Therapeutic strategies for IVD regeneration through hyaluronan/SDF-1-based hydrogel and intravenous administration of MSCs

Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation.Funding: This research was funded by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia (IUD/BIM/04293/2019) and by EUROSPINE TRF (2017_05)

Pleuroamniotic shunting--case report

Fetal hydrothorax refers to a collection of fluid within the fetal thorax that may be the result of chylous leak from the thoracic duct (primary hydrothorax) or generalized fluid retention associated with immune or no immune fetal hydrops (secondary hydrothorax). The authors' presents a case report occurred in 2002, of a pregnant woman that at 25 weeks' gestation that was referred to Maternidade Bissaya-Barreto-Coimbra because of a fetal hydrothorax at left, under tension and with cardiac decompensation signs. A fetal thoracocentesis was performed and the diagnosis was chylothorax. Because of a rapid reaccumulation of fluid a pleuroamniotic shunt was placed. The effusion and the cardiac decompensation signs regressed. The delivery was at 38 weeks' gestation. The newborn had been stable. Actually he has 10 months, is healthy and has a normal grow and development

An insight into the sialome of Simulium guianense (DIPTERA:SIMulIIDAE), the main vector of River Blindness Disease in Brazil

<p>Abstract</p> <p>Background</p> <p>Little is known about the composition and function of the saliva in black flies such as <it>Simulium guianense</it>, the main vector of river blindness disease in Brazil. The complex salivary potion of hematophagous arthropods counteracts their host's hemostasis, inflammation, and immunity.</p> <p>Results</p> <p>Transcriptome analysis revealed ubiquitous salivary protein families--such as the Antigen-5, Yellow, Kunitz domain, and serine proteases--in the <it>S. guianense </it>sialotranscriptome. Insect-specific families were also found. About 63.4% of all secreted products revealed protein families found only in <it>Simulium</it>. Additionally, we found a novel peptide similar to kunitoxin with a structure distantly related to serine protease inhibitors. This study revealed a relative increase of transcripts of the SVEP protein family when compared with <it>Simulium vittatum </it>and <it>S. nigrimanum </it>sialotranscriptomes. We were able to extract coding sequences from 164 proteins associated with blood and sugar feeding, the majority of which were confirmed by proteome analysis.</p> <p>Conclusions</p> <p>Our results contribute to understanding the role of <it>Simulium </it>saliva in transmission of <it>Onchocerca volvulus </it>and evolution of salivary proteins in black flies. It also consists of a platform for mining novel anti-hemostatic compounds, vaccine candidates against filariasis, and immuno-epidemiologic markers of vector exposure.</p

Reforming EIA systems : a critical review of proposals in Brazil.

Environmental Impact Assessment (EIA) systems are under pressure in many countries, driven by a call for efficiency and streamlining. Such a phenomenon is particularly clear in Brazil,where, in the past fewyears, a number of influential associations put forward documents proposing significant changes to environmental licensing and impact assessment regulations. So far, there is no publicly available information about any initiative towards scrutinizing those proposals. The objective of this study was to critically review the merits and drawbacks of the changes proposed in those documents. The analysis triangulated content analysis, focus group and online survey data. The focus group included ten seasoned Brazilian EIA specialists; the survey, based on Likert-scale and open-ended questions, resulted in 322 valid responses from EIA professionals. Results show that the proposals generally agree that the current EIA system, while playing a key role in mitigating impacts and enhancing project design, needs many changes.Nonetheless, the proposals neither offered solutions to overcomepolitical, technical and budget barriers, nor established a sense of priority of the most urgent issues. Findings from the focus group and the survey signaled that a number of proposed actions might face public outcry, and that those changes that do not depend on legislative action are more likely to be implementable. Previous studies about EIA reform focused mostly on the context of developed countries after changes had taken place. This study, while addressing the perspective of a large developing country in a ?before-reform? stage, shows that capacity-building is a key requirement in EIA reform

PROTOCOLO DE DESINFECÇÃO DE MOLDAGENS

Após  realizar  o  procedimento  de  confecção  de  moldagem  de prótese  é  necessário  que  haja  sua  desinfecção  com  uma  técnica  menos agressiva  que  a  esterilização.  Segue  uma  ordem  de  lavagem  com desencrostante, enxágue e desinfecção posterior. A necessidade de tal técnica tem  finalidade  de  prevenir  a  contaminação  cruzada,  causada  pela  saliva  e sangue  encontrados  na  superfície  do  molde,  que  é  considerada  de  grande potencial  de  contaminação.  Tal  procedimento  pode  ser  realizado  com  uma variedade  de  desinfectantes,  cada  um  com  uma  indicação  própria.  O  objetivo dessa mesa demonstrativa é levar ao conhecimento da comunidade acadêmica as  técnicas  de  desinfecção  de  moldagens  em  prótes

Mitochondrial echoes of first settlement and genetic continuity in El Salvador

Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador. Methodology/Principal Findings: We have carried out DNA sequencing of the entire control region of the mitochondrial DNA (mtDNA) genome in 90 individuals from El Salvador. We have also compiled more than 3,985 control region profiles from the public domain and the literature in order to carry out inter-population comparisons. The results reveal a predominant Native American component in this region: by far, the most prevalent mtDNA haplogroup in this country (at ~90%) is A2, in contrast with other North, Meso- and South American populations. Haplogroup A2 shows a star-like phylogeny and is very diverse with a substantial proportion of mtDNAs (45%; sequence range 16090–16365) still unobserved in other American populations. Two different Bayesian approaches used to estimate admixture proportions in El Salvador shows that the majority of the mtDNAs observed come from North America. A preliminary founder analysis indicates that the settlement of El Salvador occurred about 13,400±5,200 Y.B.P.. The founder age of A2 in El Salvador is close to the overall age of A2 in America, which suggests that the colonization of this region occurred within a few thousand years of the initial expansion into the Americas. Conclusions/Significance: As a whole, the results are compatible with the hypothesis that today's A2 variability in El Salvador represents to a large extent the indigenous component of the region. Concordant with this hypothesis is also the observation of a very limited contribution from European and African women (~5%). This implies that the Atlantic slave trade had a very small demographic impact in El Salvador in contrast to its transformation of the gene pool in neighbouring populations from the Caribbean facade

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

Background: The regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLE CS), it acts not as a proteinase, but as a receptor for a 1proteinase inhibitor (a 1PI, a 1antitrypsin, SerpinA1). Binding of a1PI to HLECS forms a motogenic complex. We previously demonstrated that a1PI deficiency attends HIV-1 disease and that a1PI augmentation produces increased numbers of immunocompetent circulating CD4 + lymphocytes. Herein we investigated the mechanism underlying the a 1PI deficiency that attends HIV-1 infection. Methods and Findings: Active a 1PI in HIV-1 subjects (median 17 mM, n = 35) was significantly below normal (median 36 mM, p,0.001, n = 30). In HIV-1 uninfected subjects, CD4 + lymphocytes were correlated with the combined factors a1PI, HLECS + lymphocytes, and CXCR4 + lymphocytes (r 2 = 0.91, p,0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with.220 CD4 cells/ml, CD4 + lymphocytes were correlated solely with active a 1PI (r 2 =0.93,p,0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is shown to bind and inactivate human a 1PI. Chimpanzee a 1PI differs from human a1PI by a single amino acid within the 3F5-binding epitope. Unlike human a1PI, chimpanzee a1PI did not bind 3F5 or become depleted following HIV-1 challenge, consistent with the normal CD4 + lymphocyte levels and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-a 1PI immune complexes correlated with decreased CD4 + lymphocytes in HIV-1 subjects

Echocardiographic assessment of mitral valve morphology after Percutaneous Transvenous Mitral Commissurotomy (PTMC)

<p>Abstract</p> <p>Aims</p> <p>PTMC produces significant changes in mitral valve morphology as improvement in leaflets mobility. The determinants of such improvement have not been assessed before.</p> <p>Methods and results</p> <p>The study included 291 symptomatic patients with mitral stenosis undergoing PTMC. Post-PTMC subvalvular splitting area was a determinant of post-PTMC excursion in both the anterior (B 0.16, 95% CI 0.03 to 0.30, p < 0.05) and the posterior (B 0.12, 95% CI 0.01 to 0.24, p < 0.05) leaflets. Another determinant was the post-PTMC transmitral pressure gradient for anterior (B -0.02, 95% CI -0.04 to -0.005, p < 0.01) and posterior (B -0.01, 95% CI -0.04 to -0.005, p < 0.05) leaflets excursion. The relationship between post-PTMC MVA and leaflet excursion was non-linear "S curve". There was a steep increase of both anterior (p, 0.02) and posterior (p, 0.03) leaflets excursion with increased MVA till the MVA reached a value of about 1.5 cm²; after which both linear and S curves became nearly parallel.</p> <p>Conclusion</p> <p>The improvement in leaflets excursion after PTMC is determined by several morphologic and hemodynamic changes produced in the valve. The increase in MVA improves mobility within limit; after which any further increase in MVA is not associated by a significant improvement in mobility in both leaflets.</p

Operation of a slow rate anaerobic digester treating municipal secondary sludge

This study was designed to evaluate the performance of a slow rate anaerobic digester in treating secondary sewage sludge received from one local municipal wastewater treatment plant. The digester was fed by secondary sewage sludge without any previous thickening. A series of three independent batch experiments was investigated at an operation time of 60 days. The total solids (TS) in the influent sludge contained a percentage of organic matter of 59, 63 and 54%, a concentration of volatile suspended solids (VSS) of 23.7, 29.2 and 27.8 g L-1 and a chemical oxygen demand (COD) of 51.8, 32.9 and 65.7 g L-1 for the three experiments, respectively. The operation of anaerobic digestion was stable, with no noticeable scum or foaming problems. The COD reduction in each experiment reached 29, 21 and 45% in the sludge and 95, 85 and 82% in the supernatant. The microbial indicators were surveyed by sampling the sludge throughout the digester operation and counting the number of bacteria in the sampled sludge. Counted bacteria included the total culturable, the total and fecal coliform groups, Pseudomonas aeruginosa and fecal streptococci. The percentage removal of the indicator bacteria was higher for fecal streptococci (99.9%) than for coliform bacteria (96.3%), which in turn was higher than for P. aeruginosa (95.6%). Parasitological analysis was also performed on multiple sludge samples by determination of protozoa and helminth eggs. Protozoa ( Eimeria and Entamoeba ), helminth eggs ( Ascaris , Trichuris , Toxocara , Hymenolepis ) and mites were detected in the influent sludge, and particularly among the helminth eggs, only Trichuris was detected in the effluent sludge