The many faces of VIP in neuroimmunology: a cytokine rather a neuropeptide?

10 pages, 3 figures.-- PMID: 15333575 [PubMed].Neuroimmunomodulation has experienced an explosive growth not only in basic research, but expanding to the point that prospective clinical research could be now a reality. A crucial factor for the functioning of this intimate bidirectional network was the demonstration that the immune and neuroendocrine systems speak a mutual biochemical language. This implies 1) production of neuroendocrine hormones and neuropeptides by immune cells and of cytokines by neuroendocrine cells; 2) evidence for shared receptors on cells of the immune and neuroendocrine systems; 3) effect of neuroendocrine mediators on immune functions; and 4) effect of cytokines on the neuroendocrine system. This reduces traditional differences between neurotransmitters, hormones, and immune mediators and raises the following question: what can we now regard as immune or neuroendocrine? Vasoactive intestinal peptide (VIP) is one example of this paradigm. VIP has traditionally been classified as a neuropeptide/neurotransmitter based in its capacity to mediate and regulate neuronal functions. Recent work has demonstrated that VIP is produced by T cells, especially Th2 cells, and that through specific receptors it exerts immunological functions typically ascribed to Th2 cytokines in nervous and immune systems. Here, we postulate that instead of a neuropeptide, VIP could be fully considered a type 2 cytokine with a key role in neuroimmunology.This study was supported by extramural grants from the Instituto de Salud Carlos III, Fondo de Investigacion Sanitaria, Spanish Ministry of Health (PI 030359 to D.P and PI 030526 to M.D.), from La Caixa Foundation (NE-03-009 to M.D) and from the European Union 6th Framework Grants Program (FP6-006380 to D.P).Peer reviewe

Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study

Background Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures. Go to: Patients and methods In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded. Go to: Results Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy. Conclusion Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique

Metrizable ordinal proximity measures and their aggregation

Producción CientíficaOrdered qualitative scales formed by linguistic terms are frequently used for evaluating sets of alternatives in different decision-making problems. These scales are usually implicitly considered as uniform in the sense that the psychological proximity between consecutive terms is perceived as identical. However, sometimes agents can perceive different proximities between the linguistic terms of the scale, and an appropriate method is required for aggregating these perceptions. In this paper we introduce the notion of metrizable ordinal proximity measure, discuss some aggregation procedures and propose a method based on metrics for aggregating experts’ opinions on proximities between linguistic terms on ordered qualitative scales.Ministerio de Economía, Industria y Competitividad (Project ECO2016-77900-P

Carrageenans as Sustainable Water-Processable Binders for High-Voltage NMC811 Cathodes

Poly(vinylidene fluoride) (PVDF) is the most common binder for cathode electrodes in lithium-ion batteries. However, PVDF is a fluorinated compound and requires toxic N-methyl-2-pyrrolidone (NMP) as a solvent during the slurry preparation, making the electrode fabrication process environmentally unfriendly. In this study, we propose the use of carrageenan biopolymers as a sustainable source of water-processable binders for high-voltage NMC811 cathodes. Three types of carrageenan (Carr) biopolymers were investigated, with one, two, or three sulfonate groups (SO3–), namely, kappa, iota, and lambda carrageenans, respectively. In addition to the nature of carrageenans, this article also reports the optimization of the cathode formulations, which were prepared by using between 5 wt % of the binder to a lower amount of 2 wt %. Processing of the aqueous slurries and the nature of the binder, in terms of the morphology and electrochemical performance of the electrodes, were also investigated. The Carr binder with 3SO3– groups (3SO3– Carr) exhibited the highest discharge capacities, delivering 133.1 mAh g–1 at 3C and 105.0 mAh g–1 at 5C, which was similar to the organic-based PVDF electrode (136.1 and 108.7 mAh g–1, respectively). Furthermore, 3SO3– Carr reached an outstanding capacity retention of 91% after 90 cycles at 0.5C, which was attributed to a homogeneous NMC811 and a conductive carbon particle dispersion, superior adhesion strength to the current collector (17.3 ± 0.7 N m–1 vs 0.3 ± 0.1 N m–1 for PVDF), and reduced charge-transfer resistance. Postmortem analysis unveiled good preservation of the NMC811 particles, while the 1SO3– Carr and 2SO3– Carr electrodes showed damaged morphologies.The authors acknowledge the Australian Research Council (ARC) Centre for Training Centre for Future Energy Storage Technologies (storEnergy) (IC180100049) for funding. The authors would like to thank the European Commission for financial support through funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 823989 and Spanish AEI-MINECO for funding through project PID2020-119026 GB-I00

Chaperoned amyloid proteins for immune manipulation: a-Synuclein/Hsp70 shifts immunity toward a modulatory phenotype

α-Synuclein (αSyn) is a 140-residue amyloid-forming protein whose aggregation is linked to Parkinson's disease (PD). It has also been found to play a critical role in the immune imbalance that accompanies disease progression, a characteristic that has prompted the search for an effective αSyn-based immunotherapy. In this study, we have simultaneously exploited two important features of certain heat-shock proteins (HSPs): their classical “chaperone” activities and their recently discovered and diverse “immunoactive” properties. In particular, we have explored the immune response elicited by immunization of C57BL/6 mice with an αSyn/Hsp70 protein combination in the absence of added adjuvant. Our results show differential effects for mice immunized with the αSyn/Hsp70 complex, including a restrained αSyn-specific (IgM and IgG) humoral response as well as minimized alterations in the Treg (CD4+CD25+Foxp3+) and Teff (CD4+Foxp3−) cell populations, as opposed to significant changes in mice immunized with αSyn and Hsp70 alone. Furthermore, in vitro-stimulated splenocytes from immunized mice showed the lowest relative response against αSyn challenge for the “αSyn/Hsp70” experimental group as measured by IFN-γ and IL-17 secretion, and higher IL-10 levels when stimulated with LPS. Finally, serum levels of Th1-cytokine IFN-γ and immunomodulatory IL-10 indicated a unique shift toward an immunomodulatory/immunoprotective phenotype in mice immunized with the αSyn/Hsp70 complex. Overall, we propose the use of functional “HSP-chaperoned amyloid/aggregating proteins” generated with appropriate HSP-substrate protein combinations, such as the αSyn/Hsp70 complex, as a novel strategy for immune-based intervention against synucleinopathies and other amyloid or “misfolding” neurodegenerative disorders.España, Ministerio de Economía y Competitividad SAF-2012/39720Junta de Andalucía P10-CTS-6928Junta de Andalucía P11-CTS-816

Diagnóstico clínico-ultrasonográfico de lesiones escrotales en pacientes del hospital Abel Santamaría Cuadrado

Introduction: ultrasound is a non-invasive, widely distributed and low-cost technique that constitutes the study of choice of scrotal disease.Objective: to clinically and ultrasonographically characterize patients with scrotal lesions treated at the “Abel Santamaría Cuadrado” hospital.Method: an observational, descriptive and cross-sectional study was carried out in patients with scrotal lesions treated at the “Abel Santamaría Cuadrado” General Teaching Hospital belonging to the province of Pinar del Río in the period between 2016 and 2018. The universe consisted of 62 patients. Theoretical, empirical and statistical methods were used for data collection and analysis.Results: the age group with the highest incidence was 30 to 39 years old (35,5 %). Pain was found in 61,3 % of patients, lesions that affected the left scrotum predominated (47,0 %). The presence of fluid in the scrotum was the most frequent ultrasonographic finding (48,4 %) and the disease with the highest incidence was varicocele with 43,5 %.Conclusions: scrotal ultrasound is a key piece in the evaluation of patients with symptoms at this level, both for ease of access and repetition, as well as for the great information it provides in most cases, which allows immediately, guide the process and attitude to follow in the patient.Introducción: la ecografía es una técnica no invasiva, ampliamente distribuida y de bajo costo, que constituye el estudio de elección de la enfermedad escrotal.Objetivo: caracterizar clínica y ultrasonográficamente a los pacientes con lesiones escrotales atendidos en el hospital “Abel Santamaría Cuadrado”.Método: se realizó un estudio observacional, descriptivo y transversal en pacientes con lesiones escrotales atendidos en el Hospital General Docente “Abel Santamaría Cuadrado” perteneciente a la provincia de Pinar del Río en el período comprendido entre 2016 y 2018. El universo estuvo constituido por 62 pacientes. Se emplearon métodos teóricos, empíricos y estadísticos para la recolección y el análisis de los datos.Resultados: el grupo de edad de mayor incidencia fue el de 30 a 39 años (35,5 %). El dolor se constató en un 61,3 % de los pacientes, predominaron las lesiones que afectaron el escroto izquierdo (47,0 %). La presencia de líquido en el escroto fue el hallazgo ultrasonográfico más frecuente (48,4 %) y la enfermedad de mayor incidencia fue el varicocele con un 43,5 %.Conclusiones: la ecografía escrotal es una pieza clave en la evaluación de pacientes con síntomas a este nivel, tanto por la facilidad de acceso y de repetición, como por la gran información que aporta en la mayoría de los casos, lo que permite de forma inmediata, orientar el proceso y actitud a seguir en el paciente

Anti-CXCR4 Antibody Combined With Activated and Expanded Natural Killer Cells for Sarcoma Immunotherapy

Sarcoma is one of the most severe forms of pediatric cancer and current therapies -chemotherapy and surgery- fail to eradicate the disease in half of patients. Preclinical studies combining new therapeutic approaches can be useful to design better therapies. On one hand, it is known that CXCR4 expression is implicated in rhabdomyosarcoma progression, so we analyzed relapses and chemotherapy-resistant rhabdomyosarcoma tumors from pediatric patients and found that they had particularly high levels of CXCR4 expression. Moreover, in assays in vitro, anti-CXCR4 blocking antibody (MDX1338) efficiently reduced migration and invasion of alveolar rhabdomyosarcoma RH30 cells. On the other hand, activated and expanded natural killer (NKAE) cell therapy showed high cytotoxicity against sarcoma cells in vitro and completely inhibited RH30 tumor implantation in vivo. Only the combination of MDX1338 and NKAE treatments completely suppressed metastasis in mice. In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis. These results provide the first evidence for the efficacy of this combined immunotherapy for preventing sarcoma disease dissemination.This work was supported in part by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI15/00973; Asociacion Espanola Contra el Cancer to AP-M; CRIS Foundation to Beat Cancer grant to JV, LF, and AE; and Patients' Support Associations Fundacion Mari Paz Jimenez Casado and La Sonrisa de Alex to MV and the research project

Las Tecnologías de la Información y la Comunicación (TIC) como forma investigativa interdisciplinaria con un enfoque intercultural para el proceso de formación de los estudiantes

El presente artículo manifiesta la importante concepción y uso de las tecnologías de la información como herramientas que han permitido desarrollar el proceso de enseñanza aprendizaje en la educación, facilitando tanto al docente como al alumnado la adquisición del conocimiento de forma más inmediata y amplia; el gran impacto del desarrollo tecnológico que se está originando en la actualidad ha favorecido lo que se denomina la nueva revolución social, las TIC han generado grandiosos cambios en las organizaciones culturales, sociales, económicas y educativas. Estas manifiestan una serie de características fundamentales como una vía factible a todo tipo de información, establece una comunicación inmediata, ya sea sincrónica o asincrónica, en la automatización de las actividades,  almacenamiento de numerosa información y la interacción entre computadores y usuarios. El docente cumple un rol fundamental en el conocimiento y uso de estas tecnologías, debido a la importancia didáctica que pueden tener las TIC empleadas adecuadamente en el aula de clase. Sin embargo, los docentes hoy en día no comprenden con eficacia la utilidad que puede significar el uso de las TIC en el desarrollo del proceso de formación de los estudiantes; esto se refleja en la calidad educativa. Por lo cual este manuscrito tiene como objetivo analizar Las Tecnologías de la Información y la Comunicación como forma investigativa interdisciplinaria con un enfoque intercultural para fortalecer el proceso de formación de los estudiantes

Possible role of highly activated mucosal NK cells against viral respiratory infections in children undergoing haematopoietic stem cell transplantation

Infection is the leading cause of non-relapse-related mortality after allogeneic haematopoietic stem cell transplantation (HSCT). Altered functions of immune cells in nasal secretions may influence post HSCT susceptibility to viral respiratory infections. In this prospective study, we determined T and NK cell numbers together with NK activation status in nasopharyngeal aspirates (NPA) in HSCT recipients and healthy controls using multiparametric flow cytometry. We also determined by polymerase chain reaction (PCR) the presence of 16 respiratory viruses. Samples were collected pre-HSCT, at day 0, +10, +20 and +30 after HSCT. Peripheral blood (PB) was also analyzed to determine T and NK cell numbers. A total of 27 pediatric HSCT recipients were enrolled and 16 of them had at least one viral detection (60%). Rhinovirus was the most frequent pathogen (84% of positive NPAs). NPAs of patients contained fewer T and NK cells compared to healthy controls (p = 0.0132 and p = 0.120, respectively). Viral PCR + patients showed higher NK cell number in their NPAs. The activating receptors repertoire expressed by NK cells was also higher in NPA samples, especially NKp44 and NKp46. Our study supports NK cells relevance for the immune defense against respiratory viruses in HSCT recipients.This work was supported in part by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI18/01301, CRIS Foundation to Beat Cancer, Patients’ Support Associations Fundación Mari Paz Jiménez Casado and La Sonrisa de Álex and a Small Grant Award from the European Society for Paediatric Infectious Diseases.S