Targeting and Isolation of Cancer Cells Using Micro/Nanomotors

Publication date: Available online 9 September 2017
Source:Advanced Drug Delivery Reviews
Author(s): Weiwei Gao, Berta Esteban-Fernández de Ávila, Liangfang Zhang, Joseph Wang
Micro/nanomotors distinguish themselves with in situ energy conversion capability for autonomous movement, a feature that confers remarkable potential to improve cancer treatment. In this review article, three areas are highlighted where micro/nanomotors have established themselves with unique contributions, including propelled navigation to promote cancer cell targeting, powered cell membrane penetration to enhance intracellular delivery, and steered isolation of circulating cancer cells for detection. Progress made in these areas has offered promising inspiration and opportunities aimed for enhancing the efficiency and precision of drug targeting to cancer cells, improving the capability of delivering anticancer drug into cytoplasm for bioactivity, and enabling more rapid and sensitive cancer cell detection. Herein, we review each area with highlights of the current and forthcoming micro/nanomotor techniques in advancing cancer diagnosis and treatment.

Graphical abstract

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Neurophysiological localisation of ulnar neuropathy at the elbow: validation of diagnostic criteria developed by a taskforce of the Danish Society of Clinical Neurophysiology

Publication date: Available online 9 September 2017
Source:Clinical Neurophysiology
Author(s): K. Pugdahl, S. Beniczky, B. Wanscher, B. Johnsen, E.Qerama, M. Ballegaard, K. Benedek, A. Juhl, M. Ööpik, P. Selmar, J. Sønderborg, D. Terney, A. Fuglsang-Frederiksen
ObjectiveThis study validates consensus criteria for localisation of ulnar neuropathy at elbow (UNE) developed by a taskforce of the Danish Society of Clinical Neurophysiology and compares them to the existing criteria from the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). The Danish criteria are based on combinations of conduction slowing in the segments of the elbow and forearm expressed in Z-scores, and difference between the segments in m/s. Examining fibres to several muscles and sensory fibres can increase the certainty of the localisation.MethodsDiagnostic accuracy for UNE was evaluated on 181 neurophysiological studies of the ulnar nerve from 171 peer-reviewed patients from a mixed patient-group. The diagnostic reference standard was the consensus diagnosis based on all available clinical, laboratory, and electrodiagnostic information reached by a group of experienced Danish neurophysiologists.ResultsThe Danish criteria had high specificity (98.4%) and positive predictive value (PPV) (95.2%) and fair sensitivity (76.9%). Compared to the AANEM criteria, the Danish criteria had higher specificity (p < 0.001) and lower sensitivity (p=0.02).ConclusionsThe Danish consensus criteria for UNE are very specific and have high PPV.SignificanceThe Danish criteria for UNE are reliable and well suited for use in different centres as they are based on Z-scores.



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Testing the effects of adolescent alcohol use on adult conflict-related theta dynamics

Publication date: Available online 9 September 2017
Source:Clinical Neurophysiology
Author(s): Jeremy Harper, Stephen M. Malone, William G. Iacono
ObjectiveAdolescent alcohol use (AAU) is associated with brain anomalies, but less is known about long-term neurocognitive effects. Despite theoretical models linking AAU to diminished cognitive control, empirical work testing this relationship with specific cognitive control neural correlates (e.g., prefrontal theta-band EEG dynamics) remains scarce. A longitudinal twin design was used to test the hypothesis that greater AAU is associated with reduced conflict-related EEG theta-band dynamics in adulthood, and to examine the genetic/environmental etiology of this association.MethodsIn a large (N = 718) population-based prospective twin sample, AAU was assessed at ages 11/14/17. Twins completed a flanker task at age 29 to elicit EEG theta-band medial frontal cortex (MFC) power and medial–dorsal prefrontal cortex (MFC-dPFC) connectivity. Two complementary analytic methods (cotwin control analysis; biometric modeling) were used to disentangle the genetic/shared environmental risk towards AAU from possible alcohol exposure effects on theta dynamics.ResultsAAU was negatively associated with adult cognitive control-related theta-band MFC power and MFC-dPFC functional connectivity. Genetic influences primarily underlie these associations.ConclusionsFindings provide strong evidence that genetic factors underlie the comorbidity between AAU and diminished cognitive control-related theta dynamics in adulthood.SignificanceConflict-related theta-band dynamics appear to be candidate brain-based endophenotypes/mechanisms for AAU.



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Adaptation of feedforward movement control is abnormal in patients with cervical dystonia and tremor

Publication date: Available online 9 September 2017
Source:Clinical Neurophysiology
Author(s): Laura Avanzino, Andrea Ravaschio, Giovanna Lagravinese, Gaia Bonassi, Giovanni Abbruzzese, Elisa Pelosin
ObjectiveIt is under debate whether the cerebellum plays a role in dystonia pathophysiology and in the expression of clinical phenotypes. We investigated a typical cerebellar function (anticipatory movement control) in patients with cervical dystonia (CD) with and without tremor.MethodsTwenty patients with CD, with and without tremor, and 17 healthy controls were required to catch balls of different load: 15 trials with a light ball, 25 trials with a heavy ball (adaptation) and 15 trials with a light ball (post-adaptation). Arm movements were recorded using a motion capture system. We evaluated: i) the anticipatory adjustment (just before the impact); ii) the extent and rate of the adaptation (at the impact) and (iii) the aftereffect in the post-adaptation phase.ResultsThe anticipatory adjustment was reduced during adaptation in CD patients with tremor respect to CD patients without tremor and controls. The extent and rate of adaptation and the aftereffect in the post-adaptation phase were smaller in CD with tremor than in controls and CD without tremor.ConclusionPatients with cervical dystonia and tremor display an abnormal predictive movement control.SignificanceOur findings point to a possible role of cerebellum in the expression of a clinical phenotype in dystonia.



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Enzyme-crosslinked Gene-activated Matrix for the Induction of Mesenchymal Stem Cells in Osteochondral Tissue Regeneration

Publication date: Available online 9 September 2017
Source:Acta Biomaterialia
Author(s): Yi-Hsuan Lee, Hsi-Chin Wu, Chia-Wei Yeh, Chen-Hsiang Kuan, Han-Tsung Liao, Horng-Chaung Hsu, Jui-Che Tsai, Jui-Sheng Sun, Tzu-Wei Wang
The development of osteochondral tissue engineering is an important issue for the treatment of traumatic injury or aging associated joint disease. However, the different compositions and mechanical properties of cartilage and subchondral bone show the complexity of this tissue interface, making it challenging for the design and fabrication of osteochondral graft substitute. In this study, a bilayer scaffold is developed to promote the regeneration of osteochondral tissue within a single integrated construct. It has the capacity to serve as a gene delivery platform to promote transfection of human mesenchymal stem cells (hMSCs) and the functional osteochondral tissues formation. For the subchondral bone layer, the bone matrix with organic (type I collagen, Col) and inorganic (hydroxyapatite, Hap) composite scaffold has been developed through mineralization of hydroxyapatite nanocrystals oriented growth on collagen fibrils. We also prepare multi-shell nanoparticles in different layers with a calcium phosphate core and DNA/calcium phosphate shells conjugated with polyethyleneimine to act as non-viral vectors for delivery of plasmid DNA encoding BMP2 and TGF-β3, respectively. Microbial transglutaminase is used as a cross-linking agent to crosslink the bilayer scaffold. The ability of this scaffold to act as a gene-activated matrix is demonstrated with successful transfection efficiency. The results show that the sustained release of plasmids from gene-activated matrix can promote prolonged transgene expression and stimulate hMSCs differentiation into osteogenic and chondrogenic lineages by spatial and temporal control within the bilayer composite scaffold. This improved delivery method may enhance the functionalized composite graft to accelerate healing process for osteochondral tissue regeneration.Significance of this research study:In this study, a gene-activated matrix (GAM) to promote the growth of both cartilage and subchondral bone within a single integrated construct is developed. It has the capacity to promote transfection of human mesenchymal stem cells (hMSCs) and the functional osteochondral tissues formation. The results show that the sustained release of plasmids including TGF-beta and BMP-2 from GAM could promote prolonged transgene expression and stimulate hMSCs differentiation into the osteogenic and chondrogenic lineages by spatial control manner. This improved delivery method should enhance the functionalized composite graft to accelerate healing process in vitro and in vivo for osteochondral tissue regeneration.

Graphical abstract

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Multivalent interactions between streptavidin-based pretargeting fusion proteins and cell receptors impede efficient internalization of biotinylated nanoparticles

Publication date: Available online 9 September 2017
Source:Acta Biomaterialia
Author(s): Christina L. Parker, Qi Yang, Bing Yang, Justin D. McCallen, Steven I. Park, Samuel K. Lai
Pretargeting represents a promising strategy to enhance delivery of nanoparticles. The strategy involves first introducing bispecific antibodies or fusion proteins (BFP) that can bind specific epitopes on target cells with one arm, and use the other arm to capture subsequently administered effector molecules, such as radionuclides or drug-loaded nanoparticles. Nevertheless, it remains unclear whether BFP that bind slowly- or non-internalizing epitopes on target cells can facilitate efficient intracellular delivery. Here, we investigated the cellular uptake of biotin-functionalized nanoparticles with streptavidin-scFv against TAG-72, a membrane protein on Jurkat T-cell leukemia cells. Unlike conventional active-targeted nanoparticles, we found that pretargeting resulted in preferential retention of ∼100nm nanoparticles at the plasma membrane rather than internalization into cells. We found no improvement in nanoparticle internalization by simply reducing nanoparticle concentration or surface biotin density. Interestingly, by adding both the BFP and a monoclonal antibody against TAG-72, we observed a twofold improvement in internalization of pretargeted nanoparticles. Our work illustrates that the cellular fate of pretargeted nanoparticles can be controlled by carefully tuning the interactions between pretargeting molecules and nanoparticles on the cell surface.Statement of SignificancePretargeting is a multi-step strategy that utilizes bispecific proteins that recognize both cellular epitopes and subsequently administered therapeutic molecules. This approach has been extensively studied for radiotherapy of blood cancers; however, pretargeting remains largely underexplored for nanoparticle targeting, including whether pretargeting can facilitate efficient intracellular delivery. Here, we found that high density of targeting proteins on the cell surface can effectively limit internalization of pretargeted nanoparticles. Our work underscores the need to carefully assess specific cell-pretargeting molecule pairs for applications requiring intracellular delivery, and the key design requirements for such bispecific pretargeting molecules.

Graphical abstract

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Small Molecule Adjuvants that Suppress Both Chromosomal and mcr-1 Encoded Colistin-Resistance and Amplify Colistin Efficacy in Polymyxin-Susceptible Bacteria.

Publication date: Available online 9 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): William T. Barker, Sara E. Martin, Courtney E. Chandler, T.Vu. Nguyen, Tyler L. Harris, Christopher Goodell, Roberta J. Melander, Yohei Doi, Robert K. Ernst, Christian Melander
Bacterial resistance to polymyxin antibiotics has taken on a new and more menacing form. Common are genomically-encoded resistance mechanisms to polymyxins, specifically colistin (polymyxin E), however, the plasmid-borne mobile colistin resistance–1 (mcr-1) gene has recently been identified and poses a new threat to global public health. Within six months of initial identification in Chinese swine in November 2015, the first human clinical isolation in the US was reported (Apr. 2016). Herein we report successful reversion of mcr-1-driven colistin resistance in Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli with adjuvants we previously reported as modulators of chromosomally-encoded colistin resistance. Further screening of our in-house library of nitrogen-dense heterocycles has identified additional chemical scaffolds that actively attenuate colistin resistance. Ultimately, we present a diverse cohort of adjuvants that both sensitize colistin-resistant and colistin-susceptible bacteria to this antibiotic, thus providing a potential avenue to both reduce colistin dosage and toxicity, and overcome colistin resistance.

Graphical abstract

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Eudesmane sesquiterpenes from Chinese liverwort are substrates of Cdrs and display antifungal activity by targeting Erg6 and Erg11 of Candida albicans.

Publication date: Available online 9 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Siwen Li, Hongzhuo Shi, Wenqiang Chang, Yi Li, Ming Zhang, Yanan Qiao, Hongxiang Lou
We isolated twelve sesquiterpenes from Chinese liverwort Tritomaria quinquedentata (Huds.) Buch., including four new compounds. Among them, five eudesmane sesquiterpenes were ineffective against Candida albicans wild strain SC5314 but active towards efflux pumps-deficient strain DSY654 using Alamar blue assay. Further test of the most active agent of ent-isoalantolactone (8, ent-iLL) showed that it also inhibited the yeast-to-hyphal switch of DSY654 cells. The intracellular content measurement using high performance liquid chromatography revealed that ent-iLL was intracellularly accumulated in C. albicans when efflux pumps were deficient or inhibited by Cdrs inhibitor riccardin D, suggesting that the activity of ent-iLL was compromised by efflux pumps Cdrs. Moreover, ent-iLL potentially inhibited the activity of Erg11 and Erg6 of DSY654 and thereby resulted in the alteration of sterol composition by decreasing ergosterol contents and increasing zymosterol and lanosterol accumulation. Our study demonstrated that eudesmane sesquiterpenes, as the substrates of Cdrs, could interfere with sterol synthesis of C. albicans to exert antifungal activity when co-applied with Cdrs inhibitors.

Graphical abstract

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Therapeutic Peptides for CNS indications: progress and challenges

Publication date: Available online 9 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Bruce H. Morimoto
Attacking neurodegeneration and promoting neuroprotection have been the holy grail in neurology for almost 20 years and represent an area of high unmet medical need. However, indications like Alzheimer's disease and stroke are areas in drug development fraught with failure. This review will highlight three CNS peptide programs which are tackling targets and indications in which traditional small molecule approaches have been difficult and challenging. The targets for these potential peptide therapeutics include the NMDA receptor, γ-secretase, and cyclin-dependent kinase in which direct inhibition has resulted in on-target (not compound related) problems. For example, direct inhibition of γ-secretase has resulted in gastrointestinal abnormalities and inhibition of the NMDA receptor can result in hallucinations, dizziness, out-of-body sensations, and nightmares. When confronted with show-stopping side effects, the CNS peptide programs profiled in this review strike the problem with intervention and disruption of selective protein-protein interactions. The goal of these peptide programs is to produce selective therapeutics with a better safety profile.

Graphical abstract

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Alternate dosing regimens of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma: reply from authors

Abstract

We thank the authors Lewis, Kim, and Duvic, for their reaction to our article.

The increasingly personalised medicine should also take into account individual tumour entities and their inter-individual pathways.

Therefore, we can only welcome and sustain the comments. As described in our article, it is possible, in some patients, to reduce the dose and interval frequency of Brentuximab Vedotin (BV), while continuing to have good efficacy.

This article is protected by copyright. All rights reserved.

http://ift.tt/2wimnoF

Chronic actinic dermatitis: successful treatment with PUVA photochemotherapy

Abstract

Chronic actinic dermatitis (CAD) is a debilitating photodermatosis. First line therapy consists of strict photoprotection and topical corticosteroids. Second line therapy uses systemic immunosuppression. However an alternative is needed for patients with severe CAD who cannot use systemic immunosuppressants.^1,2 Case reports and small case series suggest that PUVA may be effective.^3-6

This article is protected by copyright. All rights reserved.+

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Alternate dosing regimens of brentuximab vedotin for CD30+ cutaneous T-cell lymphoma

Abstract

Stranzenbach et al. propose alternate dosing regimens of brentuximab vedotin (BV) for CD30+ cutaneous T-cell lymphomas (CTCLs) such as mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL).¹ They emphasize that lower doses or less frequent dosing schedules for CTCL may be equally effective while limiting adverse events.

The authors indicate that CTCLs may require less aggressive therapy than systemic lymphomas such as systemic ALCL (sALCL) or Hodgkin lymphoma (HL).

This article is protected by copyright. All rights reserved.

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The value and pitfalls of biologics registries for psoriasis

Abstract

We are pleased that our initial perspective article in the BJD have sparked discussions. As indicated in our initial paper, our main critical point is the exponential growth in publications relating to drug survival as an efficacy assessment based on non-randomized registry data (Figure 1). Indeed, we ourselves have performed such drug survival analyses.¹ While we agree that methods such as propensity score matching could even out some of the between-drug variations in patient characteristics, propensity score matching is a rare sight in drug survival studies.

This article is protected by copyright. All rights reserved.

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Registries as a real-world cohort studies that are useful and necessary in the pyramid of evidence

Abstract

Egeberg et al¹ enriched us by describing the limitations of registries in psoriasis, but focusing their critical perspective on a misguided outcome measure such as "drug survival". We agree that clinicians and researchers should be cautious when using that proxy measure.^2,3However, the frequent use of this poor outcome should not cast doubts over all the capabilities of registries.

This article is protected by copyright. All rights reserved.

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The role of non-endothelial cells on the penetration of nanoparticles through the blood brain barrier

Publication date: Available online 9 September 2017
Source:Progress in Neurobiology
Author(s): Rui Pedro Moura, Andreia Almeida, Bruno Sarmento
The blood brain barrier (BBB) is a well-established cell-based membrane that circumvents the central nervous system (CNS), protecting it from harmful substances. Due to its robustness and cell integrity, it is also an outstanding opponent when it comes to the delivery of several therapeutic agents to the brain, which requires the crossing through its highly-organized structure. This regulation and cell-cell communications occur mostly between astrocytes, pericytes and endothelial cells. Therefore, alternative ways to deliver drugs to the CNS, overcoming the BBB are required, to improve the efficacy of brain target drugs. Nanoparticles emerge here as a promising drug delivery strategy, due to their ability of high drug loading and the capability to exploit specific delivery pathways that most drugs are unable to when administered freely, increasing their bioavailability in the CNS. Thus, further attempts to assess the possible influence of non-endothelial may have on the BBB translocation of nanoparticles are here revised. Furthermore, the use of macrophages and/or monocytes as nanoparticle delivery cells are also approached. Lastly, the temporarily disruption of the overall organization and normal structure of the BBB to promote the penetration of nanoparticles aimed at the CNS is described, as a synergistic path.



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Peripheral nerve pathology at fixed stage in spinal muscular atrophy with respiratory distress type 1

Publication date: Available online 9 September 2017
Source:Brain and Development
Author(s): Azusa Ikeda, Sumimasa Yamashita, Yu Tsuyusaki, Mio Tanaka, Yukichi Tanaka, Akihiro Hashiguchi, Hiroshi Takashima, Tomohide Goto
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is characterized by severe respiratory failure due to diaphragmatic paralysis and distal muscular weakness in early infancy. After an initial decline in respiratory state and motor function until 1–2years of age, residual capabilities reach a plateau.We report the peripheral neuropathological findings of a patient with SMARD1 at 1year and 1month of age, when his muscle strength and respiratory symptoms had deteriorated and then stabilized for several months. Peripheral nerve biopsy revealed severely progressed axonal degeneration. This finding suggests the rapid progression of peripheral axonal neuropathy in SMARD1 that leads to its characteristic clinical course of respiratory failure and paralysis in the early infantile period.



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Semantic incongruity attracts attention at a pre-conscious level: evidence from a TMS study

Publication date: Available online 9 September 2017
Source:Cortex
Author(s): Javier Ortiz-Tudela, Elisa Martín-Arévalo, Ana B. Chica, Juan Lupiáñez
Unpredicted objects, i.e., those that do not fit in a specific context, have been shown to quickly attract attention as a mean of extracting more information about potentially relevant items. Whether the required semantic processing triggering the attraction of attention can occur independently of participants' awareness of the object is still a highly debated topic. In the present study we make use of a change detection task in which we manipulate the semantic congruity between the to-be-detected object and the background scene. We applied inhibitory repetitive Transcranial Magnetic Stimulation (rTMS) over the right temporo-parietal junction (right TPJ) and a control location (vertex) to test the causal role of the former in the processing of objects at a pre-conscious level. Our results clearly show that semantic congruity can impact detection and identification processes in opposite ways, even when low level features are controlled for. Incongruent objects are quickly detected but poorly identified. rTMS over the right TPJ effectively diminishes contextual guidance effects on attention. These results suggest that at least some high order category processing takes place before conscious detection to direct attention towards the most informative regions of space. Moreover, here we show that rTMS over right TPJ also impacts object identification, which calls for a re-evaluation of right TPJ's role on object processing.



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Is procedural memory enhanced in Tourette syndrome? Evidence from a sequence learning task

Publication date: Available online 9 September 2017
Source:Cortex
Author(s): Ádám Takács, Andrea Kóbor, Júlia Chezan, Noémi Éltető, Zsanett Tárnok, Dezso Nemeth, Michael T. Ullman, Karolina Janacsek
Procedural memory, which is rooted in the basal ganglia, underlies the learning and processing of numerous automatized motor and cognitive skills, including in language. Not surprisingly, disorders with basal ganglia abnormalities have been found to show impairments of procedural memory. However, brain abnormalities could also lead to atypically enhanced function. Tourette syndrome (TS) is a candidate for enhanced procedural memory, given previous findings of enhanced TS processing of grammar, which likely depends on procedural memory. We comprehensively examined procedural learning, from memory formation to retention, in children with TS and typically developing (TD) children, who performed an implicit sequence learning task over two days. The children with TS showed sequence learning advantages on both days, despite a regression of sequence knowledge overnight to the level of the TD children. This is the first demonstration of procedural learning advantages in any disorder. The findings may further our understanding of procedural memory and its enhancement. The evidence presented here, together with previous findings suggesting enhanced grammar processing in TS, underscore the dependence of language on a system that also subserves visuomotor sequencing.



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Grasp preparation modulates early visual processing of size and detection of local/global stimulus features

Publication date: Available online 9 September 2017
Source:Cortex
Author(s): Xavier E. Job, José van Velzen, Jan W. de Fockert
Preparing to grasp objects facilitates visual processing of object location, orientation and size, compared to preparing actions such as pointing. This influence of action on perception reflects mechanisms of selection in visual perception tuned to current action goals, such that action relevant sensory information is prioritized relative to less relevant information. In three experiments, rather than varying movement type (grasp vs. point), the magnitude of a prepared movement (power vs. precision grasps) was manipulated while visual processing of object size, as well as local/global target detection was measured. Early event-related potentials elicited by task-irrelevant visual probes were enhanced for larger probes during power grasp preparation and smaller probes during precision grasp preparation. Local targets were detected faster following precision, relative to power grasp cues. The results demonstrate a direct influence of grasp preparation on sensory processing of size and suggest that the hierarchical dimension of objects may be a relevant perceptual feature for grasp programming. To our knowledge, this is the first evidence that preparing different magnitudes of the same basic action has systematic effects on visual processing.



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The functional effects of prior motion imagery and motion perception

Publication date: Available online 9 September 2017
Source:Cortex
Author(s): Shuai Chang, Joel Pearson
The functional sensory effects and commonalties between mental imagery of different visual features such as color, form or motion remains largely unknown. Mental imagery of static visual features, including color and orientation, can have a facilitative, priming effect on subsequent perception. However, whether motion imagery can have a similar effect remains unknown. Here we used the binocular rivalry method as a measure of motion mental imagery. After imagining or viewing motion of a particular direction, participants were required to report the dominant motion direction in a brief motion rivalry stimulus. We found that motion imagery can have a facilitative priming effect on subsequent motion rivalry perception, and this effect can be attenuated by concurrent expanding and contracting perceptual motion, but not by static or flickering uniform luminance. Unlike color or orientation imagery, the effect of motion imagery on subsequent rivalry was location independent. We also observed this facilitative priming effect with prior low-contrast perceptual motion, but prior high-contrast motion induced a suppressive effect. Simultaneous imagery and perceptual motion in opposite directions induced priming, while congruent directions did not. Counter to prior findings, these results suggest motion imagery can have a priming effect on perception and that the rivalry method can be used to assess visual motion imagery. These results provide evidence for visual imagery as a multi-feature structure.



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“The role of premotor and parietal cortex during monitoring of involuntary movement: a combined TMS and tDCS study.”

Publication date: Available online 9 September 2017
Source:Cortex
Author(s): Valentina Bruno, Carlotta Fossataro, Nadia Bolognini, Luca Zigiotto, Giuseppe Vallar, Anna Berti, Francesca Garbarini
Converging evidence on voluntary actions underlays the existence of a motor monitoring system, able to compare the predicted and the actual consequences of our movements. In this context, both the premotor cortex (PMC) and the posterior parietal cortex (PPC) play a role in action monitoring and awareness. The present study explores the role of PMC and PPC in monitoring involuntary muscle contractions induced by Transcranial Magnetic Stimulation (TMS) over the hand motor area. To this aim, the effects of transcranial Direct Current Stimulation (tDCS) over PMC and PPC were examined. Thirty-six healthy subjects were asked to perform a motor monitoring task (i.e. to verbally report hand twitches induced by TMS) after 10 minutes of tDCS. Through three experiments, the effects of cathodal, anodal and sham tDCS over the left and the right hemispheres were compared. Our results show that cathodal tDCS over the right PMC does not affect the monitoring of involuntary movements. By contrast, tDCS over both the right and the left PPC affects motor monitoring, depending on the current polarity: while cathodal tDCS increases the feeling of phantom-like movements (which actually did not occur), anodal tDCS impairs the ability to detect involuntary hand twitches (which actually took place). These findings show that the PMC is not involved in motor monitoring of involuntary movements; rather, the PPC, where multisensory stimuli converge and are processed, seems to play a crucial role.



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Assessment of active bacteria metabolizing phenolic acids in the peanut (Arachis hypogaea L.) rhizosphere

Publication date: Available online 9 September 2017
Source:Microbiological Research
Author(s): Jinguang Liu, Xingxiang Wang, Taolin Zhang, Xiaogang Li
Phenolic acids can enhance the mycotoxin production and activities of hydrolytic enzymes related to pathogenicity of soilborne fungus Fusarium oxysporum. However, characteristics of phenolic acid-degrading bacteria have not been investigated. The objectives of this study were to isolate and characterize bacteria capable of growth on benzoic and vanillic acids as the sole carbon source in the peanut rhizosphere. Twenty-four bacteria were isolated, and the identification based on 16S rRNA gene sequencing revealed that pre-exposure to phenolic acids before sowing shifted the dominant culturable bacterial degraders from Arthrobacter to Burkholderia stabilis-like isolates. Both Arthrobacter and B. stabilis-like isolates catalysed the aromatic ring cleavage via the ortho pathway, and Arthrobacter isolates did not exhibit higher C12O enzyme activity than B. stabilis-like isolates. The culture filtrate of Fusarium sp. ACCC36194 caused a strong inhibition of Arthrobacter growth but not B. stabilis-like isolates. Additionally, Arthrobacter isolates responded differently to the culture filtrates of B. stabilis-like isolates. The Arthrobacter isolates produced higher indole acetic acid (IAA) levels than B. stabilis-like isolates, but B. stabilis-like isolates were also able to produce siderophores, solubilize mineral phosphate, and exert an antagonistic activity against peanut root rot pathogen Fusarium sp. ACCC36194. Results indicate that phenolic acids can shift their dominant culturable bacterial degraders from Arthrobacter to Burkholderia species in the peanut rhizosphere, and microbial interactions might lead to the reduction of culturable Arthrobacter. Furthermore, increasing bacterial populations metabolizing phenolic acids in monoculture fields might be a control strategy for soilborne diseases caused by Fusarium spp.



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Traumatic brain injury and aggression: A systematic review and future directions using community samples

Publication date: Available online 9 September 2017
Source:Aggression and Violent Behavior
Author(s): Lisa Buckley, Sherrie-Anne Kaye, Ryan P. Stork, Justin E. Heinze, James T. Eckner
Aggression is widespread and a significant community burden, with violence-related injury deaths representing a significant public health problem. We explore aggression relative to a possible associated factor, traumatic brain injury (TBI). Our focus is on a less well studied population, those recruited through the community who may not have had hospital care or contact with the criminal justice system (e.g. were recruited in schools). This study provides a critical review of the potential relationship between aggression and traumatic brain injury. We undertook a systematic search of published literature of studies recruited through the community and found seven studies examining aggression and TBI. All studies identified a relationship between reports of TBI and aggression, however only two studies were longitudinal in design. The study focuses on the limitations of the current body of research, including in definitions of constructs, the need to understand mediating and moderating factors, and improvements needed in the overall research design of studies.



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Mastectomy Flap Thickness and Complications in Nipple-Sparing Mastectomy: Objective Evaluation using Magnetic Resonance Imaging

Background: Ischemic complications after nipple-sparing mastectomy (NSM) have been associated with numerous variables. However, the impact of NSM flap thickness has been incompletely evaluated. Methods: NSM flap thickness was determined for all NSMs from 2006 to 2016 with available pre- or postoperative breast magnetic resonance imaging (MRIs). Demographics and outcomes were stratified by those with and without ischemic complications. Results: Of 1,037 NSM reconstructions, 420 NSMs had MRI data available, which included 379 preoperative MRIs and 60 postoperative MRIs. Average total preoperative skin/subcutaneous tissue NSM flap thickness was 11.4 mm. Average total postoperative NSM flap thickness was 8.7 mm. NSMs with ischemic complications were found to have significantly thinner overall postoperative NSM flap thickness compared with those without ischemic complications (P = 0.0280). Average overall postoperative NSM flap thickness less than 8.0 mm was found to be an independent predictor of ischemic complications (odds ratio, 6.5263; P = 0.026). In NSMs with both pre- and postoperative MRIs, the overall average postoperative NSM flap thickness was 68.2% of preoperative measurements. Average overall postoperative NSM flap thickness was significantly less than average overall preoperative NSM flap thickness (P

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Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis

Publication date: Available online 9 September 2017
Source:Trends in Cell Biology
Author(s): Peter Ly, Don W. Cleveland
Cancer genome sequencing has identified chromothripsis, a complex class of structural genomic rearrangements involving the apparent shattering of an individual chromosome into tens to hundreds of fragments. An initial error during mitosis, producing either chromosome mis-segregation into a micronucleus or chromatin bridge interconnecting two daughter cells, can trigger the catastrophic pulverization of the spatially isolated chromosome. The resultant chromosomal fragments are religated in random order by DNA double-strand break repair during the subsequent interphase. Chromothripsis scars the cancer genome with localized DNA rearrangements that frequently generate extensive copy number alterations, oncogenic gene fusion products, and/or tumor suppressor gene inactivation. Here we review emerging mechanisms underlying chromothripsis with a focus on the contribution of cell division errors caused by centromere dysfunction.



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Micropatterned surface electrode for massive selective stimulation of intraepidermal nociceptive fibres.

Publication date: Available online 9 September 2017
Source:Journal of Neuroscience Methods
Author(s): Massimo Leandri, Lucio Marinelli, Antonio Siri, Luca Pellegrino
BackgroundNo satisfactory neurophysiological test for nociceptive afferents is available to date. Laser stimuli present risks of skin damage, whilst electrical stimulation through specially designed electrodes is not selective enough.New methodWe present a new electrode designed according to critical issues identified in preliminary computer simulations concerning electric field gradient through the skin. To provide selective stimulation the activating electric field must be limited to intraepidermal free nerve endings. To this end, a new interdigitated electrode (IDE) was made of conductive rails arranged in a comb-like micropattern, situated only 150μm apart from each other (150 IDE) and alternately connected to the opposite poles of the stimulator.ResultsEvoked potentials recorded from the scalp were obtained after stimulation with the 150 IDE and with a similarly designed, but more widely spaced electrode (1000μm, or 1000 IDE). Small amplitude early and medium latency components were recorded with the 1000 IDE, suggesting activation of Aβ fibres. On the other hand, the 150 IDE only evoked late responses, confirming sufficient selectivity in small fibre activation.Comparison with Existing Method(s)The main differences with existing electrodes are: 1) Microspaced interdigitated conductive rails. 2) The potentially unlimited surface of stimulation and high efficiency per surface unit, resulting in large numbers of activated nociceptors.ConclusionsA new electrode providing selective stimulation of nociceptive nerve free endings is presented. It is non-invasive, and its surface can be enlarged at will. It is expected that it may greatly help in neurophysiological assessment of conditions affecting the nociceptive pathway.



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Lack of Apparent Survival Benefit from the Use of Androgen Deprivation Therapy in Patients with High-Risk Prostate Cancer Treated with Combined External Beam Radiotherapy and Brachytherapy

Publication date: Available online 9 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): David D. Yang, Vinayak Muralidhar, Brandon A. Mahal, Paul L. Nguyen, Phillip M. Devlin, Martin T. King, Peter F. Orio
PurposeWhile level 1 evidence has demonstrated a survival benefit from the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) for patients with high-risk prostate cancer, the benefits of ADT with combined EBRT and brachytherapy for high-risk patients are unclear. We examined the association between ADT and overall survival in a national cohort of high-risk patients treated with EBRT with or without brachytherapy.Methods and MaterialsWe identified 46,325 men in the National Cancer Database diagnosed from 2004 through 2011 with high-risk prostate cancer (Gleason 8-10, clinical T3-4, or prostate-specific antigen >20 ng/mL) who were treated with EBRT with or without brachytherapy and ADT. Multivariable Cox regression adjusting for sociodemographic and clinicopathologic factors was used to identify the association between ADT and overall survival.ResultsMedian follow-ups were 48.6 and 59.2 months for patients treated with EBRT only and combined modality radiotherapy, respectively. ADT was associated with an improvement in overall survival for the 85.0% (39,361) of the study cohort managed with EBRT alone (adjusted hazard ratio 0.91, P=0.001) but not for patients treated with combined modality radiotherapy (adjusted hazard ratio 1.05, P=0.496), with a significant interaction (Pinteraction=0.036).ConclusionsAs opposed to the known survival benefit when ADT is given with EBRT, our results suggest that ADT may not improve survival for high-risk patients treated with combined EBRT and brachytherapy. Given the significant adverse effects of ADT, particularly long-term therapy, a randomized controlled trial of combined EBRT and brachytherapy with or without ADT for select high-risk patients using a non-inferiority design should be undertaken.

Teaser

The benefits of androgen deprivation therapy (ADT) with combined external beam radiotherapy and brachytherapy for patients with high-risk prostate cancer are unknown. Using a large, national cohort of high-risk patients, we found that ADT was associated with an improvement in overall survival for patients managed with EBRT alone but not for patients treated with combined modality radiotherapy, suggesting that ADT may not improve overall survival for select high-risk patients treated with combined modality radiotherapy.


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Landscape attributes as drivers of the geographical variation in density of Sapajus nigritus Kerr, 1792, a primate endemic to the Atlantic Forest

Publication date: October 2017
Source:Acta Oecologica, Volume 84
Author(s): Carla D. Hendges, Geruza L. Melo, Alberto S. Gonçalves, Felipe O. Cerezer, Nilton C. Cáceres
Neotropical primates are among the most well studied forest mammals concerning their population densities. However, few studies have evaluated the factors that influence the spatial variation in the population density of primates, which limits the possibility of inferences towards this animal group, especially at the landscape-level. Here, we compiled density data of Sapajus nigritus from 21 forest patches of the Brazilian Atlantic Forest. We tested the effects of climatic variables (temperature, precipitation), landscape attributes (number of patches, mean inter-patch isolation distance, matrix modification index) and patch size on the population density using linear models and the Akaike information criterion. Our findings showed that the density of S. nigritus is influenced by landscape attributes, particularly by fragmentation and matrix modification. Overall, moderately fragmented landscapes and those surrounded by matrices with intermediate indexes of temporal modification (i.e., crop plantations, forestry) are related to high densities of this species. These results support the assumptions that ecologically flexible species respond positively to forest fragmentation. However, the non-linear relationship between S. nigritus density and number of patches suggests that even the species that are most tolerant to forest cover changes seem to respond positively only at an intermediate level of habitat fragmentation, being dependent of both a moderate degree of forest cover and a high quality matrix. The results we found here can be a common response to fragmentation for those forest dweller species that are able to use the matrix as complementary foraging sites.



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Constructing Experience: Event Models from Perception to Action

Publication date: Available online 9 September 2017
Source:Trends in Cognitive Sciences
Author(s): Lauren L. Richmond, Jeffrey M. Zacks
Mental representations of everyday experience are rich, structured, and multimodal. In this article we consider the adaptive pressures that led to human construction of such representations, arguing that structured event representations enable cognitive systems to more effectively predict the trajectory of naturalistic everyday activity. We propose an account of how cortical systems and the hippocampus (HPC) interact to construct, maintain, and update event representations. This analysis throws light on recent research on story comprehension, event segmentation, episodic memory, and action planning. It also suggests how the growing science base can be deployed to diagnose impairments in event perception and memory, and to improve memory for everyday events.



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Phosphate-arsenate relations to affect arsenic concentration in plant tissues, growth, and antioxidant efficiency of sunflower ( Helianthus annuus L.) under arsenic stress

Abstract

Relations between phosphate and arsenate are important but inconsistent to influence arsenic (As) phytotoxicity depending on many plant and soil factors. Present research aimed to investigate the phosphate and arsenate interactions in sunflower (Helianthus annuus L.) grown in alkaline calcareous soil for 18 weeks under natural environmental conditions at three arsenate [0 (As₀), 40 (As₄₀), and 80 (As₈₀) mg As kg⁻¹ soil as sodium arsenate] and three phosphate [0 (P₀), 100 (P₁₀₀), and 200 (P₂₀₀) mg P₂O₅ kg⁻¹ soil as diammonium phosphate] levels. The plants were grown in pots according to completely randomized design with five replications. Ionic and physiological parameters were measured at 40 days after treatment completion. Arsenic contamination with As₄₀ and As₈₀ increased root and shoot As concentration with relatively higher concentration in roots, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) while decreased plant P, chlorophyll, protein, and glutathione (GSH), and consequently plant growth, yield, and yield attributes. Addition of P₁₀₀ and P₂₀₀ under As stress reduced As transfer from soil to roots to shoots, MDA concentration, SOD, CAT, and POD activities while increased GSH, leaf protein, chlorophyll, and growth characteristics as well as achene yield compared to As-treated plants without additional P. In conclusion, P-induced inhibition of As transfer from soil to roots to shoots and reduction in MDA concentration accompanied with an increase in the synthesis of protein, chlorophyll, and GSH could be the main mechanisms responsible for lowered As toxicity in sunflower, leading to mitigation of potential risks of As contamination to food chain and human health.

http://ift.tt/2vWOz5d

Analytical insight into degradation processes of aminopolyphosphonates as potential factors that induce cyanobacterial blooms

Abstract

Aminopolyphosphonates (AAPs) are commonly used industrial complexones of metal ions, which upon the action of biotic and abiotic factors undergo a breakdown and release their substructures. Despite the low toxicity of AAPs towards vertebrates, products of their transformations, especially those that contain phosphorus and nitrogen, can affect algal communities. To verify whether such chemical entities are present in water ecosystems, much effort has been made in developing fast, inexpensive, and reliable methods for analyzing phosphonates. However, unfortunately, the methods described thus far require time-consuming sample pretreatment and offer relatively high values of the limit of detection (LOD). The aim of this study was to develop an analytical approach to study the environmental fate of AAPs. Four phosphonic acids, N,N-bis(phosphonomethyl)glycine (GBMP), aminotris(methylenephosphonic) acid (ATMP), hexamethylenediamine-N,N,N′,N′-tetrakis(methylphosphonic) acid (HDTMP), and diethylenetriamine penta(methylenephosphonic) acid (DTPMP) were selected and examined in a water matrix. In addition, the susceptibility of these compounds to biotransformations was tested in colonies of five freshwater cyanobacteria—microorganisms responsible for the so-called blooms in the water. Our efforts to track the AAP decomposition were based on derivatization of N-alkyl moieties with p-toluenesulfonyl chloride (tosylation) followed by chromatographic (HPLC-UV) separation of derivatives. This approach allowed us to determine seven products of the breakdown of popular phosphonate chelators, in nanomolar concentrations and in one step. It should be noted that the LOD of four of those products, aminemethylphosphonic acid (AMPA), N-phosphomethyl glycine (NPMG), N-(methyl)aminemethanephosphonic acid (MAMPA), and N-(methyl) glycine (SAR), was set below the concentration of 50 nM. Among those substances, N-(methylamino)methanephosphonic acid (MAMPA) was identified for the first time as the product of decomposition of the examined aminopolyphosphonates.

http://ift.tt/2jduQIn

Resistance of aerobic microorganisms and soil enzyme response to soil contamination with Ekodiesel Ultra fuel

Abstract

This study determined the susceptibility of cultured soil microorganisms to the effects of Ekodiesel Ultra fuel (DO), to the enzymatic activity of soil and to soil contamination with PAHs. Studies into the effects of any type of oil products on reactions taking place in soil are necessary as particular fuels not only differ in the chemical composition of oil products but also in the composition of various fuel improvers and antimicrobial fuel additives. The subjects of the study included loamy sand and sandy loam which, in their natural state, have been classified into the soil subtype 3.1.1 Endocalcaric Cambisols. The soil was contaminated with the DO in amounts of 0, 5 and 10 cm³ kg⁻¹. Differences were noted in the resistance of particular groups or genera of microorganisms to DO contamination in loamy sand (LS) and sandy loam (SL). In loamy sand and sandy loam, the most resistant microorganisms were oligotrophic spore-forming bacteria. The resistance of microorganisms to DO contamination was greater in LS than in SL. It decreased with the duration of exposure of microorganisms to the effects of DO. The factor of impact (IF_DO) on the activity of particular enzymes varied. For dehydrogenases, urease, arylsulphatase and β-glucosidase, it had negative values, while for catalase, it had positive values and was close to 0 for acid phosphatase and alkaline phosphatase. However, in both soils, the noted index of biochemical activity of soil (BA) decreased with the increase in DO contamination. In addition, a positive correlation occurred between the degree of soil contamination and its PAH content.

http://ift.tt/2vXy88t

Contaminant characteristics and environmental risk assessment of heavy metals in the paddy soils from lead (Pb)-zinc (Zn) mining areas in Guangdong Province, South China

Abstract

In November 2016, the total metal concentrations in nine representative locations in lead (Pb)-zinc (Zn) mining areas, located in Guangdong Province, South China, were determined experimentally by flame atomic absorption spectrometer. The results indicated that the paddy soils were heavily contaminated with Cd (20.25 mg kg⁻¹), Pb (1093.03 mg kg⁻¹), and Zn (867.0 mg kg⁻¹), exceeding their corresponding soil quality standard values and background values. According to the results, the mean enrichment factor levels of the studied metals decreased in the following order: Cd > Zn > Pb > Cu > Ni > Mn > Cr. Among these metals, Cd, Pb, and Zn were predominantly influenced by widespread anthropogenic activities. The highest concentrations of the studied metal pollutants were distributed in the areas surrounding the mining activity district. Multivariate statistical analysis indicated that the major contributing sources of the studied metals were metal ore mining, smelting, and processing activities. However, the composition of soil background was another potential source. Moreover, the assessment results of environment risks showed that the potential ecological risks, in decreasing order, were Cd > Pb > Zn > Cu > Ni > Cr > Mn. Additionally, the non-carcinogenic risk represented the trend of HI _Pb > HI _Mn > HI _Zn > HI _Cu , and the carcinogenic risk ranked as CR _Cr > CR _Cd > CR _Ni . Among the environmental risk substances, Cd and Pb were the main contributors that pose ecological harm and health hazards through their serious pollution. Consequently, greater attention should be paid to this situation.

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Stability of BiFeO 3 nanoparticles via microwave-assisted hydrothermal synthesis in Fenton-like process

Abstract

Stable catalysts require high catalytic efficiency and repeated consecutive use, low mass loss, and metal leaching. This study investigated BiFeO₃ (BFO) composite with high stability and reusability using a one step microwave-assisted hydrothermal method (MAHS) to decompose bisphenol A (BPA) used as the target contaminant. After six consecutive reaction cycles in microwave-enhanced Fenton-like process (MW-Fenton-like), the removal rate of BPA decreased from 94 to 87.4% with low metal leaching ratio and mass loss. The morphology, crystal, reaction kinetics, and hydroxyl radical (·OH) were used to demonstrate the high stability of BFO-MAHS. The results indicated that the benign stability and reusability of BFO-MAHS probably occurred because (1) the thermal-effect of MW improved heating rate, which led to the rapid formation stable cube structure and (2) MW mechanical vibrations existed in the preparation process, which further enhanced the cube structure. Therefore, MAHS could be used as a green and environmental friendly method to apply in catalysts synthesis, which could immensely shorten preparation time and enhance the catalytic performance with no waste production.

http://ift.tt/2vXAoN5

Prenatal stress induced gender-specific alterations of N-methyl-d-aspartate receptor subunit expression and response to Aβ in offspring hippocampal cells

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Yuan Fang, Hui Li, Lirong Chang, Yizhi Song, Longhui Ma, Liying Lu, Zunshu Du, Yan Li, Jinping Liu, Yan Wu
Prenatal stress (PS) is one of adverse life events during pregnancy, which may increase vulnerability to cognitive impairment in adult offspring. Aβ synaptotoxicity is one important pathological factor for cognitive impairment, and PS-induced cognitive disorder is closely associated with N-Methyl-d-Aspartate receptor (NMDAR), which acts as a key mediator of Aβ synaptotoxicity. In the present study, we tried to explore whether PS affects offspring's Aβ levels and NMDAR subunit expression in a gender-specific manner in hippocampal CA and DG subregions, and whether PS affects synaptic proteins and NMDAR subunit expression in cultured offspring hippocampal cells exposed to Aβ. Pregnant SD rats with restraint stress from gestation day 8–20 were used as PS model. Morris water maze, ELISA, immunofluorescence and western blot were tested on postnatal day 90 in male and female PS offspring. Our results showed that female offspring is more vulnerable to PS-induced cognitive impairment. Surprisingly, PS enhanced Aβ1-40 levels in the hippocampal DG subregion of male offspring. Furthermore, WB results implied that the decreased GluN2A in CA of female may contribute to the PS-induced cognitive impairment, while in DG, the increased GluN2A and decreased GluN2B contributed to protective effects against Aβ. Interestingly, we found PS could alleviate Aβ synaptotoxicity in male offspring's hippocampal cells. Overall, our results provided a fundamental understanding of PS-induced gender-specific alterations of NMDAR subunit expression and the susceptibility to Aβ, and paved the road for the development of timely preventive interventions on cognitive disorders of PS offspring.



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Effects of an acute therapeutic or rewarding dose of amphetamine on acquisition of Pavlovian autoshaping and ventral striatal dopamine signaling

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): D.R. Schuweiler, J.M. Athens, J.M. Thompson, S.T. Vazhayil, P.A. Garris
Rewarding doses of amphetamine increase the amplitude, duration, and frequency of dopamine transients in the ventral striatum. Debate continues at the behavioral level about which component of reward, learning or incentive salience, is signaled by these dopamine transients and thus altered in addiction. The learning hypothesis proposes that rewarding drugs result in pathological overlearning of drug-predictive cues, while the incentive sensitization hypothesis suggests that rewarding drugs result in sensitized attribution of incentive salience to drug-predictive cues.Therapeutic doses of amphetamine, such as those used to treat attention-deficit hyperactivity disorder, are hypothesized to enhance the ventral striatal dopamine transients that are critical for reward-related learning and to enhance Pavlovian learning. However, the effects of therapeutic doses of amphetamine on Pavlovian learning are poorly understood, and the effects on dopamine transients are completely unknown.We determined the effects of an acute pre-training therapeutic or rewarding amphetamine injection on the acquisition of Pavlovian autoshaping in the intact rat. We also determined the effects of these doses on electrically evoked transient-like dopamine signals using fast-scan cyclic voltammetry in the anesthetized rat. The rewarding dose enhanced the amplitude and duration of DA signals, caused acute task disengagement, impaired learning for several days, and triggered incentive sensitization. The therapeutic dose produced smaller enhancements in DA signals but did not have similar behavioral effects. These results underscore the necessity of more studies using therapeutic doses, and suggest a hybrid learning/incentive sensitization model may be required to explain the development of addiction.



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A randomized trial of clitoral vacuum suction versus vibratory stimulation in neurogenic female orgasmic dysfunction

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Marcalee Alexander, Khurram Bashir, Craig Alexander, Lesley Marson, Raymond Rosen
ObjectiveTo examine safety and efficacy of use of a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with MS or SCI.DesignRandomized clinical trial.SettingTwo academic medical centers.ParticipantsThirty-one women including 20 with MS and 11 with SCI.InterventionA 12-week trial of the use of a CVSD versus VMain Outcome measuresFemale Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS).Results23 women (18 MS; 5 SCI) completed the study including 13/16 randomized to CVSD and 10/15 randomized to V. There was a statistically significant increase in total FSFI score (p=.011), desire (p=. 009), arousal (p=.009), lubrication (p=.008), orgasm (p=.012), and satisfaction (p=.049) and a significant decrease in distress as measured by FSDS (p=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (p=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment.ConclusionCVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious to female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Due to ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective.



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Comparative efficacy of intra-articular steroid injection and distension in patients with frozen shoulder: a systematic review and network meta-analysis

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Meng-Ting Lin, Ming-Yen Hsiao, Yu-Kang Tu, Tyng-Guey Wang
ObjectiveTo compare the efficacy of intra-articular (IA) steroid injection and distension in patients with frozen shoulder.Data SourcesDatabases, including MEDLINE (via PubMed), EMBASE, Scopus and Cochrane Library, were searched for studies published up to November 2016.Study SelectionWe included all published randomized controlled trials (RCTs), quasi-experimental studies and observational studies investigating the effectiveness of IA steroid injection, distension and physiotherapy in patients with frozen shoulder. Sixteen RCTs and one observational study were enrolled in meta-analysis.Data ExtractionFull-texts were independently reviewed and quality of RCTs was assessed with The Cochrane Collaboration's tool. The primary outcome was functional improvement; the secondary outcomes included pain reduction and external rotation (ER) improvement.Data SynthesisIn pair-wise meta-analysis, pooled standardized mean difference (SMD) of functional improvement and pain reduction revealed equal efficacy at three follow-up time points. With respect to ER improvement, distension has a superior effect as compared to IA steroid injection at short term [2–4 weeks; SMD: −0.36; 95% confidence interval (CI): −0.68∼ −0.04] and at medium term (6–16 weeks; SMD: −0.80; 95% CI: −1.32∼ −0.29). The network meta-analysis indicated a better efficacy for distension than for IA steroid injection in ER improvement only at medium term (6–16 weeks; SMD: −0.70; 95% CI: −1.19∼ −0.21).ConclusionIA steroid injection was as effective as distension in shoulder-function improvement, pain reduction and increasing ER of shoulder. Distension yielded better ER improvement at medium term but to a minor extent in the long term. For patients with predominant ER limitation, early distension could be considered the primary choice of treatment.



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Group- and individual-level responsiveness of the 3-point Berg Balance Scale and 3-point Postural Assessment Scale for Stroke Patients

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Yi-Jing Huang, Gong-Hong Lin, Shih-Chieh Lee, Yi-Miau Chen, Sheau-Ling Huang, Ching-Lin Hsieh
ObjectiveTo examine both group- and individual-level responsiveness of the 3-point Berg Balance Scale (BBS-3P) and 3-point Postural Assessment Scale for Stroke Patients (PASS-3P) in patients with stroke, and to compare the responsiveness of both 3-point measures versus their original measures (BBS and PASS) and their short forms (SFBBS and SFPASS) and between the BBS-3P and PASS-3P.DesignThe data were retrieved from a previous study wherein 212 patients were assessed at 14 and 30 days after stroke with the BBS and PASS.SettingMedical center.ParticipantsPatients with first onset of stroke within 14 days before hospitalization.Interventions.Not applicable.Main Outcome Measures.Group-level responsiveness was examined by the standardized response mean (SRM), and individual-level responsiveness was examined by the proportion of patients whose change scores exceeded the minimal detectable change of each measure. The responsiveness was compared using bootstrap approach.ResultsThe BBS-3P and PASS-3P had good group-level (SRM=0.60 and 0.56, respectively) and individual-level (48.1% and 44.8% of the patients with significant improvement, respectively) responsiveness. Bootstrap analyses showed that the BBS-3P generally had superior responsiveness to the BBS and SFBBS, and the PASS-3P had similar responsiveness to the PASS and SFPASS. The BBS-3P and PASS-3P were equally responsive to both group and individual's change.ConclusionsThe responsiveness of the BBS-3P and PASS-3P was comparable or superior to those of the original and short-form measures. We recommend the BBS-3P and PASS-3P as responsive outcome measures of balance for individuals with stroke.



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Long-term performance and user satisfaction with implanted neuroprostheses for upright mobility after paraplegia: Two to 14-year follow-up

Publication date: Available online 9 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ronald J. Triolo, Stephanie Nogan Bailey, Kevin M. Foglyano, Rudi Kobetic, Lisa M. Lombardo, Michael E. Miller, Gilles Pinault
ObjectiveTo quantify the long-term (LT) (>2 years) effects of lower extremity (LE) neuroprostheses (NPs) for standing, transfers, stepping and seated stability after spinal cord injury.DesignSingle-subject design case series with participants acting as their own concurrent controls, including retrospective data review.SettingHospital-based clinical biomechanics laboratory with experienced (>20 years in the field) research biomedical engineers, physical therapist and medical monitoring review.ParticipantsTwenty-two (19 male, 3 female) LT (6.2 ± 2.7 years) at-home users of implanted NPs for trunk and LE function with chronic (14.4 ± 7.1 years) spinal cord injury resulting in full or partial paralysis.InterventionsTechnical and clinical performance measurements, along with user satisfaction surveys.Main Outcome MeasuresKnee extension moment, maximum standing time, body weight supported by lower extremities, three functional standing tasks, two satisfaction surveys, NP usage, and stability of implanted components.ResultsStimulated knee extension strength and functional capabilities were maintained with 94% of implant recipients reporting being "very" or "moderately" satisfied with their system. Greater than half (60%) of the participants were still using their implanted NPs for exercise and function for more than 10 minutes per day on nearly half or more of the days monitored, although maximum standing times and percentage body weight through LEs decreased slightly over the follow-up interval. Stimulus thresholds were uniformly stable. Six-year survival rates for the first-generation implanted pulse generator (IPG) and epimysial electrodes were close to 90%, while those for the second-generation IPG along with the intramuscular and nerve cuff electrodes were greater than 98%.ConclusionsObjective and subjective measures of the technical and clinical performances of implanted LE NPs generally remained consistent for 22 participants after an average of 6 years of unsupervised use at home. These findings suggest that implanted LE NPs can provide lasting benefits that recipients value.



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Pneumatosis from Esophagus to Rectum: A Comprehensive Review Focusing on Clinico-Radiological Differentiation Between Benign and Life-Threatening Causes

Publication date: Available online 9 September 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Ulysses S. Torres, Camila D.F.M. Fortes, Priscila S. Salvadori, Dario A. Tiferes, Giuseppe D′Ippolito
Pneumatosis of the alimentary tract may occur from the esophagus to rectum as a result of a wide spectrum of conditions that range from benign to life-threatening. While distinguishing between these two groups is of paramount importance for an appropriate clinical management, it still remains a challenge for the radiologist in the daily practice. In the light of the current literature we provide in the present article a comprehensive review focusing on the clinical, laboratory and radiological findings that most consistently may allow such a differentiation. We also provide a pictorial essay illustrating this range of diagnoses, briefly discussing each one.



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Delayed Detection of Spontaneous Bilateral Tubal Ectopic Pregnancies After Methotrexate Treatment

Publication date: Available online 9 September 2017
Source:The Journal of Emergency Medicine
Author(s): Nicole E. Brown, Shereen A. Singer, Joe Suyama
BackgroundBilateral tubal ectopic pregnancies are a rare subset of ectopic pregnancy that can pose a diagnostic dilemma for clinicians. There is no distinct clinical presentation for bilateral tubal ectopic pregnancies, although they are typically associated with assistive reproductive techniques. In addition, there is no single diagnostic feature to help clinicians delineate bilateral tubal ectopic pregnancies from other types of ectopic pregnancy prior to passing the discriminatory zone (such as heterotopic pregnancy or twin ectopic [two gestational sacs in one tube]). Diagnosis is typically made via direct visualization intraoperatively and therefore treatment is usually surgical.Case ReportWe present a case of spontaneous bilateral tubal ectopic pregnancies diagnosed 7 days apart via transvaginal ultrasound. The patient presented to the emergency department with pelvic pain on the contralateral side of her previously diagnosed ectopic pregnancy and vaginal spotting. Bilateral adnexal masses were visualized on ultrasound and her serum beta–human chorionic gonadotropin level had a 5.9% decline from day 4 to day 7 after methotrexate administration 7 days prior; gynecology was consulted. The patient was successfully treated with an additional dose of intramuscular methotrexate without any complications.Why Should an Emergency Physician Be Aware of This?The implications of this case suggest that diagnosis of bilateral tubal ectopic pregnancies requires clinicians to have a high level of suspicion in any pregnant female with a suspected or known ectopic pregnancy who presents with pelvic pain regardless of prior diagnosis or treatment.



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Does fear extinction in the laboratory predict outcomes of exposure therapy? A treatment analog study

Publication date: Available online 8 September 2017
Source:International Journal of Psychophysiology
Author(s): Eduard Forcadell, David Torrents-Rodas, Bram Vervliet, David Leiva, Miquel Tortella-Feliu, Miquel A. Fullana
Fear extinction models have a key role in our understanding of anxiety disorders and their treatment with exposure therapy. Here, we tested whether individual differences in fear extinction learning and fear extinction recall in the laboratory were associated with the outcomes of an exposure therapy analog (ETA). Fifty adults with fear of spiders participated in a two-day fear-learning paradigm assessing fear extinction learning and fear extinction recall, and then underwent a brief ETA. Correlational analyses indicated that enhanced extinction learning was associated with better ETA outcome. Our results partially support the idea that individual differences in fear extinction learning may be associated with exposure therapy outcome, but suggest that further research in this area is needed.



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A review of the effects of physical activity and sports concussion on brain function and anatomy

Publication date: Available online 8 September 2017
Source:International Journal of Psychophysiology
Author(s): Sara Tremblay, Alvaro Pascual-Leone, Hugo Théoret
Physical activity has been associated with widespread anatomical and functional brain changes that occur following acute exercise or, in the case of athletes, throughout life. High levels of physical activity through the practice of sports also lead to better general health and increased cognitive function. Athletes are at risk, however, of suffering a concussion, the effects of which have been extensively described for brain function and anatomy. The level to which these effects are modulated by increased levels of fitness is not known. Here, we review literature describing the effects of physical activity and sports concussions on white matter, grey matter, neurochemistry and cortical excitability. We suggest that the effects of sports concussion can be coufounded by the effects of exercise. Indeed, available data show that the brain of athletes is different from that of healthy individuals with a non-active lifestyle. As a result, sports concussions take place in a context where structural/functional plasticity has occurred prior to the concussive event. The sports concussion literature does not permit, at present, to separate the effects of intense and repeated physical activity, and the abrupt removal from such activities, from those of concussion on brain structure and function.



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Response to “Re: A Systematic Review and Meta-analysis of the Association Between C-reactive Protein and Major Cardiovascular Events in Patients with Peripheral Artery Disease”

Publication date: Available online 9 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Tejas P. Singh, Dylan R. Morris, Samuel Smith, Joseph V. Moxon, Jonathan Golledge




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Central sympathetic nervous system reinforcement in obstructive sleep apnoea

The available studies on cerebrovascular reactivity and cerebral oxygenation in obstructive sleep apnoea (OSA) patients brought conflicting results, yet the overall evidence suggests that resting state cerebral perfusion is diminished in these patients. Interestingly, in a group of healthy professional breath-hold divers who are exercising very long apnoeas - episodes corresponding to the ones observed in patients with OSA - demonstrated that cerebral oxygenation may remain stable at the expense of extreme sympathetic nervous system (SNS) activation.

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Effectiveness of mechanical debridement with and without adjunct antimicrobial photodynamic therapy in the treatment of periodontal inflammation among patients with prediabetes

Publication date: Available online 9 September 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Mansour Al-Askar, Abdulaziz A. Al-Kheraif, Hameeda Bashir Ahmed, Sergio Varela Kellesarian, Hans Malmstrom, Fawad Javed
AimThe aim of the present study was to assess the effectiveness of mechanical debridement (MD) with and without adjunct antimicrobial photodynamic therapy (aPDT) in the treatment of periodontal inflammation among patients with prediabetes.MethodsDemographic information was collected using a questionnaire. Hemoglobin A1c (HbA1c) levels were measured at baseline and at 3 and 6 months' follow-up.Treatmentwise, individuals were randomly divided into 2 groups as follows: (a) Group-1, participants underwent full-mouth MD; and Group-2: participants underwent full-mouth MD with adjunct aPDT. In groups 1 and 2, full-mouth plaque index (PI), bleeding on probing (BOP) and probing pocket depth (PPD) were measured at baseline and at 3 and 6 months' follow-up. In both groups, full-mouth digital intraoral radiographs were also taken. Sample-size was estimated and statistical analysis was performed with level of significance set as P<0.05.ResultsIn total, 70 prediabetic male individuals (35 patients in group-1 and 35 in group-2) were included. At baseline, PI, BOP, number of sites with PPD ≥4mm were comparable among individuals in groups 1 and 2. In groups 1 and 2, PI (P<0.05), BOP (P<0.05), number of sites with PPD ≥4mm (P<0.05) were significantly higher at baseline compared with 3 months' follow-up. There was no statistically significant difference in PI, BOP, number of sites with PPD ≥4mm at 3 and 6 months' follow-up. At 6 months' follow-up, PI, BOP, number of sites with PPD ≥4mm were comparable to their respective baseline values. There was no statistically significant difference in CBL in both groups at 3 and 6 months' follow-up. There was no statistically significant difference in HbA1c levels among individuals in groups 1 and 2 at all-time intervals.ConclusionIn the short-term, MD is effective in reducing periodontal inflammation among patients with prediabetes. The contribution of adjunct aPDT in this regard is insignificant.



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Rare genetic variants in the sodium-dependent organic anion transporter SOAT (SLC10A6): Effects on transport function and membrane expression

Publication date: Available online 8 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Josefine Bennien, Thomas Fischer, Joachim Geyer
Sulfo-conjugated steroid hormones, such as dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate or estrone-3-sulfate are abundant in the body, but are biologically inactive at classical androgen and estrogen steroid receptors. However, after carrier-mediated import and de-conjugation by the steroid sulfatase, these compounds participate in the overall steroid regulation of reproductive organs. The sodium-dependent organic anion transporter SOAT, coded by the SLC10A6 gene, is specific for the transport of steroid sulfates and is highly expressed in testicular germ cells, including pachytene spermatocytes, secondary spermatocytes, and round spermatids. Therefore, SOAT is supposed to be involved in the regulation of spermatogenesis and male fertility. In the present study, the SLC10A6 gene was analyzed for rare genetic variants, which might affect transport function or membrane expression of SOAT. Among the 31 SOAT variants analyzed, L44P, Q75R, P107L, G109S, S112F, N113K, S133F, G241D, G263E, G294R, and Y308N showed no transport activity for DHEAS at all. In the case of P107L, G241D, G263E, and Y308N, this was most likely due to significantly reduced expression in the plasma membrane. Other variants are located directly at (Q75R, S112F, N113K) or close to (G109S, S133F, and G263E) the supposed SOAT Na⁺ binding sites and thus could disable the sodium-coupled transport cycle. If these loss-of-function SOAT variants are more frequent in men with impaired spermatogenesis or infertility needs further investigation.



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CYP17A1 inhibitor abiraterone, an anti-prostate cancer drug, also inhibits the 21-hydroxylase activity of CYP21A2

Publication date: Available online 8 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Jana Malikova, Simone Brixius-Anderko, Sameer S. Udhane, Shaheena Parween, Bernhard Dick, Rita Bernhardt, Amit V. Pandey
Abiraterone is an inhibitor of CYP17A1 which is used for the treatment of castration resistant prostate cancer. Abiraterone is known to inhibit several drug metabolizing cytochrome P450 enzymes including CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, but its effects on steroid metabolizing P450 enzymes are not clear. In preliminary results, we had observed inhibition of CYP21A2 by 1μM abiraterone. Here we are reporting the effect of abiraterone on activities of CYP21A2 in human adrenal cells as well as with purified recombinant CYP21A2. Cells were treated with varying concentrations of abiraterone for 24hours and CYP21A2 activity was measured using [³H] 17-hydroxyprogesterone as substrate. Whole steroid profile changes were determined by gas chromatography-mass spectrometry. Binding of abiraterone to purified CYP21A2 protein was measured spectroscopically. Computational docking was used to study the binding and interaction of abiraterone with CYP21A2. Abiraterone caused significant reduction in CYP21A2 activity in assays with cells and an inhibition of CYP21A2 activity was also observed in experiments using recombinant purified proteins. Abiraterone binds to CYP21A2 with an estimated Kd of 6.3μM. These inhibitory effects of abiraterone are at clinically used concentrations. A loss of CYP21A2 activity in combination with reduction of CYP17A1 activities by abiraterone could result in lower cortisol levels and may require monitoring for any potential adverse effects.



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Differential expression of vitamin D-associated enzymes and receptors in brain cell subtypes

Publication date: Available online 8 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Véréna Landel, Delphine Stephan, Xiaoying Cui, Darryl Eyles, François Feron
Accumulating evidence indicates that the active form of vitamin D, 1,25(OH)2D3, can be considered as a neurosteroid. However, the cerebral expression of vitamin D-associated enzymes and receptors remains controversial. With the idea of carrying out a comparative study in mind, we compared the transcript expression of Cyp27a1, Cyp27b1, Cyp24a1, Vdr and Pdia3 in purified cultures of astrocytes, endothelial cells, microglia, neurons and oligodendrocytes. We observed that endothelial cells and neurons can possibly transform the inactive cholecalciferol into 25(OH)D3. It can then be metabolised into 1,25(OH)2D3, by neurons or microglia, before being transferred to astrocytes where it can bind to VDR and initiate gene transcription or be inactivated when in excess. Alternatively, 1,25(OH)2D3 can induce autocrine or paracrine rapid non-genomic actions via PDIA3 whose transcript is abundantly expressed in all cerebral cell types. Noticeably, brain endothelial cells appear as a singular subtype as they are potentially able to transform cholecalciferol into 25(OH)D3 and exhibit a variable expression of Pdia3, according to 1,25(OH)2D3 level. Altogether, our data indicate that, within the brain, vitamin D may trigger major auto-/paracrine non genomic actions, in addition to its well documented activities as a steroid hormone.

Graphical abstract

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The relationship between 25-hydroxyvitamin D concentration and liver enzymes in overweight or obese adults: Cross-sectional and interventional outcomes

Publication date: Available online 9 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Negar Naderpoor, Aya Mousa, Maximilian de Courten, Robert Scragg, Barbora de Courten
Vitamin D deficiency is prevalent in individuals with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. However, there is limited and inconsistent data on the effect of vitamin D supplementation on liver function. Hepatic enzymes have been used as surrogate markers for NAFLD and have been associated with metabolic syndrome. We examined the relationships between 25-hydroxyvitamin D (25(OH)D) and γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP) in 120 drug-naïve individuals with no history of liver disease. In addition, the effect of vitamin D supplementation (100,000 loading dose of cholecalciferol followed by 4000IU daily for 16 weeks) on hepatic enzymes was investigated in a subgroup of 54 vitamin D-deficient overweight or obese individuals (28 randomised to cholecalciferol and 26 to placebo). Hepatic enzymes, anthropometric parameters, lipid profile, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp, M value) and high sensitivity C-reactive protein (hs-CRP) were measured before and after intervention. In the cross-sectional study, levels of GGT and ALT were higher in men compared to women (both p=0.001). There were no significant differences in GGT, ALT and ALP between vitamin D categories (25(OH)D<25 nmol/L, 25–50nmol/L, and >50nmol/L) and no relationships were found between the three enzymes and 25(OH)D before and after adjustment for age, sex, BMI, WHR, and insulin sensitivity (all p>0.5). In the randomised trial, 25(OH)D concentrations increased in the vitamin D group (mean change 57.0±21.3nmol/L) compared to the placebo group (mean change 1.9±15.1 nmol/L). Mean changes in GGT, ALT and ALP were not significantly different between vitamin D and placebo groups (all p>0.2). Change in 25(OH)D concentration was not correlated with changes in GGT, ALT and ALP before and after adjustments for age and sex (all p>0.1).In summary, 25(OH)D concentrations were not related to hepatic enzymes in drug-naive adults with no history of liver disease, and vitamin D supplementation had no effect on the serum levels of hepatic enzymes in vitamin D-deficient and overweight or obese, otherwise healthy individuals. Hence, vitamin D supplementation is unlikely to prevent incident NAFLD.



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Endocrine and physiological regulation of neutral fat storage in Drosophila

Publication date: Available online 8 September 2017
Source:Molecular and Cellular Endocrinology
Author(s): Michael Lehmann
After having revolutionized our understanding of the mechanisms of animal development, Drosophila melanogaster has more recently emerged as an equally valid genetic model in the field of animal metabolism. An increasing number of studies have revealed that many signaling pathways that control metabolism in mammals, including pathways controlled by nutrients (insulin, TOR), steroid hormone, glucagon, and hedgehog, are functionally conserved between mammals and Drosophila. In fact, genetic screens and analyses in Drosophila have identified new players and filled in gaps in the signaling networks that control metabolism. This review focuses on data that show how these networks control the formation and breakdown of triacylglycerol energy stores in the fat tissue of Drosophila.



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Molecular basis of androgen action on human sexual desire

Publication date: Available online 8 September 2017
Source:Molecular and Cellular Endocrinology
Author(s): Daniele Santi, Giorgia Spaggiari, Lisa Gilioli, Francesco Potì, Manuela Simoni, Livio Casarini
Reproduction is a fundamental process for the species maintenance and the propagation of genetic information. The energy expenditure for mating is overtaken by motivational stimuli, such as orgasm, finely regulated by steroid hormones, gonadotropins, neurotransmitters and molecules acting in the brain and peripheral organs. These functions are often investigated using animal models and translated to humans, where the androgens action is mediated by nuclear and membrane receptors converging in the regulation of both long-term genomic and rapid non-genomic signals. In both sexes, testosterone is a central player of this game and is involved in the regulation of sexual desire and arousal, and, finally, in reproduction through cognitive and peripheral physiological mechanisms which may decline with aging and circadian disruption. Finally, genetic variations impact on reproductive behaviours, resulting in sex-specific effect and different reproductive strategies. In this review, androgen actions on sexual desire are evaluated, focusing on the molecular levels of interaction.



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A neural signature of food semantics is associated with body-mass index

Publication date: Available online 9 September 2017
Source:Biological Psychology
Author(s): Giulio Pergola, Francesco Foroni, Paola Mengotti, Georgette Argiris, Raffaella Ida Rumiati
Visual recognition of objects may rely on different features depending on the category to which they belong. Recognizing natural objects, such as fruits and plants, weighs more on their perceptual attributes, whereas recognizing man-made objects, such as tools or vehicles, weighs more upon the functions and actions they enable. Edible objects are perceptually rich but also prepared for specific functions, therefore it is unclear how perceptual and functional attributes affect their recognition.Two event-related potentials experiments investigated: (i) whether food categorization in the brain is differentially modulated by sensory and functional attributes, depending on whether the food is natural or transformed; (ii) whether these processes are modulated by participants' body mass index. In experiment 1, healthy normal-weight participants were presented with a sentence (prime) and a photograph of a food. Primes described either a sensory feature ('It tastes sweet') or a functional feature ('It is suitable for a wedding party') of the food, while photographs depicted either a natural (e.g., cherry) or a transformed food (e.g., pizza). Prime-feature pairs were either congruent or incongruent. This design aimed at modulating N400-like components elicited by semantic processing. In experiment 1, N400-like amplitude was significantly larger for transformed food than for natural food with sensory primes, and vice versa with functional primes. In experiment 2, underweight and obese women performed the same semantic task. We found that, while the N400-like component in obese participants was modulated by sensory-functional primes only for transformed food, the same modulation was found in underweight participants only for natural food. These findings suggest that the level of food transformation interacts with participants' body mass index in modulating food perception and the underlying brain processing.



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Sustained Engagement of Attention is Associated with Increased Negative Self-Referent Processing in Major Depressive Disorder

Publication date: Available online 8 September 2017
Source:Biological Psychology
Author(s): Justin Dainer-Best, Logan T. Trujillo, David M. Schnyer, Christopher G. Beevers
This study investigated the link between self-reference and attentional engagement in adults with (n=22) and without (HC; n=24) Major Depressive Disorder (MDD). Event-related potentials (ERPs) were recorded while participants completed the Self-Referent Encoding Task (SRET). MDD participants endorsed significantly fewer positive words and more negative words as self-descriptive than HC participants. A whole-scalp data analysis technique revealed that the MDD participants had larger difference wave (negative words minus positive words) ERP amplitudes from 380–1000ms across posterior sites, which positively correlated with number of negative words endorsed. No group differences were observed for earlier attentional components (P1, P2). The results suggest that among adults with MDD, negative stimuli capture attention during later information processing; this engagement is associated with greater self-referent endorsement of negative adjectives. Sustained cognitive engagement for self-referent negative stimuli may be an important target for neurocognitive depression interventions.



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Too sweet to eat: Exploring the effects of cuteness on meat consumption

Publication date: 1 January 2018
Source:Appetite, Volume 120
Author(s): Janis H. Zickfeld, Jonas R. Kunst, Sigrid M. Hohle
Although daily meat consumption is a widespread habit, many individuals at the same time put a high value on the welfare of animals. While different psychological mechanisms have been identified to resolve this cognitive tension, such as dissociating the animal from the consumed meat or denying the animal's moral status, few studies have investigated the effects of the animal's appearance on the willingness to consume its meat. The present article explored how the perception of cuteness influences hypothetical meat consumption. We hypothesized that cuter animals would reduce the willingness to consume meat, and that this relationship would be mediated by empathy felt towards the animal. Across four pre-registered studies sampling 1074 US and Norwegian participants, we obtained some support for this prediction in the US but to a lesser degree in Norway. However, in all studies an indirect mediation effect of cuteness on meat consumption going through empathy towards the animal was observed. We also explored possible moderating and additional mediating mechanisms of trait pro-social orientation, caretaking intentions and sex effects for which we found mixed evidence. Theoretical and practical implications of the findings are discussed.



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Feasibility and reliability of digital imaging for estimating food selection and consumption from students’ packed lunches

Publication date: 1 January 2018
Source:Appetite, Volume 120
Author(s): Jennifer C. Taylor, Carolyn Sutter, Lenna L. Ontai, Adrienne Nishina, Sheri Zidenberg-Cherr
Although increasing attention is placed on the quality of foods in children's packed lunches, few studies have examined the capacity of observational methods to reliably determine both what is selected and consumed from these lunches. The objective of this project was to assess the feasibility and inter-rater reliability of digital imaging for determining selection and consumption from students' packed lunches, by adapting approaches previously applied to school lunches. Study 1 assessed feasibility and reliability of data collection among a sample of packed lunches (n = 155), while Study 2 further examined reliability in a larger sample of packed (n = 386) as well as school (n = 583) lunches. Based on the results from Study 1, it was feasible to collect and code most items in packed lunch images; missing data were most commonly attributed to packaging that limited visibility of contents. Across both studies, there was satisfactory reliability for determining food types selected, quantities selected, and quantities consumed in the eight food categories examined (weighted kappa coefficients 0.68–0.97 for packed lunches, 0.74–0.97 for school lunches), with lowest reliability for estimating condiments and meats/meat alternatives in packed lunches. In extending methods predominately applied to school lunches, these findings demonstrate the capacity of digital imaging for the objective estimation of selection and consumption from both school and packed lunches.



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A theoretical and empirical modeling of anxiety integrated with RDoC and temporal dynamics

Publication date: Available online 8 September 2017
Source:Journal of Anxiety Disorders
Author(s): Brandon Frank, Nicholas C. Jacobson, Landon Hurley, Dean McKay
The newly launched Research Domain Criteria (RDoC) emphasize specific mechanisms over diagnostic categories of psychopathology. In our view, RDoC provides a useful heuristic for mental health disorders, but does not capture the complexity of psychological data when proposed mechanisms are viewed as static entities. However, temporal and complex system dynamics may advance RDoC's utility. By investigating temporal patterns within trajectories and the interaction of complex networks, we propose that dynamic modeling provides comprehensive methods with which to investigate the etiopathology and maintenance of mental health disorders. We examine applications of dynamical systems to periphery physiology, an RDoC construct that has been widely used in psychological science. A review of the literature suggests methodological problems with aggregate and reductive models. We present a dynamical systems modeling of anxiety which suggests avenues for future biomarker research. This model appears congruent with RDoC and recent learning theory.



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Epithelial-mesenchymal transition of tumor budding in colorectal cancer: the mystery of CD44-positive stromal cells

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Simona Gurzu, Laura Banias, Zsolt Kovacs, Ioan Jung




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Angiomyomatous Hamartoma of Lymph Nodes, Revisited: Clinico-pathologic Study of 21 Cases, Emphasizing Its Distinction from Lymphangioleiomyomatosis of Lymph Nodes

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Michelle Moh, Ankur Sangoi, Joseph T. Rabban
Angiomyomatous hamartoma of lymph nodes (AMH-LN) is an uncommon benign proliferation of smooth muscle, blood vessels, collagenous stroma and adipocytes, most commonly affecting inguinal LN. A similar constellation of cell types constitutes various members of the perivascular epithelioid cell tumor (PEComa) family, including lymphangioleiomyomatosis (LAM) which can involve LN in women. Because some LN-LAM patients have tuberous sclerosis complex (TSC) and/or other PEComa family lesions, it is clinically relevant to distinguish LN-LAM from AMH-LN. Given their similar features, however, the possibility that AMH-LN is a morphologic variant of LN-LAM merits inquiry. The dual melanocytic and myoid immunophenotype distinguishes the PEComa family from its mimics. Cathepsin K has recently emerged as a more sensitive marker for the PEComa family than HMB-45, which can be weak and focal,but cathepsin K has not been studied in AMH-LN. This study evaluated 21 AMH-LN for clinical, morphologic and immunophenotypic features of LN-LAM. None (0/21) had TSC or PEComas. Thirteen (62%) were male, unlike LN-LAM which is restricted to women. All cases exhibited intraparenchymal proliferation of variable size, thick-walled blood vessels within collagenous stroma containing a sparse to focally cellular population of haphazardly distributed smooth muscle cells. Admixed adipocytes were commonly present. None exhibited classical features of LN-LAM such as subcapsular localization, extranodal extension, intralymphatic growth, compact nests, branching lymphatic channels, plump cell shape or foamy / clear cytoplasm. None exhibited any staining for cathepsin K, HMB45, or MiTF. There is no clinical, morphologic or immunohistochemical evidence to suggest that AMH-LN is a variant of LN-LAM.



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Characterization of genome-wide copy number aberrations in colonic mixed adenoneuroendocrine carcinoma and neuroendocrine carcinoma reveals recurrent amplification of PTGER4 and MYC genes

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Namita Sinha, Daniel Gaston, Daniel Manders, Marissa Goudie, Makoto Matsuoka, Tao Xie, Weei-Yuarn Huang
Colonic Mixed adenoneuroendocrine Carcinoma (MANEC) is an aggressive neoplasm with worse prognosis compared to adenocarcinoma. To gain a better understanding of the molecular features of colonic MANEC, we characterized the genome-wide copy number aberrations (CNA) of 14 MANECs and 5 neuroendocrine carcinomas using the OncoScan FFPE assay. Compared to 269 colonic adenocarcinomas, 19 of 42 chromosomal arms of MANEC exhibited a similar frequency of major aberrant events as adenocarcinomas, and 13 chromosomal arms exhibited a higher frequency of copy number gains. Among them, the most significant chromosomal arms were 5p (77% vs. 13%, P=1.2E-05) and 8q (85% vs. 33%, P=0.0018). The genomic identification of significant targets in cancers (GISTIC) algorithm identified seven peaks that drive the tumorgenesis of MANEC. For all except 5p13.1, the peaks largely overlapped with those of adenocarcinoma. Two tumors exhibited MYC amplification localized in 8q24.21 and two tumors exhibited PTGER4 amplification localized in 5p13.1. A total of eight tumors exhibited high copy number gain of PTGER4 and/or MYC. While the frequency of MYC amplification was similar to adenocarcinoma (10.5% vs. 4%, P=0.2), the frequency of PTGER4 amplification was higher than adenocarcinoma (10.5% vs. 0.3%, P=0.01). Our study demonstrates similar, but also distinct, CNAs in MANEC compared to adenocarcinoma and suggests an important role for the MYC pathway of colonic carcinoma with neuroendocrine differentiation. The discovery of recurrent PTGER4 amplification implies a potential of exploring targeting therapy to the prostaglandin synthesis pathways in a subset of these tumors.



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Histone 3.3 Mutations in Giant Cell Tumor and Giant Cell-Rich Sarcomas of Bone

Publication date: Available online 9 September 2017
Source:Human Pathology
Author(s): Alberto Righi, Irene Mancini, Marco Gambarotti, Piero Picci, Gabriella Gamberi, Cristina Marraccini, Angelo Paolo Dei Tos, Lisa Simi, Pamela Pinzani, Alessandro Franchi
Mutually exclusive histone 3.3 gene mutations have been recognized in chondroblastoma and giant cell tumor of bone (GCTB), which may be useful for differential diagnostic purposes in morphologically ambiguous cases. While over 90% of GCTB presents histone 3.3 variants exclusively in the H3F3A gene, chondroblastoma is mutated mainly in H3F3B. In this study we examined a series of giant cell rich primary bone tumors, aiming to evaluate the possible diagnostic role of histone 3.3 mutations in the differential diagnosis between GCTB and giant cell rich sarcomas. Sixteen cases of non-metastatic GCTB, 9 GCTB with lung metastases, and 35 giant cell-rich sarcomas were selected from our institutional archives. Eight chondroblastomas were used as controls. Direct sequencing for the presence of H3F3A and H3F3B variants in coding region between codons 1 and 42, including the hot spot codons (28, 35 and 37) was performed on DNA extracted from formalin-fixed paraffin-embedded tissue using conventional polymerase chain reaction (PCR) and fast COamplification at Lower Denaturation temperature-PCR (COLD-PCR). Overall, 24 GCTB (96%) presented a mutation in the H3F3A gene (15 of 16 non metastatic and 9 of 9 metastatic). Five sarcomas harbored a H3F3A mutation (3 p.G35 W, 1 p.G35 L and 1 p.G35E), and these were all secondary malignant GCTB. In conclusion, we confirm that H3F3A mutational testing may be a useful adjunct to differentiate GCTB from giant cell rich sarcomas. Although the presence of H3F3A mutations does not exclude with certainty a diagnosis of sarcoma, the possibility of a malignant evolution of GCTB should also be considered.



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