Healthy Sitting Behaviour Enhancement using a Smart Chair System

The aim of this paper is to present a smart chair prototype to monitor the sitting behaviour of people in wheelchair to re-educate them about long periods of time standing still and in the same position and giving them a feedback about this. The project is mainly focused on those who have been in a wheelchair for a short time. The sitting posture monitoring in the developed smart chair system can help or promote people to achieve and maintain healthy sitting behaviour, and prevent or reduce diseases caused by poor sitting behaviour, like bedsores (pressure ulcers)

ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation

UNLABELLED: Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro. In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments, along with ISG15 knockout (ISG15(-/-)) cells, revealed an anti-RSV effect of the molecule. Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral activity via protein ISGylation. This antiviral activity requires high levels of ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal washes from infants infected with RSV, pointing to a possible antiviral role of the molecule in vivo. These results advance our understanding of the innate immune response elicited by RSV and open new possibilities to control infections by the virus. IMPORTANCE: At present, no vaccine or effective treatment for human respiratory syncytial virus (RSV) is available. This study shows that interferon-stimulated gene 15 (ISG15) lowers RSV growth through protein ISGylation. In addition, ISG15 accumulation highly correlates with the RSV load in nasopharyngeal washes from children, indicating that ISG15 may also have an antiviral role in vivo. These results improve our understanding of the innate immune response to RSV and identify ISG15 as a potential target for virus control.This work was supported by grant PI11/00590 from Fondo de Investigación Sanitaria to I.M.S

In-depth comparison of the metabolic and pharmacokinetic behaviour of the structurally related synthetic cannabinoids AMB-FUBINACA and AMB-CHMICA in rats

Synthetic cannabinoids receptor agonists (SCRAs) are often almost completely metabolised, and hence their pharmacokinetics should be carefully evaluated for determining the most adequate biomarker in toxicological analysis. Two structurally related SCRAs, AMB-FUBINACA and AMB-CHMICA, were selected to evaluate their in vivo metabolism and pharmacokinetics using male Sprague-Dawley rats. Brain, liver, kidney, blood (serum) and urine samples were collected at different times to assess the differences in metabolism, metabolic reactions, tissue distribution and excretion. Both compounds experimented O-demethyl reaction, which occurred more rapidly for AMB-FUBINACA. The parent compounds and O-demethyl metabolites were highly bioaccumulated in liver, and were still detected in this tissue 48 h after injection. The different indazole/indole N-functionalisation produced diverse metabolic reactions in this moiety and thus, different urinary metabolites were formed. Out of the two compounds, AMB-FUBINACA seemed to easily cross the blood-brain barrier, presenting higher brain/serum concentrations ratio than AMB-CHMICA

Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors

Gastrointestinal neoplasms; Oncolytic virotherapy; Tumor microenvironmentNeoplasias gastrointestinales; Viroterapia oncolítica; Microambiente tumoralNeoplàsies gastrointestinals; Viroteràpia oncolítica; Microambient tumoralBackground VCN-01 is an oncolytic adenovirus (Ad5 based) designed to replicate in cancer cells with dysfunctional RB1 pathway, express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. This phase I clinical trial was aimed to find the maximum tolerated dose/recommended phase II dose (RP2D) and dose-limiting toxicity (DLT) of the intravenous delivery of the replication-competent VCN-01 adenovirus in patients with advanced cancer. Methods Part I: patients with advanced refractory solid tumors received one single dose of VCN-01. Parts II and III: patients with pancreatic adenocarcinoma received VCN-01 (only in cycle 1) and nab-paclitaxel plus gemcitabine (VCN-concurrent on day 1 in Part II, and 7 days before chemotherapy in Part III). Patients were required to have anti-Ad5 neutralizing antibody (NAbs) titers lower than 1/350 dilution. Pharmacokinetic and pharmacodynamic analyses were performed. Results 26% of the patients initially screened were excluded based on high NAbs levels. Sixteen and 12 patients were enrolled in Part I and II, respectively: RP2D were 1×1013 viral particles (vp)/patient (Part I), and 3.3×1012 vp/patient (Part II). Fourteen patients were included in Part III: there were no DLTs and the RP2D was 1×1013 vp/patient. Observed DLTs were grade 4 aspartate aminotransferase increase in one patient (Part I, 1×1013 vp), grade 4 febrile neutropenia in one patient and grade 5 thrombocytopenia plus enterocolitis in another patient (Part II, 1×1013 vp). In patients with pancreatic adenocarcinoma overall response rate were 50% (Part II) and 50% (Part III). VCN-01 viral genomes were detected in tumor tissue in five out of six biopsies (day 8). A second viral plasmatic peak and increased hyaluronidase serum levels suggested replication after intravenous injection in all patients. Increased levels of immune biomarkers (interferon-γ, soluble lymphocyte activation gene-3, interleukin (IL)-6, IL-10) were found after VCN-01 administration. Conclusions Treatment with VCN-01 is feasible and has an acceptable safety. Encouraging biological and clinical activity was observed when administered in combination with nab-paclitaxel plus gemcitabine to patients with pancreatic adenocarcinoma.MB-P, EB, and MC were funded by CDTI (PANCATHER project IDI-20130759). The clinical study was supported by VCN Biosciences

Ratio of the Dead to Wounded (D/W) Indicators and Associated Factors in Major Earthquakes of America from 1960 to 2011

Corrigendum to “Ratio of the Dead to Wounded (D/W) Indicators and Associated Factors in Major Earthquakes of America from 1960 to 2011”. Journal of Earthquakes 2015; 436960, http://dx.doi.org/10.1155/2015/436960.The paper presented deals with the casualties, mortality, and morbidity occurred during the major earthquakes of America during a period of 51 years. The work provides statistical evidence that the deaths/wounded (D/W) ratio used for many agencies in the planning of the preparation and response activities to earthquakes does not fit the relation 1 : 3. In addition, a model is presented in order to evaluate the possible association between different analysis variables such as the subregion of the American continent affected, population density, HDI, and the time and magnitude of the earthquake and the effects of these on the death toll, the number of the wounded, and the D/W indexes. Although the model generated it is not robust enough for decision making, it could be useful and improvable in order to apply it in the planning and management of these kinds of natural disasters. For these reasons, we think that it would be interesting to do further progress in this line of research by making a more comprehensive study of the variables associated with mortality and morbidity, using a more representative sample of earthquakes that sure will confirm the results presented in this work.This work was funded by the Spanish Field Epidemiology Training Program and was done as part of research activities of Ana Ayuso-Alvárez, M.S., Marcello S. Rossi S., D.S., and Dante Culqui, M.S., in the Spanish Field Epidemiology Training Program.S

Incidence and risk factors for acute gastroenteritis among pilgrims following the French way to Santiago de Compostela (Spain) in summer 2008.

[ES] Conocer la incidencia de gastroenteritis aguda en los peregrinos del Camino de Santiago, los factores de riesgo asociados y su caracterización microbiológica. Se diseñaron dos estudios simultáneos, uno transversal mediante encuestas autocumplimentadas de peregrinos llegados a Santiago y otro de casos y controles a los peregrinos en el camino. Se hizo un análisis multivariado mediante regresión logística. En el estudio transversal la densidad de incidencia fue de 23,5 episodios de gastroenteritis aguda por 1.000 peregrinos-día (intervalo de confianza del 95% [IC95%]: 18,9–29,4/103). En el estudio de casos y controles los factores de mayor riesgo fueron la edad <20 años (odds ratio [OR]=4,72; IC95%: 2,16–10,28), viajar en grupo (tres personas o más) (OR=1,49; IC95%: 0,98–2,28) y consumir agua no embotellada (OR=2,09; IC95%: 0,91–4,82). Norovirus fue el microorganismo aislado con más frecuencia (56%). Ser peregrino menor de 20 años, realizar el camino en grupo y consumir agua no embotellada se asocian con un mayor riesgo de presentar gastroenteritis aguda. [EN] To determine the incidence of acute gastroenteritis in pilgrims on St. James' Way, as well as associated risk factors and microbiological characteristics. Two studies were designed simultaneously: a cross-sectional study through self-completed questionnaires among pilgrims reaching Santiago, and a case-control study of pilgrims traveling along the Way. Multivariate analysis was performed using logistic regression. In the cross-sectional study, the incidence rate was 23.5 episodes of acute gastroenteritis/10³ pilgrims-day (95% CI: 18.9-2.4/10³. In the case-control study, the major risk factors were age <20 years (OR=4.72; 95% CI: 2.16-10.28), traveling in groups (three or more) (OR=1.49; 95% CI: 0.98-2.28), and drinking unbottled water (OR=2.09; 95% CI: 0.91-4.82). The most frequent etiologic agent was norovirus (56%). Age less than 20 years, traveling in groups and drinking unbottled water were important risk factors for acute gastroenteritis.Para desarrollar el trabajo de campo, el Centro Nacional de Epidemiología (Instituto de Salud Carlos III) financió el desplazamiento y las dietas de los miembros del PEAC, la Consellería de Sanidade de Galicia aportó el material técnico necesario y cedió un vehículo para los desplazamientos a lo largo del Camino, y S.A. de Xestion do Xacobeo facilitó el alojamiento de los investigadores de campo.S

Grupo español de cirugía torácica asistida por videoimagen: método, auditoría y resultados iniciales de una cohorte nacional prospectiva de pacientes tratados con resecciones anatómicas del pulmón

Introduction: our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). Methods: we conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for '90-day mortality' and 'Grade IIIb-V complications'. Results: the series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). Conclusions: more than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort

TGFBR1 Intralocus Epistatic Interaction as a Risk Factor for Colorectal Cancer

In colorectal cancer (CRC), an inherited susceptibility risk affects about 35% of patients, whereas high-penetrance germline mutations account for <6% of cases. A considerable proportion of sporadic tumors could be explained by the coinheritance of multiple low-penetrance variants, some of which are common. We assessed the susceptibility to CRC conferred by genetic variants at the TGFBR1 locus. We analyzed 14 polymorphisms and the allele-specific expression (ASE) of TGFBR1 in 1025 individuals from the Spanish population. A case-control study was undertaken with 504 controls and 521 patients with sporadic CRC. Fourteen polymorphisms located at the TGFBR1 locus were genotyped with the iPLEX Gold (MassARRAY-Sequenom) technology. Descriptive analyses of the polymorphisms and haplotypes and association studies were performed with the SNPator workpackage. No relevant associations were detected between individual polymorphisms or haplotypes and the risk of CRC. The TGFBR1*9A/6A polymorphism was used for the ASE analysis. Heterozygous individuals were analyzed for ASE by fragment analysis using cDNA from normal tissue. The relative level of allelic expression was extrapolated from a standard curve. The cutoff value was calculated with Youden's index. ASE was found in 25.4% of patients and 16.4% of controls. Considering both bimodal and continuous types of distribution, no significant differences between the ASE values of patients and controls were identified. Interestingly, a combined analysis of the polymorphisms and ASE for the association with CRC occurrence revealed that ASE-positive individuals carrying one of the most common haplotypes (H2: 20.7%) showed remarkable susceptibility to CRC (RR: 5.25; 95% CI: 2.547–5.250; p<0.001) with a synergy factor of 3.7. In our study, 54.1% of sporadic CRC cases were attributable to the coinheritance of the H2 haplotype and TGFBR1 ASE. These results support the hypothesis that the allelic architecture of cancer genes, rather than individual polymorphisms, more accurately defines the CRC risk