Neural Representations of Belief Concepts: A Representational Similarity Approach to Social Semantics

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The present experiment identified neural regions that represent a class of concepts that are independent of perceptual or sensory attributes. During functional magnetic resonance imaging scanning, participants viewed names of social groups (e.g. Atheists, Evangelicals, and Economists) and performed a one-back similarity judgment according to 1 of 2 dimensions of belief attributes: political orientation (Liberal to Conservative) or spiritualism (Spiritualist to Materialist). By generalizing across a wide variety of social groups that possess these beliefs, these attribute concepts did not coincide with any specific sensory quality, allowing us to target conceptual, rather than perceptual, representations. Multi-voxel pattern searchlight analysis was used to identify regions in which activation patterns distinguished the 2 ends of both dimensions: Conservative from Liberal social groups when participants focused on the political orientation dimension, and spiritual from Materialist groups when participants focused on the spiritualism dimension. A cluster in right precuneus exhibited such a pattern, indicating that it carries information about belief-attribute concepts and forms part of semantic memory—perhaps a component particularly concerned with psychological traits. This region did not overlap with the theory of mind network, which engaged nearby, but distinct, parts of precuneus. These findings have implications for the neural organization of conceptual knowledge, especially the understanding of social groups.</span>

http://ift.tt/2lqYzcG

Differential Contribution of Low- and High-level Image Content to Eye Movements in Monkeys and Humans

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Oculomotor selection exerts a fundamental impact on our experience of the environment. To better understand the underlying principles, researchers typically rely on behavioral data from humans, and electrophysiological recordings in macaque monkeys. This approach rests on the assumption that the same selection processes are at play in both species. To test this assumption, we compared the viewing behavior of 106 humans and 11 macaques in an unconstrained free-viewing task. Our data-driven clustering analyses revealed distinct human and macaque clusters, indicating species-specific selection strategies. Yet, cross-species predictions were found to be above chance, indicating some level of shared behavior. Analyses relying on computational models of visual saliency indicate that such cross-species commonalities in free viewing are largely due to similar low-level selection mechanisms, with only a small contribution by shared higher level selection mechanisms and with consistent viewing behavior of monkeys being a subset of the consistent viewing behavior of humans.</span>

http://ift.tt/2mtqEFm

Representational Similarity Mapping of Distributional Semantics in Left Inferior Frontal, Middle Temporal, and Motor Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Language comprehension engages a distributed network of frontotemporal, parietal, and sensorimotor regions, but it is still unclear how meaning of words and their semantic relationships are represented and processed within these regions and to which degrees lexico-semantic representations differ between regions and semantic types. We used fMRI and representational similarity analysis to relate word-elicited multivoxel patterns to semantic similarity between action and object words. In left inferior frontal (BA 44-45-47), left posterior middle temporal and left precentral cortex, the similarity of brain response patterns reflected semantic similarity among action-related verbs, as well as across lexical classes-between action verbs and tool-related nouns and, to a degree, between action verbs and food nouns, but not between action verbs and animal nouns. Instead, posterior inferior temporal cortex exhibited a reverse response pattern, which reflected the semantic similarity among object-related nouns, but not action-related words. These results show that semantic similarity is encoded by a range of cortical areas, including multimodal association (e.g., anterior inferior frontal, posterior middle temporal) and modality-preferential (premotor) cortex and that the representational geometries in these regions are partly dependent on semantic type, with semantic similarity among action-related words crossing lexical-semantic category boundaries.</span>

http://ift.tt/2lqUJ3c

Functional and Quantitative MRI Mapping of Somatomotor Representations of Human Supralaryngeal Vocal Tract

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Speech articulation requires precise control of and coordination between the effectors of the vocal tract (e.g., lips, tongue, soft palate, and larynx). However, it is unclear how the cortex represents movements of and contact between these effectors during speech, or how these cortical responses relate to inter-regional anatomical borders. Here, we used phase-encoded fMRI to map somatomotor representations of speech articulations. Phonetically trained participants produced speech phones, progressing from front (bilabial) to back (glottal) place of articulation. Maps of cortical myelin proxies (R₁= 1/T₁) further allowed us to situate functional maps with respect to anatomical borders of motor and somatosensory regions. Across participants, we found a consistent topological map of place of articulation, spanning the central sulcus and primary motor and somatosensory areas, that moved from lateral to inferior as place of articulation progressed from front to back. Phones produced at velar and glottal places of articulation activated the inferior aspect of the central sulcus, but with considerable across-subject variability. R₁ maps for a subset of participants revealed that articulator maps extended posteriorly into secondary somatosensory regions. These results show consistent topological organization of cortical representations of the vocal apparatus in the context of speech behavior.</span>

http://ift.tt/2mtmBst

Evidence for an Optimal Algorithm Underlying Signal Combination in Human Visual Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>How does the cortex combine information from multiple sources? We tested several computational models against data from steady-state electroencephalography (EEG) experiments in humans, using periodic visual stimuli combined across either retinal location or eye-of-presentation. A model in which signals are raised to an exponent before being summed in both the numerator and the denominator of a gain control nonlinearity gave the best account of the data. This model also predicted the pattern of responses in a range of additional conditions accurately and with no free parameters, as well as predicting responses at harmonic and intermodulation frequencies between 1 and 30 Hz. We speculate that this model implements the optimal algorithm for combining multiple noisy inputs, in which responses are proportional to the weighted sum of both inputs. This suggests a novel purpose for cortical gain control: implementing optimal signal combination via mutual inhibition, perhaps explaining its ubiquity as a neural computation.</span>

http://ift.tt/2lr8Y83

Neurexins 1–3 Each Have a Distinct Pattern of Expression in the Early Developing Human Cerebral Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Neurexins (NRXNs) are presynaptic terminal proteins and candidate neurodevelopmental disorder susceptibility genes; mutations presumably upset synaptic stabilization and function. However, analysis of human cortical tissue samples by RNAseq and quantitative real-time PCR at 8–12 postconceptional weeks, prior to extensive synapse formation, showed expression of all three <span style="font-style:italic;">NRXN</span>s as well as several potential binding partners. However, the levels of expression were not identical; <span style="font-style:italic;">NRXN1</span> increased with age and <span style="font-style:italic;">NRXN2</span> levels were consistently higher than for <span style="font-style:italic;">NRXN3</span>. Immunohistochemistry for each NRXN also revealed different expression patterns at this stage of development. NRXN1 and NRXN3 immunoreactivity was generally strongest in the cortical plate and increased in the ventricular zone with age, but was weak in the synaptogenic presubplate (pSP) and marginal zone. On the other hand, NRXN2 colocalized with synaptophysin in neurites of the pSP, but especially with GAP43 and CASK in growing axons of the intermediate zone. Alternative splicing modifies the role of NRXNs and we found evidence by RNAseq for exon skipping at splice site 4 and concomitant expression of KHDBRS proteins which control this splicing. NRXN2 may play a part in early cortical synaptogenesis, but NRXNs could have diverse roles in development including axon guidance, and intercellular communication between proliferating cells and/or migrating neurons.</span>

http://ift.tt/2mtq8XS

The Influence of Alertness on the Spatial Deployment of Visual Attention is Mediated by the Excitability of the Posterior Parietal Cortices

<span class="paragraphSection"><div class="boxTitle">Abstract</div>With a reduced level of alertness, healthy individuals typically show a rightward shift when deploying visual attention in space. The impact of alertness on the neural networks governing visuospatial attention is, however, poorly understood. By using a transcranial magnetic stimulation twin-coil approach, the present study aimed at investigating the effects of an alertness manipulation on the excitability of the left and the right posterior parietal cortices (PPCs), crucial nodes of the visuospatial attentional network. Participants' visuospatial attentional deployment was assessed with a free visual exploration task and concurrent eye tracking. Their alertness level was manipulated through the time of the day, that is, by testing chronotypically defined evening types both during their circadian on- and off-peak times. The results revealed an increased excitability of the left compared with the right PPC during low alertness. On the horizontal dimension, these results were accompanied by a significant rightward shift in the center and a bilateral narrowing in the periphery of the visual exploration field, as well as a central upward shift on the vertical dimension. The findings show that the manipulation of non-spatial attentional aspects (i.e., alertness) can affect visuospatial attentional deployment and modulate the excitability of areas subtending spatial attentional control.</span>

http://ift.tt/2lr58Mv

Age- and Sex-Dependent Impact of Repeated Social Stress on Intrinsic and Synaptic Excitability of the Rat Prefrontal Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Stress is implicated in psychiatric illnesses that are characterized by impairments in cognitive functions that are mediated by the medial prefrontal cortex (mPFC). Because sex and age determine stress vulnerability, the effects of repeated social stress occurring during early adolescence, mid-adolescence, or adulthood on the cellular properties of male and female rat mPFC Layer V neurons in vitro were examined. Repeated resident–intruder stress produced age- and sex-specific effects on mPFC intrinsic and synaptic excitability. Mid-adolescents were particularly vulnerable to effects on intrinsic excitability. The maximum number of action potentials (APs) evoked by increasing current intensity was robustly decreased in stressed male and female mid-adolescent rats compared with age-matched controls. These effects were associated with stress-induced changes in AP half-width, amplitude, threshold, and input resistance. Social stress at all ages generally decreased synaptic excitability by decreasing the amplitude of spontaneous excitatory postsynaptic potentials. The results suggest that whereas social stress throughout life can diminish the influence of afferents driving the mPFC, social stress during mid-adolescence additionally affects intrinsic characteristics of mPFC neurons that determine excitability. The depressant effects of social stress on intrinsic and synaptic mPFC neurons may underlie its ability to affect executive functions and emotional responses, particularly during adolescence.</span>

http://ift.tt/2mtn91t

Parsing the Role of the Hippocampus in Approach–Avoidance Conflict

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The hippocampus plays a central role in the approach–avoidance conflict that is central to the genesis of anxiety. However, its exact functional contribution has yet to be identified. We designed a novel gambling task that generated approach–avoidance conflict while controlling for spatial processing. We fit subjects' behavior using a model that quantified the subjective values of choice options, and recorded neural signals using functional magnetic resonance imaging (fMRI). Distinct functional signals were observed in anterior hippocampus, with inferior hippocampus selectively recruited when subjects rejected a gamble, to a degree that covaried with individual differences in anxiety. The superior anterior hippocampus, in contrast, uniquely demonstrated value signals that were potentiated in the context of approach–avoidance conflict. These results implicate the anterior hippocampus in behavioral avoidance and choice monitoring, in a manner relevant to understanding its role in anxiety. Our findings highlight interactions between subregions of the hippocampus as an important focus for future study.</span>

http://ift.tt/2lr1fa4

An Examination of the Neural Unreliability Thesis of Autism

<span class="paragraphSection"><div class="boxTitle">Abstract</div>An emerging neuropathological theory of Autism, referred to here as "the neural unreliability thesis," proposes greater variability in moment-to-moment cortical representation of environmental events, such that the system shows general instability in its impulse response function. Leading evidence for this thesis derives from functional neuroimaging, a methodology ill-suited for detailed assessment of sensory transmission dynamics occurring at the millisecond scale. Electrophysiological assessments of this thesis, however, are sparse and unconvincing. We conducted detailed examination of visual and somatosensory evoked activity using high-density electrical mapping in individuals with autism (<span style="font-style:italic;">N</span> = 20) and precisely matched neurotypical controls (<span style="font-style:italic;">N</span> = 20), recording large numbers of trials that allowed for exhaustive time-frequency analyses at the single-trial level. Measures of intertrial coherence and event-related spectral perturbation revealed no convincing evidence for an unreliability account of sensory responsivity in autism. Indeed, results point to robust, highly reproducible response functions marked for their exceedingly close correspondence to those in neurotypical controls</span>

http://ift.tt/2mtqQ7i

Structural Pathways Supporting Swift Acquisition of New Visuomotor Skills

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Human skill learning requires fine-scale coordination of distributed networks of brain regions linked by white matter tracts to allow for effective information transmission. Yet how individual differences in these anatomical pathways may impact individual differences in learning remains far from understood. Here, we test the hypothesis that individual differences in structural organization of networks supporting task performance predict individual differences in the rate at which humans learn a visuomotor skill. Over the course of 6 weeks, 20 healthy adult subjects practiced a discrete sequence production task, learning a sequence of finger movements based on discrete visual cues. We collected structural imaging data, and using deterministic tractography generated structural networks for each participant to identify streamlines connecting cortical and subcortical brain regions. We observed that increased white matter connectivity linking early visual regions was associated with a faster learning rate. Moreover, the strength of multiedge paths between motor and visual modules was also correlated with learning rate, supporting the potential role of extended sets of polysynaptic connections in successful skill acquisition. Our results demonstrate that estimates of anatomical connectivity from white matter microstructure can be used to predict future individual differences in the capacity to learn a new motor–visual skill, and that these predictions are supported both by direct connectivity in visual cortex and indirect connectivity between visual cortex and motor cortex.</span>

http://ift.tt/2lr3b2i

Cortical Circuit for Binding Object Identity and Location During Multiple-Object Tracking

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Sustained multifocal attention for moving targets requires binding object identities with their locations. The brain mechanisms of identity-location binding during attentive tracking have remained unresolved. In 2 functional magnetic resonance imaging experiments, we measured participants' hemodynamic activity during attentive tracking of multiple objects with equivalent (multiple-object tracking) versus distinct (multiple identity tracking, MIT) identities. Task load was manipulated parametrically. Both tasks activated large frontoparietal circuits. MIT led to significantly increased activity in frontoparietal and temporal systems subserving object recognition and working memory. These effects were replicated when eye movements were prohibited. MIT was associated with significantly increased functional connectivity between lateral temporal and frontal and parietal regions. We propose that coordinated activity of this network subserves identity-location binding during attentive tracking.</span>

http://ift.tt/2mtmTzy

Synaptic Phospholipid Signaling Modulates Axon Outgrowth via Glutamate-dependent Ca 2+ -mediated Molecular Pathways

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Altered synaptic bioactive lipid signaling has been recently shown to augment neuronal excitation in the hippocampus of adult animals by activation of presynaptic LPA₂-receptors leading to increased presynaptic glutamate release. Here, we show that this results in higher postsynaptic Ca²⁺ levels and in premature onset of spontaneous neuronal activity in the developing entorhinal cortex. Interestingly, increased synchronized neuronal activity led to reduced axon growth velocity of entorhinal neurons which project via the perforant path to the hippocampus. This was due to Ca²⁺-dependent molecular signaling to the axon affecting stabilization of the actin cytoskeleton. The spontaneous activity affected the entire entorhinal cortical network and thus led to reduced overall axon fiber numbers in the mature perforant path that is known to be important for specific memory functions. Our data show that precise regulation of early cortical activity by bioactive lipids is of critical importance for proper circuit formation.</span>

http://ift.tt/2lqYlCh

The Cytoarchitecture of Domain-specific Regions in Human High-level Visual Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>A fundamental hypothesis in neuroscience proposes that underlying cellular architecture (cytoarchitecture) contributes to the functionality of a brain area. However, this hypothesis has not been tested in human ventral temporal cortex (VTC) that contains domain-specific regions causally involved in perception. To fill this gap in knowledge, we used cortex-based alignment to register functional regions from living participants to cytoarchitectonic areas in ex vivo brains. This novel approach reveals 3 findings. First, there is a consistent relationship between domain-specific regions and cytoarchitectonic areas: each functional region is largely restricted to 1 cytoarchitectonic area. Second, extracting cytoarchitectonic profiles from face- and place-selective regions after back-projecting each region to 20-μm thick histological sections indicates that cytoarchitectonic properties distinguish these regions from each other. Third, some cytoarchitectonic areas contain more than 1 domain-specific region. For example, face-, body-, and character-selective regions are located within the same cytoarchitectonic area. We summarize these findings with a parsimonious hypothesis incorporating how cellular properties may contribute to functional specialization in human VTC. Specifically, we link computational principles to correlated axes of functional and cytoarchitectonic segregation in human VTC, in which parallel processing across domains occurs along a lateral–medial axis while transformations of information within domain occur along an anterior–posterior axis.</span>

http://ift.tt/2mtqNZa

Association of Protein Distribution and Gene Expression Revealed by PET and Post-Mortem Quantification in the Serotonergic System of the Human Brain

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Regional differences in posttranscriptional mechanisms may influence in vivo protein densities. The association of positron emission tomography (PET) imaging data from 112 healthy controls and gene expression values from the Allen Human Brain Atlas, based on post-mortem brains, was investigated for key serotonergic proteins. PET binding values and gene expression intensities were correlated for the main inhibitory (5-HT_1A) and excitatory (5-HT_2A) serotonin receptor, the serotonin transporter (SERT) as well as monoamine oxidase-A (MAO-A), using Spearman's correlation coefficients (<span style="font-style:italic;">r</span>_s) in a voxel-wise and region-wise analysis. Correlations indicated a strong linear relationship between gene and protein expression for both the 5-HT_1A (voxel-wise <span style="font-style:italic;">r</span>_s = 0.71; region-wise <span style="font-style:italic;">r</span>_s = 0.93) and the 5-HT_2A receptor (<span style="font-style:italic;">r</span>_s = 0.66; 0.75), but only a weak association for MAO-A (<span style="font-style:italic;">r</span>_s = 0.26; 0.66) and no clear correlation for SERT (<span style="font-style:italic;">r</span>_s = 0.17; 0.29). Additionally, region-wise correlations were performed using mRNA expression from the HBT, yielding comparable results (5-HT_1A<span style="font-style:italic;">r</span>_s = 0.82; 5-HT_2A<span style="font-style:italic;">r</span>_s = 0.88; MAO-A <span style="font-style:italic;">r</span>_s = 0.50; SERT <span style="font-style:italic;">r</span>_s = −0.01). The SERT and MAO-A appear to be regulated in a region-specific manner across the whole brain. In contrast, the serotonin-1A and -2A receptors are presumably targeted by common posttranscriptional processes similar in all brain areas suggesting the applicability of mRNA expression as surrogate parameter for density of these proteins.</span>

http://ift.tt/2lqZvOb

Repetition Suppression and Memory for Faces is Reduced in Adults with Autism Spectrum Conditions

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Autism spectrum conditions (ASC) are associated with a number of atypicalities in face processing, including difficulties in face memory. However, the neural mechanisms underlying this difficulty are unclear. In neurotypical individuals, repeated presentation of the same face is associated with a reduction in activity, known as repetition suppression (RS), in the fusiform face area (FFA). However, to date, no studies have investigated RS to faces in individuals with ASC, or the relationship between RS and face memory. Here, we measured RS to faces and geometric shapes in individuals with a clinical diagnosis of an ASC and in age and IQ matched controls. Relative to controls, the ASC group showed reduced RS to faces in bilateral FFA and reduced performance on a standardized test of face memory. By contrast, RS to shapes in object-selective regions and object memory did not differ between groups. Individual variation in face-memory performance was positively correlated with RS in regions of left parietal and prefrontal cortex. These findings suggest difficulties in face memory in ASC may be a consequence of differences in the way faces are stored and/or maintained across a network of regions involved in both visual perception and short-term/working memory.</span>

http://ift.tt/2mtqnBZ

Age-Dependent Effects of Catechol- O -Methyltransferase ( COMT ) Gene Val 158 Met Polymorphism on Language Function in Developing Children

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The genetic basis controlling language development remains elusive. Previous studies of the catechol-<span style="font-style:italic;">O</span>-methyltransferase (COMT) Val¹⁵⁸Met genotype and cognition have focused on prefrontally guided executive functions involving dopamine. However, <span style="font-style:italic;">COMT</span> may further influence posterior cortical regions implicated in language perception. We investigated whether <span style="font-style:italic;">COMT</span> influences language ability and cortical language processing involving the posterior language regions in 246 children aged 6–10 years. We assessed language ability using a language test and cortical responses recorded during language processing using a word repetition task and functional near-infrared spectroscopy. The <span style="font-style:italic;">COMT</span> genotype had significant effects on language performance and processing. Importantly, Met carriers outperformed Val homozygotes in language ability during the early elementary school years (6–8 years), whereas Val homozygotes exhibited significant language development during the later elementary school years. Both genotype groups exhibited equal language performance at approximately 10 years of age. Val homozygotes exhibited significantly less cortical activation compared with Met carriers during word processing, particularly at older ages. These findings regarding dopamine transmission efficacy may be explained by a hypothetical inverted U-shaped curve. Our findings indicate that the effects of the <span style="font-style:italic;">COMT</span> genotype on language ability and cortical language processing may change in a narrow age window of 6–10 years.</span>

http://ift.tt/2lr4Ogp

Tratamiento con 177Lu-DOTATATE: pasado, presente y futuro

Publication date: March–April 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular, Volume 36, Issue 2
Author(s): M. Estorch




http://ift.tt/2me4gPx

Temporal and spatial localization of prediction-error signals in the visual brain

Publication date: Available online 28 February 2017
Source:Biological Psychology
Author(s): Patrick Johnston, Jonathan Robinson, Athanasios Kokkinakis, Samuel Ridgeway, Michael Simpson, Sam Johnson, Jordy Kaufman, Andrew W. Young
It has been suggested that the brain pre-empts changes in the environment through generating predictions, although real-time eletrophysiological evidence of prediction violations in the domain of visual perception remain elusive. In a series of experiments we showed participants sequences of images that followed a predictable implied sequence or whose final image violated the implied sequence. Through careful design we were able to use the same final image transitions across predictable and unpredictable conditions, ensuring that any differences in neural responses were due only to preceding context and not to the images themselves. EEG and MEG recordings showed that early (N170) and mid-latency (N300) visual evoked potentials were robustly modulated by images that violated the implied sequence across a range of types of image change (expression deformations, rigid-rotations and visual field location). This modulation occurred irrespective of stimulus object category. Although the stimuli were static images, MEG source reconstruction of the early latency signal (N/M170) localised expectancy violation signals to brain areas associated with motion perception. Our findings suggest that the N/M170 can index mismatches between predicted and actual visual inputs in a system that predicts trajectories based on ongoing context. More generally we suggest that the N/M170 may reflect a "family" of brain signals generated across widespread regions of the visual brain indexing the resolution of top-down influences and incoming sensory data. This has important implications for understanding the N/M170 and investigating how the brain represents context to generate perceptual predictions.



http://ift.tt/2mdDqam

Image Gallery: Hypopharynx carcinoma overlapped by cervicofacial actinomycosis

A 36-year-old man, a smoker, with impaired dental status, presented with a 1-year history of a tumour-like formation on the neck (a, b). The lesion had begun simultaneously with complains of a recurrent pharyngitis.

This article is protected by copyright. All rights reserved.

http://ift.tt/2mt6Ku0

Occupational Exposures to Mists and Vapours from Strong Inorganic Acids; and Other Industrial Chemicals.

http://ift.tt/2lcmstn

Refining the Concept of Scientific Inference When Working with Big Data: Proceedings of a Workshop.

The concept of utilizing big data to enable scientific discovery has generated tremendous excitement and investment from both private and public sectors over the past decade, and expectations continue to grow. Using big data analytics to identify complex patterns hidden inside volumes of data that have never been combined could accelerate the rate of scientific discovery and lead to the development of beneficial technologies and products. However, producing actionable scientific knowledge from such large, complex data sets requires statistical models that produce reliable inferences (NRC, 2013). Without careful consideration of the suitability of both available data and the statistical models applied, analysis of big data may result in misleading correlations and false discoveries, which can potentially undermine confidence in scientific research if the results are not reproducible. In June 2016 the National Academies of Sciences, Engineering, and Medicine convened a workshop to examine critical challenges and opportunities in performing scientific inference reliably when working with big data. Participants explored new methodologic developments that hold significant promise and potential research program areas for the future. This publication summarizes the presentations and discussions from the workshop.

http://ift.tt/2mKN54R

NICE Citizens Council Report on Age [Internet].

The Citizens Council provides NICE with a public perspective on overarching moral and ethical issues that NICE should take into account when producing guidance. Made up of members of the public, broadly representative of the adult UK population, the Council operates through a "citizens' jury" style meeting, to explore and respond to a question set by NICE.

http://ift.tt/2lcrt4W

NICE Citizens Council Reports [Internet].

The Citizens Council provides NICE with a public perspective on overarching moral and ethical issues that NICE should take into account when producing guidance. Made up of members of the public, broadly representative of the adult UK population, the Council operates through a "citizens' jury" style meeting, to explore and respond to a question set by NICE. Following each meeting, a report is prepared and presented to the NICE Board.

http://ift.tt/2mKGCH9

Inequalities in Health [Internet].

The Citizens Council provides NICE with a public perspective on overarching moral and ethical issues that NICE should take into account when producing guidance. Made up of members of the public, broadly representative of the adult UK population, the Council operates through a "citizens' jury" style meeting, to explore and respond to a question set by NICE.

http://ift.tt/2mKFwuL

Iwr1 facilitates RNA polymerase II dynamics during transcription elongation

Publication date: Available online 28 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Natalia Gómez-Navarro, Lorena Peiró-Chova, Francisco Estruch
Iwr1 is an RNA polymerase II (RNPII) interacting protein that directs nuclear import of the enzyme which has been previously assembled in the cytoplasm. Here we present genetic and molecular evidence that links Iwr1 with transcription. Our results indicate that Iwr1 interacts with RNPII during elongation and is involved in the disassembly of the enzyme from chromatin. This function is especially important in resolving problems posed by damage-arrested RNPII, as shown by the sensitivity of iwr1 mutants to genotoxic drugs and the Iwr1's genetic interactions with RNPII degradation pathway mutants. Moreover, absence of Iwr1 causes genome instability that is enhanced by defects in the DNA repair machinery.



http://ift.tt/2mduPEz

miR-16 controls myoblast proliferation and apoptosis through directly suppressing Bcl2 and FOXO1 activities

Publication date: Available online 28 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Xinzheng Jia, Hongjia Ouyang, Bahareldin Ali Abdalla, Haiping Xu, Qinghua Nie, Xiquan Zhang
Myogenesis mainly involves several steps including myoblast proliferation, differentiation, apoptosis and fusion. Except for muscle specific regulators, few miRNAs were proved to coordinate this complex process. Here, we reported that miR-16 inhibited myoblast proliferation and promoted myoblast apoptosis by directly targeting Bcl2 and FOXO1. The expression level of miR-16 was significantly decreased in the hypertrophic pectoral muscle compared to the normal pectoral muscle in chicken. In vitro, elevating miR-16 significantly inhibited myoblast proliferation and promoted myoblast apoptosis, resulting in about 11.2% cells arrested in G1 phase and 12.3% apoptotic cells in the early stage. Bioinformatic and biochemical analyses revealed Bcl2 and FOXO1 as direct targets of miR-16. Consist to the effect of miR-16 on myogenesis, specific inhibition of Bcl2 or FOXO1 significantly suppressed myoblast proliferation and induced myoblast apoptosis, indicating that both Bcl2 and FOXO1 contributed to miR-16 regulatory function in myogenesis. Interestingly, FOXO1, as the core target, mediated multiple growth-related pathways induced by miR-16 such as PI3K-AKT-MAPK and PI3K-AKT-mTOR. Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) revealed that 234 annotated genes bound by FOXO1 in the early-differentiated myoblasts, which were significantly enriched in myogenic proliferation, death and hypotrophy. Altogether, we proposed that miR-16 acted as a coordinated mediator to suppress myogenesis in avian through the control of myoblast proliferation and apoptosis. These findings have provided a novel mechanism whereby miR-16 represses Bcl2 and FOXO1 expression to maintain myoblast growth and skeletal muscle mass.



http://ift.tt/2mKyo1L

Field Elective Volume De-Intensification for Oropharyngeal and Laryngeal Squamous Cell Carcinoma

Conditions:   Head and Neck Cancer;   Carcinoma, Squamous Cell;   Neoplasms, Oral;   Neoplasms, Pharyngeal
Interventions:   Radiation: Intensity Modulated Radiation Therapy;   Drug: chemotherapy
Sponsor:   University of Texas Southwestern Medical Center
Recruiting - verified February 2017

http://ift.tt/2mKLwnC

Iron Accumulation, Glutathione Depletion, and Lipid Peroxidation Must Occur Simultaneously during Ferroptosis and are Mutually Amplifying Events

Publication date: Available online 28 February 2017
Source:Medical Hypotheses
Author(s): Robert L. Bertrand
Ferroptosis is a recently discovered form of regulated necrosis that involves iron-dependent lipid peroxidation. How cells die once ferroptosis is triggered remains unclear. Ferroptosis is hypothesized to require three critical events: (1) Accumulation of redox-active iron, (2) glutathione depletion, and (3) lipid peroxidation. It is proposed that these three events must unfold simultaneously because stopping any critical event also stops ferroptosis. These events are hypothesized to amplify in severity through positive feedback loops. The cause of death in ferroptosis is therefore the synergistic combination of antioxidant depletion, iron toxicity, and membrane denaturation. The relevance of these feedback loops for cancer and neurodegenerative therapies is discussed.

Graphical abstract

http://ift.tt/2lqatDD

A new in vivo method to retard progression of intervertebral disc degeneration through stimulation of endogenous stem cells with simvastatin

Publication date: Available online 28 February 2017
Source:Medical Hypotheses
Author(s): Zenan Huang, Liang Zhang, Xinmin Feng, Tao Chen, Songchao Bi




http://ift.tt/2lqgDU5

Biodegradable microrobots for targeting cell delivery

Publication date: Available online 28 February 2017
Source:Medical Hypotheses
Author(s): Pouria TirgarBahnamiri, Shadab Bagheri-Khoulenjani
These days, cell delivery is considered a potential method for treatment of many genetic diseases or tissue regeneration applications. In conventional cell delivery methods, cells are encapsulated in or cultured on biocompatible polymers. However, the main problem with these carriers is their lack of targeting ability. For tissue regeneration or many cell treatments, it is needed to deliver cells to a specific site of action. Magnetic microrobots based onindustrial photoresistshave been studied in literature for magnetically controllable carriers. However, there are some issues about biodegradation and removal of these microrobots from the body. In this paper, we hypothesis fabrication of new generation of biodegradable magnetic microrobots based on additive manufacturing methods to overcome this problem and to bring this evolving field to a new level.



http://ift.tt/2msM3hJ

The spread of EBV to ectopic lymphoid aggregates may be the final common pathway in the pathogenesis of ME/CFS

Publication date: Available online 28 February 2017
Source:Medical Hypotheses
Author(s): Willy Eriksen
According to the hypothesis presented here, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops over 3 steps: Step 1 is characterized by the aggregation of lymphoid cells in dorsal root ganglia or other nervous structures. The cause of this formation of ectopic lymphoid aggregates may be an acute infection, asymptomatic reactivations of a common neurotropic virus, exposure to a neurotoxin, or physical injury to peripheral nerves. In step 2, Epstein-Barr virus (EBV)-infected lymphocytes or monocytes bring EBV from the circulation to one or several of these lymphoid aggregates, whereupon cell-to-cell transmission of EBV and proliferation of latently EBV-infected lymphocytes lead to the presence of many EBV-infected cells in the lymphoid aggregates. The EBV-infected cells in the aggregates ignite an inflammation in the surrounding nervous tissue. This local inflammation elicits, in turn, a wave of glial cell activation that spreads from the EBV-infected area to parts of the nervous system that are not EBV-infected, disturbing the neuron-glial interaction in both the peripheral - and central nervous system. In step 3, immune cell exhaustion contributes to a consolidation of the pathological processes. There might be a cure: Infusions of autologous EBV-specific T-lymphocytes can perhaps remove the EBV-infected cells from the nervous system.



http://ift.tt/2lqjNY3

Hypothesis: A perfect day conveys internal time

Publication date: Available online 28 February 2017
Source:Medical Hypotheses
Author(s): J.V. Groß, L. Fritschi, T.C. Erren
In 2007 the International Agency for Research on Cancer [IARC] concluded "shift work that involves circadian disruption is probably carcinogenic to humans" (Group 2A). To investigate the "probable" causal link, information on individual chronobiology is needed to specify exposures to circadian disruption associated with shift work. In epidemiological studies this information is usually assessed by questionnaire. The most widely used Morningness-Eveningness-Questionnaire (MEQ) and MunichChronoTypeQuestionnaire (MCTQ) reveal information on circadian type (MEQ) and actual sleep behaviour (MCTQ). As a further option we suggest to obtain preferred sleep times by using what we call the perfect day (PD) approach. We hypothesize that a PD – as a day of completely preferred sleep behaviour – captures pristine internal time. We argue that the PD approach may measure internal time more accurately than the MEQ and MCTQ which convey influences by work and social time pressures. The PD approach may therefore reduce misclassifications of internal time and reveal circadian disruption caused by different shift systems.



http://ift.tt/2msRbT6

Stream of consciousness: quantum and biochemical assumptions regarding psychopathology

Publication date: Available online 28 February 2017
Source:Medical Hypotheses
Author(s): Lucio Tonello, Massimo Cocchi, Fabio Gabrielli, Jack A. Tuszynski
The accepted paradigms of mainstream neuropsychiatry appear to be incompletely adequate and in various cases offer equivocal analyses. However, a growing number of new approaches are being proposed that suggest the emergence of paradigm shifts in this area. In particular, quantum theories of mind, brain and consciousness seem to offer a profound change to the current approaches. Unfortunately these quantum paradigms harbor at least two serious problems. First, they are simply models, theories, and assumptions, with no convincing experiments supporting their claims. Second, they deviate from contemporary mainstream views of psychiatric illness and do so in revolutionary ways. We suggest a possible way to integrate experimental neuroscience with quantum models in order to address outstanding issues in psychopathology. A key role is played by the phenomenon called the "stream of consciousness", which can be linked to the so-called "Gamma Synchrony"(GS), which is clearly demonstrated by EEG data. In our novel proposal, a unipolar depressed patient could be seen as a subject with an altered stream of consciousness. In particular, some clues suggest that depression is linked to an "increased power" stream of consciousness. It is additionally suggested that such an approach to depression might be extended to psychopathology in general with potential benefits to diagnostics and therapeutics in neuropsychiatry.



http://ift.tt/2lqjM6r

Risk Factors for Skin Infections in Mycosis Fungoides

Background: Mycosis fungoides (MF) is the most frequent type of primary cutaneous natural killer and T-cell lymphoma. MF-required immunosuppressive therapies and MF-related immunosuppressive characteristics render patients with MF more prone to infections. Aim: To describe the clinical features of cutaneous infections observed in MF patients. Materials and Methods: A series of 56 MF patients were followed prospectively over 3 years and screened for cutaneous infections. Type of Study: Prospective observational study. Results: Four herpes simplex virus type-I (HSV-I), 2 staphylococcal (S. aureus) impetiginizations and 2 Malassezia infections were detected in single isolated plaque/patch stage MF as well as 1 varicella zoster virus infection (herpes zoster, HZ) and 2 cases of cellulitis in 10 patients. All patients presented advanced MF. All the diagnoses were delayed due to atypical clinical presentations. Conclusions: Patients with advanced MF should be particularly monitored for skin infections, especially by HSV and S. aureus. Unexplained exacerbation or the sudden appearance of oozing or ulcerations in MF lesions should initiate a search for viral or bacterial agents. Cellulitis and HZ can be severer and prolonged in MF patients.
Dermatology

http://ift.tt/2mdi3G9

Cutaneous Neoplasms in Myotonic Dystrophy Type 1

Background: The most frequent skin features associated with myotonic dystrophy type 1 (DM1) are frontal alopecia and pilomatrixomas. Several reports suggest that the incidence of basal cell carcinoma is increased in DM1. However, two recently published studies examining this topic have contradictory results. Objective: To retrospectively study the incidence of cutaneous tumours in patients with DM1. Methods: The clinical features of 102 Caucasian patients diagnosed with DM1 at Bellvitge Hospital in Barcelona, Spain, were retrospectively analysed. Clinical charts of the patients were reviewed, and cutaneous tumours diagnosed in our hospital were recorded. A group of 103 Caucasian patients matched for age and sex were used as the control group. Results: A total of 56 male and 46 female patients with DM1 were included in the study (mean age 49.07 years, SD 13.02). At least 1 basal cell carcinoma was diagnosed in 6 patients in the DM1 group versus 3 patients in the control group (p = 0.332). The mean age at diagnosis of the first basal cell carcinoma was 51 years compared with 66 years in the control group (p = 0.035). Five patients with DM1 presented pilomatrixomas versus none in the control group (p = 0.029). We did not detect any melanoma in our DM1 patients. Conclusion: Basal cell carcinomas appeared at a significantly younger age in our DM1 patients than in the general population, and this suggests that, at least in some patients, DM1 may predispose to the development of basal cell carcinomas.
Dermatology

http://ift.tt/2mEBpRU

Electrochemical biosensing strategies for DNA methylation analysis

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Tanvir Hossain, Golam Mahmudunnabi, Mostafa Kamal Masud, Md. Nazmul Islam, Lezanne Ooi, Konstantin Konstantinov, Md Shahriar Al Hossain, Boris Martinac, Gursel Alici, Nam-Trung Nguyen, Muhammad J.A. Shiddiky
DNA methylation is one of the key epigenetic modifications of DNA that results from the enzymatic addition of a methyl group at the fifth carbon of the cytosine base. It plays a crucial role in cellular development, genomic stability and gene expression. Aberrant DNA methylation is responsible for the pathogenesis of many diseases including cancers. Over the past several decades, many methodologies have been developed to detect DNA methylation. These methodologies range from classical molecular biology and optical approaches, such as bisulfite sequencing, microarrays, quantitative real-time PCR, colorimetry, Raman spectroscopy to the more recent electrochemical approaches. Among these, electrochemical approaches offer sensitive, simple, specific, rapid, and cost-effective analysis of DNA methylation. Additionally, electrochemical methods are highly amenable to miniaturization and possess the potential to be multiplexed. In recent years, several reviews have provided information on the detection strategies of DNA methylation. However, to date, there is no comprehensive evaluation of electrochemical DNA methylation detection strategies. Herein, we address the recent developments of electrochemical DNA methylation detection approaches. Furthermore, we highlight the major technical and biological challenges involved in these strategies and provide suggestions for the future direction of this important field.



http://ift.tt/2lpYPIY

Graphite paper-based bipolar electrode electrochemiluminescence sensing platform

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Xin Zhang, Shou-Nian Ding
In this work, aiming at the construction of a disposable, wireless, low-cost and sensitive system for bioassay, we report a closed bipolar electrode electrochemiluminescence (BPE-ECL) sensing platform based on graphite paper as BPE for the first time. Graphite paper is qualified as BPE due to its unique properties such as excellent electrical conductivity, uniform composition and ease of use. This simple BPE-ECL device was applied to the quantitative analysis of oxidant (H2O2) and biomarker (CEA) respectively, according to the principle of BPE sensing―charge balance. For the H2O2 analysis, Pt NPs were electrodeposited onto the cathode through a bipolar electrodeposition approach to promote the sensing performance. As a result, this BPE-ECL device exhibited a wide linear range of 0.001–15mM with a low detection limit of 0.5µM (S/N=3) for H2O2 determination. For the determination of CEA, chitosan-multi-walled carbon nanotubes (CS-MWCNTs) were employed to supply a hydrophilic interface for immobilizing primary antibody (Ab1); and Au@Pt nanostructures were conjugated with secondary antibody (Ab2) as catalysts for H2O2 reduction. Under the optimal conditions, the BPE-ECL immunodevice showed a wide linear range of 0.01–60ngmL⁻¹ with a detection limit of 5.0pgmL⁻¹ for CEA. Furthermore, it also displayed satisfactory selectivity, excellent stability and good reproducibility. The developed method opened a new avenue to clinical bioassay.



http://ift.tt/2lnZ8nH

Rapid and sensitive detection of microRNA via the capture of fluorescent dyes-loaded albumin nanoparticles around functionalized magnetic beads

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Tianxiang Wei, Dan Du, Zhaoyin Wang, Weiwei Zhang, Yuehe Lin, Zhihui Dai
MicroRNAs (miRNAs) play important roles in gene regulation and cancer development. Nowadays, it is still a challenge to detect low-abundance miRNAs. Here, we present a magnetic fluorescent miRNA sensing system for the rapid and sensitive detection of miRNAs from cell lysates and serum samples. In this system, albumin nanoparticles (Alb NPs) were prepared from inherent biocompatible bovine serum albumin (BSA). A large number of fluorescent dyes were loaded into Alb NPs to make Alb NPs serve as signal molecular nanocarriers for signal amplification. Benefited from the reactive functional groups-carboxyl groups of Alb NPs, p19 protein, a viral protein that can bind and sequester short RNA duplex effectively and selectively, was modified successfully to the surface of the fluorescent dyes-loaded Alb NPs, thus enabling the probe:target miRNA duplex recognition and binding. Followed by the introduction of gold nanoparticles coated magnetic microbeads (Au NPs-MBs), which were prepared through a novel and simple method, the system combined the merits of the rapid and efficient collection given by MBs with the good affinities to attach probe molecules endowed by the coated gold layer. A broad linear detection range of 10fM–10nM and a low detection limit of 9fM were obtained within 100min by detecting a model target miRNA-21. The feasibility of this method for rapid and sensitive quantification might advance the use of miRNAs as biomarkers in clinical praxis significantly.

Graphical abstract

http://ift.tt/2lpPCR2

Gold-modified indium tin oxide as a transparent window in optoelectronic diagnostics of electrochemically active biofilms

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Igor Schmidt, Alaaeldin Gad, Gregor Scholz, Heidi Boht, Michael Martens, Meinhard Schilling, Hutomo Suryo Wasisto, Andreas Waag, Uwe Schröder
Microbial electrochemical technologies (METs) are one of the emerging green bioenergy domains that are utilizing microorganisms for wastewater treatment or electrosynthesis. Real-time monitoring of bioprocess during operation is a prerequisite for understanding and further improving bioenergy harvesting. Optical methods are powerful tools for this, but require transparent, highly conductive and biocompatible electrodes. Whereas indium tin oxide (ITO) is a well-known transparent conductive oxide, it is a non-ideal platform for biofilm growth. Here, a straightforward approach of surface modification of ITO anodes with gold (Au) is demonstrated, to enhance direct microbial biofilm cultivation on their surface and to improve the produced current densities. The trade-off between the electrode transmittance (critical for the underlying integrated sensors) and the enhanced growth of biofilms (crucial for direct monitoring) is studied. Au-modified ITO electrodes show a faster and reproducible biofilm growth with three times higher maximum current densities and about 6.9 times thicker biofilms compared to their unmodified ITO counterparts. The electrochemical analysis confirms the enhanced performance and the reversibility of the ITO/Au electrodes. The catalytic effect of Au on the ITO surface seems to be the key factor of the observed performance improvement since the changes in the electrode conductivity and their surface wettability are relatively small and in the range of ITO. An integrated platform for the ITO/Au transparent electrode with light-emitting diodes was fabricated and its feasibility for optical biofilm thickness monitoring is demonstrated. Such transparent electrodes with embedded catalytic metals can serve as multifunctional windows for biofilm diagnostic microchips.

Graphical abstract

http://ift.tt/2lpPEbC

Service Learning in Radiology Education

Publication date: Available online 28 February 2017
Source:Academic Radiology
Author(s): Pauley T. Gasparis, William D. Kerridge, Richard B. Gunderman




http://ift.tt/2m7EWKC

Altered composition of epidermal lipids correlates with Staphylococcus aureus colonization status in Atopic Dermatitis.

Related Articles

Altered composition of epidermal lipids correlates with Staphylococcus aureus colonization status in Atopic Dermatitis.

Br J Dermatol. 2017 Feb 28;:

Authors: Li S, Villarreal M, Stewart S, Choi J, Indra G, Babineau DC, Philpot C, David G, Yoshida T, Boguniewicz M, Hanifin J, Beck LA, Leung D, Simpson E, Indra AK

Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by disrupted epidermal barrier functions.(1) Stratum corneum (SC) consists of corneocytes and a lipid-rich extracellular matrix, which plays a key role in epidermal permeability barrier (EPB) functions.(2,3) Major lipid constituents of the SC are ceramides (CERs), free fatty acids (FFAs), cholesterol and triglycerides (TGs).(2,3) Staphylococcus aureus (S.aureus) colonization is an important trigger of AD.(4) Comprehensive profiling of SC lipids using S.aureus colonization status, and association between S.aureus colonization and skin lipid composition, has never been documented. This article is protected by copyright. All rights reserved.

PMID: 28244066 [PubMed - as supplied by publisher]

http://ift.tt/2lW87hA

Calcium hydroxylapatite: A review on safety and complications

Summary

Background

Radiesse^®, or calcium hydroxylapatite (CaHA), is a biodegradable, biostimulatory soft tissue filler suitable for deeper folds and wrinkles. In the literature, good results have been documented with the use of CaHA and patient satisfaction scores are high. This study reviews the current literature on safety and complications of CaHA.

Methods

A literature search in MEDLINE/PubMed electronic database was conducted. A total of 21 articles were included and screened for reports of adverse events (AEs).

Results

Twenty-one peer-reviewed articles, published between 2004 and 2015, were included. A total of 5081 treatments with CaHA were performed on 2779 patients. A total of 173 (3%) AEs were reported. The assessed types of AEs consisted of nodules (n=166, 96%), persistent inflammation/swelling (n=4, 2%), persistent erythema (n=2, 1%), and overcorrection (n=1, 1%).

Conclusion

Based on the results in this study, CaHA appears to have a good safety profile. Nodules are by far the most common AE. Of the reported nodules, 49% occurred in "dynamic" areas currently known for having a higher tendency for nodules. Several treatment approaches exist for managing CaHA nodules; however, in most cases, CaHA nodules are not visible and resolve without intervention.

http://ift.tt/2m7ANqh

CONTENTS 1

Publication date: January–February 2017
Source:Materials Today, Volume 20, Issue 1





http://ift.tt/2lpynz2

CONTENTS 2

Publication date: January–February 2017
Source:Materials Today, Volume 20, Issue 1





http://ift.tt/2msmihw

Role of Cyclooxygenase-2 Pathway in Creating an Immunosuppressive Microenvironment and in Initiation and Progression of Wilms' Tumor

Publication date: March 2017
Source:Neoplasia, Volume 19, Issue 3
Author(s): Paramahamsa Maturu, Devin Jones, E. Cristy Ruteshouser, Qianghua Hu, Joseph M Reynolds, John Hicks, Nagireddy Putluri, Suhendan Ekmekcioglu, Elizabeth A. Grimm, Chen Dong, Willem W Overwijk
Wilms' tumors (WT), which accountfor 6% of all childhood cancers, arise from dysregulated differentiation of nephrogenic progenitor cells from embryonic kidneys. Though there is an improvement in the prognosis of WT, still 10% of patients with WT die due to recurrence. Thus more effective treatment approaches are necessary. We previously characterized the inflammatory microenvironment in human WT and observed the robust expression of COX-2. The aim of this study was to extend our studies to analyze the role of COX-2 pathway components in WT progression using a mouse model of WT. Herein, COX-2 pathway components such as COX-2, HIF1-α, p-ERK1/2, and p-STAT3 were upregulated in mouse and human tumor tissues. In our RPPA analysis, COX-2 was up-regulated in M15 cells after Wt1 gene was knocked down. Flow cytometry analysis showed the increased infiltration of immune suppressive inflammatory cells such as pDC's and Treg cells in tumors. The chemotactic chemokines responsible for the infiltration of these cells were also induced in CCR5 and CXCR4 dependent manner respectively. The immunosuppressive cytokines IL-10, TGF-β, and TNF-α were also up-regulated. Furthermore, more pronounced Th2 and Treg induced cytokine response was observed than Th1 response in tumors. Basing on all these evidences it is speculated that COX-2 pathway may be a beneficial target for the treatment of WT. It may be most effective as an adjuvant therapy together with other inhibitors. Thus, our current study provides a good rationale for initiating animal studies to confirm the efficacy of COX-2 inhibitors in decreasing tumor cell growth in vivo.



http://ift.tt/2m7urXA

Corrigendum to “CXCL1-Mediated Interaction of Cancer Cells with Tumor-Associated Macrophages and Cancer-Associated Fibroblasts Promotes Tumor Progression in Human Bladder Cancer” [Neoplasia 18 (2016) 636–646]

Publication date: March 2017
Source:Neoplasia, Volume 19, Issue 3
Author(s): Makito Miyake, Shunta Hori, Yosuke Morizawa, Yoshihiro Tatsumi, Yasushi Nakai, Satoshi Anai, Kazumasa Torimoto, Katsuya Aoki, Nobumichi Tanaka, Keiji Shimada, Noboru Konishi, Michihiro Toritsuka, Toshifumi Kishimoto, Charles J. Rosser, Kiyohide Fujimoto




http://ift.tt/2mEeUN5

Corrigendum to “Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells” [Neoplasia 14 (2012) 463–475]

Publication date: March 2017
Source:Neoplasia, Volume 19, Issue 3
Author(s): Yu-Chin Lin, Meng-Hsuan Wu, Tzu-Tang Wei, Shu-Hui Chuang, Kuen-Feng Chen, Ann-Lii Cheng, Ching-Chow Chen




http://ift.tt/2mE4AEF

The use of an optimized chimeric envelope glycoprotein enhances the efficiency of retrograde gene transfer of a pseudotyped lentiviral vector in the primate brain

Publication date: Available online 28 February 2017
Source:Neuroscience Research
Author(s): Soshi Tanabe, Ken-ichi Inoue, Hitomi Tsuge, Shiori Uezono, Kiyomi Nagaya, Maki Fijiwara, Shigeki Kato, Kazuto Kobayashi, Masahiko Takada
Lentiviral vectors have been used not only for various basic research experiments, but also for a wide range of gene therapy trials in animal models. The development of a pseudotyped lentiviral vector with the property of retrograde infection allows us to introduce foreign genes into neurons that are localized in regions innervating the site of vector injection. Here, we report the efficiency of retrograde gene transfer of a recently developed FuG-E pseudotyped lentiviral vector in the primate brain by comparing its transduction pattern with that of the parental FuG-C pseudotyped vector. After injection of the FuG-E vector encoding green fluorescent protein (GFP) into the striatum of macaque monkeys, many GFP-immunoreactive neurons were found in regions projecting to the striatum, such as the cerebral cortex, thalamus, and substantia nigra. Quantitative analysis revealed that in all regions, the number of neurons retrogradely transduced with the FuG-E vector was larger than in the FuG-C vector injection case. It was also confirmed that the FuG-E vector displayed explicit neuronal specificity to the same extent as the FuG-C vector. This vector might promote approaches to pathway-selective gene manipulation and provide a powerful tool for effective gene therapy trials against neurological disorders through enhanced retrograde delivery.



http://ift.tt/2mcB6k2

Antitumor activity of interferon-β1a in hormone refractory prostate cancer with neuroendocrine differentiation

Abstract

Purpose

Type I interferons (IFN-α and IFN-β) are a class of cytokines that exert several biological activities, such as modulation of cell proliferation and differentiation and of the immune system. Although these cytokines interact with a common receptor complex, IFN-β showed a more potent antitumor activity than IFN-α in several tumor models. New recombinant human IFN-β products, such as IFN-β1a and IFN-β1b, have been produced in order to improve the stability and bioavailability of natural IFN-β. In this report, we analyzed the effects of recombinant IFN-β1a on the cell proliferation of two human androgen-resistant prostate cancer cell lines with neuroendocrine differentiation (DU-145, PC-3) and related mechanisms of action.

Methods

The effects of IFN-β1a on the cell growth proliferation, cell cycle, and apoptosis have been evaluated in DU-145 and PC-3 cells through MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. Moreover, the expression of neuron-specific enolase (NSE), cleaved caspase-3, caspase-8, and PARP was evaluated through Western blotting.

Results

IFN-β1a showed a significant anti-proliferative activity in both androgen-resistant cell lines. This effect was related to cell cycle perturbation and induction in apoptosis, as shown by flow cytometric analysis, the activation of caspase-3 and caspase-8 and PARP cleavage during incubation with IFN-β1a. Moreover, this cytokine reduced the expression of NSE in both cell lines.

Conclusions

Recombinant IFN-β1a (Rebif) showed a potent in vitro anti-proliferative activity in androgen-resistant prostate cancer cells, and it could represent a promising tool for the treatment of this tumor.

http://ift.tt/2lVO82t

ASSFN Society News

Stereotact Funct Neurosurg 2017;95:71

http://ift.tt/2m72mzW

Erratum

Stereotact Funct Neurosurg 2017;95:69

http://ift.tt/2lpc3FI

WSSFN Society News

Stereotact Funct Neurosurg 2017;95:70

http://ift.tt/2m7qzpB

ESSFN The Mission

Stereotact Funct Neurosurg 2017;95:72

http://ift.tt/2lphnsH

Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM)

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): M.J. Duffy, N. Harbeck, M. Nap, R. Molina, A. Nicolini, E. Senkus, F. Cardoso
Biomarkers play an essential role in the management of patients with invasive breast cancer. For selecting patients likely to respond to endocrine therapy, both oestrogen receptors (ERs) and progesterone receptors (PRs) should be measured on all newly diagnosed invasive breast cancers. On the other hand, for selecting likely response to all forms of anti-HER2 therapy (trastuzumab, pertuzumab, lapatinib or ado-trastuzumab emtansine), determination of HER2 expression or gene copy number is mandatory. Where feasible, measurement of ER, PR and HER2 should be performed on recurrent lesions and the primary invasive tumour. Although methodological problems exist in the determination of Ki67, because of its clearly established clinical value, wide availability and low costs relative to the available multianalyte signatures, Ki67 may be used for determining prognosis, especially if values are low or high. In oestrogen receptor (ER)-positive, HER2-negative, lymph node–negative patients, multianalyte tests such as urokinase plasminogen activator (uPA)-PAI-1, Oncotype DX, MammaPrint, EndoPredict, Breast Cancer Index (BCI) and Prosigna (PAM50) may be used to predict outcome and aid adjunct therapy decision-making. Oncotype DX, MammaPrint, EndoPredict and Prosigna may be similarly used in patients with 1–3 metastatic lymph nodes. All laboratories measuring biomarkers for patient management should use analytically and clinically validated assays, participate in external quality assurance programs, have established assay acceptance and rejection criteria, perform regular audits and be accredited by an appropriate organisation.



http://ift.tt/2lxI1Rf

DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Srikant Ambatipudi, Steve Horvath, Flavie Perrier, Cyrille Cuenin, Hector Hernandez-Vargas, Florence Le Calvez-Kelm, Geoffroy Durand, Graham Byrnes, Pietro Ferrari, Liacine Bouaoun, Athena Sklias, Véronique Chajes, Kim Overvad, Gianluca Severi, Laura Baglietto, Françoise Clavel-Chapelon, Rudolf Kaaks, Myrto Barrdahl, Heiner Boeing, Antonia Trichopoulou, Pagona Lagiou, Androniki Naska, Giovanna Masala, Claudia Agnoli, Silvia Polidoro, Rosario Tumino, Salvatore Panico, Martijn Dollé, Petra H.M. Peeters, N. Charlotte Onland-Moret, Torkjel M. Sandanger, Therese H. Nøst, Elisabete Weiderpass Vainio, J. Ramón Quirós, Antonio Agudo, Miguel Rodriguez-Barranco, José María Huerta Castaño, Aurelio Barricarte, Ander Matheu Fernández, Ruth C. Travis, Paolo Vineis, David C. Muller, Elio Riboli, Marc Gunter, Isabelle Romieu, Zdenko Herceg
Aim of the studyA vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification.MethodsHere, we profiled DNA methylation changes in a nested case–control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age.ResultsWe observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007–1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007–1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020–1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03–1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls.ConclusionEpigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility.

Graphical abstract

http://ift.tt/2lxGQkC

Allergic broncho-pulmonary aspergillosis following treatment with an anti-program death 1 monoclonal antibody therapy

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): P. Pradere, J.M. Michot, S. Champiat, F.X. Danlos, A. Marabelle, O. Lambotte, L. Albiges, J. Le Pavec




http://ift.tt/2lxGOcu

Management of recalcitrant hemi-facial spasm with upper eyelid gold weight insertion

Abstract

Hemi-facial spasm (HFS) has a presentation of variable severity but is consistently troublesome for the affected individual who can suffer significant social embarrassment from the persistent and unpredictable facial twitching. Here, we present a case of a 62-year-old male with a 17-year history of left hemi-facial spasm secondary to compression of the facial nerve at the root exit zone by an ectatic ipsilateral posterior inferior cerebellar artery. His HFS failed neurosurgical intervention, and medical therapies were found to be ineffective or poorly tolerated. His HFS was noted to be exacerbated on forced eye closure and subsequently it was observed that he was compensating with incomplete eye closure on the affected side. Surgical placement of an upper lid gold weight has significantly diminished the severity and frequency of his HFS symptoms and obviated the need for an orbicularis oculi myectomy.

Level of Evidence: Level V, therapeutic study.

http://ift.tt/2m761NU

Computed tomography angiography (CTA) assisted preoperative planning and volume calculation of deep inferior epigastric artery perforator (DIEP) flap for breast reconstruction

Abstract

Background

The use of the deep inferior epigastric artery perforator (DIEP) flap has gained popularity as a technique for autologous breast reconstruction. This surgery entails finely dissecting the perforators of the deep inferior epigastric artery passing through the rectus abdominis muscle, while deciding which of the perforators will best supply the flap. Computed tomography angiography (CTA) has emerged as the imaging modality of choice for preoperative evaluation. This study evaluates the accuracy of CTA in identifying perforator anatomy and flap volume calculation, as well as its impact on the patient's outcome.

Methods

A prospective study was conducted. Thirty-two consecutive patients that underwent CT angiography prior to unilateral DIEP flap reconstruction surgery were included in the study. The control group was composed of 32 patients, who were operated on by the same surgical team, using the same surgical technique, prior to the initiation of the CTA study. The imaging provided by CTA was correlated with actual intra-operative findings. Operative time, the duration of hospital stay, and postoperative complications were assessed. The volume of the flap as calculated by CT was compared to the flap's actual weight after harvest.

Results

CTA identified 285 perforators; of these, 278 were found intra-operatively. There was no statistically significant difference between the data provided by the CT and intra-operative findings. The use of CTA was associated with decreased operating time (unilateral, 424 versus 546 min, p < 0.0001) and significantly decreased hospitalization (unilateral, 7.6 versus 11.6 days, p = 0.0002). There was good correlation between the volume of the flap as calculated by CT and the flap's measured weight after harvest (1117 cm³ versus 1181 g, r = 0.774).

Conclusions

CTA is an accurate tool in planning and calculating flap volume of DIEP flap and is associated with improved outcomes.

Level of Evidence: Level III, diagnostic study.

http://ift.tt/2lp4NcW

Pandemic Edited by Matt Leacock

<span class="paragraphSection">Z-ManGames, Roseville, Minnesota (Telephone: 651-382-880; E-mail: info@f2zentertainment.com; Website: http://ift.tt/Mcgu1k), 2008, $39.99</span>

http://ift.tt/2mJyAy7

Maternal and Early Childhood Determinants of Women's Body Size in Midlife: Overall Cohort and Sibling Analyses

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Observational evidence suggests that adult body size has its roots earlier in life, yet few life-course studies have data on siblings with which to control for family-level confounding. Using prospective data from the Early Determinants of Mammographic Density Study (<span style="font-style:italic;">n</span> = 1,108; 1959–2008), we examined the association of maternal prepregnancy body mass index (BMI; weight (kg)/height (m)²), gestational weight gain (GWG), birth size, and childhood growth factors with adult BMI in daughters at midlife using quantile, linear, and logistic regression models. We compared overall cohort findings (<span style="font-style:italic;">n</span> = 1,108) with sibling differences (<span style="font-style:italic;">n</span> = 246 sibling sets). Results derived by all 3 regression methods supported positive and independent associations of prepregnancy BMI, GWG, and percentile change in early childhood growth with BMI in daughters at midlife. Sibling analyses demonstrated that higher GWG was independently related to a higher adult BMI in daughters, particularly for the highest 90th quantile of adult BMI (β = 0.64 (standard error, 0.26) BMI units). Greater increases in weight percentiles between 1 and 4 years of age within siblings were also associated with higher adult BMI in the 75th quantile (β = 0.06 (standard error, 0.03) kg). Thus, even after consideration of the role of family-level fixed effects, maternal GWG and childhood weight gain are associated with adult body size in midlife.</span>

http://ift.tt/2mJEr6P

Milk, Fruit and Vegetable, and Total Antioxidant Intakes in Relation to Mortality Rates: Cohort Studies in Women and Men

<span class="paragraphSection"><div class="boxTitle">Abstract</div>High milk consumption might shorten life span through increased oxidative stress. We aimed to determine whether higher mortality rates with high milk consumption are modified by fruit and vegetable intake or total antioxidant intake (oxygen radical absorbance capacity). We used information from food frequency questionnaires completed by 61,420 women in a Swedish cohort (22,391 deaths from the 1987–1990 baseline onward), 36,714 women from a second survey (1997) of this cohort, and 45,280 Swedish men (15,478 deaths from the 1998 baseline onward). Compared with low consumption of milk (<1 glass/day) and high consumption of fruits/vegetables (≥5 servings/day), time-updated information revealed an adjusted hazard ratio for death of 2.79 (95% confidence interval (CI): 2.42, 3.21) in women who consumed ≥3 glasses of milk/day and <1 serving/day of fruit/vegetables and a hazard ratio of 1.60 (95% CI: 1.40, 1.82) in women who consumed the same amount of milk but ≥5 servings/day of fruits/vegetables. The same comparisons in men, based on a single food frequency questionnaire, displayed hazard ratios of 1.31 (95% CI: 1.14, 1.51) and 1.07 (95% CI: 0.97, 1.18), respectively. Total antioxidant consumption showed similar patterns as fruit/vegetable intakes. Dietary antioxidant intake, especially in women, seems to modify the elevated death rate associated with high milk consumption.</span>

http://ift.tt/2lbaz6Y

Plurality of Birth and Infant Mortality Due to External Causes in the United States, 2000–2010

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Risk of death during the first year of life due to external causes, such as unintentional injury and homicide, may be higher among twins and higher-order multiples than among singletons in the United States. We used national birth cohort linked birth–infant death data (2000–2010) to evaluate the risk of infant mortality due to external causes in multiples versus singletons in the United States. Risk of death from external causes during the study period was 3.6 per 10,000 live births in singletons and 5.1 per 10,000 live births in multiples. Using log-binomial regression, the corresponding unadjusted risk ratio was 1.40 (95% confidence interval (CI): 1.30, 1.50). After adjustment for maternal age, marital status, race/ethnicity, and education, the risk ratio was 1.68 (95% CI: 1.56, 1.81). Infant deaths due to external causes were most likely to occur between 2 and 7 months of age. Applying inverse probability weighting and assuming a hypothetical intervention where no infants were low birth weight, the adjusted controlled direct effect of plurality on infant mortality due to external causes was 1.64 (95% CI: 1.39, 1.97). Twins and higher-order multiples were at greater risk of infant mortality due to external causes, particularly between 2 and 7 months of age, and this risk appeared to be mediated largely by factors other than low-birth-weight status.</span>

http://ift.tt/2lbcacU

RE: “METHODS FOR HANDLING MISSING VARIABLES IN RISK PREDICTION MODELS”

http://ift.tt/2mJAT48

Type- and Subtype-Specific Influenza Forecast

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Prediction of the growth and decline of infectious disease incidence has advanced considerably in recent years. As these forecasts improve, their public health utility should increase, particularly as interventions are developed that make explicit use of forecast information. It is the task of the research community to increase the content and improve the accuracy of these infectious disease predictions. Presently, operational real-time forecasts of total influenza incidence are produced at the municipal and state level in the United States. These forecasts are generated using ensemble simulations depicting local influenza transmission dynamics, which have been optimized prior to forecast with observations of influenza incidence and data assimilation methods. Here, we explore whether forecasts targeted to predict influenza by type and subtype during 2003–2015 in the United States were more or less accurate than forecasts targeted to predict total influenza incidence. We found that forecasts separated by type/subtype generally produced more accurate predictions and, when summed, produced more accurate predictions of total influenza incidence. These findings indicate that monitoring influenza by type and subtype not only provides more detailed observational content but supports more accurate forecasting. More accurate forecasting can help officials better respond to and plan for current and future influenza activity.</span>

http://ift.tt/2lbbAf0

The Associations of Atrial Fibrillation With the Risks of Incident Invasive Breast and Colorectal Cancer

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Atrial fibrillation (AF) is a common arrhythmia that poses a significant risk of stroke. Cross-sectional and case-control studies have shown evidence of associations between AF and breast or colorectal cancer, but there have been no longitudinal studies in which this has been assessed. We prospectively examined a cohort of 93,676 postmenopausal women enrolled in the Women's Health Initiative from 1994 to 1998 to determine whether there are relationships between baseline AF and the development of invasive breast or colorectal cancer. The prevalence of self-reported physician diagnosis of AF at baseline was 5.1%. Over approximately 15 years of follow-up, the incidence of invasive breast cancer was 5.7%, and the incidence of colorectal cancer was 1.6%. Adjusted hazard ratios and 95% confidence intervals were obtained using Cox proportional hazards models. We found no significant association between AF and incident colorectal cancer, but we did see a 19% excess risk of invasive breast cancer among those with AF (adjusted hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.03, 1.38). Additional adjustment for baseline use of cardiac glycosides attenuated the association between AF and invasive breast cancer (HR = 1.01, 95% CI: 0.85, 1.20). Cardiac glycoside use was strongly associated with incident invasive breast cancer (HR = 1.68, 95% CI: 1.33, 2.12) independent of AF and other confounders. Mechanisms of the associations among breast cancer, AF, and cardiac glycosides need further investigation.</span>

http://ift.tt/2mJHfRg

THE AUTHORS REPLY

http://ift.tt/2lbsRVt

Invited Commentary: An Ingenious Approach to Examining the Relationship Between Maternal Stress and Offspring Health?

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The potentially deleterious effects on offspring health of excess maternal stress in pregnancy are important to understand—both whether observed associations are causal and through what mechanisms their effects may exert an influence. In this issue of the <span style="font-style:italic;">Journal</span>, Räikkönen et al. (<span style="font-style:italic;">Am J Epidemiol</span>. 2012;000(0):000–000) provide an ingenious test of a potential pathway through which maternal stress may influence offspring development. Licorice consumption is known to disrupt the ability of the placental enzyme 11β-hydroxysteroid dehydrogenase type 2 to inactivate cortisol before it reaches the fetus, leading to higher levels of cortisol exposure. Higher levels of cortisol exposure are also hypothesized to underlie the mechanism through which maternal stress may disrupt fetal development. Thus licorice consumption may serve, in some ways, to mimic maternal stress. The authors report associations between heavy licorice consumption during pregnancy and a wide range of offspring outcomes, including changes in pubertal timing, intelligence quotient, and mental health. In our view, these results should be considered preliminary; more work needs to be completed to determine the relationship of prenatal licorice consumption to these outcomes. Nonetheless, these intriguing and suggestive results demonstrate that this line of work should be given high priority, and they set the stage for additional research moving forward.</span>

http://ift.tt/2mJFGTg

Räikkönen et al. Respond to “Maternal Stress and Offspring Health”

http://ift.tt/2lb9mN2

Maternal Licorice Consumption During Pregnancy and Pubertal, Cognitive, and Psychiatric Outcomes in Children

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Earlier puberty, especially in girls, is associated with physical and mental disorders. Prenatal glucocorticoid exposure influences the timing of puberty in animal models, but the human relevance of those findings is unknown. We studied whether voluntary consumption of licorice, which contains glycyrrhizin (a potent inhibitor of placental 11β-hydroxysteroid dehydrogenase type 2, the "barrier" to maternal glucocorticoids), by pregnant women was associated with pubertal maturation (height, weight, body mass index for age, difference between current and expected adult height, Tanner staging, score on the Pubertal Development Scale), neuroendocrine function (diurnal salivary cortisol, dexamethasone suppression), cognition (neuropsychological tests), and psychiatric problems (as measured by the Child Behavior Checklist) in their offspring. The children were born in 1998 in Helsinki, Finland, and examined during 2009–2011 (mean age = 12.5 (standard deviation (SD), 0.4) years; <span style="font-style:italic;">n</span> = 378). Girls exposed to high maternal glycyrrhizin consumption (≥500 mg/week) were taller (mean difference (MD) = 0.4 SD, 95% confidence interval (CI): 0.1, 0.8), were heavier (MD = 0.6 SD, 95% CI: 0.2, 1.9), and had higher body mass index for age (MD = 0.6 SD, 95% CI: 0.2, 0.9). They were also 0.5 standard deviations (95% CI: 0.2, 0.8) closer to adult height and reported more advanced pubertal development (<span style="font-style:italic;">P</span> < 0.04). Girls and boys exposed to high maternal glycyrrhizin consumption scored 7 (95% CI: 3.1, 11.2) points lower on tests of intelligence quotient, had poorer memory (<span style="font-style:italic;">P</span> < 0.04), and had 3.3-fold (95% CI: 1.4, 7.7) higher odds of attention deficit/hyperactivity disorder problems compared with children whose mothers consumed little to no glycyrrhizin (≤249 mg/week). No differences in cortisol levels were found. Licorice consumption during pregnancy may be associated with harm for the developing offspring.</span>

http://ift.tt/2mJIKir

Body Mass Index and Amyotrophic Lateral Sclerosis: A Study of US Military Veterans

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Amyotrophic lateral sclerosis (ALS) may be associated with low body mass index (BMI) at the time of diagnosis. However, the role of premorbid BMI in the development of ALS and survival after diagnosis remains unclear. In 2005–2010, we interviewed 467 patients with ALS from the US National Registry of Veterans with ALS and 975 frequency-matched veteran controls. In this sample, we evaluated the association of BMI and BMI change at different ages with ALS risk using unconditional logistic models and with survival after ALS diagnosis using Cox proportional hazards models. After adjustment for confounders, compared with a moderate increase in BMI between ages 25 and 40 years, stable or decreasing BMI was positively associated with ALS risk (odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.20, 2.16). A 1-unit increase in BMI at age 40 years (OR = 0.95, 95% CI: 0.91, 0.98) but not at age 25 years (OR = 0.99, 95% CI: 0.95, 1.03) was inversely associated with ALS. These associations were similar for bulbar and spinal ALS but stronger for those with a delay of less than 1 year between symptom onset and diagnosis. We found no association between prediagnosis BMI and survival. A decreasing BMI from early to middle age and a low BMI in middle age may be positively associated with ALS risk.</span>

http://ift.tt/2lbjO74

IL-33 induces both regulatory B cells and regulatory T cells in dextran sulfate sodium-induced colitis

Publication date: May 2017
Source:International Immunopharmacology, Volume 46
Author(s): Junfeng Zhu, Ying Xu, Chunyu Zhu, Jian Zhao, Xinrui Meng, Siyao Chen, Tianqi Wang, Xue Li, Li Zhang, Changlong Lu, Hongsheng Liu, Xun Sun
Interleukin (IL)-33 is a member of the IL-1 family. Serum levels of IL-33 are increased in inflammatory bowel diseases (IBD), suggesting that IL-33 is involved in the pathogenesis of IBD, although its role is not clear. In this study, we investigated the role of IL-33 in the regulation of T-helper (Th) cell and B cell responses in mesenteric lymph nodes (MLN) in mice with dextran sulfate sodium (DSS)-induced colitis. Here, we showed that IL-33-treated mice were susceptible to DSS-induced colitis as compared with PBS-treated mice. The production of spontaneous inflammatory cytokines production by macrophages or dendritic cells (DC) in MLN significantly increased, and the responses of Th2, regulatory T cells (Treg) and regulatory B cells (Breg) were markedly upregulated, while Th1 responses were significantly downregulated in MLN of IL-33-treated mice with DSS-induced colitis. Our results demonstrate that IL-33 contributes to the pathogenesis of DSS-induced colitis in mice by promoting Th2 responses, but suppressing Th1 responses, in MLN. Moreover, IL-33 treatment increased Breg and Treg responses in MLN in mice with DSS-induced colitis. Therefore, modulation of IL-33/ST2 signaling is implicated as a novel biological therapy for inflammatory diseases associated with Th1 responses.



http://ift.tt/2m6UFJW

Convective storms and non-classical low-level jets during high ozone level episodes in the Amazon region: An ARM/GOAMAZON case study

Publication date: April 2017
Source:Atmospheric Environment, Volume 155
Author(s): Cléo Q. Dias-Junior, Nelson Luís Dias, José D. Fuentes, Marcelo Chamecki
In this work, we investigate the ozone dynamics during the occurrence of both downdrafts associated with mesoscale convective storms and non-classical low-level jets. Extensive data sets, comprised of air chemistry and meteorological observations made in the Amazon region of Brazil over the course of 2014–15, are analyzed to address several questions. A first objective is to investigate the atmospheric thermodynamic and dynamic conditions associated with storm-generated ozone enhancements in the Amazon region. A second objective is to determine the magnitude and the frequency of ground-level ozone enhancements related to low-level jets. Ozone enhancements are analyzed as a function of wind shear, low-level jet maximum wind speed, and altitude of jet core. Strong and sudden increases in ozone levels are associated with simultaneous changes in variables such as horizontal wind speed, convective available potential energy, turbulence intensity and vertical velocity skewness. Rapid increases in vertical velocity skewness give support to the hypothesis that the ozone enhancements are directly related to downdrafts. Low-level jets associated with advancing density currents are often present during and after storm downdrafts that transport ozone-enriched air from aloft to the surface.



http://ift.tt/2lp13Zf

Developing high-resolution urban scale heavy-duty truck emission inventory using the data-driven truck activity model output

Publication date: April 2017
Source:Atmospheric Environment, Volume 155
Author(s): Harikishan Perugu, Heng Wei, Zhuo Yao
Air quality modelers often rely on regional travel demand models to estimate the vehicle activity data for emission models, however, most of the current travel demand models can only output reliable person travel activity rather than goods/service specific travel activity. This paper presents the successful application of data-driven, Spatial Regression and output optimization Truck model (SPARE-Truck) to develop truck-related activity inputs for the mobile emission model, and eventually to produce truck specific gridded emissions. To validate the proposed methodology, the Cincinnati metropolitan area in United States was selected as a case study site. From the results, it is found that the truck miles traveled predicted using traditional methods tend to underestimate — overall 32% less than proposed model— truck miles traveled. The coefficient of determination values for different truck types range between 0.82 and 0.97, except the motor homes which showed least model fit with 0.51. Consequently, the emission inventories calculated from the traditional methods were also underestimated i.e. −37% for NOx, −35% for SO2, -43% for VOC, −43% for BC, −47% for OC and - 49% for PM2.5. Further, the proposed method also predicted within ∼7% of the national emission inventory for all pollutants. The bottom-up gridding methodology used in this paper could allocate the emissions to grid cell where more truck activity is expected, and it is verified against regional land-use data. Most importantly, using proposed method it is easy to segregate gridded emission inventory by truck type, which is of particular interest for decision makers, since currently there is no reliable method to test different truck-category specific travel-demand management strategies for air pollution control.



http://ift.tt/2m75ZWG

A few steps closer to answering the unanswered questions about higher calorie refeeding

http://ift.tt/2lbgNDT

Outcomes of an inpatient medical nutritional rehabilitation protocol in children and adolescents with eating disorders

Abstract

Background

Medical stabilization through inpatient nutritional rehabilitation is often necessary for patients with eating disorders (EDs) but includes the inherent risk of refeeding syndrome. Here we describe our experience of implementing and sustaining an inpatient nutritional rehabilitation protocol designed to strategically prepare patients with EDs and their families for discharge to a home setting in an efficient and effective manner from a general adolescent medicine unit. We report outcomes at admission, discharge, and 4-weeks follow-up.

Methods

Protocol development, implementation, and unique features of the protocol, are described. Data were collected retrospectively as part of a continuous quality improvement (QI) initiative. Safety outcomes were the clinical need for phosphorus, potassium, and magnesium supplementation, other evidence of refeeding syndrome, and unexpected readmissions within one month of discharge. The value outcome was length of stay (LOS). Treatment outcomes were the percentage median BMI (MBMI) change from admission to discharge, and from discharge to 4-weeks follow-up visit.

Results

A total of 215 patients (88% F, 12% M) were included. Patients averaged 15.3 years old (5.8–23.2y); 64% had AN, 18% had atypical anorexia (AtAN), 6% bulimia nervosa (BN), 5% purging disorder (PD), 4% avoidant-restrictive food intake disorder (ARFID), and 3% had an unspecified food and eating disorder (UFED). Average LOS was 11 days. Initial mean calorie level for patients at admission was 1466 and at discharge 3800 kcals/day. Phosphorus supplementation for refeeding hypophosphatemia (RH) was needed in 14% of inpatients; full-threshold refeeding syndrome did not occur. Only 3.8% were rehospitalized in the thirty days after discharge. Patients averaged 86.1% of a median MBMI for age and gender, 91.4% MBMI at discharge, and 100.9% MBMI at 4-weeks follow-up. Mean percentage MBMI differences between time points were significantly different (admission-discharge: 5.3%, p <0.001; discharge-follow-up: 9.2%, p <0.001).

Conclusions

Implementation of the CHOP inpatient nutritional rehabilitation protocol aimed at rapid, efficient, and safe weight gain and integration of caregivers in treatment of patients with diverse ED diagnoses led to excellent QI outcomes in percentage MBMI at discharge and 4-weeks follow-up, while maintaining a short LOS and low rates of RH phosphorus supplementation.

http://ift.tt/2lVrc3E

Involvement of pregnane X receptor in the suppression of carboxylesterases by metformin in vivo and in vitro, mediated by the activation of AMPK and JNK signaling pathway

Publication date: 1 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 102
Author(s): Enfang Shan, Zhu Zhu, Shuangcheng He, Dongbao Chu, Dinghao Ge, Yunran Zhan, Wei Liu, Jian Yang, Jing Xiong
Type 2 diabetes mellitus (T2D) is a complex metabolic disorder requiring polypharmacy treatment in clinic, with metformin being widely used antihyperglycemic drug. However, the mechanisms of metformin as a perpetrator inducing potential drug-drug interactions and adverse drug reactions are scarcely known to date. Carboxylesterases (CESs) are major hydrolytic enzymes highly expressed in the liver, including mouse carboxylesterase 1d (Ces1d) and Ces1e. In the present study, experiments are designed to investigate the effects and mechanisms of metformin on Ces1d and Ces1e in vivo and in vitro. In results, metformin suppresses the expression and activity of Ces1d and Ces1e in a dose- and time-dependent manner. The decreased expression of nuclear receptor PXR and its target gene P-gp indicates the involvements of PXR in the suppressed expression of carboxylesterases by metformin. Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125. It implies that the activation of AMPK and JNK pathways mediates the suppression of carboxylesterases by metformin. The findings deserve further elucidation including clinical trials and have a potential to make contribution for the rational medication in the treatment of T2D patients.

Graphical abstract

http://ift.tt/2lVfaHj

Candidate immune biomarkers for radioimmunotherapy

Publication date: Available online 28 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Antonin Levy, Giulia Nigro, Philippe J. Sansonetti, Eric Deutsch
Newly available immune checkpoint blockers (ICB), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials.Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy.



http://ift.tt/2mrZgHz

Osteopontin splice variants and polymorphisms in Cancer Progression and Prognosis

Publication date: Available online 28 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Marco Antonio Briones-Orta, S. Eréndira Avendaño-Vázquez, Diana Ivette Aparicio-Bautista, Jason D. Coombes, Georg F. Weber, Wing-Kin Syn
Osteopontin (OPN) is an extracellular matrix protein that is overexpressed in various cancers and promotes oncogenic features including cell proliferation, survival, migration, and angiogenesis, among others. OPN can participate in the regulation of the tumor microenvironment, affecting both cancer and neighboring cells. Here, we reviewed the roles of OPN splice variants (a, b, c) in cancer development, progression, and prognosis, and also discussed the identities of isoforms 4 and 5. We also discussed how single-nucleotide polymorphisms (SNPs) of the OPN gene are an additional factor influencing the level of OPN in individuals, modulating the risks of cancer development and outcome.



http://ift.tt/2lxKlaA

Heterogeneity in phenotype of hyperinsulinism caused by activating glucokinase mutations: a novel mutation and its functional characterization

Abstract

Background

Mutations in the GCK gene lead to different forms of GCK-disease, activating mutations cause hyperinsulinemic hypoglycemia while inactivating mutations cause monogenic diabetes. Hyperinsulinism (HI) is a heterogeneous condition with a significant genetic component. The major causes are channelopathies, the other forms are rare and being caused by mutations in genes such as GCK.

Objective

To describe the clinical and genetic presentation of four families with activating GCK mutations, and to explore the pathogenicity of the novel mutation identified through functional studies.

Results

Four cases of HI with mutations in GCK were identified. These include one novel mutation (p.Trp99Cys). Functional analysis of the purified mutant fusion protein GST-GCK-p.Trp99Cys demonstrated that p.Trp99Cys is an activating mutation since it induces a higher affinity for glucose and increases the relative activity index more than 11 times. Moreover, the thermal stability of the mutant protein was similar to that of its wild-type. All patients were responsive to diazoxide treatment. One of the mutations arose de novo, and two were dominantly inherited, although only one of them from an HI affected parent. The age of presentation in our cases varied widely from the neonatal period to adulthood.

Conclusion

The clinical phenotype of the GCK activating mutation carriers was heterogeneous, the severity of symptoms and age at presentation varied markedly between affected individuals, even within the same family. The novel activating GCK mutation (p.Trp99Cys) has a strong activating effect in vitro although it has been identified in one case of a milder and late-onset form of HI.

This article is protected by copyright. All rights reserved.

http://ift.tt/2laTWbC

Editors, Contents, Cover details

Publication date: March 2017
Source:Trends in Cognitive Sciences, Volume 21, Issue 3





http://ift.tt/2mJJ0Ok