Superparamagnetic Poly (3-hydroxybutyrate-co-3 hydroxyvalerate) (PHBV) nanoparticles for biomedical applications

Indexación: ScieloBackground: The progress in material science and the recent advances in biodegradable/biocompatible polymers and magnetic iron oxide nanoparticles have led to develop innovative diagnostic and therapeutic strategies for diseases based on multifunctional nanoparticles, which include contrast medium for magnetic resonance imaging, agent for hyperthermia and nanocarriers for targeted drug delivery. The aim of this work is to synthesize and characterize superparamagnetic iron oxide (magnetite), and to encapsulate them into poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles for biomedical applications. Results: The magnetite nanoparticles were confirmed by X-ray diffraction and exhibited a size of 22.3 ± 8.8 nm measured by transmission electron microscopy (TEM). Polymeric PHBV nanoparticles loaded with magnetite (MgNPs) were analyzed using dynamic light scattering and showed a size of 258.6 ± 35.7 nm and a negative zeta potential (-10.8 ± 3.5 mV). The TEM examination of MgNPs exhibited a spherical core-shell structure and the magnetic measurements showed in both, non-encapsulated magnetite and MgNPs, a superparamagnetic performance. Finally, the in vitro studies about the magnetic retention of MgNPs in a segment of small intestine of rats showed an active accumulation in the region of the magnetic field. Conclusions: The results obtained make the MgNPs suitable as potential magnetic resonance imaging contrast agents, also promoting hyperthermia and even as potential nanocarriers for site-specific transport and delivery of drugs. Keywords: hyperthermia, magnetic resonance image (MRI), magnetite, PHBV, polymeric nanoparticles.http://ref.scielo.org/cxt57

Neisseria gonorrhoeae challenge increases matrix metalloproteinase-8 expression in fallopian tube explants

Indexación: Scopus.Background: Neisseria gonorrhoeae (Ngo) is the etiological agent of gonorrhea, a sexually transmitted infection that initially infects the female lower genital tract. In untreated women, the bacteria can ascend to the upper genital reproductive tract and infect the fallopian tube (FTs), which is associated with salpingitis and can lead to impaired FT function and infertility. The extracellular matrix (ECM) plays an important role in cell migration and differentiation in the female genital tract, and some pathogens modify the ECM to establish successful infections. The ECM is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), their endogenous inhibitors; MMP deregulation causes pathological conditions in a variety of tissues. Results: The aim of this work was to analyze the expression and localization of MMP-3, MMP-8, MMP-9, and TIMP-1 in FT explants during Ngo infection using real-time PCR, immunohistochemistry, zymography and ELISA. No significant variations in MMP-3, MMP-9, and TIMP-1 transcript levels were observed. In contrast, a significant increase (p < 0.05) was observed for MMP-8 expression and was accompanied by stromal immunoreactivity in infected explants. ELISA results supported these findings and showed that MMP-8 release increased upon gonococcal infection. Conclusions: Our results indicate that gonococcal infection induces increased MMP-8 expression, which might contribute to FT damage during infection. © 2017 Juica, Rodas, Solar, Borda, Vargas, Muñoz, Paredes, Christodoulides and Velasquez.https://www.frontiersin.org/articles/10.3389/fcimb.2017.00399/ful

Citizen meets social science : Predicting volunteer involvement in a global freshwater monitoring experiment

FreshWater Watch is a global citizen science project that seeks to advance the understanding and stewardship of freshwater ecosystems across the globe through analysis of their physical and chemical properties by volunteers. To date, literature concerning citizen science has mainly focused on its potential to generate unprecedented volumes of data. In this paper, we focus instead on the data relating to the volunteer experience and ask key questions about volunteer engagement with the project. For example, we ask what factors influence: a) volunteer data submission following a training event and b) the number of water quality samples volunteers subsequently submit. We used a binomial model to identify the factors that influence the retention of volunteers after training. In addition, we used a generalized linear model (GLM) to examine the factors that affected the number of samples each citizen scientist submitted. In line with other citizen science projects, most people trained did not submit any data, and 1% of participants contributed 47% of the data. We found that the statistically significant factors associated with submission of data after training were: whether training was given on how to upload data, the number of volunteers that attended the training, whether the volunteer was assigned to a research team, the outside temperature, and the average engagement of others in the training group. The statistically significant factors associated with the quantity of data submitted were: the length of time volunteers were active in the project, whether training took place as part of a paid work day, the difficulty of the sampling procedure, how socially involved volunteers were in the project, average sampling group size, and engagement with online learning modules. Based on our results, we suggest that intrinsic motivation may be important for predicting volunteer retention after training and the number of samples collected subsequently. We suggest that, to maximize the contribution of citizen science to our understanding of the world around us, there is an urgent need to better understand the factors that drive volunteer retention and engagement

Superparamagnetic Poly (3-hydroxybutyrate-co-3 hydroxyvalerate) (PHBV) nanoparticles for biomedical applications

Background: The progress in material science and the recent advances in biodegradable/biocompatible polymers and magnetic iron oxide nanoparticles have led to develop innovative diagnostic and therapeutic strategies for diseases based on multifunctional nanoparticles, which include contrast medium for magnetic resonance imaging, agent for hyperthermia and nanocarriers for targeted drug delivery. The aim of this work is to synthesize and characterize superparamagnetic iron oxide (magnetite), and to encapsulate them into poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles for biomedical applications. Results: The magnetite nanoparticles were confirmed by X-ray diffraction and exhibited a size of 22.3 \ub1 8.8 nm measured by transmission electron microscopy (TEM). Polymeric PHBV nanoparticles loaded with magnetite (MgNPs) were analyzed using dynamic light scattering and showed a size of 258.6 \ub1 35.7 nm and a negative zeta potential (-10.8 \ub1 3.5 mV). The TEM examination of MgNPs exhibited a spherical core-shell structure and the magnetic measurements showed in both, non-encapsulated magnetite and MgNPs, a superparamagnetic performance. Finally, the in vitro studies about the magnetic retention of MgNPs in a segment of small intestine of rats showed an active accumulation in the region of the magnetic field. Conclusions: The results obtained make the MgNPs suitable as potential magnetic resonance imaging contrast agents, also promoting hyperthermia and even as potential nanocarriers for site-specific transport and delivery of drugs

Omics-driven identification and elimination of valerolactam catabolism in Pseudomonas putida KT2440 for increased product titer.

Pseudomonas putida is a promising bacterial chassis for metabolic engineering given its ability to metabolize a wide array of carbon sources, especially aromatic compounds derived from lignin. However, this omnivorous metabolism can also be a hindrance when it can naturally metabolize products produced from engineered pathways. Herein we show that P.&nbsp;putida is able to use valerolactam as a sole carbon source, as well as degrade caprolactam. Lactams represent important nylon precursors, and are produced in quantities exceeding one million tons per year (Zhang et&nbsp;al., 2017). To better understand this metabolism we use a combination of Random Barcode Transposon Sequencing (RB-TnSeq) and shotgun proteomics to identify the oplBA locus as the likely responsible amide hydrolase that initiates valerolactam catabolism. Deletion of the oplBA genes prevented P.&nbsp;putida from growing on valerolactam, prevented the degradation of valerolactam in rich media, and dramatically reduced caprolactam degradation under the same conditions. Deletion of oplBA, as well as pathways that compete for precursors L-lysine or 5-aminovalerate, increased the titer of valerolactam from undetectable after 48 h of production to ~90 mg/L. This work may serve as a template to rapidly eliminate undesirable metabolism in non-model hosts in future metabolic engineering efforts

Omics-driven identification and elimination of valerolactam catabolism in Pseudomonas putida KT2440 for increased product titer.

Pseudomonas putida is a promising bacterial chassis for metabolic engineering given its ability to metabolize a wide array of carbon sources, especially aromatic compounds derived from lignin. However, this omnivorous metabolism can also be a hindrance when it can naturally metabolize products produced from engineered pathways. Herein we show that P. putida is able to use valerolactam as a sole carbon source, as well as degrade caprolactam. Lactams represent important nylon precursors, and are produced in quantities exceeding one million tons per year (Zhang et al., 2017). To better understand this metabolism we use a combination of Random Barcode Transposon Sequencing (RB-TnSeq) and shotgun proteomics to identify the oplBA locus as the likely responsible amide hydrolase that initiates valerolactam catabolism. Deletion of the oplBA genes prevented P. putida from growing on valerolactam, prevented the degradation of valerolactam in rich media, and dramatically reduced caprolactam degradation under the same conditions. Deletion of oplBA, as well as pathways that compete for precursors L-lysine or 5-aminovalerate, increased the titer of valerolactam from undetectable after 48 h of production to ~90 mg/L. This work may serve as a template to rapidly eliminate undesirable metabolism in non-model hosts in future metabolic engineering efforts

Una estética de la vivienda de interés social: desarrollos progresivos en Palmira, Colombia (2000-2017)

This case study explores the progressive development of social housing projects in the city of Palmira (Colombia) between 2000 and 2017. Here particular attention is paid to aesthetic parameters through three main concepts: perception, form and function. The methodological approach brought together four qualitative tools for data gathering and analysis: document review, field observations (field diaries, notes and photographic record); interviews (with users representatives of constructors and public servants), and; the development of urban profiles. The findings suggest that social housing units constitute an unfinished project, that, shaped by the subjectivity of their inhabitants’, generates conflict with public spaces. Despite their diversity, the interventions follow identifiable patterns, commonly linked to inadequacies in the original designs.Este estudio de caso explora los desarrollos progresivos de la vivienda de interés social (VIS) en la ciudad de Palmira (Colombia) entre los años 2000 y 2017, prestando particular atención a su dimensión estética, a partir de tres ejes fundamentales: percepción, forma y función. La aproximación metodológica agrupó cuatro herramientas cualitativas de recolección y análisis de datos: revisión documental, observación in situ (diarios de campo, levantamientos y registro fotográfico), entrevistas (a usuarios, representantes de constructoras y servidores públicos) y desarrollo de perfiles urbanos. Los hallazgos sugieren que la VIS constituye un proyecto inacabado, que, determinado por la subjetividad de los habitantes, genera relaciones conflictivas con el espacio público. Pesa a su diversidad, las intervenciones siguen patrones asociados a la solución de carencias en los diseños originales

Tumour heterogeneity in glioblastoma assessed by MRI texture analysis: a potential marker of survival

Objective: The main objective of this retrospective work was the study of three-dimensional (3D) heterogeneity measures of post-contrast pre-operative MR images acquired with T1 weighted sequences of patients with glioblastoma (GBM) as predictors of clinical outcome. Methods: 79 patients from 3 hospitals were included in the study. 16 3D textural heterogeneity measures were computed including run-length matrix (RLM) features (regional heterogeneity) and co-occurrence matrix (CM) features (local heterogeneity). The significance of the results was studied using Kaplan?Meier curves and Cox proportional hazards analysis. Correlation between the variables of the study was assessed using the Spearman?s correlation coefficient. Results: Kaplan?Meyer survival analysis showed that 4 of the 11 RLM features and 4 of the 5 CM features considered were robust predictors of survival. The median survival differences in the most significant cases were of over 6 months. Conclusion: Heterogeneity measures computed on the post-contrast pre-operative T1 weighted MR images of patients with GBM are predictors of survival. Advances in knowledge: Texture analysis to assess tumour heterogeneity has been widely studied. However, most works develop a two-dimensional analysis, focusing only on one MRI slice to state tumour heterogeneity. The study of fully 3D heterogeneity textural features as predictors of clinical outcome is more robust and is not dependent on the selected slice of the tumour

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London