Immunogenetic features of steroid-sensitive nephrotic syndrome and focal segmental glomeru losclerosis in Brazilian patients of the northeast region of the state of São Paulo

A síndrome nefrótica corticossensível (SNCS) e a glomerulonefrite esclerosante segmentar e focal (GESF) compartilham características imunológicas e patogênicas. Foram estudados 93 pacientes brasileiros (46 com SNCS e 47 com GESF) e 104 indivíduos-controle, para caracterizar os perfis imunogenéticos dessas variedades de síndromes nefróticas idiopáticas. Os antígenos HLA-A, -B e –DR foram tipificados, usando-se método sorológico. Embora nenhuma associação com os antígenos HLA-A ou –B fosse observada, as freqüências dos antígenos HLAB7 e –B12 estavam significantemente elevadas nos pacientes com SNCS. Os antígenos HLADR7, HLA-DR1 e a combinação de antígenos HLA-DR1/DR7 estavam significantemente elevados nos pacientes com SNCS, em relação aos indivíduos-controle, ou em relação aos pacientes com GESF. A avaliação somente de pacientes caucasóides revelou que o antígeno HLA-DR7 continuava elevado nos pacientes com SNCS. O haplótipo HLA-B7/DR7 estava significantemente elevado nos pacientes com SNCS e GESF. Embora a população brasileira seja altamente miscigenada, a freqüência do antígeno HLA-DR7, que confere susceptibilidade a SNCS em outras populações, estava também elevada na série de pacientes caucasóides aqui estudada.Steroid-sensitive nephrotic syndrome (SSNS) and focal segmental glomerulosclerosis (FSGC) share immunologic and pathogenetic features. We studied 93 Brazilian patients (46 with SSNS and 47 with FSGC) and 104 control subjects with the objective of characterizing the immunogenetic profile of these varieties of idiopathic nephrotic syndrome. HLA-A, -B, and -DR antigens were typed using a complement-dependent microlymphocytotoxicity assay. No significanty association was observed with HLA-A or -B antigens in either group; however, HLA-B7 and -B12 antigens were increased in SSNS patients. HLA-DR7, -DR1 and the combination of HLA-DR1/DR7 antigens were significantly increased in the total group of patients with SSNS compared to controls or to FGSC patients. The study of only Caucasoid individuals revealed that HLA-DR7 antigen remained significantly increased in SSNS patients. The HLA-B7/DR7 haplotype was siginificantly increased in both SSNS and FSGC patients. Although the Brazilian population is highly miscigenated, the same antigen (HLA-DR7) which confers susceptibility to SSNS in other Caucasian population is still prevalent in this series

Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury

© 2015 Enoki 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. Reactive oxygen species (ROS) and nitric oxide (NO) are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX), one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1) influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and nitrotyrosine (a nitrative marker) in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites) and IFN-? in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs

Cumulative network-meta-analyses, practice guidelines and actual prescriptions of drug treatments for postmenopausal osteoporosis: a study protocol for cumulative network meta-analyses and meta-epidemiological study

Introduction: Cumulative network meta-analysis (NMA) is a method to provide a global comparison of multiple treatments with real-time update to evidence users. Several studies investigated the ranking of cumulative NMA and the recommendations of practice guidelines. However, to the best of our knowledge, no study has evaluated the cumulative NMA ranking and prescription patterns. Here, we present a protocol for a meta-epidemiological investigation to compare the results of cumulative NMA with the recommendations in postmenopausal osteoporosis practice guidelines and with the actual prescriptions. Method and analysis: We will use the data of primary trials from the upcoming postmenopausal osteoporosis clinical practice guideline of the Endocrine Society. We will conduct cumulative NMA using all eligible trials and generate hierarchy of treatment rankings by using the surface under the cumulative ranking curve. We will search practice guidelines in relevant society websites. Two review authors will extract the practice recommendations. We will use data from the Medical Expenditures Panel Survey, a US representative sample of the non-institutionalised population, to determine the prescription patterns. Ethics and dissemination: Because all data will be retrieved from public databases, institutional review board approval is not required. We will publish our findings in a peer-reviewed journal and present key findings at conferences. Trial registration number: UMIN000031894: Pre-results

Cumulative network-meta-analyses, practice guidelines and actual prescriptions of drug treatments for postmenopausal osteoporosis: a study protocol for cumulative network meta-analyses and meta-epidemiological study

Introduction Cumulative network meta-analysis (NMA) is a method to provide a global comparison of multiple treatments with real-time update to evidence users. Several studies investigated the ranking of cumulative NMA and the recommendations of practice guidelines. However, to the best of our knowledge, no study has evaluated the cumulative NMA ranking and prescription patterns. Here, we present a protocol for a meta-epidemiological investigation to compare the results of cumulative NMA with the recommendations in postmenopausal osteoporosis practice guidelines and with the actual prescriptions. Method and analysis We will use the data of primary trials from the upcoming postmenopausal osteoporosis clinical practice guideline of the Endocrine Society. We will conduct cumulative NMA using all eligible trials and generate hierarchy of treatment rankings by using the surface under the cumulative ranking curve. We will search practice guidelines in relevant society websites. Two review authors will extract the practice recommendations. We will use data from the Medical Expenditures Panel Survey, a US representative sample of the non-institutionalised population, to determine the prescription patterns. Ethics and dissemination Because all data will be retrieved from public databases, institutional review board approval is not required. We will publish our findings in a peer-reviewed journal and present key findings at conferences. Trial registration number UMIN000031894: Pre-results.</p

Physician characteristics associated with proper assessment of overstated conclusions in research abstracts: A secondary analysis of a randomized controlled trial

Objectives: Little is known about the physician characteristics associated with appraisal skills of research evidence, especially the assessment of the validity of study methodology. This study aims to explore physician characteristics associated with proper assessment of overstated conclusions in research abstracts. Design: A secondary analysis of a randomized controlled trial. Setting and participants: We recruited 567 volunteers from the Japan Primary Care Association. Methods: Participants were randomly assigned to read the abstract of a research paper, with or without an overstatement, and to rate its validity. Our primary outcome was proper assessment of the validity of its conclusions. We investigated the association of physician characteristics and proper assessment using logistic regression models and evaluated the interaction between the associated characteristics and overstatement. Results: We found significant associations between proper assessment and post-graduate year (odds ratio [OR] = 0.67, 95% confidence interval [CI] 0.49 to 0.91, for every 10-year increase) and research experience as a primary investigator (PI; OR = 2.97, 95% CI 1.65 to 5.34). Post-graduate year and PI had significant interaction with overstatement (P = 0.015 and < 0.001, respectively). Among participants who read abstracts without an overstatement, post-graduate year was not associated with proper assessment (OR = 1.04, 95% CI 0.82 to 1.33), and PI experience was associated with lower scores of the validity (OR = 0.58, 95% CI 0.35 to 0.96). Conclusion: Physicians who have been in practice longer should be trained in distinguishing overstatements in abstract conclusions. Physicians with research experience might be informed that they tend to rate the validity of research lower regardless of the presence or absence of overstatements