Impact of Physical Exercise Alone or in Combination with Cognitive Remediation on Cognitive Functions in People with Schizophrenia: A Qualitative Critical Review

: Physical exercise and cognitive remediation represent the psychosocial interventions with the largest basis of evidence attesting their effectiveness in improving cognitive performance in people living with schizophrenia according to recent international guidance. The aims of this review are to provide an overview of the literature on physical exercise as a treatment for cognitive impairment in schizophrenia and of the studies that have combined physical exercise and cognitive remediation as an integrated rehabilitation intervention. Nine meta-analyses and systematic reviews on physical exercise alone and seven studies on interventions combining physical exercise and cognitive remediation are discussed. The efficacy of physical exercise in improving cognitive performance in people living with schizophrenia is well documented, but more research focused on identifying moderators of participants response and optimal modalities of delivery is required. Studies investigating the effectiveness of integrated interventions report that combining physical exercise and cognitive remediation provides superior benefits and quicker improvements compared to cognitive remediation alone, but most studies included small samples and did not explore long-term effects. While physical exercise and its combination with cognitive remediation appear to represent effective treatments for cognitive impairment in people living with schizophrenia, more evidence is currently needed to better understand how to implement these treatments in psychiatric rehabilitation practice

Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients

AbstractAmyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS's pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin–myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin–myosin interaction; this in turn might contribute to the pathogenesis of ALS

Cyto/Biocompatibility of Dopamine Combined with the Antioxidant Grape Seed-Derived Polyphenol Compounds in Solid Lipid Nanoparticles

none10The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). Hence, the aim of this investigation is to co-administer the missing DA and the antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) in order to increase the levels of the neurotransmitter (which is unable to cross the Blood Brain Barrier) and reducing the oxidative stress (OS) related to PD, respectively. Methods: For this purpose, we chose Solid Lipid Nanoparticles (SLN), because they have been already proven to increase DA uptake in the brain. DA-SLN adsorbing GSE (GSE/DA-SLN) were formulated and subjected to physico-chemical characterization, and their cytocompatibility and protection against OS were examined. Results: GSE was found on SLN surface and release studies evidenced the efficiency of GSE in preventing DA autoxidation. Furthermore, SLN showed high mucoadhesive strength and were found not cytotoxic to both primary Olfactory Ensheathing and neuroblastoma SH-SY5Y cells by MTT test. Co-administration of GSE/DA-SLN and the OS-inducing neurotoxin 6-hydroxydopamine (100 μM) resulted in an increase of SH-SY5Y cell viability. Conclusions: Hence, SLN formulations containing DA and GSE may constitute interesting candidates for non-invasive nose-to-brain delivery.openAdriana Trapani, Lorenzo Guerra, Filomena Corbo, Stefano Castellani, Enrico Sanna, Loredana Capobianco, Anna Grazia Monteduro, Daniela Erminia Manno, Delia Mandracchia, Sante Di Gioia and Massimo ConeseTrapani, Adriana; Guerra, Lorenzo; Corbo, Filomena; Castellani, Stefano; Sanna, Enrico; Capobianco, Loredana; Monteduro, ANNA GRAZIA; Manno, Daniela Erminia; Mandracchia, Delia; Di Gioia and Massimo Conese, Sant

Ruta geomonumental: materiales de construcción utilizados en el Monasterio de Santa María de Pelayos de la Presa y antiguas canteras explotadas para la extracción de la piedra granítica (Madrid).

9 págs, 8 figuras.-- Itinerario incluido entre las actividades de divulgación y comunicación social de la Semana de la Ciencia y la Tecnología en el CSIC (Consejo Superior de Investigaciones Científicas, Nov 2010): http://www.madrimasd.org/semanaciencia/2010/.-- Texto correspondiente a la memoria entregada a los participantes que asistieron a la ruta geomonumentalLas Rutas Geomonumentales suponen una metodología diferente para la difusión cultural y científica del patrimonio arquitectónico, atendiendo a los materiales pétreos, naturales y artificiales, que lo configuran. El prefijo “Geo” indica el fuerte condicionante geológico que tradicionalmente ha influido en los asentamientos urbanos y en su desarrollo, así como la relación existente entre la arquitectura y la geología, en tanto que gran parte de los materiales de construcción se extraen de la tierra. Además, el comportamiento y deterioro de los materiales pétreos está en gran parte condicionado por el entorno que rodea a los inmuebles que constituyen. El Monasterio de Pelayos de la Presa resulta un inmueble ideal para realizar una Ruta Geomonumental como la que se propone. Por un lado, para la construcción del monasterio se utilizaron muy diversos materiales pétreos de construcción (naturales y artificiales) y su emplazamiento en gran parte estuvo condicionado por la existencia de canteras de granito en la zona. Por otro, el estado de conservación que presenta el inmueble, posibilita atender a interesantes aspectos constructivos y a formas de deterioro sufridas por los materiales, así como a las causas que las generan.Peer reviewe

The cognitive and behavioural profile of Amyotrophic Lateral Sclerosis: Application of the consensus criteria

Abstract. OBJECTIVE: The study aims to assess the spectrum of cognitive and behavioural disorders in patients affected by Amyotrophic Lateral Sclerosis (ALS) according to the recent consensus criteri

Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose‐to‐Brain Delivery Application

Background: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginate-dopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and 1H- NMR spectroscopies, as well as in vitro mucoadhesive and release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 μg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administratio

Intratumoral injection of TLR9 agonist promotes an immunopermissive microenvironment transition and causes cooperative antitumor activity in combination with anti-PD1 in pancreatic cancer

Background: Complex tumor and immune microenvironment render pancreatic ductal adenocarcinoma (PDAC) resistant to immune checkpoint inhibitors (ICIs). Therefore, a strategy to convert the immune hostile into an immunopermissive tumor is required. Recent studies showed that intratumoral injection of Toll-like receptor 9 agonist IMO-2125 primes the adaptive immune response. Phase I and II trials with intratumoral IMO-2125 demonstrated its safety and antitumoral activity. Methods: We generated an array of preclinical models by orthotopically engrafting PDAC-derived cell lines in syngeneic mice and categorized them as high, low and no immunogenic potential, based on the ability of tumor to evoke T lymphocyte or NK cell response. To test the antitumor efficacy of IMO-2125 on locally treated and distant sites, we engrafted cancer cells on both flanks of syngeneic mice and treated them with intratumoral IMO-2125 or vehicle, alone or in combination with anti-PD1 ICI. Tumor tissues and systemic immunity were analyzed by transcriptomic, cytofluorimetric and immunohistochemistry analysis. Results: We demonstrated that intratumoral IMO-2125 as single agent triggers immune system response to kill local and distant tumors in a selected high immunogenic subtype affecting tumor growth and mice survival. Remarkably, intratumoral IMO-2125 in combination with systemic anti-PD1 causes a potent antitumor effect on primary injected and distant sites also in pancreatic cancer models with low immunogenic potential, preceded by a transition toward an immunopermissive microenvironment, with increase in tumor-infiltrating dendritic and T cells in tumor and lymph nodes. Conclusion: We demonstrated a potent antitumor activity of IMO-2125 and anti-PD1 combination in immunotherapy-resistant PDAC models through the modulation of immune microenvironment, providing the rationale to translate this strategy into a clinical setting

Oxidized alginate dopamine conjugate: In vitro characterization for nose-to-brain delivery application

Background: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginatedopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and1H-NMR spectroscopies, as well as in vitro mucoadhesive and release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 µg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administration