Functional heterogeneity of the UpaH autotransporter protein from uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) are responsible for the majority of urinary tract infections(UTI). To cause UTI, UPEC must adhere to epithelial cells of the urinary tract and overcome the shear flow forces of urine. This function is primarily mediated by fimbrial adhesins, which mediate specific attachment to host cell receptors. Another group of adhesins that contribute to UPEC mediated UTI are autotransporter (AT) proteins. AT proteins possess a range of virulence properties such as adherence, aggregation, invasion and biofilm formation. One recently characterized AT protein of UPEC is UpaH, a large AIDA-I type AT protein that contributes to biofilm formation and bladder colonization. In this study, we have characterized a series of naturally occurring variants of UpaH. We demonstrate that extensive sequence variation exists within the passenger-encoding domain of UpaH variants from different UPEC strains. This sequence variation is associated with functional heterogeneity with respect to the ability of UpaH to mediate biofilm formation. In contrast, all of the UpaH variants examined retained a conserved ability to mediate binding to extracellular matrix (ECM) proteins. Bioinformatic analysis of the UpaH passenger domain identified a conserved region (UpaHCR) and hydrophobic region (UpaHHR). Deletion of these domains reduced biofilm formation but not binding to ECM proteins. Despite variation in upaH sequence, the transcription of upaH was repressed by a conserved mechanism involving the global regulator H-NS, and mutation of the hns gene relieved this repression. Overall, our findings shed new light on the regulation and function of the UpaH AT protein

Isolamento e caracterização de cepas de Saccharomyces cerevisiae de interesse em produção de vinho

Despite the availability of several Saccharomyces cerevisiae commercial strains intended for wine production, strains isolated from winery regions are usually more adapted to their own climatic conditions, grapes and also partially responsible for particular characteristics that frequently identify specific wines and regions. Thus the microbiota of an important winery region (Colombo) was studied in order to isolate and characterize S. cerevisiae strains that could be used on wine production. From 61 yeasts isolated, 14 were identified as S. cerevisiae. Some of them showed fermentative characteristics even better than commercial strains indicating that they could be applied on wine production in order to increase the quality and assure the particular wine characteristics of that region

Minimal inhibitory concentration (MIC) determination of disinfectant and/or sterilizing agents

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Due to the growing number Of Outbreaks of infection in hospital and nurseries, it becomes essential to set up a sanitation program that indicates that the appropriate chemical agent was chosen for application in the most effective way. Validating the effectiveness of decontamination and disinfection is ail important and often challenging task. In order to study and compare the behavior of selected microorganisms, they Were Submitted to minimal inhibitory concentration (MIC). The MIC intervals, which reduced bacteria Populations over 6 log10, were: 59 to 156 mg/L of quaternary ammonium compounds (QACs)- 63 to 10000 mg/L of chlorhexidine; 1375 to 3250 mg/L of glutaraldehyde; 39 to 246 mg/L of formaldehyde; 43750 to 87500 mg/L of ethanol; 1250 to 6250 mg/L of iodine in polyvinyl-pyrolidone complexes, 150 to 4491 mg/L of chlorine-releasing-agents (CRAs) and 469 to 2500 mg/L of hydrogen pet-oxide. Chlorhexidine showed non inhibitory activity over germinating spores. A. calcoaceticus showed resistance to the majority of the agents tested, followed by E. cloacae and S. marcescens.452241248Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Choice of sterilizing/disinfecting agent - determination of the Decimal Reduction Time (D-Value)

Efforts to diminish the transmission of infections include programs in which disinfectants play a crucial role. Hospital surfaces and medical devices are potential sources of cross contamination, and each instrument, surface or area in a health care unit can be responsible for spread of infection. The decimal reduction time was used to study and compare the behavior of selected strains of microorganisms. The highest D-values for various bacteria were obtained for the following solutions: (i) 0.1% sodium dichloroisocyanurate (pH 7.0) - E. coil and A. calcoaceticus (D = 5.9 min); (ii) sodium hypochlorite (pH 7.0) at 0.025% for B. stearothermophilus (D = 24 min), E. coil and E. cloacae (D = 7.5 min); at 0.05% for B. stearothermophilus (D = 9.4 min) and E. coli (D = 6.1 min). The suspension studies were an indication of the disinfectant efficacy on a surface. The data in this study reflect the formulations used and may vary from product to product. The expected effectiveness from the studied formulations shows that the tested agents can be recommended for surface disinfection as stated in present guidelines and emphasize the importance and need to develop routine and novel programs to evaluate product utility.45470170

Cost Analysis Of Pharmaceutical Care Provided To Hiv-infected Patients: An Ambispective Controlled Study

Background: Studies have shown that pharmaceutical care can result in favorable clinical outcomes in human immunodeficiency virus (HIV)-infected patients, however, few studies have assessed the economic impact. The objective of this study was to evaluate the clinical and economic impact of pharmaceutical care of HIV-infected patients. Methods: A controlled ambispective study was conducted in Brazil from January 2009 to June 2012. Patients were allocated to either intervention or control group. The control group was followed according to standard care while the intervention group was also followed by a pharmacist at each physician appointment for one year. Effectiveness outcomes included CD4+ count, viral load, absence of co-infections and optimal immune response, and economic outcomes included expenses of physician and pharmaceutical appointments, laboratory tests, procedures, and hospitalizations, at six months and one year. Results: Intervention and control groups included 51 patients each. We observed significant decreases in total pharmacotherapy problems during the study. At six months, the intervention group contained higher percentages of patients without co-infections and of patients with CD4+ >500 cells/mm3. None of the differences between intervention and control group considering clinical outcomes and costs were statistically significant. However, at one year, the intervention group showed higher percentage of better clinical outcomes and generated lower spending (not to procedures). An additional health care system daily investment of US$1.45, 1.09, 2.13, 4.35, 1.09, and 0.87 would be required for each additional outcome of viral load <50 copies/ml, absence of co-infection, CD4+ >200, 350, and 500 cells/mm3, and optimal immune response, respectively. Conclusion: This work demonstrated that pharmaceutical care of HIV-infected patients, for a one-year period, was able to decrease the number of pharmacotherapy problems. However, the clinical outcomes and the costs did not have statistical difference but showed higher percentage of better clinical outcomes and lower costs for some items.231(2008) Secretária de Vigilância em Saúde, Programa Nacional de DST e Aids: Recomendações Para Terapia Anti-retroviral em Adultos Infectados Pelo HIV, , http://www.ensp.fiocruz.br/portal-ensp/judicializacao/pdfs/491.pdf, Brazil, Ministry of HealthDipiro, J., Talbert, R., Yees, G., Matzke, G., Wells, B., Posey, L., (2007) Pharmacotherapy: A Pathophysiologic Approach, , 6th edition. Rio de Janeiro: Mcgraw Hill Companie;Okie, S., Fighting HIV-Lessons from Brazil (2006) N Engl J Med, 354, pp. 1977-1981Ma, A., Chen, D.M., Chau, F.M., Saberi, P., Improving adherence and clinical outcomes through an HIV pharmacist's interventions (2010) AIDS Care, 22, pp. 1189-1194Carcelero, E., Tuset, M., Martin, M., De Lazzari, E., Codina, C., Miró, J., Gatell, J., Evaluation of antiretroviral-related errors and interventions by the clinical pharmacist in hospitalized HIV-infected patients (2011) HIV Med, 12, pp. 494-499Hirsch, J., Gonzales, M., Rosenquist, A., Miller, T., Gilmer, T., Best, B., Antiretroviral therapy adherence, medication use, and health care costs during 3 years of a community pharmacy medication therapy management program for Medi-Cal beneficiaries with HIV/AIDS (2011) J Manag Care Pharm, 17, pp. 213-223March, K., Mak, M.M., Louie, S.G., Effects of pharmacists' interventions on patient outcomes in an HIV primary care clinic (2007) Am J Heal Syst Pharm, 64, pp. 2574-2578Mocroft, A., Youle, M., Moore, A., Sabin, C.A., Madge, S., Lepri, A.C., Tyrer, M., Phillips, A.N., Reasons for modification and discontinuation of antiretrovirals: Results from a single treatment centre (2001) AIDS, 15, pp. 185-194Saberi, P., Dong, B.J., Johnson, M.O., Greenblatt, R.M., Cocohoba, J.M., The impact of HIV clinical pharmacists on HIV treatment outcomes: A systematic review (2012) Patient Prefer Adherence, 6, pp. 297-322Schumock, G.T., Butler, M.G., Meek, P.D., Vermeulen, L.C., Arondekar, B.V., Bauman, J.L., Evidence of the Economic Benefit of Clinical Pharmacy Services: 1996-2000 (2003) Pharmacotherapy, 23, pp. 113-132Bozek, P.S., Perdue, B.E., Bar-Din, M., Weidle, P.J., Effect of pharmacist interventions on medication use and cost in hospitalized patients with or without HIV infection (1998) Am J Health Syst Pharm, 55, pp. 1151-1155Engles-Horton, L.L., Skowronski, C., Mostashari, F., Altice, F.L., Clinical guidelines and pharmacist intervention program for HIV-infected patients requiring granulocyte colony-stimulating factor therapy (1999) Pharmacotherapy, 19, pp. 356-362Horberg, M., Hurley, L., Silverberg, M., Kinsman, C., Quesenberry, C., Effect of clinical pharmacists on utilization of and clinical response to antiretroviral therapy (2007) J Acquir Immune Defic Syndr, 44, pp. 531-539De Rijdt, T., Willems, L., Simoens, S., Economic effects of clinical pharmacy interventions: A literature review (2008) Am J Health Syst Pharm, 65, pp. 1161-1172Areda, C.A., Bonizio, R.C., Freitas, O., Pharmacoeconomy : An indispensable tool for the rationalization of health costs (2011) Braz J Pharm Sci, 47, pp. 231-240Bavinger, C., Bendavid, E., Niehaus, K., Olshen, R.A., Olkin, I., Sundaram, V., Wein, N., Desai, M., Risk of cardiovascular disease from antiretroviral therapy for HIV : A systematic review (2013) PLoS One, 8, p. e59551Dube, M.P., Disorders of glucose metabolism in patients infected with human immunodeficiency virus (2000) Clin Infect Dis, 31, pp. 1467-1475Friis-Møller, N., Sabin, C.A., Weber, R., D'Arminio Monforte, A., El-Sadr, W.M., Reiss, P., Thiébaut, R., Lundgren, J.D., Combination antiretroviral therapy and the risk of myocardial infarction (2003) N Engl J Med, 349, pp. 1993-2003Crum-Cianflone, N., Roediger, M.P., Eberly, L., Headd, M., Marconi, V., Ganesan, A., Weintrob, A., Fraser, S., Infectious Disease Clinical Research Program HIV Working Group, Agan BK: Increasing rates of obesity among HIV-infected persons during the HIV epidemic (2010) PLoS One, 5, p. e10106Strand, L.M., Cipolle, R.J., Morley, P.C., Documenting the clinical pharmacists activities: Back to basics (1988) Drug Intell Clin Pharm, 22, pp. 63-67Pharmacy Workup Notes, , http://www.pharmacy.umn.edu/medmanagenotes/Molino, C.G.R.C., Carnevale, R.C., Rodrigues, A.T., Visacri, M.B., Moriel, P., Mazzola, P.G., Impact of pharmacist interventions on drug-related problems and laboratory markers in outpatients with human immunodeficiency virus infection (2014) Ther Clin Risk Manag, 10, pp. 631-639SGTAP - Sistema de Gerenciamento da Tabela de Procedimentos, Medicamentos e OPM Do SUS, , http://sigtap.datasus.gov.br/tabela-unificada/app/sec/inicio.jspRuiz, I., Olry, A., López, M.A., Prada, J.L., Causse, M., Prospective, randomized, two-arm controlled study to evaluate two interventions to improve adherence to antiretroviral therapy in Spain (2010) Enferm Infecc Microbiol Clin, 28, pp. 409-415Martin, S., Wolters, P., Calabrese, S., Toledo-Tamula, M.A., Wood, L.V., Roby, G., Elliott-Desorbo, D.K., The antiretroviral regimen complexity index. A novel method of quantifying regimen complexity (2007) J Acquir Immune Defic Syndr, 45, pp. 535-544Mok, S., Minson, Q., Drug-related problems in hospitalized patients with HIV infection (2008) Am J Health Syst Pharm, 65, pp. 55-59Rastegar, D., Knight, A., Monolakis, J., Antiretroviral medication errors among hospitalized patients with HIV infection (2006) Clin Infect Dis, 43, pp. 933-938Pastakia, S., Corbett, A., Raasch, R., Napravnik, S., Correll, T., Frequency of HIV-related medication errors and associated risk factors in hospitalized patients (2008) Ann Pharmacother, 42, pp. 491-497Misson, J., Clark, W., Kendall, M., Therapeutic advances: Protease inhibitors for the treatment of HIV-1 infection (1997) J Clin Pharm Ther, 22, pp. 109-117Osterberg, L., Blaschke, T., Adherence to medication (2005) N Engl J Med, 353, pp. 487-497Langford, S.E., Ananworanich, J., Cooper, D.A., Predictors of disease progression in HIV infection : A review (2007) Aids Res Ther, 4, pp. 1-14(2012), http://www.aids.gov.br/sites/default/files/anexos/publicacao/2011/50652/boletim_aids_2011_final_m_pdf_26659.pdf, Brazil, Ministry of Health, Secretaria de Vigilancia em Saúde, Departamento de DST Aids e Hepatites Virais: Boletim Epidemiológico - AIDS e DSTMcPherson-Baker, S., Malow, R.M., Penedo, F., Jones, D.L., Schneiderman, N., Klimas, N.G., Enhancing adherence to combination antiretroviral therapy in non-adherent HIV-positive men (2000) AIDS Care, 12, pp. 399-404Shen, J., Sun, Q., Zhou, X., Wei, Y., Qi, Y., Zhu, J., Yan, T., Pharmacist interventions on antibiotic use in inpatients with respiratory tract infections in a Chinese hospital (2011) Int J Clin Pharm, 33 (6), pp. 929-933Yen, Y.-H., Chen, H.-Y., Wuan-Jin, L., Lin, Y.-M., Shen, W.C., Cheng, K.-J., Clinical and economic impact of a pharmacist-managed I.V.-to-P.O. Conversion service for levofloxacin in Taiwan (2012) Int J Clin Pharmacol Ther, 50, pp. 136-141Brennan, T.A., Dollear, T.J., Hu, M., Matlin, O.S., Shrank, W.H., Choudhry, N.K., Grambley, W., An integrated pharmacy-based program improved medication prescription and adherence rates in diabetes patients (2012) Health Aff (Millwood), 31, pp. 120-129Lee, A.J., Boro, M.S., Knapp, K.K., Meier, J.L., Korman, N.E., Clinical and economic outcomes of pharmacist recommendations in a Veterans Affairs medical center (2002) Am J Health Syst Pharm, 59, pp. 2070-2077Janknegt, R., Van Der Meer, J.W.M., Sequential therapy with intravenous and oral cephalosporins (1994) J Antimicrob Chemother, 33, pp. 169-177Preços Máximos de Medicamentos Por Princípio Ativo Para Compras Públicas - Monodrogas/preços Fábrica (PF) e Preço Máximo de Venda Ao Governo (PMVG), , http://portal.anvisa.gov.br/wps/wcm/connect/de29e2004baf729293c5dbbc0f9d5b29/LISTA_CONFORMIDADE_GOV_2012-06-19.pdf?MOD=AJPERES, Accessed July 12, 2014

Differentially expressed plasmatic microRNAs in Brazilian patients with Coronavirus disease 2019 (COVID-19): preliminary results

Background: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is known that host microRNAs (miRNAs) can be modulated to favor viral infection or to protect the host. Herein, we report preliminary results of a study aiming at identifying differentially expressed plasmatic miRNAs in Brazilian patients with COVID-19. Methods and results: miRNAs were extracted from the plasma of eight patients with COVID-19 (four patients with mild COVID-19 and four patients with severe/critical COVID-19) and four healthy controls. Patients and controls were matched for sex and age. miRNA expression levels were detected using high-throughput sequencing. Differential miRNA expression and enrichment analyses were further evaluated. A total of 18 miRNAs were differentially expressed between patients with COVID-19 and controls. miR-4433b-5p, miR-6780b-3p, miR-6883-3p, miR-320b, miR-7111-3p, miR-4755-3p, miR-320c, and miR-6511a-3p were the most important miRNAs significantly involved in the PI3K/AKT, Wnt/β-catenin, and STAT3 signaling pathways. Moreover, 42 miRNAs were differentially expressed between severe/critical and mild patients with COVID-19. miR-451a, miR-101-3p, miR-185-5p, miR-30d-5p, miR-25-3p, miR-342-3p, miR-30e-5p, miR-150-5p, miR-15b-5p, and miR-29c-3p were the most important miRNAs significantly involved in the Wnt/β-catenin, NF-κβ, and STAT3 signaling pathways. Conclusions: If validated by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in a larger number of participants, the miRNAs identified in this study might be used as possible biomarkers for the diagnosis and severity of COVID-19

Sequencing and functional annotation of avian pathogenic Escherichia coli serogroup O78 strains reveals the evolution of E. coli lineages pathogenic for poultry via distinct mechanisms

Avian pathogenic Escherichia coli (APEC) causes respiratory and systemic disease in poultry. Sequencing of a multilocus sequence type 95 (ST95) serogroup O1 strain previously indicated that APEC resembles E. coli causing extraintestinal human diseases. We sequenced the genomes of two strains of another dominant APEC lineage (ST23 serogroup O78 strains χ7122 and IMT2125) and compared them to each other and to the reannotated APEC O1 sequence. For comparison, we also sequenced a human enterotoxigenic E. coli (ETEC) strain of the same ST23 serogroup O78 lineage. Phylogenetic analysis indicated that the APEC O78 strains were more closely related to human ST23 ETEC than to APEC O1, indicating that separation of pathotypes on the basis of their extraintestinal or diarrheagenic nature is not supported by their phylogeny. The accessory genome of APEC ST23 strains exhibited limited conservation of APEC O1 genomic islands and a distinct repertoire of virulence-associated loci. In light of this diversity, we surveyed the phenotype of 2,185 signature-tagged transposon mutants of χ7122 following intra-air sac inoculation of turkeys. This procedure identified novel APEC ST23 genes that play strain- and tissue-specific roles during infection. For example, genes mediating group 4 capsule synthesis were required for the virulence of χ7122 and were conserved in IMT2125 but absent from APEC O1. Our data reveal the genetic diversity of E. coli strains adapted to cause the same avian disease and indicate that the core genome of the ST23 lineage serves as a chassis for the evolution of E. coli strains adapted to cause avian or human disease via acquisition of distinct virulence genes