Factors of influence upon overall survival in the treatment of intracranial MPNSTs. Review of the literature and report of a case

BACKGROUND: Intracranial malignant peripheral nerve sheath tumors are rare entities that carry a poor prognosis. To date, there are no established therapeutic strategies for these tumors. METHODS: We review the present treatment modalities and present the current therapeutic dilemmas. We perform a statistical analysis to evaluate the prognostic factors for Overall Survival of these patients. Additionally, we present our experience with a 64-year-old man with a MPNST of the left cerebellopontine angle. RESULTS: To our best knowledge, forty three patients with intracranial MPNSTs, including our case, have been published in the international literature. Our analysis showed gross total resection, radiotherapy and female gender to be beneficial prognostic factors of survival in the univariate analysis. Gross total resection was recognized as the only independent predictor of prolonged Overall Survival. In our case, we performed a gross total resection followed for the first time by stereotactically guided radiotherapy. CONCLUSION: Considering the results of the statistical analysis and the known advantages of the stereotaxy, we suggest aggressive surgery followed by stereotactically guided radiotherapy as therapy of choice

Mentale Gehalte und erweiterter Geist: Warum das Argument der Nichtabgeleitetheit scheitert

Hundertmark F. Mentale Gehalte und erweiterter Geist: Warum das Argument der Nichtabgeleitetheit scheitert. In: Michel JG, Boström KJ, Pohl M, eds. Ist der Geist im Kopf?: Beiträge zur These des erweiterten Geistes. Münster: mentis; 2016: 133-160.Der These des erweiterten Geistes zufolge befinden sich manche mentalen Repräsentationen außerhalb der körperlichen Grenzen der Wesen, zu denen sie gehören. Einer der stärksten Einwände gegen diese These stellt das Argument der Nichtabgeleitetheit von Frederick Adams, Ken Aizawa und Jerry Fodor dar. Dieses Argument setzt voraus, dass genuine mentale Repräsentationen nichtabgeleitete Gehalte haben – ihre semantischen Eigenschaften sind also nicht durch Absichten, Wünsche oder Konventionen konstituiert. Repräsentationen mit nichtabgeleitetem Gehalt finden sich jedoch, so das Argument weiter, nur innerhalb der körperlichen Grenzen mentaler Wesen. Ich werde dafür argumentieren, dass das Argument der Nichtabgeleitetheit scheitert, da es insbesondere bei Tieren externe Repräsentationen gibt, deren Gehalt nichtabgeleitet ist. Dies folgt jedenfalls aus der aussichtsreichsten Theorie nichtabgeleiteter Repräsentationen, der Teleosemantik, und es gibt gute Gründe anzunehmen, dass auch andere naturalistische Gehaltstheorien dieselbe Implikation haben

Open Access

Haptoglobin phenotype prevalence and cytokine profiles during Plasmodium falciparum infection in Dogon and Fulani ethnic groups living in Mal

Recollection in the human hippocampal-entorhinal cell circuitry

The hippocampus is involved both in episodic memory recall and scene processing. Here, the authors show that hippocampal neurons first process scene cues before coordinating memory-guided pattern completion in adjacent entorhinal cortex

The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes

OBJECTIVE-Our previous studies suggest that the SNARE protein synaptosomal-associated protein of 23 kDa (SNAP23) is involved in the link between increased lipid levels and insulin resistance in cardiomyocytes. The objective was to determine whether SNAP23 may also be involved in the known association between lipid accumulation in skeletal muscle and insulin resistance/type 2 diabetes in humans, as well as to identify a potential regulator of SNAP23. RESEARCH DESIGN AND METHODS-We analyzed skeletal muscle biopsies from patients with type 2 diabetes and healthy, insulin-sensitive control subjects for expression (mRNA and protein) and intracellular localization (subcellular fractionation and immunohistochemistry) of SNAP23, and for expression of proteins known to interact with SNARE proteins. Insulin resistance was determined by a euglycemic hyperinsulinemic clamp Potential mechanisms for regulation of SNAP23 were also investigated in the skeletal muscle cell line L6. RESULTS-We showed increased SNAP23 levels in skeletal muscle from patients with type 2 diabetes compared with that from lean control subjects Moreover, SNAP23 was redistributed from the plasma membrane to the microsomal/cytosolic compartment in the patients with the type 2 diabetes Expression of the SNARE-interacting protein Munc18c was higher in skeletal muscle from patients with type 2 diabetes Studies in L6 cells showed that Munc18c promoted the expression of SNAP23. CONCLUSIONS-We have translated our previous in vitro results into humans by showing that there is a change in the distribution of SNAP23 to the interior of the cell in skeletal muscle from patients with type 2 diabetes. We also showed that Munc18c is a potential regulator of SNAP23. Diabetes 59: 1870-1878, 201

Electric current circuits in astrophysics

Cosmic magnetic structures have in common that they are anchored in a dynamo, that an external driver converts kinetic energy into internal magnetic energy, that this magnetic energy is transported as Poynting fl ux across the magnetically dominated structure, and that the magnetic energy is released in the form of particle acceleration, heating, bulk motion, MHD waves, and radiation. The investigation of the electric current system is particularly illuminating as to the course of events and the physics involved. We demonstrate this for the radio pulsar wind, the solar flare, and terrestrial magnetic storms

Conditions for transformative learning for sustainable development: a theoretical review and approach

Continued unsustainability and surpassed planetary boundaries require not only scientific and technological advances, but deep and enduring social and cultural changes. The purpose of this article is to contribute a theoretical approach to understand conditions and constraints for societal change towards sustainable development. In order to break with unsustainable norms, habits, practices, and structures, there is a need for learning for transformation, not only adaption. Based on a critical literature review within the field of learning for sustainable development, our approach is a development of the concept of transformative learning, by integrating three additional dimensions—Institutional Structures, Social Practices, and Conflict Perspectives. This approach acknowledges conflicts on macro, meso, and micro levels, as well as structural and cultural constraints. It contends that transformative learning is processual, interactional, long-term, and cumbersome. It takes place within existing institutions and social practices, while also transcending them. The article adopts an interdisciplinary social science perspective that acknowledges the importance of transformative learning in order for communities, organizations, and individuals to be able to deal with global sustainability problems, acknowledging the societal and personal conflicts involved in such transformation

Prognostic Role of Survivin and Macrophage Infiltration Quantified on Protein and mRNA Level in Molecular Subtypes Determined by RT-qPCR of KRT5, KRT20, and ERBB2 in Muscle-Invasive Bladder Cancer Treated by Adjuvant Chemotherapy

Objectives: Bladder cancer is a heterogeneous malignancy. Therefore, it is difficult to find single predictive markers. Moreover, most studies focus on either the immunohistochemical or molecular assessment of tumor tissues by next-generation sequencing (NGS) or PCR, while a combination of immunohistochemistry (IHC) and PCR for tumor marker assessment might have the strongest impact to predict outcome and select optimal therapies in real-world application. We investigated the role of proliferation survivin/BIRC5 and macrophage infiltration (CD68, MAC387, CLEVER-1) on the basis of molecular subtypes of bladder cancer (KRT5, KRT20, ERBB2) to predict outcomes of adjuvant treated muscle-invasive bladder cancer patients with regard to progression-free survival (PFS) and disease-specific survival (DSS). Materials and Methods: We used tissue microarrays (TMA) from n = 50 patients (38 males, 12 female) with muscle-invasive bladder cancer. All patients had been treated with radical cystectomy followed by adjuvant triple chemotherapy. Median follow-up time was 60.5 months. CD68, CLEVER-1, MAC387, and survivin protein were detected by immunostaining and subsequent visual inspection. BIRC5, KRT5, KRT20, ERBB2, and CD68 mRNAs were detected by standardized RT-qPCR after tissue dot RNA extraction using a novel stamp technology. All these markers were evaluated in three different centers of excellence. Results: Nuclear staining rather than cytoplasmic staining of survivin predicted DSS as a single marker with high levels of survivin being associated with better PFS and DSS upon adjuvant chemotherapy (p = 0.0138 and p = 0.001, respectively). These results were validated by the quantitation of BIRC5 mRNA by PCR (p = 0.0004 and p = 0.0508, respectively). Interestingly, nuclear staining of survivin protein was positively associated with BIRC5 mRNA, while cytoplasmic staining was inversely related, indicating that the translocation of survivin protein into the nucleus occurred at a discrete, higher level of its mRNA. Combining survivin/BIRC5 levels based on molecular subtype being assessed by KRT20 expression improved the predictive value, with tumors having low survivin/BIRC5 and KRT20 mRNA levels having the best survival (75% vs. 20% vs. 10% 5-year DSS, p = 0.0005), and these values were independent of grading, node status, and tumor stage in multivariate analysis (p = 0.0167). Macrophage infiltration dominated in basal tumors and was inversely related with the luminal subtype marker gene expression. The presence of macrophages in survivin-positive or ERBB2-positive tumors was associated with worse DSS. Conclusions: For muscle-invasive bladder cancer patients, the proliferative activity as determined by the nuclear staining of survivin or RT-qPCR on the basis of molecular subtype characteristics outperforms single marker detections and single technology approaches. Infiltration by macrophages detected by IHC or PCR is associated with worse outcome in defined subsets of tumors. The limitations of this study are the retrospective nature and the limited number of patients. However, the number of molecular markers has been restricted and based on predefined assumptions, which resulted in the dissection of muscle-invasive disease into tumor–biological axes of high prognostic relevance, which warrant further investigation and validation.</p

Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma

PURPOSE: Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. MATERIALS AND METHODS: We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. RESULTS: Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. CONCLUSIONS: Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases