Silicic Acid and Beer Consumption Reverses the Metal Imbalance and the Prooxidant Status Induced by Aluminum Nitrate in Mouse Brain

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Abstract: Background: Emerging evidence suggests that by affecting mineral balance, aluminum (Al) may enhance some events associated with neurodegenerative diseases. Aim: To examine the effect of Al(NO3)3 exposure on brain Al, cooper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), silicon (Si), and zinc (Zn) levels, and the metal-change implication in brain oxidant and inflammatory status. Methods: Four groups of six-week-old male NMRI mice were treated for three months: i) controls, administrated with deionized water; ii) Al, which received Al(NO3)3; iii) Al+silicic acid, which were given Al(NO3)3 plus silicic acid; and iv) Al+beer, which received Al(NO3)3 plus beer. Results: Brain Al and TBARS levels and TNFα and GPx expressions increased, while Cu, Mn, and Zn levels, and catalase and CuZn-SOD expression decreased (at least, p < 0.05) in Al versus control animals. Al, Si, and TBARS levels and TNFα expression decreased (p < 0.05) in Al+silicic acid and Al+beer specimens while Cu, Mn, and Zn levels and antioxidant expression increased versus the Al group. Brain Al levels correlated negatively with those of Cu, Fe, Mn, and Zn, and catalase, CuZn-SOD, and GPx enzyme expressions but positively with Si and TBARS levels and TNFα expression. Two components of the principal component analysis (PCA) explained 71.2% of total data variance (p < 0.001). PCA connected the pro-oxidant markers with brain Al content, while brain Zn and Cu levels were closer to antioxidant enzyme expression. Conclusion: Administration of Al(NO3)3 induced metal imbalance, inflammation, and antioxidant status impairment in the brain. Those effects were blocked to a significant extent by silicic acid and beer administration

Paradigm of tunable clustering using binarization of consensus partition matrices (Bi-CoPaM) for gene discovery

Copyright @ 2013 Abu-Jamous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies.National Institute for Health Researc

Environmental health : reflexions of the Brazilian Association of Post-Graduation in Collective Health - ABRASCO

O Brasil, apesar de sua extraordinária biodiversidade e do enorme potencial instalado para desenvolver ações integradas na temática do ambiente, não tem dado, do ponto de vista programático, a prioridade que o tema ambiente merece. A Associação Brasileira de Pós-Graduação em Saúde Coletiva-ABRASCO reconheceu a importância de organizar um Grupo Temático “Saúde e Ambiente” para, de maneira mais organizada, participar da luta pelo desenvolvimento sustentável, através da ação política no campo da saúde coletiva, em busca de ambientes saudáveis e da promoção da saúde. O objetivo principal deste Grupo Temático-GT foi contribuir para que o tema da saúde ambiental seja internalizado no campo da Saúde Coletiva. Método: O Grupo escolheu três eixos para discussão em uma oficina do V Congresso Brasileiro de Epidemiologia, em Curitiba, no ano de 2002. O resultado resultado do debate ocorrido foi apresentado segundo três eixos: identificação do campo teórico-conceitual em Saúde Ambiente; a política de saúde e ambiente; o caminho metodológico. A conclusão foi apresentada no formato de uma agenda do GT para o biênio 2002-2004. _______________________________________________________________________________________ ABSTRACTNot with standing its extraordinary biodiversity and enormous installed potential to develop actions integrated in to the topic of environmental health, Brazil has not given the environmental the priority the subject deserves from the programmatic, point of view. The Brazilian Association of Post-Graduation in Collective Health - ABRASCO recognized the importance of organizing a Thematic Group “Health and Environment” in order to, in a more organized fashion, participate in the struggle for sustainable development, through political action in collective health, oriented to wards health environments and health promotion. The main objective of this Thematic Group was to facilitate the subject of the environmental health to be internalized in to the field of the Collective Health. Method: The theme was debated in a workshop during the V Brazilian Congress of Epidemiology in Curitiba, in 2002. Results were presented according to three axes: 1- Identification of the theoretical-conceptual field in Environmental Health; 2- the politics of health and environment; 3- methodological route. The general conclusion was presented as an agenda for ABRASCO’s Thematic Group in Environmental Health for the biennial 2002-2004

An All-Organic Flexible Visible Light Communication System

Visible light communication systems can be used in a wide variety of applications, from driving to home automation. The use of wearables can increase the potential applications in indoor systems to send and receive specific and customized information. We have designed and developed a fully organic and flexible Visible Light Communication system using a flexible OLED, a flexible P3HT:PCBM-based organic photodiode (OPD) and flexible PCBs for the emitter and receiver conditioning circuits. We have fabricated and characterized the I-V curve, modulation response and impedance of the flexible OPD. As emitter we have used a commercial flexible organic luminaire with dimensions 99 × 99 × 0.88 mm, and we have characterized its modulation response. All the devices show frequency responses that allow operation over 40 kHz, thus enabling the transmission of high quality audio. Finally, we integrated the emitter and receiver components and its electronic drivers, to build an all-organic flexible VLC system capable of transmitting an audio file in real-time, as a proof of concept of the indoor capabilities of such a system.This Project was funded by Comunidad de Madrid through the SINFOTON-CM Research Program (S2013/MIT-2790), and the Spanish Ministry of Economy, the Agencia Estatal de Investigación and European Union's FEDER through the TEC2016-77242-C3-(1-R, 2-R and 3-R) AEI/FEDER, UE Projects

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants

RAD51D mutations have been recently identified in breast (BC) and ovarian cancer (OC) families. Although an etiological role in OC appears to be present, the association of RAD51D mutations and BC risk is more unclear. We aimed to determine the prevalence of germline RAD51D mutations in Spanish BC/OC families negative for BRCA1/BRCA2 mutations. We analyzed 842 index patients: 491 from BC/OC families, 171 BC families, 51 OC families and 129 patients without family history but with early-onset BC or OC or metachronous BC and OC. Mutation detection was performed with high-resolution melting, denaturing high-performance liquid chromatography or Sanger sequencing. Three mutations were found in four families with BC and OC cases (0.82%). Two were novel: c.1A>T (p.Met1?) and c.667+2_667+23del, leading to the exon 7 skipping and one previously described: c.674C>T (p.Arg232*). All were present in BC/OC families with only one OC. The c.667+2_667+23del cosegregated in the family with one early-onset BC and two bilateral BC cases. We also identified the c.629C>T (p.Ala210Val) variant, which was predicted in silico to be potentially pathogenic. About 1% of the BC and OC Spanish families negative for BRCA1/BRCA2 are carriers of RAD51D mutations. The presence of several BC mutation carriers, albeit in the context of familial OC, suggests an increased risk for BC, which should be taken into account in the follow-up and early detection measures. RAD51D testing should be considered in clinical setting for families with BC and OC, irrespective of the number of OC cases in the family

Knowledge, Attitudes, and Practices Regarding COVID-19 Among Healthcare Workers in Venezuela:An Online Cross-Sectional Survey

Background: The deterioration of Venezuela's health system in recent years undoubtedly contributes to an increased impact of the COVID-19 pandemic. Understanding healthcare workers' (HCWs) knowledge, attitudes, and practices (KAPs) toward COVID-19 in the early stages of the pandemic could inform their medical training and improve their preparedness. Methods: A online national cross-sectional survey was conducted between May 26th and May 30th, 2020, to assess KAPs among HCWs in Venezuela. Results: A total of 1,441 HCWs from all 24 regions of the country responded to the survey. The mean age of the HCWs was 44 (SD [standard deviation] 14) years; most were women (66.4%). Most HCWs were specialized doctors (48%), followed by nurses (13%) and resident doctors (12.3%). The majority of HCWs had good knowledge (76.3%), obtained information mainly from scientific literature (85.4%); had negative attitudes (53.6%), felt uncomfortable with their work during the current pandemic (59.8%); and reported appropriate practices (76.9%). However, participation in COVID-19 related training was absent in more than half of the HCWs. Positive attitudes were significantly more frequent in frontline workers than in non-frontline workers (p = 0.001). Bioanalysts, students, and doctors were more likely to have good knowledge; participating in training was a predictor for positive attitudes and older age was an appropriate practice predictor. Conclusions: HCWs, knowledge in Venezuela could be improved by strengthening education and training programs. Strategies should focus on reducing fear and improving attitudes toward the care of COVID-19 patients, as well as the promotion of preventive practices

Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors

Parasitic diseases cause similar to 500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase) and TRACK (Trypanosoma receptor for activated C-kinase). We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase), may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology.National Institutes of HealthStanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USAUniv Sao Paulo, Inst Quim, Dept Bioquim, BR-05508 Sao Paulo, SP, BrazilMcGill Univ, Res Inst, Natl Reference Ctr Parasitol, Montreal, PQ, CanadaUniv Autonoma Yucatan, Ctr Invest Reg Dr Hideyo Noguchi, Parasitol Lab, Merida, Yucatan, MexicoStanford Univ, Biomat & Adv Drug Delivery Lab, Stanford, CA 94305 USAUniv Estadual Campinas, Inst Chem, Campinas, SP, BrazilUniv Fed Sao Paulo, Dept Ciencias Biol, Campus Diadema, Sao Paulo, BrazilMcGill Univ, Inst Parasitol, Quebec City, PQ, CanadaMcGill Univ, Ctr Host Parasite Interact, Quebec City, PQ, CanadaUniv Fed Sao Paulo, Dept Ciencias Biol, Campus Diadema, Sao Paulo, BrazilNIH: TW008781-01C-IDEANIH: AI078505Web of Scienc

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