Assessment of the corneal collagen organization after chemical burn using second harmonic generation microscopy

The organization of the corneal stoma is modified due to different factors, including pathology, surgery or external damage. Here the changes in the organization of the corneal collagen fibers during natural healing after chemical burn are investigated using second harmonic generation (SHG) imaging. Moreover, the structure tensor (ST) was used as an objective tool for morphological analyses at different time points after burn (up to 6 months). Unlike control corneas that showed a regular distribution, the collagen pattern at 1 month of burn presented a non-organized arrangement. SHG signal levels noticeably decreased and individual fibers were hardly visible. Over time, the healing process led to a progressive re-organization of the fibers that could be quantified through the ST. At 6 months, the stroma distribution reached values similar to those of control eyes and a dominant direction of the fibers re-appeared. The present results show that SHG microscopy imaging combined with the ST method is able to objectively monitor the temporal regeneration of the corneal organization after chemical burn. Future implementations of this approach into clinically adapted devices would help to diagnose and quantify corneal changes, not only due to chemical damages, but also as a result of disease or surgical procedures

pH in exhaled breath condensate and nasal lavage as a biomarker of air pollution-related inflammation in street traffic-controllers and office-workers

OBJECTIVE: To utilize low-cost and simple methods to assess airway and lung inflammation biomarkers related to air pollution. METHODS: A total of 87 male, non-smoking, healthy subjects working as street traffic-controllers or office-workers were examined to determine carbon monoxide in exhaled breath and to measure the pH in nasal lavage fluid and exhaled breath condensate. Air pollution exposure was measured by particulate matter concentration, and data were obtained from fixed monitoring stations (8-h work intervals per day, during the 5 consecutive days prior to the study). RESULTS: Exhaled carbon monoxide was two-fold greater in traffic-controllers than in office-workers. The mean pH values were 8.12 in exhaled breath condensate and 7.99 in nasal lavage fluid in office-workers; these values were lower in traffic-controllers (7.80 and 7.30, respectively). Both groups presented similar cytokines concentrations in both substrates, however, IL-1β and IL-8 were elevated in nasal lavage fluid compared with exhaled breath condensate. The particulate matter concentration was greater at the workplace of traffic-controllers compared with that of office-workers. CONCLUSION: The pH values of nasal lavage fluid and exhaled breath condensate are important, robust, easy to measure and reproducible biomarkers that can be used to monitor occupational exposure to air pollution. Additionally, traffic-controllers are at an increased risk of airway and lung inflammation during their occupational activities compared with office-workers.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade de São Paulo Faculdade de Medicina Department of PathologyUniversidade de São Paulo Faculdade de Medicina Department of PhysiotherapyPhilipps University Department of PulmonologyLeiden University Medical Center Department of PulmonologyUniversidade Federal de São Paulo (UNIFESP) School of Medicine Department of PneumologyPneumology Division Pneumology DivisionInstituto do Coracao Instituto do CoracaoUniversidade de São Paulo Faculdade de MedicinaUniversidade de São Paulo Faculdade de Medicina Department of Internal MedicineUniversidade de São Paulo Public Health Faculty Department of EpidemiologyUniversidade de São Paulo Institute of Mathematics and StatisticsUNIFESP, School of Medicine Department of PneumologyFAPESP: 07/51605-9FAPESP: 09/50056-7CNPq: 555.223/06-0SciEL

pH in exhaled breath condensate and nasal lavage as a biomarker of air pollution-related inflammation in street traffic-controllers and office-workers

OBJECTIVE: To utilize low-cost and simple methods to assess airway and lung inflammation biomarkers relatedto air pollution.METHODS: A total of 87 male, non-smorking, healthy subjects working as street traffic-controllers or office-workers were examined to determine carbon monoxide in ixhaled breath and to measure the pH in nasal lavage fluid and exhaled breath condensate. Air pollution exposure was measured by particulate matter concentration, and data were obtained from fixed monitoring stations (8-h work intervals per day, during the 5 consecutive days prior to the study).RESULTS: Exhaled carbon monoxide was two-fold greater in traffic-controllers than in office-workers. The mean pH values were 8.12 in exhaled breath condensate and 7.99 in nasal lavage fluid in office-workers; these values concentrations in both substrates, however, Il-aB and IL-8 were elevated in nasal lavage fluid compared with exhaled breath condensate. The particulate matter concentration weas greater at the workplace of traffic-controllers compared with that of office-workers.CONCLUSION: The pH values of nasal lavage fluid and exhaled breath condensate are important, robust, easy to measure and reproducible biomarkers that can be used to monitor occupational exposure to air pollution. Additionally, traffic-controllers are at an increased risk of airway and lung inflammation during their occupational activities compared with office-workers

New direct alcohol and hydrogen fuel cells for naval and aeronautical applications (PILCONAER)

In the current context of demand for reliable, low cost and low environmental impact energy sources, many countries and companies are mostly focused on fuel cells (FC) in fields as transportation and stationary power generation and portable devices. Lately, FCs have begun to be applied in naval and aeronautical systems due to its high efficiency, low noise and environmental advantages. These applications could range from propulsion systems to auxiliary power units(APU). The main problems associated with the use of FCs in these areas are the current high cost due to the materials used, i.e. Nafion and Pt, the lack of durability testing in these specific conditions, security issues to flammability and high H2 pressures and low availability as a fuel, or the toxicity of methanol used as a fuel, and specific parameters such as weight in aircraft applications and volume in marine applications. Currently it is working on each of these issues, and at this point the ethanol as direct fuel is considered crucial. The use of ethanol as fuel has the advantage of easy transportation, storage and refueling, and is nontoxic. Bioethanol is a promising energy source, produced from raw materials containing sugar or starch. These raw materials exists in all parts of the world and is renewable, which involves the use of local energy sources contributing to the diversification of energy supply, reducing import dependence, increasing security of supply and generating new opportunities for agriculture. The main objective of the project is the development of low power stacks (stacks) fed with methanol (DMFC)and ethanol (DEFC) based on the development of new catalysts and membranes. PILCONAER aims contributing to the development of a sustainable use technology, further commitment to the restoration of the natural environment and biodiversity conservation

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Extracellular histones activate autophagy and apoptosis via mTOR signaling in human endothelial cells

Circulating histones have been proposed as targets for therapy in sepsis and hyperinflammatory symptoms. However, the proposed strategies have failed in clinical trials. Although different mechanisms for histone-related cytotoxicity are being explored, those mediated by circulating histones are not fully understood. Extracellular histones induce endothelial cell death, thereby contributing to the pathogenesis of complex diseases such as sepsis and septic shock. Therefore, the comprehension of cellular responses triggered by histones is capital to design effective therapeutic strategies. Here we report how extracellular histones induce autophagy and apoptosis in a dose-dependent manner in cultured human endothelial cells. In addition, we describe how histones regulate these pathways via Sestrin2/AMPK/ULK1-mTOR and AKT/mTOR. Furthermore, we evaluate the effect of Toll-like receptors in mediating autophagy and apoptosis demonstrating how TLR inhibitors do not prevent apoptosis and/or autophagy induced by histones. Our results confirm that histones and autophagic pathways can be considered as novel targets to design therapeutic strategies in endothelial damage

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Sin3b interacts with Myc and decreases Myc levels

Myc expression is deregulated in many human cancers. A yeast two-hybrid screen has revealed that the transcriptional repressor Sin3b interacts with Myc protein. Endogenous Myc and Sin3b co-localize and interact in the nuclei of human and rat cells, as assessed by co-immunoprecipitation, immunofluorescence, and proximity ligation assay. The interaction is Max-independent. A conserved Myc region (amino acids 186-203) is required for the interaction with Sin3 proteins. Histone deacetylase 1 is recruited to Myc-Sin3b complexes, and its deacetylase activity is required for the effects of Sin3b on Myc. Myc and Sin3a/b co-occupied many sites on the chromatin of human leukemia cells, although the presence of Sin3 was not associated with gene down-regulation. In leukemia cells and fibroblasts, Sin3b silencing led to Myc up-regulation, whereas Sin3b overexpression induced Myc deacetylation and degradation. An analysis of Sin3b expression in breast tumors revealed an association between low Sin3b expression and disease progression. The data suggest that Sin3b decreases Myc protein levels upon Myc deacetylation. As Sin3b is also required for transcriptional repression by Mxd-Max complexes, our results suggest that, at least in some cell types, Sin3b limits Myc activity through two complementary activities: Mxd-dependent gene repression and reduction of Myc levels

Obstetric outcomes of sars-cov-2 infection in asymptomatic pregnant women

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms