Self-Assembling Ferritin Nanoplatform for Development of Infectious Hematopoietic Necrosis Virus (IHNV) Vaccine

Self-assembling protein nanoparticles are used as a novel vaccine design platform to improve the stability and immunogenicity of safe subunit vaccines, while providing broader protection against viral infections. In this study, by genetically fusing the virus glycoprotein to the H. pylori ferritin as a scaffold (FerritVac), we constructed a self-assembling Infectious Hematopoietic Necrosis Virus (IHNV) nanovaccine. IHNV is a WOAH-listed disease for which there are currently no therapeutic treatments and no globally available commercial vaccine. Despite the introduction of an exogenous fragment, the FerritVac NPs show excellent stability same as Ferritin NPs under different storage, pH and temperature conditions, mimicking the harsh gastrointestinal condition of rainbow trout, the main IHNV host. MTT viability assays showed no cytotoxicity of FerritVac or Ferritin NPs in zebrafish cell culture incubated with different doses of up to 100 µg/mL for 14 hours. In trout head kidney macrophages, FerritVac NPs upregulated expression of innate antiviral immunity, IHNV and other fish rhabdovirus infection gene markers (mx, vig1, ifit5 and isg-15). This novel vaccine nano-self-assembly approach offers significant commercial potential for non-mammalian viruses and the control of fish viral diseases. In this study, we demonstrate the development of a soluble recombinant glycoprotein of IHNV in the E. coli system using the ferritin self-assembling nanoplatform, as a biocompatible, stable and effective foundation to rescue and produce soluble protein and enable oral administration and antiviral induction for development of a complete IHNV vaccine

Good practice regarding smoking cessation management in Spain: Challenges and opportunities for primary care physicians and nurses

INTRODUCTION We analyze the activities carried out by primary care (PC) physicians and nurses with respect to smoking cessation and evaluate their self-reported training, knowledge, and behavior. METHODS A cross-sectional study was conducted including 1514 PC physicians and nurses from June 2016 to March 2017, in Spain. The main variable was Good Practice (GP) in attention to smokers. To identify associated factors, a multilevel logistic regression model was used adjusted for sex, age, type of center, contract, years of employment, tobacco consumption, and self-reported training/knowledge. RESULTS Of the 792 physicians and 722 nurses, 48.6% referred to GP in smoking cessation management. The finding related to: being a non-smoker (OR=1.8; 95% CI: 1.2-2.5) or ex-smoker (OR= 1.4; 95% CI: 1.02-2.1), having a good level of knowledge (OR=1.8; 95% CI: 1.3-2.4) and training (OR=2.4; 95% CI: 1.8-3.2), and, to a lesser extent, being female (OR=1.3; 95% CI: 1.03-1.7), and work experience >10 years (OR=1.4; 95% CI: 1.03-1.9). The main GP barriers were: lack of time (45.5%), organizational problems (48.4%), and 35.4% lack of training. CONCLUSIONS The GP of PC physicians and nurses regarding smoking cessation management is related to being non-smokers or ex-smokers, and having sufficient training and knowledge. Lack of time and organizational problems were considered to be the main barriers. The promotion of training activities in the Spanish National Health Service with the support of scientific societies is required

Recombinant Proteins for Assembling as Nano- and Micro-Scale Materials for Drug Delivery : A Host Comparative Overview

Altres ajuts: CIBER - Consorcio Centro de Investigación Biomédica en Red CB06/01/0014; María Zambrano postdoctoral researcher contract (677904)By following simple protein engineering steps, recombinant proteins with promising applications in the field of drug delivery can be assembled in the form of functional materials of increasing complexity, either as nanoparticles or nanoparticle-leaking secretory microparticles. Among the suitable strategies for protein assembly, the use of histidine-rich tags in combination with coordinating divalent cations allows the construction of both categories of material out of pure polypeptide samples. Such molecular crosslinking results in chemically homogeneous protein particles with a defined composition, a fact that offers soft regulatory routes towards clinical applications for nanostructured protein-only drugs or for protein-based drug vehicles. Successes in the fabrication and final performance of these materials are expected, irrespective of the protein source. However, this fact has not yet been fully explored and confirmed. By taking the antigenic RBD domain of the SARS-CoV-2 spike glycoprotein as a model building block, we investigated the production of nanoparticles and secretory microparticles out of the versions of recombinant RBD produced by bacteria (Escherichia coli), insect cells (Sf9), and two different mammalian cell lines (namely HEK 293F and Expi293F). Although both functional nanoparticles and secretory microparticles were effectively generated in all cases, the technological and biological idiosyncrasy of each type of cell factory impacted the biophysical properties of the products. Therefore, the selection of a protein biofabrication platform is not irrelevant but instead is a significant factor in the upstream pipeline of protein assembly into supramolecular, complex, and functional materials

Coenzyme Q10-Responsive Ataxia: 2-Year-Treatment Follow-up

[EN] We assessed the clinical outcome after coenzyme Q(10) (CoQ(10)) therapy in 14 patients presenting ataxia classified into two groups according to CoQ(10) values in muscle (deficient or not). We performed an open-label prospective study: patients were evaluated clinically (international cooperative ataxia rating scale [ICARS] scale, MRI, and videotape registration) at baseline and every 6 months during a period of 2 years after CoQ(10) treatment (30 mg/kg/day). Patients with CoQ(10) deficiency showed a statistically significant reduction of ICARS scores (Wilcoxon test: P = 0.018) after 2 years of CoQ(10) treatment when compared with baseline conditions. In patients without CoQ(10) deficiency, no statistically significant differences were observed in total ICARS scores after therapy, although I patient from this group showed a remarkable clinical amelioration. Biochemical diagnosis of CoQ(10) deficiency was a useful tool for the selection of patients who are good candidates for treatment as all of them responded to therapy. However, the remarkable clinical response in I case without CoQ(10) deficiency highlights the importance of treatment trials for identification of patients with CoQ(10)-responsive ataxia.This work was supported by grants from the Fondo de Investigacion Sanitaria (FIS PI080663 and PI080307). The CIBERER is an initiative of the Instituto de Salud Carlos III (ISCIII MICIN, Spain). We are grateful to patients and their families for their kind collaboration and to Professor Di Mauro for the critical revision of the article. We acknowledge Dr. M. Lluch for fibroblast cultures and the expert technical assistance of Sonia Moliner. R. Artuch is supported by the program Intensificacion de la Actividad Investigadora (ISCIII). The research activity of M. Pineda, A. Aracil, A. Mas, P. Navas, and P. Briones was funded by Fondo de Investigacion Sanitaria and CSIC. R. Montero, M.M. O'Callaghan, D. Martinez, and F. Palau were funded by the CIBERER. C. Espinos has a "Miguel Servet" contract (FIS).Pineda, M.; Montero, R.; Aracil, A.; O'callaghan, MM.; Mas, A.; Espinós-Armero, CÁ.; Martínez-Rubio, D.... (2010). Coenzyme Q10-Responsive Ataxia: 2-Year-Treatment Follow-up. Movement Disorders. 25(9):1262-1268. https://doi.org/10.1002/mds.231291262126825

Recombinant Proteins for Assembling as Nano- and Micro-Scale Materials for Drug Delivery: A Host Comparative Overview

By following simple protein engineering steps, recombinant proteins with promising applications in the field of drug delivery can be assembled in the form of functional materials of increasing complexity, either as nanoparticles or nanoparticle-leaking secretory microparticles. Among the suitable strategies for protein assembly, the use of histidine-rich tags in combination with coordinating divalent cations allows the construction of both categories of material out of pure polypeptide samples. Such molecular crosslinking results in chemically homogeneous protein particles with a defined composition, a fact that offers soft regulatory routes towards clinical applications for nanostructured protein-only drugs or for protein-based drug vehicles. Successes in the fabrication and final performance of these materials are expected, irrespective of the protein source. However, this fact has not yet been fully explored and confirmed. By taking the antigenic RBD domain of the SARS-CoV-2 spike glycoprotein as a model building block, we investigated the production of nanoparticles and secretory microparticles out of the versions of recombinant RBD produced by bacteria (Escherichia coli), insect cells (Sf9), and two different mammalian cell lines (namely HEK 293F and Expi293F). Although both functional nanoparticles and secretory microparticles were effectively generated in all cases, the technological and biological idiosyncrasy of each type of cell factory impacted the biophysical properties of the products. Therefore, the selection of a protein biofabrication platform is not irrelevant but instead is a significant factor in the upstream pipeline of protein assembly into supramolecular, complex, and functional materials

A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia

Background: We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN). Patients and methods: The data from the FINITE study (n ¼ 1133) and University of Salamanca Hospital (USH) FN registry (n ¼ 296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups. Results: The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status X2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade X2 (National Cancer Institute Common Toxicity Criteria), monocytes o200/mm3 , and stress-induced hyperglycaemia. The nomogram predictions appeared to be well calibrated in both data sets (Hosmer–Lemeshow test, P40.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a X116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value. Conclusions: We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN

Prediction of long-term outcomes of HIV-infected patients developing non-AIDS events using a multistate approach

Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013. Prospective multicenter cohort study. Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced ("NAE development"); from alive and NAE-experienced to death ("Death after NAE"); and from alive and NAE-free to death ("Death without NAE"). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition "Death after NAE". 8,789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval [CI], 26.80-30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition "Death after NAE" was 12.1 (95%CI, 4.90-29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45-6.57) for intermediate-severity; and 9.85 (5.45-17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11-3.84), ag

The Spanish version of Face-Name Associative Memory Exam (S-FNAME) performance is related to amyloid burden in Subjective Cognitive Decline

The Face-Name Associative Memory Exam (FNAME) is a paired associative memory test created to detect memory deficits in individuals with preclinical Alzheimer’s disease (AD). Worse performance on FNAME in cognitively healthy individuals were found related to higher amyloid beta (Aβ) burden measured with Positron-Emission-Tomography using 11C-PiB (PiB-PET). We previously reported normative data of a Spanish version of FNAME (S-FNAME) in cognitively healthy Spanish-speaking subjects. The aim of the present study was to determine whether performance on S-FNAME was associated with Aβ burden in subjective cognitive decline (SCD) individuals. 200 SCD subjects received neurological and neuropsychological assessments, including the S-FNAME and the Word List task from the Wechsler-Memory-Scale-III (WMS-III). Moreover, they received an MRI and (18)F-Florbetaben Positron-Emission-Tomography (FBB-PET) to measure Aβ burden. Three cognitive factor composites were derived for the episodic memory measures (face-name [SFN-N], face-occupation [SFN-O] and WMS-III) to determine whether episodic memory performance was related to Aβ deposition. Higher global Aβ deposition was significantly related to worse performance on SFN-N but not with SFN-O or WMS-III Composite. Moreover, worse SFN-N performance was significantly related to higher Aβ deposition in bilateral Posterior Cingulate Cortex. The S-FNAME may be a promising neuropsychological tool for detecting SCD individuals with preclinical AD

Prevalencia de consumo de tabaco en trabajadores hospitalarios: metaanálisis en 45 hospitales catalanes = Smoking prevalence in hospital workers: meta-analysis in 45 Catalan hospitals

El 'Grupo de coordinadores de los Hospitales de la Red' está compuesto por: Sandra Bigordà Palau, Jaume González, Maite Elvira, Francesc Abella, Montserrat Pie, Lourdes Rofes, Tere Catalán, Joaquim Guasch, Joana Carrasco, Dolors Benito, Upe González, Peio Solà, Rosa Sunyer, Rosa Carreras, Sílvia Molina, Beatriu Castells, Ma Antònia Raich, Francesc Fibla, Merce Palau, Consol Serra, David de la Rosa, Francesc Macià, Andrea Burón, Ruth Ripoll, Marta Solé, José María Sánchez, M. Antònia Pajin, Mercè Santos Asensio, Cristina Pinet, Jordi Bugés, Claudia Guevara, Jaume Prat, Marga Cano, Pilar Pena, ˜ Gemma Mayor, Joana Guerrero, Manel Roda, Fernando Pommier, Montserrat Contel, Albert Tresserras Puyuelo, Francesc Soler, Miquel Vilardell, Jorge Sanz, Catalina Serra Carbonell y Manel SantinàObjective: To estimate the prevalence of smoking in workers from hospitals within the Catalan Network for Smoke-free hospitals from 2009 to 2012 according to workers' sociodemographic characteristics and the type of hospital. Method: A meta-analysis was performed of prevalence surveys from representative samples of workers from 45 hospitals. The combined prevalence for all hospitals was calculated using a regression model with a random effects model weighted by sample size. Results: The overall prevalence of smoking was 28.1% (95%. CI: 26.1 to 30.0%) with a maximum and minimum of 40.3% and 19.1%, respectively. The health professionals with the lowest prevalence of smoking were physicians (16.4%; 95%CI: 12.9 to 19.9) and nurses (25.4%; 95%CI 21.6 to 29.2). Conclusion: The prevalence of smoking in hospital health workers was lower than in the general population of working age. Physicians were the group with the lowest smoking prevalence. Smoking cessation should be promoted among other professional groupsObjetivo: Estimar la prevalencia de consumo de tabaco en trabajadores/as de los hospitales miembros de la Red Catalana de Hospitales sin Humo según sus características sociodemográficas y tipo de hospital al que pertenecen, en el período 2009-2012. Método: Metaanálisis de encuestas de prevalencia en muestras representativas de trabajadores/as de 45 hospitales (2009-2012). La prevalencia conjunta se calculó mediante un modelo de regresión con efectos aleatorios ponderado por el tamaño muestral. Resultados: La prevalencia global de consumo de tabaco es del 28,1% (intervalo de confianza del 95% [IC95%]: 26,1-30,0%), con valores máximos y mínimos del 40,3% y el 19,1%. Los grupos con menor prevalencia son el colectivo médico (16,4%; IC95%: 12,9-19,9%) y el colectivo de enfermería (25,4%; IC95%: 21,6-29,2%). Conclusión: La prevalencia de consumo de tabaco en trabajadores/as hospitalarios/as es menor que en la población general en edad laboral, siendo el colectivo médico el menos fumador. Es necesario implementar acciones que faciliten el abandono del tabaco en el resto de los colectivo