Unravelling the influence of affective stimulation on functional neurological symptoms: A pilot experiment examining potential mechanisms

Background: Differences in affective processing have previously been shown in functional neurological disorder (FND); however, the mechanistic relevance is uncertain. We tested the hypotheses that highly arousing affective stimulation would result in elevated subjective functional neurological symptoms (FNS), and this would be associated with elevated autonomic reactivity. The possible influence of cognitive detachment was also explored. Method: Individuals diagnosed with FND (motor symptoms/seizures; n=14) and healthy controls (n=14) viewed Positive, Negative and Neutral images in blocks, while passively observing the stimuli ( € Watch') or detaching themselves ( € Distance'). The FND group rated their primary FNS, and all participants rated subjective physical (arousal, pain, fatigue) and psychological states (positive/negative affect, dissociation), immediately after each block. Skin conductance (SC) and heart rate (HR) were monitored continuously. Results: FNS ratings were higher after Negative compared with Positive and Neutral blocks in the FND group (p=0.002, •p2=0.386); however, this effect was diminished in the Distance condition relative to the Watch condition (p=0.018, •p2=0.267). SC and/or HR correlated with FNS ratings in the Negative-Watch and Neutral-Distance conditions (r values=0.527-0.672, p values=0.006-0.035). The groups did not differ in subjective affect or perceived arousal (p values=0.541-0.919, •p2=<0.001-0.015). Conclusions: Emotionally significant events may exert an influence on FNS which is related to autonomic activation rather than altered subjective affect or perceived arousal. This influence may be modulated by cognitive detachment. Further work is needed to determine the relevance and neural bases of these processes in specific FND phenotypes

Anti-Helicobacter pylori activity and immunostimulatory effect of extracts from Byrsonima crassa Nied. (Malpighiaceae)

<p>Abstract</p> <p>Background</p> <p>Several <it>in vitro </it>studies have looked at the effect of medicinal plant extracts against <it>Helicobacter pylori </it>(<it>H. pylori</it>). Regardless of the popular use of <it>Byrsonima crassa </it>(<it>B. crassa</it>) as antiemetic, diuretic, febrifuge, to treat diarrhea, gastritis and ulcers, there is no data on its effects against <it>H. pylori</it>. In this study, we evaluated the anti-<it>H. pylori </it>of <it>B. crassa </it>leaves extracts and its effects on reactive oxygen/nitrogen intermediates induction by murine peritoneal macrophages.</p> <p>Methods</p> <p>The minimal inhibitory concentration (MIC) was determined by broth microdilution method and the production of hydrogen peroxide (H₂O₂) and nitric oxide (NO) by the horseradish peroxidase-dependent oxidation of phenol red and Griess reaction, respectively.</p> <p>Results</p> <p>The methanolic (MeOH) and chloroformic (CHCl₃) extracts inhibit, <it>in vitro</it>, the growth of <it>H. pylori </it>with MIC value of 1024 μg/ml. The MeOH extract induced the production H₂O₂and NO, but CHCl₃extract only NO.</p> <p>Conclusion</p> <p>Based in our results, <it>B. crassa </it>can be considered a source of compounds with anti-<it>H. pylori </it>activity, but its use should be done with caution in treatment of the gastritis and peptic ulcers, since the reactive oxygen/nitrogen intermediates are involved in the pathogenesis of gastric mucosal injury induced by ulcerogenic agents and <it>H. pylori </it>infections.</p

Potential prognostic value of heat-shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Introduction Evaluating the expression of signaling molecule proteins from the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol-3-kinase (PI3K) pathway in invasive breast cancers may identify prognostic marker(s) associated with early relapse. Methods Immunohistochemical analyses of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), PI3K-p110α, phospho-AKT, phospho-p70S6 kinase, phospho-S6 ribosomal protein, phospho-RAF, phospho-p44/42 MAPK, and heat-shock protein 90 (HSP90) were performed on tumor samples from 212 patients with invasive breast cancer. Statistically significant relations between protein expression, clinicopathologic factors, and relapse-free survival (RFS) were analyzed. Results Expression of HSP90 was associated with 5-year RFS, as well as T stage, N stage, histologic grade, estrogen receptor (ER) expression, human epidermal growth factor receptor 2 (HER2) expression, and the Ki-67 proliferation index. On multivariate analysis, coexpression of HSP90 and PI3K-p110α or expression of HSP90 along with PTEN loss demonstrated significantly worse RFS. In subgroup analyses, both exhibited strong prognostic significance in HER2-positive cases, but not in HER2-negative cases. Conclusions The coexpression of HSP90 with PI3K-p110α or expression of HSP90 along with PTEN loss has a potential as a molecular prognostic marker to predict early relapse in patients with invasive breast cancers

Outlook for inverse design in nanophotonics

Recent advancements in computational inverse design have begun to reshape the landscape of structures and techniques available to nanophotonics. Here, we outline a cross section of key developments at the intersection of these two fields: moving from a recap of foundational results to motivation of emerging applications in nonlinear, topological, near-field and on-chip optics.Comment: 13 pages, 6 figure

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

Challenges and opportunities for integrating lake ecosystem modelling approaches

A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others (‘reinventing the wheel’). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available (‘having tunnel vision’). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and trait-based models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its ‘leading principle’, there are many opportunities for combining approaches. We take the point of view that a single ‘right’ approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative view on the functioning of lake ecosystems. We end with a set of specific recommendations that may be of help in the further development of lake ecosystem model

Outcome Measures for Functional Neurological Disorder: A Review of the Theoretical Complexities.

The development and selection of optimal outcome measures is increasingly recognized as a key component of evidence-based medicine, particularly the need for the development of a standardized set of measures for use in clinical trials. This process is particularly complex for functional neurological disorder (FND) for several reasons. FND can present with a wide range of symptoms that resemble the full spectrum of other neurological disorders. Additional physical (e.g., pain, fatigue) and psychological (e.g., depression, anxiety) symptoms are commonly associated with FND, which also can be highly disabling with implications for prognosis, and warrant concurrent assessment, despite an unclear etiological relationship with FND. Furthermore, several unique clinical aspects of FND make it likely that the usual prioritization of "objective" (or clinician-rated) over "subjective" (or patient-rated) measures might not be appropriate. Self-report measures may be more clinically meaningful in this patient population. Despite being a common and disabling disorder, there has been little research into outcome measures in FND, and to date trials have largely used measures designed for the assessment of other disorders. An international FND Core Outcome Measure group (FND-COM) has been established to develop a consensus battery of outcomes for FND: a "core outcome set." In this perspective article, the authors reviewed the process of outcome measure development and selection before considering the specific features of FND affecting the development of a core outcome set, as well as a research agenda to optimize outcome measurement in this complex neuropsychiatric disorder