine serum albumin. Based on these analyses, we propose and describe strategies for enhancing the overall colloidal stability of detonation NDs and their resilience to aggregation. Our findings provide a practical framework towards the reduction in size of the bio-conjugates employed to probe complex biological systems, and the advancement of bio-imaging techniques with minimal perturbation of the molecular trafficking in cellular and organelle systems.
Graphical abstract
http://ift.tt/2FyQRaU
Inorganic nanoparticles: a potential cancer therapy for human welfare
Publication date: Available online 31 January 2018
Source:International Journal of Pharmaceutics
Author(s): Arivalagan Pugazhendhi, Thomas Nesakumar Jebakumar Immanuel Edison, Indira Karuppusamy, Brindhadevi Kathirvel
Cancer is an abnormal condition leading to uncontrolled cell division which causes damage to the body tissues. Around 100 types of cancer are studied so far namely breast cancer, lung cancer, skin cancer, prostate cancer, colon cancer and lymphoma. Major cancer therapies include chemotherapy, surgery and radiations but their major drawbacks are non-specifically distributed antitumor agents, uneven delivery of drug concentration to the tumour and low monitoring. Nanoparticles (NPs) are the newly trending field of nanomedicine implied in cancer therapy. The structural characteristics of NPs makes them excellent mode for targeting and penetrating the abnormal cell growth caused by cancer. They can potentially enter the abnormal cells causing DNA damage and determine the defects in the genes. Apart from targeting cancer cells they also aid in drug delivery, imaging of abnormal cells, release and monitoring of therapeutic agents against cancer. The present review deals with the inorganic NPs mediated pharmacotherapy, potential strategies for developing drug delivery system, evaluate the merits and demerits of traditional chemotherapy and nanotheraphy for significantly improving the treatment of cancers.
Graphical abstract
http://ift.tt/2E5shRW
A novel method for the preparation of fluorescent C60 poly(amino acid) composites and their biological imaging
Publication date: Available online 31 January 2018
Source:Journal of Colloid and Interface Science
Author(s): Dazhuang Xu, Meiying Liu, Qiang Huang, Junyu Chen, Hongye Huang, Fengjie Deng, Jianwen Tian, Yuanqing Wen, Xiaoyong Zhang, Yen Wei
Recently, fullerene (C60) and its derivatives have been widely explored for many applications owing to their enriched physical and chemical properties. Specifically, the synthesis and biomedical applications of fluorescent C60 have been extensively investigated previously. However, the preparation of polymer-functionalized fluorescent C60 has not been reported thus far. In this study, water-dispersible fluorescent C60 polymer composites were successfully synthesized through the combination of the thiol-ene click reaction and subsequent ring-opening polymerization. First, 2-aminoethanethiol was introduced on the surface of C60 by the thiol-ene click reaction. The surface of amino group-functionalized C60 (C60-NH2) was further modified with poly(amino acid)s via ring-open polymerization of GluEG N-carboxyanhydrides (NCAs). The morphology, functional groups, optical properties and biocompatibility were examined by a number of characterization equipment and assays in detail. We demonstrated that the resultant fluorescent C60 poly(amino acid) (C60-GluEG) composites have a small size (about 5 nm), high water dispersibility, intense fluorescence and high photostability. Cell viability results implied that the C60-GluEG composites possess low cytotoxicity. Moreover, these C60-GluEG composites can easily penetrate into live cells, indicating their great potential for biological imaging applications.
Graphical abstract
http://ift.tt/2FA32Ep
Diamond, Carbon Nanotubes and Graphene for Biomedical Applications
Publication date: 2018
Source:Reference Module in Biomedical Sciences
Author(s): Aaqil Rifai, Elena Pirogova, Kate Fox
Carbon based materials are becoming more prevalent in biomedical applications. In particular, materials like diamond, carbon nanotubes and graphene are widely used across medicine in applications such as electrodes, tissue engineering, optics, biomedical engineering, medical implants, medical devices, and sensors. In this reference module, we focus on broad applications where diamond, carbon nanotubes and graphene are preferably utilized for their beneficial properties describing in depth the key advantages of their selection and the future advances that may be offered.
http://ift.tt/2FviAcv
Patient Reported Sexual Aid Utilization and Efficacy following Radiation Therapy for Localized Prostate Cancer
Publication date: Available online 31 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Robert T. Dess, Theresa P. Devasia, Nima Aghdam, William C. Jackson, Payal D. Soni, Clayton P. Smith, Amyre L. Mitchell, Simeng Suy, Daniel A. Hamstra, Shruti Jolly, Paul L. Nguyen, Felix Y. Feng, Matthew J. Schipper, Ted A. Skolarus, David C. Miller, Daniela A. Wittmann, Sean P. Collins, Daniel E. Spratt
PurposeErectile dysfunction is common after treatment for localized prostate cancer. Longitudinal data regarding medication and device practice patterns and efficacy in men treated are lacking. Herein, we report sexual health related quality of life (HRQOL) outcomes and utilization and efficacy of sexual aids in a contemporary cohort.Materials and MethodsBetween 2008-2013, 471 consecutive men with localized prostate cancer were treated on two institutional protocols (NCTXXXXXXXX, NCTXXXXXXXX) or on a prospective institutional registry with patient-reported HRQOL. All patients were treated with ultra-hypofractionated radiotherapy. Erectile function (EF) was defined as "firm enough for intercourse" with or without aids per EPIC-26 (n=222 at baseline); results apply to this cohort unless specifically noted. Sexual aid utilization and efficacy was patient-reported. Multivariable-analysis of EF was performed.ResultsMedian follow-up was 60 months, median age was 67, and 70% had intermediate- or high-risk disease per NCCN. At 24 and 60 months, questionnaire response rates were 86% and 67%, and EF was retained in 53% and 41%, respectively. Baseline sexual aid utilization was 37% (n=82) and was associated with lower 24-month EF preservation on multivariable-analysis (adjusted-odds-ratio: 0.49 95%CI 0.26-0.92). By 60 months, 70% of men had tried aids. Of those who found aids helpful at baseline, 84-89% reported continued benefit at 24-60 months. Among aid-naïve patients, efficacy was 80% with first-time use within 12 months and 70% >12 months post-radiotherapy (p=0.02). Among men who developed erectile dysfunction, but found sexual aids helpful, 25% were not current users at 60 months.ConclusionsOne third of men utilized sexual aids at baseline, which doubled by 5-years post-radiotherapy. Self-reported efficacy was high, and sustained. Despite significant declines in EF, a number of men reported helpfulness of aids, but were not active users. Future study is required to understand drivers of aid utilization to optimize post-treatment sexual function.
Teaser
Among a prospectively followed cohort of 471 men treated with radiation therapy for prostate cancer, we demonstrate that sexual aid use is common at baseline, increases with time, and is helpful to many. However, a substantial number of men reported benefit, but were not currently using aids, and future study is required to optimize post-treatment sexual function.http://ift.tt/2EtTBXW
Appraisal of late radiation-induced oral microvascular changes at the patient-side
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Renée Helmers, Nina F. Straat, Arash Navran, Tim A.P. Nai Chung Tong, David N. Teguh, Robert A. van Hulst, Jan de Lange, Dan M.J. Milstein
ObjectivesLate radiation-induced tissue toxicity in the head and neck (HN) region is associated with ulceration and osteoradionecrosis as a result of a detrimental effect on the underlying tissue microvasculature. The aim of this investigation was to determine the clinical feasibility of examining and measuring late irradiation changes in the oral microcirculation of HN cancer patients using the novel CytoCam video microscope system.Materials and methodsIn 30 HN cancer patients and 30 age-matched controls, bilateral video images were recorded noninvasively of the oral microcirculation of the buccal mucosa and mandibular gingiva. Tissue perfusion parameters such as functional capillary density (FCD), buccal blood vessel diameter (Øbv), and microcirculatory flow index (MFI) were analyzed.ResultsNo difference was observed for mean buccal mucosa FCD in irradiated vs. healthy tissue, whereas a lower mean gingival FCD in irradiated vs. healthy tissue was observed (34±17 cpll/mm2 vs. 68±19 cpll/mm2; p<0.001). A significant difference in mean buccal Øbv of 16±3 μm was measured compared to 14±1 μm in control buccal mucosa (p<0.001). No significant difference in MFI was observed between the two groups.ConclusionQuantifying oral microcirculatory injury associated with late irradiation effects using the CytoCam was feasible in HN cancer patients. Results indicate that marked differences in tissue-specific microcirculatory measurements of angioarchitecture, diminished capillary density, and extensively dilated blood vessel diameters are associated with late irradiation effects in HN cancer patients.
Teaser
Late irradiation microvascular effects in oral mucosa can easily be measured at the patient sideAnatomic differences in angioarchitecture and angiomorphology highlight pathologies Decreased capillary density in mandibular gingiva is associated with late radiation-induced microvascular effects Oral mucosal perfusion and microangiopathies occur differently in different tissueshttp://ift.tt/2DQVjRK
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