Effect of Preexisting Neutralizing Antibodies on the Anti-tumor Immune Response Induced by Chimeric Human Papillomavirus Virus-like Particle Vaccines

AbstractChimeric human papillomavirus virus-like particles (HPV cVLPs) carrying HPV16 E7 protein are potent vaccines for inducing cell-mediated immunity (CMI) against HPV-induced tumors in animal models. We tested the hypothesis that virion-neutralizing antibodies generated during an initial vaccination might prevent effective boosting of CMI to the cVLPs. Mice with circulating HPV16-neutralizing antibodies, generated by direct immunization with wild-type VLPs or by passive transfer of hyperimmune anti-HPV16 VLP mouse sera, were subsequently vaccinated with HPV16 E7-containing cVLPs. Mice with preexisting neutralizing antibodies were not protected from HPV16 E7-positive TC-1 tumor challenge, compared to the protection seen in mice lacking these antibodies. Antibody-coated VLPs bound very inefficiently to receptor-positive cell lines, suggesting that one of the mechanisms of antibody interference is blocking of VLP binding to its receptor and thereby uptake of VLPs by antigen-presenting cells. Our results suggest that repetitive vaccination with a cVLP for induction of cellular immune responses to an incorporated antigen may be of limited effectiveness due to the presence of neutralizing antibodies against the capsid proteins induced after the first application. This limitation could potentially be overcome by boosting with cVLPs containing the same target antigen incorporated into other papillomavirus-type VLPs

Evaluation of a chitosan-based edible film as carrier of natamycin to improve the storability of saloio cheese

The purpose of this study was to evaluate the effects of the application of chitosan coating containing natamycin on the physicochemical and microbial properties of semi-hard cheese. Three cheese groups were prepared: samples without coating, samples coated with chitosan and with chitosan containing 0.50 mg mL−1 of natamycin, whose minimum inhibitory concentration was previously determinated on cheese surface. Microbiological analyses showed that natamycin coated samples presented a decrease on moulds/yeasts of 1.1 log (CFU g−1) compared to control after 27 days of storage. Addition of natamycin also affected O2 and CO2 permeability, increasing from 7.12 to 7.68 × 10−15 g·(Pa s m)−1, and from 10.69 to 64.58 × 10−14 g·(Pa s m)−1, respectively. The diffusion coefficient values of natamycin from the film to phosphate buffered saline solution and to the cheese were 3.60 × 10−10 and 1.29 × 10−12 cm2 s−1, respectively. This study demonstrated that chitosan-based coating/films can be used as release system containing natamycin to create an additional hurdle for moulds/yeasts in cheese thus contributing to extend its shelf-life.Plan Galego de Investigación, Desenvolvemento e Innovación Tecnolóxica-Incite (Xunta de GaliciaFundação para a Ciência e a Tecnologia (FCT

Magnetite Nanoparticles as Solar Photo-Fenton Catalysts for the Degradation of the 5-Fluorouracil Cytostatic Drug

Heterogeneous catalysts based on magnetite nanoparticles, Fe3O4, were prepared by the chemical coprecipitation method using iron (III) chloride as a salt precursor. The physicochemical properties of the nanoparticles were determined by different techniques and the efficiency was evaluated for the degradation of the cytostatic drug, 5-fluorouracil (5-FU), in aqueous solution by photo-Fenton process under simulated solar radiation. The most influential parameters, namely pH of the solution, catalyst load, H2O2 dosage, and use of radiation, were studied and optimized in the degradation process. The optimal conditions to achieve a 100% degradation of 5-FU (10 mg L-1) and a high mineralization degree (76%) were established at the acidic pH of 3.0, 100 mg L-1 of catalyst loading, and 58 mM of H2O2 under simulated solar radiation. The contribution of iron leaching to the catalyst deactivation, the role of the dissolved iron ions on homogenous reactions, and the stability of the catalyst were assessed during consecutive reaction cycles.Spanish Project, FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades B-RNM-486-UGR2

Does Integrated Behavioral Health Care Reduce Mental Health Disparities for Latinos? Initial Findings

Integrated behavioral health care (IBHC) is a model of mental health care service delivery that seeks to reduce stigma and service utilization barriers by embedding mental health professionals into the primary care team. This study explored whether IBHC service referrals, utilization, and outcomes were comparable for Latinos and non-Latino White primary care patients. Data for the current study were collected from 793 consecutive patients (63.8% Latino; M age = 29.02 years [SD = 17.96]; 35.1% under 18 years; 65.3% women; 54.3% uninsured) seen for behavioral health services in 2 primary care clinics during a 10.5 month period. The most common presenting concerns were depression (21.6%), anxiety (18.5%), adjustment disorder (13.0%), and externalizing behavior problems (9.8%). Results revealed that while Latino patients had significantly lower self-reported psychiatric distress, significantly higher clinician-assigned global assessment of functioning scores, and fewer received a psychiatric diagnosis at their initial visit compared to non-Latino White patients, both groups had comparable utilization rates, comparable and clinically significant improvements in symptoms (Cohen’s d values \u3e .50), and expressed high satisfaction with integrated behavioral services. These data provide preliminary evidence suggesting integration of behavioral health services into primary care clinics may help reduce mental health disparities for Latinos

Diagnoses, Intervention Strategies, and Rates of Functional Improvement in Integrated Behavioral Health Care Patients

Objective—Compared with more traditional mental health care, integrated behavioral health care (IBHC) offers greater access to services and earlier identification and intervention of behavioral and mental health difficulties. The current study examined demographic, diagnostic, and intervention factors that predict positive changes for IBHC patients. Method—Participants were 1,150 consecutive patients (mean age = 30.10 years, 66.6% female, 60.1% Hispanic, 47.9% uninsured) seen for IBHC services at 2 primary care clinics over a 34-month period. Patients presented with depressive (23.2%), anxiety (18.6%), adjustment (11.3%), and childhood externalizing (7.6%) disorders, with 25.7% of patients receiving no diagnosis. Results—The most commonly delivered interventions included behavioral activation (26.1%), behavioral medicine-specific consultation (14.6%), relaxation training (10.3%), and parent-management training (8.5%). There was high concordance between diagnoses and evidence-based intervention selection. We used latent growth curve modeling to explore predictors of baseline global assessment of functioning (GAF) and improvements in GAF across sessions, utilizing data from a subset of 117 patients who attended at least 3 behavioral health visits. Hispanic ethnicity and being insured predicted higher baseline GAF, while patients with an anxiety disorder had lower baseline GAF than patients with other diagnoses. Controlling for primary diagnosis, patients receiving behavioral activation or exposure therapy improved at faster rates than patients receiving other interventions. Demographic variables did not relate to rates of improvement. Conclusion—Results suggest even brief IBHC interventions can be focused, targeting specific patient concerns with evidence-based treatment components

Atlas de Cuidados Paliativos en Latinoamérica. Edición Cartográfica 2013

El Atlas de Cuidados Paliativos en Latinoamérica es un estudio descriptivo de análisis comparativo de datos y/o estimaciones sobre el desarrollo de servicios e iniciativas de Cuidados Paliativos en Latinoamérica. El desarrollo y modelo del Atlas de Cuidados Paliativos en Latinoamérica se basó en el Atlas de Cuidados Paliativos de la Asociación Europea de Cuidados Paliativos (EAPC). La información se obtuvo por medio de una encuesta semi-estructurada a profesionales de Cuidados Paliativos en cada país. Este instrumento fue elaborado por Tania Pastrana, Carlos Centeno y Liliana De Lima y contó con la asesoría de Isabel Torres. El instrumento fue probado en un estudio piloto con 6 personas y de acuerdo a los resultados se hicieron los cambios necesarios. En esta primera versión del Atlas Latinoamericano de Cuidados Paliativos fueron incluidos 19 países latinoamericanos, con lenguaje oficial español o portugué

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio