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Cancer stem cells (CSC), a small population of neoplastic cells, are associated with worse prognosis. The aim of this study was to evaluate the expression of ALDH1, CD117, CD133 and OCT4; potential markers of CSC; and their associations with the prognosis of women diagnosed with cervical cancer. This retrospective cohort study included 126 women diagnosed with cervical cancer whose biopsies were analyzed by immunohistochemistry. Median values of marked cells were used to define cutoff points for low and high expression. For specific survival, multivariate analyses showed statistical significance for lymph node metastases (HR 8.15; 95% CI 3.00-22.18) and borderline significance for high CD133 expression (p = 0.058). For overall survival, multivariate analyses showed statistical significance for IIA-IVB staging (HR 4.60; 95% CI 1.46-14.56), lymph node metastases (HR 5.13; 95% CI 12.02-13.03) and high CD133 expression (2.67; 95% CI 1.11-6.43). Considering only women with SCC, the same clinicopathological variables were associated with worse specific and overall survival in univariate analyses. However, higher expression of CD 133 (HR 11.10; 95% CI 2.42-50.94 and 6.00; 95% CI 2.02-17.87) and staging IIA-IVB (HR 5.96; 95% CI 1.30-27.34 and HR 12.47; 95% CI 2.45-63.54) respectively impacted negatively specific and overall survival, as multivariate analyses showed. Secondarily, it was observed that ALDH1 expression was associated with adenocarcinoma and CD117 expression with squamous cells carcinoma. Higher expression of CD133 was associated with worse specific and overall survival, indicating that it could have relevance as a clinical marker and therapeutic target.
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The Fundão dam collapse was one of the largest mining-related disasters globally. It resulted in the release of mining tailings containing heavy metals, which contaminated the Doce River in southeastern Brazil. This study assessed the effects of acute exposure of Danio rerio embryos to sediments contaminated by mine tailings six years after the Fundão dam collapse. The study sites included P2, P3, and P4 in the upper Doce River, as well as site P1 on the Piranga River, an uncontaminated river. Sediment samples were analyzed for 10 metals/metalloid by atomic absorption spectrometry. In the assays, embryos were exposed to sediment from P1-P4 sites, and uncontaminated quartz was used as control sediment. Various biomarkers were applied to assess biological responses, and the integrated biomarker response (IBR) index was calculated for each site. Sediment samples revealed elevated levels of As, Cr, Cu, Hg, and Ni beyond Brazilian legislation limits. At 96-h exposure, embryo mortality rates exceeded 20% in P1, P2, and P3, higher than the control and P4 (p < 0.0001). Hatching rates ranged from 60 to 80% in P1, P2, and P3, lower than the control and P4 (p < 0.001). Larvae exposed to P2 sediment (closest to the Fundão dam) exhibited skeletal, physiological, and sensory malformations. Neurotoxicity was indicated by increased acetylcholinesterase activity and reduced spontaneous movements in embryos exposed to Doce River sediment. Contamination also increased metallothionein and heat shock protein 70 levels, along with changes in cell proliferation and apoptosis. Principal component analysis showed a good correlation between metals/metalloid in the sediment and larval morphometric endpoints. The IBR index highlighted suitable biomarkers for monitoring metal contamination in fish embryos. Overall, our findings suggest that sediment toxicity following the Fundão dam failure may compromise the sustainability of fish communities in the Doce River.
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Embrião não Mamífero , Monitoramento Ambiental , Sedimentos Geológicos , Metais Pesados , Rios , Poluentes Químicos da Água , Peixe-Zebra , Animais , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Rios/química , Sedimentos Geológicos/química , Embrião não Mamífero/efeitos dos fármacos , Brasil , Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Metais Pesados/análise , Biomarcadores/metabolismo , MineraçãoRESUMO
OBJECTIVE: The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. METHODS: The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. RESULTS: This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. CONCLUSIONS: In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.
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Proteína Forkhead Box O3 , Leiomioma , Neoplasias Uterinas , Humanos , Feminino , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Neoplasias Uterinas/metabolismo , Pessoa de Meia-Idade , Leiomioma/genética , Leiomioma/patologia , Leiomioma/metabolismo , Adulto , Imuno-Histoquímica , Regulação Neoplásica da Expressão Gênica/genética , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Leiomiossarcoma/metabolismo , Tumor de Músculo Liso/genética , Tumor de Músculo Liso/patologia , Tumor de Músculo Liso/metabolismo , Regulação para Cima , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , Idoso , Miométrio/metabolismo , Miométrio/patologiaRESUMO
Beer is a beverage that contains gluten and cannot be consumed by people with celiac disease. In this context, the enzyme prolyl endoprotease (PEP) can be used to reduce the gluten content in beer. The present study aimed to produce the PEP from Aspergillus sp. FSDE 16 using solid-state fermentation with 5 conditions and comparing with a similar commercial enzyme produced from Aspergillus niger in the production of a gluten-free beer. The results of the performed cultures showed that during the culture, the most increased protease activity (54.46 U/mL) occurred on the 4th day. In contrast, for PEP, the highest activity (0.0356 U/mL) was obtained on the 3rd day of culture in condition. Regarding beer production, cell growth, pH, and total soluble solids showed similar behavior over the 7 days for beers produced without enzyme addition or with the addition of commercial enzyme and with the addition of the enzyme extract produced. The addition of the enzyme and the enzyme extract did not promote changes, and all the beers produced showed similar and satisfactory results, with acid pH between 4 and 5, total soluble solids ranging from 4.80 to 5.05, alcohol content ranging from 2.83% to 3.08%, and all beers having a dark character with deep amber and light copper color. Gluten removal was effectively using the commercial enzyme and the enzyme produced according to condition (v) reaching gluten concentrations equal to 17 ± 5.31 and 21.19 ± 11.28 ppm, respectively. In this way, the production of the enzyme by SSF and its application in the removal of gluten in beer was efficient.
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Cerveja , Serina Endopeptidases , Humanos , Cerveja/análise , Serina Endopeptidases/química , Serina Endopeptidases/metabolismo , Prolil Oligopeptidases , Fermentação , Glutens/análise , Glutens/metabolismo , Aspergillus niger , Extratos VegetaisRESUMO
Abstract Objective The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. Methods The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. Results This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. Conclusions In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.
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Understorey herbs form a diverse and understudied plant assemblage in tropical forests. Although several studies and research teams have long been dedicated to the study of this conspicuous vegetation component in Amazonia, no effort to unify the data has been undertaken to date. In contrast to trees and other life forms for which major data compilations already exist, a unified database dedicated to herbs is still lacking. Part of the problem is in defining what is a herb and how to effectively sample herb assemblages. In this article, we describe the database HERBase, an exhaustive compilation of published and unpublished data on herb inventories in Amazonia. We also describe the structure, functioning, and guidelines for data curation and integration in HERBase. We were able to compile information from 1381 plots from all six Amazonian geographic regions. Based on this dataset, we describe and discuss sampling and knowledge gaps, priority areas for new collections, and recommend sampling protocols to facilitate data integration in the future. This novel database provides a unique biodiversity data repository on understorey herbs that will enable new studies on community ecology and biogeography.(AU)
As ervas do sub-bosque formam um componente diversificado e pouco estudado em florestas tropicais. Embora vários estudos e grupos de pesquisa tenham se dedicado ao estudo desse componente conspícuo na Amazônia, nenhum esforço foi feito até o momento para unificar essas informações. Em contraste com árvores e outros grupos de plantas para os quais já existem grandes compilações de dados, uma base de dados unificada dedicada às ervas ainda não existe. Parte do problema está em definir o que é uma erva e como amostrar comunidados de ervas de forma eficiente. Neste artigo descrevemos a base de dados HERBase, uma compilação exaustiva de dados publicados e não publicados sobre inventários de ervas na Amazônia. Também descrevemos a estrutura, funcionamento e diretrizes para curadoria e integração de dados na HERBase. Conseguimos compilar informações de 1381 parcelas de todas as seis regiões geográficas amazônicas. Com base nesses dados, descrevemos e discutimos lacunas de amostragem e conhecimento, apontamos áreas prioritárias para novas coletas e recomendamos protocolos de amostragem para facilitar a integração de dados no futuro. Essa nova base de dados fornece dados únicos de biodiversidade sobre ervas do sub-bosque que permitirão novos estudos sobre ecologia e biogeografia de comunidades.(AU)
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Florestas , Magnoliopsida/anatomia & histologia , Ecossistema Amazônico , Base de Dados , GleiquêniasRESUMO
Two major concerns associated with cancer development in Paraná state, South Brazil, are environmental pollution and the germline TP53 p.R337H variant found in 0.27−0.30% of the population. We assessed breast cancer (BC) risk in rural (C1 and C2) and industrialized (C3) subregions, previously classified by geochemistry, agricultural productivity, and population density. C2 presents lower organochloride levels in rivers and lower agricultural outputs than C1, and lower levels of chlorine anions in rivers and lower industrial activities than C3. TP53 p.R337H status was assessed in 4658 women aged >30 years from C1, C2, and C3, subsequent to a genetic screening (Group 1, longitudinal study). BC risk in this group was 4.58 times higher among TP53 p.R337H carriers. BC prevalence and risk were significantly lower in C2 compared to that in C3. Mortality rate and risk associated with BC in women aged >30 years (n = 8181 deceased women; Group 2) were also lower in C2 than those in C3 and C1. These results suggest that environmental factors modulate BC risk and outcome in carriers and noncarriers.
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Adherence to treatment and use of co-medication, but also molecular factors such as CYP2D6 genotype, affect tamoxifen metabolism, with consequences for early breast cancer prognosis. In a prospective study of 149 tamoxifen-treated early-stage breast cancer patients from Brazil followed up for 5 years, we investigated the association between the active tamoxifen metabolite (Z)-endoxifen at 3 months and event-free survival (EFS) adjusted for clinico-pathological factors. Twenty-five patients (16.8%) had recurred or died at a median follow-up of 52.3 months. When we applied a putative 15 nM threshold used in previous independent studies, (Z)-endoxifen levels below the threshold showed an association with shorter EFS in univariate analysis (p = 0.045) and after adjustment for stage (HR 2.52; 95% CI 1.13-5.65; p = 0.024). However, modeling of plasma concentrations with splines instead of dichotomization did not verify a significant association with EFS (univariate analysis: p = 0.158; adjusted for stage: p = 0.117). Hence, in our small exploratory study, the link between impaired tamoxifen metabolism and early breast cancer recurrence could not be unanimously demonstrated. This inconsistency justifies larger modeling studies backed up by mechanistic pharmacodynamic analyses to shed new light on this suspected association and the stipulation of an appropriate predictive (Z)-endoxifen threshold.
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Biodegradable cardiac patches have been able to induce improvement in left ventricular (LV) remodeling. A novel scaffold patch made with collagen and silk-fibroin (COL-SF) was further associated to polyaniline (PANi) to increase conductivity. Thus, this study investigated the safety of the association of PANi to a patch, and the improvement in LV remodeling in a myocardial infarct (MI) rat model. Wistar rats underwent MI induction. MI was confirmed with echocardiographic and after 2 weeks, animals (n = 10/group) were randomized into: (a) COL-SF hyaluronic acid patch, (b) PANi hyaluronic acid patch, (c) MI Control (just repeat thoracotomy). Healthy animals were also followed. Echocardiography was performed at pre-treatment, and at 2-, 4-, and 8-weeks post-treatment. Hearts underwent hemodynamic evaluation on Langendorff apparatus and histology for LV thickness and percent of infarct size. Liver, kidneys, and blood samples were evaluated for biochemical, hematological, oxidative stress, and histology. There was a tendency of lower %infarct size in patched animals. LV thickness was higher in the patched animals than controls. Functional echocardiographic indices %Fractional shortening and %LV ejection fraction decreased in the MI control group, but not in the patched animals. PANi presented higher %LVEF versus MI control. PANi presented higher liver transaminases; no morphological changes were observed in histology. Elevation of antioxidant markers was observed. COL-SF and PANi patches were able to induce better remodeling features compared to MI controls on %infarct size and LV thickness and have not presented echocardiographic worsening. Polyaniline may present a slight improvement on LV remodeling, despite associated to signs of hepatotoxicity and pro-oxidant effect.
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Fibroínas , Infarto do Miocárdio , Compostos de Anilina , Animais , Colágeno/farmacologia , Ácido Hialurônico/farmacologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Ratos , Ratos Wistar , Remodelação VentricularRESUMO
This study concerns the millipede genus Leptherpum Attems, 1931, which contains nine valid species distributed across the Amazonian rainforest of northeastern South America. The type species L. carinovatum (Attems, 1898) is reexamined based on the type material and high-resolution photographs, including the first scanning electron micrographs of this species. The following three new species are described: Leptherpum tialaura sp. nov. from the state of Pará, Brazil; Leptherpum battirolai sp. nov. from the state of Amazonas, Brazil; and Leptherpum buenovillegasi sp. nov. from the commune of Maripasoula, French Guiana. A brief review of Leptherpum taxonomy and geographic distribution is provided, along with a key to males.
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This study concerns the millipede genus Leptherpum Attems, 1931, which contains nine valid species distributed across the Amazonian rainforest of northeastern South America. The type species L. carinovatum (Attems, 1898) is reexamined based on the type material and high-resolution photographs, including the first scanning electron micrographs of this species. The following three new species are described: Leptherpum tialaura sp. nov. from the state of Pará, Brazil; Leptherpum battirolai sp. nov. from the state of Amazonas, Brazil; and Leptherpum buenovillegasi sp. nov. from the commune of Maripasoula, French Guiana. A brief review of Leptherpum taxonomy and geographic distribution is provided, along with a key to males.
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Animais , Quilópodes/anatomia & histologia , Quilópodes/classificação , Ecossistema AmazônicoRESUMO
The millipede Chondromorpha xanthotricha, supposedly native to Sri Lanka and southern India, is considered a pantropical species occurring in Southeast Asia, North America, Mesoamerica, the Caribbean, Central America and northern South America. Here we report the first record of this species for Brazil, in the central Amazon region of the country, with taxonomic notes and images of male and female specimens.(AU)
O diplópode Chondromorpha xanthotricha, supostamente nativo do Sri Lanka e sul da Índia, é considerado uma espécie pantropical com ocorrência no Sudeste Asiático, América do Norte, Mesoamérica, Caribe, América Central e norte da América do Sul. Aqui nós reportamos o primeiro registro dessa espécie para o Brasil, na região central da Amazônia brasileira, com notas taxonômicas e ilustrações de espécimes macho e fêmea.(AU)
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Animais , Masculino , Feminino , Espécies Introduzidas , Quilópodes/classificação , Especificidade da Espécie , BrasilRESUMO
Studies concerning the cytogenetics of Gleicheniaceae have been scarce, especially those employing evolutionary approaches. Two chromosome number evolutionary models have been hypothesized for Gleicheniaceae. One proposes that ancestral haploid numbers were small and that the chromosome numbers of extant species evolved through polyploidy. The other model proposes that, at the genus level, fern chromosome evolution occurred from ancestors with essentially the same high chromosome numbers seen in living lineages. Neither of those hypotheses has been tested based on phylogenetic frameworks. We sought to (i) present the state of the art of Gleicheniaceae chromosome numbers; (ii) test the two evolutionary models of chromosome numbers within a phylogenetic framework; (iii) test correlations between DNA contents and chromosome numbers in the family. We report here DNA C-values for five species, which increases the number of investigated taxa nearly twofold and report two new genera records. Ancestral state chromosome reconstruction corroborates the hypothesis that ancestral chromosome numbers in Gleicheniaceae were as high as those of extant lineages. Our results demonstrate the possible role of dysploidy in the evolutionary chromosome history of Gleicheniaceae at the genus level and suggest that the relationship between chromosome number and DNA content does not appear to be linear.
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Gleiquênias , Cromossomos de Plantas/genética , Análise Citogenética , Evolução Molecular , Gleiquênias/genética , FilogeniaRESUMO
Bisphenol A (BPA) is an organic synthetic compound used in the plastic industry with endocrine disrupting activity. Although it is frequently found in surface waters, few studies have investigated its impact on fish gametogenesis, particularly when associated with natural stressors. In this regard, the present study evaluated BPA toxicity on spermatogenesis in the lambari Astyanax bimaculatus under controlled conditions and its interactive effects with water temperature. Adult specimens were exposed in duplicate to 40 µg/L and 400 µg/L BPA at 23 °C and 28 °C for 21 days; the control group did not receive BPA. Testicular samples were collected and analyzed using different cellular and molecular techniques. The results showed a significant reduction in the gonadosomatic index in the BPA-treated groups at both temperatures. A decrease in the testicular levels of 11-ketotestosterone was observed in the 400 µg/L BPA group at 23 °C, 17ß-estradiol increased significantly in the treated groups at 28 °C, and vitellogenin showed no difference between the treatments. The morphometric analysis of spermatogenesis revealed a significant increase in the proportion of spermatogonia, spermatocytes, and Sertoli cells in the treated groups, with a higher proportion at 23 °C than at 28 °C. Otherwise, the proportion of spermatozoa was significantly lower in the BPA-treated groups, with a greater reduction at 23 °C. In addition, BPA also stimulated spermatogonial proliferation in the treated groups, but apoptosis was significantly increased in spermatids at 23 °C. Testis-ova, cell degeneration, and chromatin alterations in spermatids and Sertoli cells were observed in the germinal epithelium of the BPA-treated groups. The integrated biomarker response (IBR) index revealed that the analyzed endpoints are suitable for assessing estrogenic contamination. Taken together, our results indicate that the interactive effects of BPA and temperature contribute to the impairment of spermatogenesis in A. bimaculatus with more severe effects observed on sperm production at 23 °C than at 28 °C.
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The Program for Biodiversity Research (PPBio) is an innovative program designed to integrate all biodiversity research stakeholders. Operating since 2004, it has installed long-term ecological research sites throughout Brazil and its logic has been applied in some other southern-hemisphere countries. The program supports all aspects of research necessary to understand biodiversity and the processes that affect it. There are presently 161 sampling sites (see some of them at Supplementary Appendix), most of which use a standardized methodology that allows comparisons across biomes and through time. To date, there are about 1200 publications associated with PPBio that cover topics ranging from natural history to genetics and species distributions. Most of the field data and metadata are available through PPBio web sites or DataONE. Metadata is available for researchers that intend to explore the different faces of Brazilian biodiversity spatio-temporal variation, as well as for managers intending to improve conservation strategies. The Program also fostered, directly and indirectly, local technical capacity building, and supported the training of hundreds of undergraduate and graduate students. The main challenge is maintaining the long-term funding necessary to understand biodiversity patterns and processes under pressure from global environmental changes.
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Biodiversidade , Ecossistema , Brasil , Conservação dos Recursos Naturais , Humanos , ConhecimentoRESUMO
Identifying plant species requires considerable knowledge and can be difficult without complete specimens. Fourier-transform near-infrared spectroscopy (FT-NIR) is an effective technique for discriminating plant species, especially angiosperms. However, its efficacy has never been tested on ferns. Here we tested the accuracy of FT-NIR at discriminating species of the genus Microgramma. We obtained 16 spectral readings per individual from the adaxial and abaxial surfaces of 100 specimens belonging to 13 species. The analyses included all 1557 spectral variables. We tested different datasets (adaxial + abaxial, adaxial, and abaxial) to compare the correct identification of species through the construction of discriminant models (Linear discriminant analysis and partial least squares discriminant analysis) and cross-validation techniques (leave-one-out, K-fold). All analyses recovered an overall high percentage (> 90%) of correct predictions of specimen identifications for all datasets, regardless of the model or cross-validation used. On average, there was > 95% accuracy when using partial least squares discriminant analysis and both cross-validations. Our results show the high predictive power of FT-NIR at correctly discriminating fern species when using leaves of dried herbarium specimens. The technique is sensitive enough to reflect species delimitation problems and possible hybridization, and it has the potential of helping better delimit and identify fern species.
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Gleiquênias , Espectroscopia de Luz Próxima ao Infravermelho , Análise Discriminante , Análise dos Mínimos Quadrados , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
OBJECTIVE: To assess the reliability of the Institute for Healthcare Improvement's Global Trigger Tool (IHI-GTT) between nurses and medical students as primary reviewers to measure adverse events (AEs). DESIGN: Interrater reliability study. SETTING: A 500-bed general public hospital in Belo Horizonte, Brazil. PARTICIPANTS: A randomly selected sample of 220 hospital admissions of adults (≥18 years) from Oct-Nov, 2016. INTERVENTION: Two 4th-5th year-medical students and two experienced nurses applied a Portuguese-translated version of the IHI-GTT to medical records. The role of medical reviewer was performed by two senior physicians specialists in Internal Medicine. MAIN OUTCOME MEASURES: Ability to identify AEs was compared between pairs and against medical reviewer through percentage inter-examiner agreement and Kappa coefficient (K). Two outcomes -- "AE identification" and "category of harm" -- were evaluated according to two different denominators -- "admissions" (the total number of admissions evaluated in the sample; reflects the presence or not of at least one AE in each admission) and "all possibilities of agreement" (obtained by adding each identified AE to the admissions without events; allows agreement assessment to be performed for each AE individually). RESULTS: Were identified 199 adverse events in 90 hospitalizations, with rates of 40.9% of admissions with AEs, 76.1 AEs/1,000 patient-days and 90.5 AEs/100 admissions. Comparing student-pair and nurse-pair, we found K = 0.76 (95% IC 0.62-0.88) and K = 0.17 (95% IC 0.06-0.27) for "AE identification" outcome and K = 0.28 (95% IC 0.01-0.55) and K = 0.46 (95% IC 0.28-0.64) for "category of harm" outcome to denominators "admission" and "all possibilities of agreement", respectively. There was no significant difference between the performances of the different primary reviewers composed in any analyses. CONCLUSION: IHI-GTT reliability varies considerably depending on the denominator used to calculate agreement. As the purpose of the tool is, in addition to measuring, promoting opportunities for quality of care improvement, the individual analysis of the AEs seems more appropriate. Further studies are needed to assess the implications of the slight agreement reached between primary reviewers on the test's overall accuracy. Moreover, advanced medical students may be considered for primary review in settings where unavailability of staff is a barrier to IHI-GTT adoption.