In vitro effects of cocaine on tunneling nanotube formation and extracellular vesicle release in glioblastoma cell cultures

The effects of cocaine (150 nM, 300 nM, and 150 μM) on human glioblastoma cell cultures were studied on tunneling nanotube formation (1-h cocaine treatment) and extracellular vesicle release (1-, 3-, and 8-h cocaine treatment). Cocaine significantly increased the number of tunneling nanotubes only at the lowest concentration used. The release of extracellular vesicles (mainly exosomes) into the medium was stimulated by cocaine at each concentration used with a maximum effect at the highest concentration tested (150 μM). Moreover, cocaine (150 nM) significantly increased the number of vesicles with 61-80 nm diameter while at concentrations of 300 nM and 150 μM, and the smaller vesicles (30-40 nm diameter) were significantly increased with a reduction of the larger vesicles (41-60 nm diameter). A time dependence in the release of extracellular vesicles was observed. In view of the proposed role of these novel intercellular communication modes in the glial-neuronal plasticity, it seems possible that they can participate in the processes leading to cocaine addiction. The molecular target/s involved in these cocaine effects could be specific molecular components of plasma membrane lipid rafts and/or cocaine-induced modifications in cytoplasmic lipid composition

Neural damage biomarkers during open carotid surgery versus endovascular approach

BACKGROUND: Carotid endarterectomy (CEA) is the gold standard for treating severe carotid artery stenosis, whereas carotid artery stenting (CAS) represents an endovascular alternative. The objective of this study was to assess the potential neural damage following open or endovascular carotid surgery measured by peripheral blood concentration of 3 biomarkers: S100β, matrix metalloproteinase-9 (MMP-9), and d-dimer. METHODS: Data for this prospective investigation were obtained from the Carotid Markers study (January 2010-2011), which sought to measure the levels of specific biomarkers of neuronal damage and thrombosis on candidates to CEA or CAS presenting at the Department of Vascular Surgery of the Nuovo Ospedale S. Agostino Estense of Modena (Italy) at baseline and at 24 hr after surgery. Relevant medical comorbidities were noted. RESULTS: A total of 113 consecutive patients were enrolled in the study, 41 in the endarterectomy group and 72 in the endovascular group. The baseline levels of the studied biomarkers did not show any statistically significant difference between the groups with the exception of MMP-9, which showed higher concentrations in the endovascular group (median 731 vs. 401, P = 0.0007), while 24 hr after surgery the endarterectomy group featured significantly higher peripheral blood concentrations of MMP-9, S100β, and d-dimer. Conversely, no significant difference was detected in the endovascular group except the d-dimer level. CONCLUSIONS: Neural damage biomarkers demonstrated a substantial difference between open and endovascular carotid surgery, which, if performed in selected patients, may become a less invasive alternative to CEA

Therapist reactions to patient personality: A pilot study of clinicians’ emotional and neural responses using three clinical vignettes from "In Treatment" series

Introduction: Therapists’ responses to patients play a crucial role in psychotherapy and are considered a key component of the patient–clinician relationship, which promotes successful treatment outcomes. To date, no empirical research has ever investigated therapist response patterns to patients with different personality disorders from a neuroscience perspective. Methods: In the present study, psychodynamic therapists (N = 14) were asked to complete a battery of instruments (including the Therapist Response Questionnaire) after watching three videos showing clinical interactions between a therapist and three patients with narcissistic, histrionic/borderline, and depressive personality disorders, respectively. Subsequently, participants’ high-density electroencephalography (hdEEG) was recorded as they passively viewed pictures of the patients’ faces, which were selected from the still images of the previously shown videos. Supervised machine learning (ML) was used to evaluate whether: (1) therapists’ responses predicted which patient they observed during the EEG task and whether specific clinician reactions were involved in distinguishing between patients with different personality disorders (using pairwise comparisons); and (2) therapists’ event-related potentials (ERPs) predicted which patient they observed during the laboratory experiment and whether distinct ERP components allowed this forecast. Results: The results indicated that therapists showed distinct patterns of criticized/devalued and sexualized reactions to visual depictions of patients with different personality disorders, at statistically systematic and clinically meaningful levels. Moreover, therapists’ late positive potentials (LPPs) in the hippocampus were able to determine which patient they observed during the EEG task, with high accuracy. Discussion: These results, albeit preliminary, shed light on the role played by therapists’ memory processes in psychotherapy. Clinical and neuroscience implications of the empirical investigation of therapist responses are discussed

Constraining holographic technicolor

We obtain a new bound on the value of Peskin-Takeuchi S parameter in a wide class of bottom-up holographic models for technicolor. Namely, we show that weakly coupled holographic description in these models implies S>>0.2. Our bound is in conflict with the results of electroweak precision measurements, so it strongly disfavors the models we consider.Comment: 8 pages; journal versio

The intergenerational transmission of attachment during middle childhood in lesbian, gay, and heterosexual parent families through assisted reproduction: The mediating role of reflective functioning

the present study examined the attachment patterns distribution of 60 lesbian mothers, 50 gay fathers, and 42 heterosexual parents through assisted reproduction and their 76 children, using the Adult Attachment Interview (AAI) and the Friends and Family Interview (FFI), respectively. the study also explored the intergenerational transmission of attachment through reflective functioning (AAI-RF). all families lived in italy and children were aged 6-12 years (Myears = 8.11, SD = 2.17; 48.68% assigned female at birth). the AAI patterns distribution was similar across family types and did not significantly differ from international and national normative data. similarly, children's FFI attachment patterns were evenly distributed between family types, and no significant differences emerged in comparison to international and national normative data referring to middle childhood samples. mediational models revealed that, in all three family types, parents with greater AAI coherence of mind exhibited higher AAI-RF, which, in turn, was associated with increased FFI attachment security in children. Furthermore, parents' AAI coherence of mind directly influenced children's FFI attachment security. the results support and expand hypotheses regarding the intergenerational transmission of attachment in lesbian, gay, and heterosexual parent families through assisted reproduction, while offering unique indications to support these families during middle childhood

Reference pricing with endogenous generic entry

In this paper we study the effect of reference pricing on pharmaceutical prices and ex-penditures when generic entry is endogenously determined. We develop a Salop-type model where a brand-name producer competes with generic producers in terms of prices. In the market there are two types of consumers: (i) brand biased consumers who choose between brand-name and generic drugs, and (ii) brand neutral consumers who choose between the different generic drugs. We find that, for a given number of firms, reference pricing leads to lower prices of all products and higher brand-name market shares compared with a reimbursement scheme based on simple coinsurance. Thus, in a free entry equilibrium, the number of generics is lower under reference pricing than under coinsurance, implying that the net effects of reference pricing on prices and expenditures are ambiguous. Allowing for price cap regulation, we show that the negative effect on generic entry can be reversed, and that reference pricing is more likely to result in cost savings than under free pricing. Our results shed light on the mixed empirical evidence on the effects of reference pricing on generic entry.COMPETEQRENFEDER,Fundação para a Ciência e a Tecnologia (FCT

Flavor Dependence of the S-parameter

We extend the results of [arXiv:1006.0207 [hep-lat]] by computing the S-parameter at two loops in the perturbative region of the conformal window. Consistently using the expression for the location of the infra-red fixed point at the two-loop order we express the S-parameter in terms of the number of flavors, colors and matter representation. We show that S, normalized to the number of flavors, increases as we decrease the number of flavors. Our findings support the conjecture presented in [arXiv:1006.0207 [hep-lat]] according to which the normalized value of the S-parameter at the upper end of the conformal window constitutes the lower bound across the entire phase diagram for the given underlying asymptotically free gauge theory. We also show that the non-trivial dependence on the number of flavors merges naturally with the non-perturbative estimate of the S-parameter close to the lower end of the conformal window obtained using gauge duality [arXiv:1007.0254 [hep-ph]]. Our results are natural benchmarks for lattice computations of the S-parameter for vector-like gauge theories.Comment: Version to match the one published in Phys. Lett. B. The file is prepared in the 2-columns RevTeX format has 9 pages, 4 figures and one tabl

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

Tollip Is a Mediator of Protein Sumoylation

Tollip is an interactor of the interleukin-1 receptor involved in its activation. The endosomal turnover of ubiquitylated IL-1RI is also controlled by Tollip. Furthermore, together with Tom1, Tollip has a general role in endosomal protein traffic. This work shows that Tollip is involved in the sumoylation process. Using the yeast two-hybrid technique, we have isolated new Tollip partners including two sumoylation enzymes, SUMO-1 and the transcriptional repressor Daxx. The interactions were confirmed by GST-pull down experiments and immunoprecipitation of the co-expressed recombinants. More specifically, we show that the TIR domain of the cytoplasmic region of IL-1RI is a sumoylation target of Tollip. The sumoylated and unsumoylated RanGAP-1 protein also interacts with Tollip, suggesting a possible role in RanGAP-1 modification and nuclear-cytoplasmic protein translocation. In fact, Tollip is found in the nuclear bodies of SAOS-2/IL-1RI cells where it colocalizes with SUMO-1 and the Daxx repressor. We conclude that Tollip is involved in the control of both nuclear and cytoplasmic protein traffic, through two different and often contrasting processes: ubiquitylation and sumoylation