IJMS, Vol. 17, Pages 110: Retinal Cell Degeneration in Animal Models

The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage.

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IJMS, Vol. 17, Pages 115: Cerebellar Expression of the Neurotrophin Receptor p75 in Naked-Ataxia Mutant Mouse

Spontaneous mutation in the lysosomal acid phosphatase 2 (Acp2) mouse (nax—naked-ataxia mutant mouse) correlates with severe cerebellar defects including ataxia, reduced size and abnormal lobulation as well as Purkinje cell (Pc) degeneration. Loss of Pcs in the nax cerebellum is compartmentalized and harmonized to the classic pattern of gene expression of the cerebellum in the wild type mouse. Usually, degeneration starts in the anterior and posterior zones and continues to the central and nodular zones of cerebellum. Studies have suggested that the p75 neurotrophin receptor (NTR) plays a role in Pc degeneration; thus, in this study, we investigated the p75NTR pattern and protein expression in the cerebellum of the nax mutant mouse. Despite massive Pc degeneration that was observed in the nax mouse cerebellum, p75NTR pattern expression was similar to the HSP25 pattern in nax mice and comparable with wild type sibling cerebellum. In addition, immunoblot analysis of p75NTR protein expression did not show any significant difference between nax and wild type sibling (p > 0.5). In comparison with wild type counterparts, p75NTR pattern expression is aligned with the fundamental cytoarchitecture organization of the cerebellum and is unchanged in the nax mouse cerebellum despite the severe neurodevelopmental disorder accompanied with Pc degeneration.

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IJMS, Vol. 17, Pages 109: Morphological and Cellular Features of Innate Immune Reaction in Helicobacter pylori Gastritis: A Brief Review

Innate and adaptive immunity are both involved in acute and chronic inflammatory processes. The main cellular players in the innate immune system are macrophages, mast cells, dendritic cells, neutrophils, eosinophils, and natural killer (NK), which offer antigen-independent defense against infection. Helicobacter pylori (H. pylori) infection presents peculiar characteristics in gastric mucosa infrequently occurring in other organs; its gastric colonization determines a causal role in both gastric carcinomas and mucosa-associated lymphoid tissue lymphoma. In contrast, an active role for Epstein-Barr virus (EBV) has been identified only in 9% of gastric carcinomas. The aim of the present review is to discuss the role of cellular morphological effectors in innate immunity during H. pylori infection and gastric carcinogenesis.

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IJMS, Vol. 17, Pages 108: In Vitro and in Vivo Neuroprotective Effects of Walnut (Juglandis Semen) in Models of Parkinson’s Disease

Monoamine oxidase (MAO) catalyzes the oxidative deamination of monoamines including dopamine (DA). MAO expression is elevated in Parkinson's disease (PD). An increase in MAO activity is closely related to age, and this may induce neuronal degeneration in the brain due to oxidative stress. MAO (and particularly monoamine oxidase B (MAO-B)) participates in the generation of reactive oxygen species (ROS), such as hydrogen peroxide that are toxic to dopaminergic cells and their surroundings. Although the polyphenol-rich aqueous walnut extract (JSE; an extract of Juglandis Semen) has been shown to have various beneficial bioactivities, no study has been dedicated to see if JSE is capable to protect dopaminergic neurons against neurotoxic insults in models of PD. In the present study we investigated the neuroprotective potential of JSE against 1-methyl-4-phenylpyridinium (MPP+)- or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicities in primary mesencephalic cells and in a mouse model of PD. Here we show that JSE treatment suppressed ROS and nitric oxide productions triggered by MPP+ in primary mesencephalic cells. JSE also inhibited depletion of striatal DA and its metabolites in vivo that resulted in significant improvement in PD-like movement impairment. Altogether our results indicate that JSE has neuroprotective effects in PD models and may have potential for the prevention or treatment of PD.

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IJMS, Vol. 17, Pages 113: In Silico Insight into Potential Anti-Alzheimer’s Disease Mechanisms of Icariin

Herbal compounds that have notable therapeutic effect upon Alzheimer's disease (AD) have frequently been found, despite the recent failure of late-stage clinical drugs. Icariin, which is isolated from Epimedium brevicornum, is widely reported to exhibit significant anti-AD effects in in vitro and in vivo studies. However, the molecular mechanism remains thus far unclear. In this work, the anti-AD mechanisms of icariin were investigated at a target network level assisted by an in silico target identification program (INVDOCK). The results suggested that the anti-AD effects of icariin may be contributed by: attenuation of hyperphosphorylation of tau protein, anti-inflammation and regulation of Ca2+ homeostasis. Our results may provide assistance in understanding the molecular mechanism and further developing icariin into promising anti-AD agents.

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Neural correlates of the food/non-food visual distinction

Publication date: Available online 14 January 2016
Source:Biological Psychology
Author(s): Kleovoulos Tsourides, Shahriar Shariat, Hossein Nejati, Tapan K. Gandhi, Annie Cardinaux, Christopher T. Simons, Ngai-Man Cheung, Vladimir Pavlovic, Pawan Sinha
An evolutionarily ancient skill we possess is the ability to distinguish between food and non-food. Our goal here is to identify the neural correlates of visually driven 'edible-inedible' perceptual distinction. We also investigate correlates of the finer-grained likability assessment. Our stimuli depicted food or non-food items with sub-classes of appealing or unappealing exemplars. Using data-classification techniques drawn from machine-learning, as well as evoked-response analyses, we sought to determine whether these four classes of stimuli could be distinguished based on the patterns of brain activity they elicited. Subjects viewed 200 images while in a MEG scanner. Our analyses yielded two successes and a surprising failure. The food/non-food distinction had a robust neural counterpart and emerged as early as 85ms post-stimulus onset. The likable/non-likable distinction too was evident in the neural signals when food and non-food stimuli were grouped together, or when only the non-food stimuli were included in the analyses. However, we were unable to identify any neural correlates of this distinction when limiting the analyses only to food stimuli. Taken together, these positive and negative results further our understanding of the substrates of a set of ecologically important judgments and have clinical implications for conditions like eating-disorders and anhedonia.



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The Clinical Internship for Radiology

Publication date: Available online 14 January 2016
Source:Academic Radiology
Author(s): Valerie P. Jackson




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High-content cell death imaging using quantum dot-based TIRF microscopy for the determination of anticancer activity against breast cancer stem cell

We report a two color monitoring of drug-induced cell deaths using total internal reflection fluorescence (TIRF) as a novel method to determine anticancer activity. Instead of cancer cells, breast cancer stem cells (CSCs) were directly tested in the present assay to determine the effective concentration (EC₅₀) values of camptothecin and cisplatin. Phosphatidylserine and HMGB1 protein were concurrently detected to observe apoptotic and necrotic cell death induced by anticancer drugs using quantum dot (Qdot)-antibody conjugates. Only 50-to-100 breast CSCs were consumed at each cell chamber due to the high sensitivity of Qdot-based TIRF. The high sensitivity of Qdot-based TIRF, that enables the consumption of a small number of cells, is advantageous for cost-effective large-scale drug screening. In addition, unlike MTT assay, this approach can provide a more uniform range of EC₅₀ values because the average values of single breast CSCs fluorescence intensities are observed to acquire EC₅₀ values as a function of dose. This research successfully demonstrated the possibility that Qdot-based TIRF can be widely used as an improved alternative to MTT assay for the determination of anticancer drug efficacies.

This study attempted a two color monitoring of drug-induced cell deaths using quantum dot probe-based total internal reflection fluorescence (TIRF) as a novel optical detection method to determine anticancer activity against breast cancer stem cell (BCSC). The apoptotic and necrotic BCSC deaths induced by camptothecin were concurrently monitored. Qdot-based TIRF as an improved alternative to MTT assay was successfully demonstrated for the quantitative determination of anticancer activity.

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Damage models and assessment methods

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Bridging the Gap Between Continuous Sedation Until Death and Physician-Assisted Death: A Focus Group Study in Nursing Homes in Flanders, Belgium

The distinction between continuous sedation until death (CSD) and physician-assisted death (PAD) has become a topic of medical ethical debate. We conducted 6 focus groups to examine how nursing home clinicians perceive this distinction. For some, the difference is clear whereas others consider CSD a form of euthanasia. Another group situates CSD between pain relief and ending life. Arguments for these perspectives refer to the following themes: intention, dosage of sedative drugs, unconsciousness, and the pace of the dying process. Generally, CSD is considered emotionally easier to deal with since it entails a gradual dying process. Nursing home clinicians have diverging perceptions of the relation between CSD and PAD; some consider CSD to be more than a purely palliative measure, that is, also as a means to hasten death.

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Mentally Challenging Activities Key to a Healthy Aging Mind

Recent evidence suggests that engaging in enjoyable and enriching lifestyle activities may be associated with maintaining cognitive vitality. However, the underlying mechanism accounting for cognitive enhancement effects have been poorly understood.

Investigators at the University of Texas at Dallas proposed that only tasks that involved sustained mental effort and challenge would facilitate cognitive function. Senior author Denise Park and lead author Ian McDonough compared changes in brain activity in 39 older adults that resulted from the performance of high-challenge activities that required new learning and sustained mental effort compared to low-challenge activities that did not require active learning. All of the participants underwent a battery of cognitive tests and brain scans using functional magnetic resonance imaging (fMRI), an MRI technology that measures brain activity by detecting changes associated with blood flow.

Participants were randomly assigned to the high-challenge, low-challenge, or placebo groups. The high-challenge group spent at least 15 hours per week for 14 weeks learning progressively more difficult skills in digital photography, quilting, or a combination of both. The low-challenge group met for 15 hours per week to socialize and engage in activities related to subjects such as travel and cooking with no active learning component. The placebo group engaged in low-demand cognitive tasks such as listening to music, playing simple games, or watching classic movies. All participants were tested before and after the 14-week period and a subset was retested a year later.

The high-challenge group demonstrated better memory performance after the intervention, and an increased ability to modulate brain activity more efficiently to challenging judgments of word meaning in the medial frontal, lateral temporal, and parietal cortex regions of the brain. These are brain areas associated with attention and semantic processing. Some of this enhanced brain activity was maintained a year later. This increased neural efficiency in judging words was demonstrated by participants showing lowered brain activity when word judgments were easy and increasing activity when they became hard. This is a pattern of response typical of young adults. Before participating in the high-challenge intervention, the older adults were processing every item, both easy and hard, with maximum brain activity. After participation, they were able to modulate their brain activity to the demands of the task, thus showing a more efficient use of neural resources. This change in modulation was not observed in the low-challenge group.

The findings show that mentally demanding activities may be neuroprotective and an important element for maintaining a healthy brain into late adulthood.

"The present findings provide some of the first experimental evidence that mentally-challenging leisure activities can actually change brain function and that it is possible that such interventions can restore levels of brain activity to a more youth-like state. However, we would like to conduct much larger studies to determine the universality of this effect and understand who will benefit the most from such an intervention," explained senior author Denise C. Park, PhD, of the Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas.

Ian McDonough, who is now an assistant professor of Psychology at the University of Alabama and was first author on the study, said: "The study clearly illustrates that the enhanced neural efficiency was a direct consequence of participation in a demanding learning environment. The findings superficially confirm the familiar adage regarding cognitive aging of 'Use it or lose it.'"

Denise Park added, "Although there is much more to be learned, we are cautiously optimistic that age-related cognitive declines can be slowed or even partially restored if individuals are exposed to sustained, mentally challenging experiences."

#  #  #

NOTES FOR EDITORS

"The Synapse Project: Engagement in Mentally Challenging Activities Enhances Neural Efficiency," by Ian M. McDonough, Sara Haber, Gérard N. Bischof, and Denise C. Park. Restorative Neurology and Neuroscience, Volume 33, Issue 6 (2015), DOI: 10.3233/RNN-150533, published by IOS Press.

This article is openly available at http://ift.tt/1TZDpht. For additional information contact Daphne Watrin, IOS Press at +31 20 688 3355 or d.watrin@iospress.nl. Journalists wishing to interview the authors should contact Alex Lyda, Communications Manager, The University of Texas at Dallas, at 972-883-3783 or alyda@utdallas.edu.

ABOUT RESTORATIVE NEUROLOGY AND NEUROSCIENCE (RNN)

An interdisciplinary journal under the editorial leadership of Bernhard Sabel, PhD, Restorative Neurology and Neuroscience publishes papers relating the plasticity and response of the nervous system to accidental or experimental injuries and their interventions, transplantation, neurodegenerative disorders and experimental strategies to improve regeneration or functional recovery and rehabilitation. Experimental and clinical research papers adopting fresh conceptual approaches are encouraged. The overriding criteria for publication are novelty, significant experimental or clinical relevance and interest to a multidisciplinary audience.

RNN Editorial Office
Prof. Dr. Bernhard Sabel
Institut für Medizinische Psychologie
Medizinische Fakultät
Otto-v.-Guericke Universität Magdeburg
39120 Magdeburg/Germany
Tel: +49-391-672-1800
Fax: +49-391-672-1803
Email: rnn@med.ovgu.de

ABOUT IOS PRESS

Commencing its publishing activities in 1987, IOS Press serves the information needs of scientific and medical communities worldwide. IOS Press now (co-)publishes over 100 international journals and about 75 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.

IOS Press continues its rapid growth, embracing new technologies for the timely dissemination of information. All journals are available electronically and an e-book platform was launched in 2005.

Headquartered in Amsterdam with satellite offices in the USA, Germany, India and China, IOS Press has established several strategic co-publishing initiatives. Notable acquisitions included Delft University Press in 2005 and Millpress Science Publishers in 2008.

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Successful treatment for sorafenib-induced liver dysfunction: a report of case with liver biopsy

Abstract

Sorafenib is an oral multikinase inhibitor with anti-proliferative and anti-angiogenic effects and is used worldwide for the treatment of advanced or metastatic hepatocellular carcinoma (HCC). While the significant survival benefit of sorafenib in patients with advanced HCC was demonstrated, various treatment-related adverse events might happen. Of them, the incidence of drug-related severe liver dysfunction rarely occurs (<1 %) but is one of the serious adverse events by sorafenib. The authors highlight the case of a 71-year-old man with metastatic HCC with sorafenib-related fatal liver dysfunction (T-Bil 28.6 mg/dL, AST 1611 IU/L, ALT 1098 IU/L) 2 months later even without either intrahepatic viable HCC or hepatitis B virus (HBV) reactivation. Then, the liver dysfunction was improved following aggressive treatment using hyperbaric oxygen. A liver biopsy demonstrated cholestasis, degeneration, and necrosis in hepatocytes with lymphocyte infiltration. Thus, sorafenib rarely can induce liver dysfunction characterized by cholestatic and hepatocellular injury types, and it could be a fatal event. Clinicians should pay attention to any increase in the liver enzymes in these patients.

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A higher frequency of CD4+CXCR5+ T follicular helper cells in patients with newly diagnosed Henoch–Schönlein purpura nephritis

Publication date: March 2016
Source:International Immunopharmacology, Volume 32
Author(s): Zhihui Zhang, Songchen Zhao, Li Zhang, Rebecca Crew, Nan Zhang, Xiguang Sun, Yanfang Jiang
T follicular helper (TFH) cells play an important role in the humoral immune responses. The aim of this study was to examine the frequency of different subsets of CD4⁺CXCR5⁺ TFH cells and B cells in patients with new-onset Henoch–Schönlein purpura nephritis (HSPN). The numbers of different subsets of CD4⁺CXCR5⁺ TFH cells, B cells and the constituents of serum cytokines were detected in a total of 25 patients with newly diagnosed HSPN before and after treatment, and in 14 healthy controls (HC). The potential connection of these cells with the clinical characteristics in HSPN patients was analyzed. The numbers of circulating CD4⁺CXCR5⁺, CD4⁺CXCR5⁺ICOS⁺ and CD4⁺CXCR5⁺PD-1⁺ TFH cells, CD86⁺CD19⁺, CD38⁺CD19⁺ B cells and serum IL-2, IL-4, IL-17A, IL-21 and IFN-γ were significantly higher in HSPN patients (p<0.05) than in HC. Before and after treatment the numbers of CD4⁺CXCR5⁺ TFH cells were negatively correlated with the values of eGFR (r=−0.7162, p<0.05; r=−0.732, p<0.05, respectively). Similarly the numbers of CD4⁺CXCR5⁺PD-1⁺ TFH cells were negatively correlated with 24-h urinary proteins (r=−0.4013, p<0.05; r=−0.7857, p<0.05, respectively), and the numbers of CD4⁺CXCR5⁺ICOS⁺ TFH cells were positively correlated with the levels of serum IL-21 (r=0.5186, p<0.05; r=0.8503, p<0.05, respectively) and 24-h urinary protein (r=0.6045, p<0.05; r=0.833, p<0.05, respectively) in these patients, regardless of treatment. Following treatment the numbers of CD4⁺CXCR5⁺, CD4⁺CXCR5⁺PD-1⁺, and CD4⁺CXCR5⁺ICOS⁺ TFH cells, as well as serum levels of IL-21 were significantly reduced, however IL-4 levels were noticeably increased (p<0.05). A higher frequency of circulating CD4⁺CXCR5⁺ TFH cells existed in patients with HSPN and may be a viable therapeutic target.



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External syntax and the cumulative effect in subject sub-extraction: an experimental evaluation

In this paper, we test the Cumulative Effect proposed by Haegeman et al. (2014). In particular, we focus on the role of factors of external syntax in the modulation of subject opacity to extraction, addressing different constraints presented in Haegeman et al. (2104). Two sets of formal acceptability judgments are presented. In the first experiment, we address the opacity of subjects from a broad point of view, in order to assess whether subject DPs are more resistant to extraction than other DPs. The results confirm that subject constituents are more opaque to extraction than object constituents. In the second experiment, we address the impact on the modulation of the Cumulative Effect of three different constraints individually: the Freezing Principle, the Inactivity Condition and the Edge Condition. We did that through the manipulation of two different factors: the position of the extraction site and the predicate type. The results do not confirm the predictions made by the Cumulative Effect, since the interaction between different factors does not appear to be additive and incremental. We, then, discuss an alternative perspective, recently proposed by Bianchi and Chesi (2104), according to which the opacity of subjects is a function of the syntax semantics interface.

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De kwaliteit van gehechtheidsrelaties in kaart brengen: Vertaling van een onderzoekstraditie naar de klinische praktijk

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Tolken opleiden voor de gezondheidssector: een nieuw spoor

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Matthias van Rossum, Werkers van de wereld. Globalisering, arbeid en interculturele ontmoetingen tussen Aziatische en Europese zeelieden in dienst van de VOC, 1600-1800. (Hilversum:Verloren, 2014) 448 p., isbn 978-90-8704-419-0

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Modeling information diffusion in social media as provenance with W3C PROV

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Design of reservoir computing systems for noise-robust speech and handwriting recognition

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Interactive comparison of triple pattern fragments query approaches

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The association between childhood stress and body composition, and the role of stress-related lifestyle factors: cross-sectional findings from the baseline ChiBS survey

Stress has been hypothesised to be involved in obesity development, also in children. More research is needed into the role of lifestyle factors in this association. This study investigates the cross-sectional relationship between stress and body composition and, more importantly, the possible moderating or mediating role of lifestyle factors. A total of 355 Belgian children (5-10 years old) participating in the baseline 'Children's Body composition and Stress' survey were included in this study. The following variables were studied: psychosocial stress (i.e. stressful events, emotions and behavioural/emotional problems, salivary cortisol), stress-related lifestyle factors (high-caloric snack consumption frequency, screen exposure time and sleep duration) and body composition parameters [BMI z-score, waist to height ratio (WHtR)]. Using linear regression analyses (adjusted for sex, age and socio-economic status), the relation between stress and body composition and, more importantly, the possible moderating or mediating role of lifestyle factors was tested. No association was observed between body composition and negative emotions, conduct and emotional problems and salivary cortisol. However, negative life events were positively and happiness was negatively associated with BMI z-score and WHtR. Peer problems and WHtR were positively associated in girls only. These associations were not significantly reduced after correction for lifestyle factors. Nevertheless, all lifestyle parameters moderated one or more stress-body composition associations, resulting in even more significant relations after subgroup analysis. Childhood stress was positively related to both overall and central adiposity measures with lifestyle factors acting as moderators but not as mediators. Thus, lifestyle could be a vulnerability factor in stress-induced adiposity, creating a perspective for multi-factorial obesity prevention, targeting stress and lifestyle factors in parallel.

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Sleep time and cardiovascular risk factors in adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study

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Strain measurements in precast concrete segments of a shield-driven tunnel

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Return to Play After Hamstring Injuries: A Qualitative Systematic Review of Definitions and Criteria

Abstract

Background

More than half of the recurrent hamstring injuries occur within the first month after return-to-play (RTP). Although there are numerous studies on RTP, comparisons are hampered by the numerous definitions of RTP used. Moreover, there is no consensus on the criteria used to determine when a person can start playing again. These criteria need to be critically evaluated, in an attempt to reduce recurrence rates and optimize RTP.

Objective

To carry out a systematic review of the literature on (1) definitions of RTP used in hamstring research and (2) criteria for RTP after hamstring injuries.

Study Design

Systematic review.

Methods

Seven databases (PubMed, EMBASE/MEDLINE, CINAHL, PEDro, Cochrane, SPORTDiscus, Scopus) were searched for articles that provided a definition of, or criteria for, RTP after hamstring injury. There were no limitations on the methodological design or quality of articles. Content analysis was used to record and analyze definitions and criteria for RTP after hamstring injury.

Results

Twenty-five papers fulfilled inclusion criteria, of which 13 provided a definition of RTP and 23 described criteria to support the RTP decision. "Reaching the athlete's pre-injury level" and "being able to perform full sport activities" were the primary content categories used to define RTP. "Absence of pain", "similar strength", "similar flexibility", "medical staff clearance", and "functional performance" were core themes to describe criteria to support the RTP decision after hamstring injury.

Conclusion

Only half of the included studies provided some definition of RTP after hamstring injury, of which reaching the athlete's pre-injury level and being able to perform full sport activities were the most important. A wide variety of criteria are used to support the RTP decision, none of which have been validated. More research is needed to reach a consensus on the definition of RTP and to provide validated RTP criteria to facilitate hamstring injury management and reduce hamstring injury recurrence.

PROSPERO systematic review registration number: CRD42015016510.

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On the Inertia Effects on the Darcy Law: Numerical Implementation and Confrontation of Micromechanics-Based Approaches

Abstract

In this paper, we investigate the nonlinear deviation of the Darcy law in the domain of high pressure gradient. Classically, the (linear) Darcy law can be deduced from asymptotic homogenization approaches and the numerical resolution of the Stokes flow problem on the unit cell of the porous medium. At high-speed steady flow of a fluid, nonlinear effects on the macroscopic filtration law arise and are accounted by considering the convection term in the Navier–Stokes equation. These nonlinear effects has been often studied in asymptotic homogenization framework by expanding the solution in power series at low Reynolds number. This has two advantages: (i) The Navier–Stokes problems are replaced by a chain of linear problems with source terms which depend on the solution at lower order, and (ii) the macroscopic nonlinear filtration law is derived in the form of a polynom. We develop a Fast Fourier Transform (FFT)-based numerical algorithm to compute the solution of this elementary problems and to compute the higher-order permeability tensors in connection with the morphology of the porous medium. The results are then compared to the solution of the full Navier–Stokes problem by means of finite element method (FEM) which allows evaluating the capacity of the expansion method to account for the nonlinear effects. We determine the convergence radius of the polynomial series, and we give the limit of the series expansion method in terms of the Reynolds number.

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MiR-205 suppresses autophagy and enhances radiosensitivity of prostate cancer cells by targeting TP53INP1

OBJECTIVE: This study aimed to investigate the role of miR-205 in radiosensitivity and autophagy of prostate cancer cells and to explore its regulative effect on TP53INP1.

MATERIALS AND METHODS: MiR-205 expression was compared in three prostate cancer cell lines (DU145, PC-3 and LNCaP) and one normal human prostate epithelial cell line (RWPE-1). The effect of irradiation-induced autophagy on radiosensitivity of the cancer cells and the effect of miR-205 on irradiation-induced autophagy were explored. The regulative effect of miR-205 on TP53INP1 and the function of this axis was further studied.

RESULTS: Ectopic expression of miR-205 substantially reduced the survival fraction of both DU145 and LNCaP cells to irradiation and inhibited irradiation-induced autophagy. Irradiation-induced autophagy acted as a protective mechanism in prostate cancer cells. TP53INP1 is a direct functional target of miR-205 in irradiation-induced autophagy and radiosensitivity regulation.

CONCLUSIONS: The miR-205/TP53INP1 mediated autophagy pathway might be an important molecular mechanism regulating radiosensitivity of prostate cancer cells and represents a potential therapeutic target for prostate cancer.

L'articolo MiR-205 suppresses autophagy and enhances radiosensitivity of prostate cancer cells by targeting TP53INP1 sembra essere il primo su European Review.

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Clinical significance of sCIP2A levels in breast cancer

OBJECTIVE: It has previously found that human oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) was overexpressed in breast cancer, and was positively correlated with lymph node metastasis of the patients. This study aimed to investigate the association between serum CIP2A and prognosis of breast cancer. Then, we investigated whether CIP2A could be as a therapeutic target in breast cancer treatment.

PATIENTS AND METHODS: Preoperative CIP2A levels of 240 patients with breast cancer and 480 cases of controls were measured by ELISA method. The association of CIP2A levels with clinicopathological outcomes was investigated by univariate and multivariate analyses. The effect of CIP2A on breast cancer MDA-MB-231 cells was evaluated by CIP2A siRNA-mediated depletion of the CIP2A protein followed by an analysis of cell proliferation, invasion, colony growth, and xenograft growth and metastasis.

RESULTS: The serum CIP2A levels in patients with breast cancer were (79.0±74.2) ng/mL, which was significantly higher than that in those controls (25.6±21.4) ng/mL for male and (24.8±20.6) ng/mL for female control. Higher preoperative CIP2A levels were significantly associated with the American Joint Committee on Cancer (AJCC) stage, histological grade and lymph node metastasis. Patients with elevated CIP2A levels showed worse survival. In multivariate analysis, elevated preoperative CIP2A levels were independent prognostic factors. Patients with high CIP2A levels had significantly shorter overall survival (OS) and disease-free survival (DFS) times. Knockdown of CIP2A by stable CIP2A siRNA transfection inhibited MDA-MB-231 cell proliferation, invasion, colony growth in vitro, and xenograft growth and metastasis in vivo.

CONCLUSIONS: Our results suggest that serum CIP2A is significantly higher in patients with breast cancer, which is a potential biomarker to make a distinction between breast cancer patients and healthy controls. Higher serum CIP2A levels positively associated with the aggressive phenotype of breast cancer, and forecasts poor prognosis for patients with breast cancer. Knockdown of CIP2A may be a novel target for prevention and treatment of breast cancer.

L'articolo Clinical significance of sCIP2A levels in breast cancer sembra essere il primo su European Review.

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Correlation between intensity modulated radiotherapy and bone marrow suppression in breast cancer

OBJECTIVE: To study the correlation factors of bone marrow suppression in breast cancer radiotherapy and find out the method to guide the target area, dose limitation for breast cancer to reduce the risk of bone marrow suppression.

PATIENTS AND METHODS: 72 cases of breast cancer patients were collected through retrospective, clinical control study. For patients with Grade 0-3, bone marrow suppression in the course of radiotherapy, the dose-volume parameters (V5, V10, V20, V30, V50, D20, D40, D60, D80, D100, Min, Max, Dmean) of the chest and rib of each patient were collected and analyzed from multiple points including tumor stage, age, lesion location, surgical approach, chemotherapy regimen and the number of cycles, bone dose-volume parameters.

RESULTS: The relative parameters of the rib in the middle and severe bone marrow suppression group were significantly higher than those in the mild bone marrow depression group and the p values of V5, V10, V20, V30, Dmean, D40, D60, D80, D100 were less than 0.05. The difference of V50 in the two groups was statistically significant (p <0.05). For chemotherapy regimens containing doxorubicin, epirubicin, cyclophosphamide, the differences between bone marrow suppression group and non-bone marrow suppression were statistically significant (p =0.002).

CONCLUSIONS: The dose-volume parameters of the rib radiation is one of the main factors causing the suppression of bone marrow in radiotherapy, and the volume of the 50Gy irradiation is also a contribution to the bone marrow. For patients accepted chemotherapy with doxorubicin, epirubicin, cyclophosphamide before radiotherapy, bone marrow suppression is more likely to occur during radiotherapy. After radical mastectomy or the volume of thoracic rib is increased because of the small breast, the occurrence of bone marrow suppression is increased. The effects of radiation on the bone marrow suppression were small, while its effect on the ribs was more evident, especially on the ribs V20 and Dmean and the difference was statically significant.

L'articolo Correlation between intensity modulated radiotherapy and bone marrow suppression in breast cancer sembra essere il primo su European Review.

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SF3B1 and EIF1AX mutations occur in primary leptomeningeal melanocytic neoplasms; yet another similarity to uveal melanomas

Abstract

Introduction

Like uveal melanomas, primary leptomeningeal melanocytic neoplasms (LMNs) frequently carry GNAQ and GNA11 mutations. However, it is currently unknown whether these LMNs harbor mutations in BAP1, SF3B1 and/or EIF1AX like uveal melanomas as well. In this study, we used Sanger sequencing for the detection of mutations in SF3B1 (hotspots in exon 14 and 15) and EIF1AX (exon 1 and 2 and flanking intronic regions) in a series of 24 primary LMNs. Additionally, BAP1 immunohistochemistry was used as a surrogate marker for the detection of inactivating mutations in the BAP1 gene.

Results

Mutations in either SF3B1 or EIF1AX were identified in 8 out of 24 primary LMNs (33 %). The presence of these mutations was mutually exclusive and occurred in primary LMNs of different malignancy grades (melanocytomas, intermediate-grade melanocytic tumors, melanomas). Complete absence of nuclear BAP1 staining as is typically seen in BAP1-mutated tumors was not observed.

Conclusions

Our finding that an SF3B1 or EIF1AX mutation is present in a substantial subset of primary LMNs underscores that these tumors genetically resemble uveal melanoma and are different from cutaneous melanoma at the genetic level. This information may not only aid in the differential diagnosis of primary versus metastatic melanocytic tumor in/around the central nervous system, but also in the identification of more promising therapeutic approaches targeting the molecular pathways involved in the oncogenesis of LMNs. As none of the primary LMNs in our series showed complete loss of nuclear BAP1 protein, it is unlikely that BAP1 mutations are frequent in these tumors but the role of this gene warrants further investigation.

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Bilateral hypertrophy of masseteric and temporalis muscles, our fifteen patients and review of literature

OBJECTIVE: The association of bilateral hypertrophy of temporalis and masseteric muscles is a rare clinical entity. The origin of the condition is unclear, causing cosmetic problems, pain, and functional impairment.

PATIENTS AND METHODS: In this paper we analyzed 15 patients treated at the Department of Maxillo-Facial Surgery of the University of Naples Federico II, from 2000 to 2013, for temporalis and/or masseteric muscle hypertrophy, and in particular, a rare case of a patient with a marked bilateral swelling of the temporalis and masseteric region, in conjunction with a review of the literature.

RESULTS: Fourteen patients have not any kind of postoperatively problems. The last patient had been aware of the swelling for many years and complained of recurrent headaches. We adopted a new protocol fort this patients and the patient was very pleased with the treatment results, and reported a reduction in headaches and a continuation of his well-being, in addition to greater self-confidence. The last follow-up was performed three years after the first treatment, and the patient showed a complete resolution of his symptoms, and just a small increase of the swelling.

CONCLUSIONS: The treatment of temporalis and masseteric hypertrophy with Botulin toxin could be an effective option compared to conservative treatment or surgical intervention, although the review of the literature shows that this is only a temporary treatment. In fact, surgery still remains the best option.
The treatment must be repeated every 4/6 months for 2-3 consecutive years before having stable benefits. To overcome this problem, an association with a bite treatment allowed us to achieve more lasting and more stable results over time without a recurrence of symptoms between the treatments. Furthermore, this association has enabled us to obtain a more rapid reduction of the hypertrophy.

L'articolo Bilateral hypertrophy of masseteric and temporalis muscles, our fifteen patients and review of literature sembra essere il primo su European Review.

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Iron labeled adipose stem cells and neovascularization in rabbit calvarial critical-sized defects.

Publication date: Available online 14 January 2016
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Olli-Pekka Lappalainen, Marianne Haapea, Raisa Serpi, Siri Lehtonen, Leena Ylikontiola, Jarkko Korpi, Willy Serlo, George K.B. Sándor
ObjectiveThe aim of this study was to evaluate the presence of iron labelled adipose stem cells at the 2 week time point and vascular changes at the 2 and 6 week time points using two different types of scaffolds.Study designThis study included 22 White New Zealand adult male rabbits. In 6 rabbits full-thickness calvarial critical-sized defects were filled with autogenous adipose stem cells labelled with iron oxide seeded onto two scaffolds, namely solid bioactive glass (BAG) or porous tricalcium phosphate granules (TCP) used on reciprocal sides of the skull. Eleven rabbits were implanted with adipose stem cell seeded scaffolds without iron labeling for analysis of vascular changes. Five defects were left empty as negative control defects. The specimens were analyzed histologically at the 2 and 6 week time points.ResultsThe TCP group showed significantly more vascularity compared to BAG group. A greater number of labelled stem cells were identified in the TCP group compared to the BAG group, but the difference was not statistically significant.ConclusionsThis study reveals differences in stem cell distribution and revascularization of the calvarial defect which may be biomaterial dependent.



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Issue Information

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Outcomes after viral load rebound on fi rst-line antiretroviraltreatment in children with HIV in the UK and Ireland:an observational cohort study.

Childs, T; Shingadia, D; Goodall, R; Doerholt, K; Lyall, H; Duong, T; Judd, A; Childs, T; Shingadia, D; Goodall, R; Doerholt, K; Lyall, H; Duong, T; Judd, A; Gibb, DM; Collins, IJ; - view fewer (2015) Outcomes after viral load rebound on fi rst-line antiretroviraltreatment in children with HIV in the UK and Ireland:an observational cohort study. Lancet HIV , 2 (4) e151-e158. 10.1016/S2352-3018(15)00021-1 . Green open access

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Solidification of nanosuspensions for the production of solid oral dosage forms and inhalable dry powders

Malamatari, M; Somavarapu, S; Taylor, KMG; Buckton, G; (2016) Solidification of nanosuspensions for the production of solid oral dosage forms and inhalable dry powders. Expert Opinion on Drug Delivery 10.1517/17425247.2016.1142524. .

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Translation studies and metaphor studies: Possible paths of interaction between two well-established disciplines

Shuttleworth, M; (2014) Translation studies and metaphor studies: Possible paths of interaction between two well-established disciplines. In: Miller, DR and Monti, E, (eds.) Tradurre Figure / Translating Figurative Language. (pp. 53-65). Centro di Studi Linguistico-Culturali (CeSLiC): Bologna, Italy. Green open access

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Development of Prognosis in Palliative care Study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study.

Gwilliam, B; Keeley, V; Todd, C; Gittins, M; Roberts, C; Kelly, L; Barclay, S; Gwilliam, B; Keeley, V; Todd, C; Gittins, M; Roberts, C; Kelly, L; Barclay, S; Stone, PC; - view fewer (2015) Development of Prognosis in Palliative care Study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study. BMJ Supportive & Palliative Care , 5 (4) pp. 390-398. 10.1136/bmjspcare-2012-d4020rep . Green open access

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Home Making: The Power of Ordinary Politics

Pilkey, BS; (2015) Home Making: The Power of Ordinary Politics. Harvard Design Magazine , 41 (Fall) pp. 64-65.

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Phonological Working Memory Limitations and Agrammatism: Is There a Causal Relationship between the Two?

Varkanitsa, M; Kasselimis, D; Potagas, C; van de Koot, H; (2014) Phonological Working Memory Limitations and Agrammatism: Is There a Causal Relationship between the Two? In: Frontiers in Psychology Conference Abstracts: Academy of Aphasia - 52nd Annual Meeting. Frontiers Research Foundation: Miami, FL, USA. Green open access

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Structure and electronic properties of porous manganese oxides.

Arnold, D.C.; (2004) Structure and electronic properties of porous manganese oxides. Doctoral thesis, University of London. Green open access

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Optical Interconnects: Test and Measurement

Selviah, DR; Baghsiahi, H; Wang, K; Tao, R; (2014) Optical Interconnects: Test and Measurement. Presented at: EPIC Symposium on Optical Interconnect in Data Centers, Berlin, Germany.

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Tools to Assess Pain or Lack of Comfort in Dementia: A Content Analysis

Van Der Steen, JT; Sampson, EL; Van Den Block, L; Lord, K; Vankova, H; Pautex, S; Vandervoort, A; Van Der Steen, JT; Sampson, EL; Van Den Block, L; Lord, K; Vankova, H; Pautex, S; Vandervoort, A; Radbruch, L; Shvartzman, P; Sacchi, V; De Vet, HCW; Van Den Noortgate, NJA; - view fewer (2015) Tools to Assess Pain or Lack of Comfort in Dementia: A Content Analysis. Journal of Pain and Symptom Management , 50 (5) pp. 659-675. 10.1016/j.jpainsymman.2015.05.015 .

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The value of molecular stratification for CEBPA_DM and NPM1_MUT_FLT3_WT genotypes in older patients with acute myeloid leukaemia

Dickson, GJ; Bustraan, S; Hills, RK; Ali, A; Goldstone, AH; Burnett, AK; Linch, DC; Dickson, GJ; Bustraan, S; Hills, RK; Ali, A; Goldstone, AH; Burnett, AK; Linch, DC; Gale, RE; - view fewer (2015) The value of molecular stratification for CEBPA_DM and NPM1_MUT_FLT3_WT genotypes in older patients with acute myeloid leukaemia. British Journal of Haematology 10.1111/bjh.13873 . Green open access

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Time resolved excited state photo-engineering.

Armoogum, D.A.; (2004) Time resolved excited state photo-engineering. Doctoral thesis, University of London. Green open access

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Error Metric for Indoor 3D Point Cloud Registration

Lachhani, K; Duan, J; Baghsiahi, H; Willman, E; Selviah, DR; (2014) Error Metric for Indoor 3D Point Cloud Registration. In: Coleman, S and Gardiner, B and Kerr, D, (eds.) Proceedings: IMVIP 2014: 2014 Irish Machine Vision and Image Processing. (pp. pp. 34-42). IPRCS Irish Pattern Recognition and Classification Society: Derry-Londonderry, UK. Green open access

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The encrypted object: The secret world of sixties sculpture.

Applin, J.L.; (2004) The encrypted object: The secret world of sixties sculpture. Doctoral thesis, University of London. Green open access

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MIMO fuzzy control for autonomous mobile robot

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Extending the possibilities of biopartitioning chromatography for improved prediction of in vivo drug absorption

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Consequences of tibial tunnel geometry in anatomical single bundle ACL surgery

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Insights resulting from quantitative bioanalysis in studies of drugs and driving

In this study we examined the value of quantitative bioanalysis of drugs in studies on drugs and driving. Based on the fact that the use of psychoactive substances should not be combined with driving, one could argue that, especially for routine testing for driving under influence of drugs, reporting quantitative results is not necessary and that it is sufficient to determine the presence or absence of a drug (class) to study the prevalence of drugged driving or to estimate the crash risk. The example of alcohol, where crash risk is increasing exponentially with increasing blood alcohol concentrations (hence using a low cut-off for the presence of alcohol underestimates crash risk) suggests that using quantitative drug concentrations in bio-fluids might have added value. In the Belgian DUID-legislation both oral fluid and blood samples are taken and analysed with similar cut-offs. An objective of this thesis was to investigate the effect of using these similar cut-offs in paired samples of oral fluid and blood in a population of general drivers. For this purpose a dataset of almost 3000 paired samples was investigated. Quantitative analysis showed that 2.6 times more drivers confirmed positive in oral fluid compared to blood. Although the Belgian traffic law amendment (introducing both oral fluid screening and confirmation) went into force on October 1st, 2010, confirmation is still performed on blood samples but with lower cut-offs than before. To assess the influence of this change in enforcement procedure on the number of false positive screenings, two datasets of approximately 4000 positive screening cases each were compared. Quantitative analysis disclosed that fewer false positive screenings were observed since the implementation of the new legislation and that more recent drug use was targeted. The total number of positive screenings has dropped with the new legislation, but this is solely due to a lower number of positive screenings for cannabis, which can be explained by the much longer detection window of THCCOOH in urine (previous legislation) than THC in oral fluid (current legislation). Most risk estimations are calculated based on nominal categorisation (positive or negative) of the cases and controls. The concentration found in the biological matrices can also be of interest. We compared the distribution of plasma concentrations of several psychoactive substances between the general driving population (n= 2750) and seriously injured drivers (n= 377). Quantitative analysis illustrated that higher amphetamine and benzoylecgonine concentrations were found in injured drivers. In addition, a trend towards higher concentrations of benzodiazepines and Z-drugs was also observed. Accident risks should therefore also be assessed in relation to substance concentrations not only the presence or absence of a drug in a biological sample. Self-reporting is the most widely used method to measure prevalence of use of psychoactive substances. In the Belgian roadside study both questionnaire data and results of bioanalysis were collected. An objective of this thesis was to investigate the consistency between self-report and results of bioanalysis. Data on 2949 respondents providing questionnaire data and the results of bioanalysis of blood and/or oral fluid samples were investigated. Quantitative analysis revealed that the self-reported data underestimated the use of cannabis and that this underestimation was most obvious for recent use. Besides the fact that the DUID legislation requires quantitative bioanalysis of drug concentrations, quantitative bioanalysis is also of significant importance in epidemiological research on drug use and in research on accident risks associated with psychoactive substances.

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Separation of transglutaminase by thermo-responsive affinity precipitation using l-thyroxin as ligand

Transglutaminase (TGase) is widely used in the food industry. In this study, TGase was purified by affinity precipitation using l-thyroxin, coupled to a thermo-responsive polymer (P NBN ), as an affinity ligand. The lower critical solution temperature and recovery of the affinity polymer were 31.0 °C and 99.6 %, respectively. The optimal adsorption condition was 0.02 mol/L phosphate buffer (pH 5.0). The recoveries 99.01 % (protein) and 98.85 % (activity) were obtained by 0.2 mol/L Gly–NaOH buffer (pH 10.0) as the elution agent. Circular dichroism spectroscopy and FortéBio Octet system were used to explore the interactions between l-thyroxin and TGase. The results show that l-thyroxin is suitable for affinity precipitation of TGase. The purity of the final product was verified using sodium dodecyl sulfate polyacrylamide gel electrophoresis.

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