Production of the prolyl endoprotease (PEP) from Aspergillus sp. FSDE 16 by solid-state fermentation (SSF) and use for producing a gluten-free beer.

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.

Phylogenomic evolutionary insights in the fern family Gleicheniaceae.

The pantropical fern family Gleicheniaceae comprises approximately 157 species. Seven genera are currently recognized in the family, although their monophyly is still uncertain due to low sampling in phylogenetic studies. We examined the monophyly of the genera through extended sampling, using the first phylogenomic inference of the family including data from both nuclear and plastid genomes. Seventy-six samples were sequenced (70 Gleicheniaceae species and six outgroups) using high throughput sequencing, including all seven currently recognized genera. Plastid and nuclear data were recovered and assembled; the nuclear data was phased to reduce paralogy as well as hybrid noise in the final recovered topology. Maximum likelihood trees were built for each locus, and a concatenated dataset was built for both datasets. A species tree based on a multispecies coalescent model was generated, and divergence time analyses performed. We here present the first genomic phylogenetic inferences concerning Gleicheniaceae, confirming the monophyly of most genera except Sticherus, which we recovered as paraphyletic. Although most of the extant genera of Gleicheniaceae originated during the Mesozoic, several genera show Neogene and even Quaternary diversifications, and our results suggest that reticulation and polyploidy may have played significant roles during this diversification. However, some genera, such as Rouxopteris and Stromatopteris, appear to represent evolutionary relicts.

HybPhaser identifies hybrid evolution in Australian Thelypteridaceae.

Hybridisation has been proposed to play an important role in fern evolution, but has been difficult to investigate. This study explores the utility of target sequence capture and read-to-reference phasing of putative hybrids to investigate the role of evolutionary reticulation in ferns using Australian Thelypteridaceae as a model. The bioinformatics workflow HybPhaser was used to assess divergence between alleles, phase sequence reads to references and construct accessions resembling parental haplotypes. These accessions were included in phylogenetic and network analyses to detect hybrids and infer their parentage. This approach identified two novel hybrid lineages in Thelypteridaceae, one occurring between two different genera (Abacopteris and Christella), and another as part of a complex of Christella. In addition, hybrid phasing successfully reduced conflicting data and improved overall resolution in the Thelypteridaceae phylogeny, highlighting the power of this approach for reconstructing evolutionary history in reticulated lineages.

Using near-infrared spectroscopy to discriminate closely related species: a case study of neotropical ferns.

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.

Assessment of the reliability of the IHI Global Trigger Tool: new perspectives from a Brazilian study.

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.

Biomarker responses induced by bisphenol A on spermatogenesis in a Neotropical teleost fish are temperature-dependent.

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.

State of the art in cytogenetics, insights into chromosome number evolution, and new C-value reports for the fern family Gleicheniaceae.

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.

The Program for Biodiversity Research in Brazil: The role of regional networks for biodiversity knowledge, dissemination, and conservation.

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.

Phylogenetic systematics, morphological evolution, and natural groups in neotropical Phlegmariurus (Lycopodiaceae).

The Neotropical clade of the lycophyte genus Phlegmariurus is comprised of an estimated 150 described species and exhibits exceptional morphological and ecological diversity. Because of their simple morphology, frequent convergent evolution, and the recentness of the group's diversification, the delimitation of species and species groups has remained challenging. Here, we present a robustly support phylogeny of Neotropical Phlegmariurus based on six chloroplast markers and ca. 70% of known species, and use ancestral character state reconstruction to investigate morphological evolution in the clade, and define natural species groups. The Neotropical species of Phlegmariurus form a clade that also includes a small number of Afro-Madagascan species. A morphologically and ecologically variable group of species from southeastern Brazil form a monophyletic group and represent a parallel radiation to principally Andean lineages. Species groups in Neotropical Phlegmariurus that were previously recognized based on morphology are not monophyletic. We find support for 11 morphologically cohesive and well-supported species groups. Morphological homoplasy is common in Phlegmariurus and complicates infrageneric classification of the Neotropical taxa. Our results provide a useful framework for identifying species groups and understanding patterns of morphological evolution in Neotropical Phlegmariurus. The radiation of the Brazilian species remains poorly understood and requires further study.

Hyperbaric oxygen therapy as adjuvant for treating wound complications after extensive resection for vulvar malignancy.

INTRODUCTION: Necrosis, wound breakdown, and infection represent major complications associated with radical vulvectomy. We aimed to analyze the feasibility of hyperbaric oxygen (HBO2) therapy as an adjunctive treatment for such complications. METHODS: We performed a retrospective analysis of the medical records, clinical charts, and operative records of vulvar cancer patients who underwent hyperbaric oxygen therapy after extensive surgical resection in our institute between 2012 and 2016, with a comparison of the clinical outcomes of patients with similar surgical procedures andsevere wound complications who did not undergo HBO2. RESULTS: A total of 16 patients were included in the study. In the subgroup treated with HBO2, seven patients were identified. Two patients had primary surgery, while five had recurrent surgery (of these, two had previously undergone radiation therapy). Six patients received reconstructive flaps (five myocutaneous and onefasciocutaneous), while one patient had primary suture. Dehiscence, ischemia and necrosis were estimated to cover 30%-80% of the surgical surface area. Surgical debridement was performed in six patients. Daily 90-minute sessions in the hyperbaric chamber were performed at a pressure of 2.2 atmospheres absolute, with partial oxygen pressure of 1672 mbar. Infection control and satisfactory healing were achieved using 10-61 sessions. All patients in the subgroup who did not receive HBO2 required surgical debridement due to partial or near-total flap necrosis, with two reconstructive interventions required. CONCLUSIONS: Hyperbaric oxygen therapy was an efficient adjuvant for wound healing and infection control in managing wound complications after extensive vulvar resections.

Global phylogeny and biogeography of the fern genus Ctenitis (Dryopteridaceae), with a focus on the Indian Ocean region.

The diverse and pantropical genus Ctenitis, in the Dryopteridaceae, has been largely ignored in phylogenetic studies until now. In this study, we fill in this gap by reconstructing the first comprehensive phylogeny of the genus including 53 species currently recognized in the genus Ctenitis, among which seven species formerly were assigned to the genus Pseudotectaria and one to Heterogonium. Special emphasis was given to the sampling of species occurring in the African-Indian Ocean region. The presented results include reconstruction of a biogeographic scenario based on estimated divergence times and ancestral area reconstruction. Our findings confirm the inclusion, within Ctenitis, of the Indian Ocean species formerly placed in Pseudotectaria and Heterogonium. The crown group divergence was estimated to date back to the Oligocene or Early Miocene. The biogeographical scenario indicates an initial divergence of the Asian-Pacific ranges and the neotropical ranges, and a subsequent colonization of the Afro-Madagascan region by a lineage with neotropical ancestors. The Afro-Madagascan lineage splits into a lineage endemic to the Mascarene islands and a lineage occurring in Madagascar, the Comoros and Africa. The range expansion towards Africa and Madagascar was estimated to date back to the late Miocene, whereas the estimated ages for the onset of the diversification of the Mascarene diversity is consistent with the ages of these young, volcanic islands. The absence of any extant species of Ctenitis with a multi-continental distribution range and the rarity of inter-island dispersal and speciation in the Indian Ocean region suggest a limited contribution of long distance dispersal to the biogeographical history of this fern genus, versus a high contribution of local speciation.

Molecular phylogeny of the fern family Blechnaceae (Polypodiales) with a revised genus-level treatment.

Blechnaceae, a leptosporangiate fern family nested within eupolypods II, comprises 200-250 species, typically divided among seven to nine genera. Despite recent molecular studies of the family, it still lacks a modern taxonomic update based on broad sampling from the two centres of diversity-the Neotropics and Australasia/Oceania. To test generic circumscriptions, we have assembled the broadest dataset thus far, from three plastid regions (rbcL, rps4-trnS, trnL-trnF) and with taxonomic sampling focused on both major diversity centres. Our sampling includes 156 taxa and 178 newly generated sequences. We recognize three subfamilies, each corresponding to a highly supported clade across all analyses (maximum parsimony, Bayesian inference and maximum likelihood). The genera Salpichlaena, Stenochlaena and Telmatoblechnum are monophyletic, while Blechnum is polyphyletic, because Brainea, Doodia and Sadleria all nest within it. We outline and explain a plan to resolve the polyphyly of Blechnum by recognizing additional, monophyletic, segregate genera.

Towards a phylogenetic generic classification of Thelypteridaceae: Additional sampling suggests alterations of neotropical taxa and further study of paleotropical genera.

Thelypteridaceae is one of the largest fern families, having about 950 species and a cosmopolitan distribution but with most species occurring in tropical and subtropical regions. Its generic classification remains controversial, with different authors recognizing from one up to 32 genera. Phylogenetic relationships within the family have not been exhaustively studied, but previous studies have confirmed the monophyly of the lineage. Thus far, sampling has been inadequate for establishing a robust hypothesis of infrafamilial relationships within the family. In order to understand phylogenetic relationships within Thelypteridaceae and thus to improve generic reclassification, we expand the molecular sampling, including new samples of Old World taxa and, especially, many additional neotropical representatives. We also explore the monophyly of exclusively or mostly neotropical genera Amauropelta, Goniopteris, Meniscium, and Steiropteris. Our sampling includes 68 taxa and 134 newly generated sequences from two plastid genomic regions (rps4-trnS and trnL-trnF), plus 73 rps4 and 72 trnL-trnF sequences from GenBank. These data resulted in a concatenated matrix of 1980 molecular characters for 149 taxa. The combined data set was analyzed using maximum parsimony and bayesian inference of phylogeny. Our results are consistent with the general topological structure found in previous studies, including two main lineages within the family: phegopteroid and thelypteroid. The thelypteroid lineage comprises two clades; one of these included the segregates Metathelypteris, Coryphopteris, and Amauropelta (including part of Parathelypteris), whereas the other comprises all segregates of Cyclosorus s.l., such as Goniopteris, Meniscium, and Steiropteris (including Thelypteris polypodioides, previously incertae sedis). The three mainly neotropical segregates were found to be monophyletic but nested in a broadly defined Cyclosorus. The fourth mainly neotropical segregate, Amauropelta, was found to include species considered to be part of Parathelypteris. In Old World thelypteroids, which correspond to nearly half the diversity in the family, an increase in sampling is still needed to resolve relationships and circumscription of genera, particularly in the christelloid clade (i.e., Amphineuron, Chingia, Christella, Pneumatopteris, Pronephrium, and Sphaerostephanos). Based on currently available knowledge, we propose the recognition of 16 genera in the family.

Effectiveness of an aquatic exercise program and low-level laser therapy on articular cartilage in an experimental model of osteoarthritis in rats.

OBJECTIVE: The aim of this study was to evaluate the effects of an aquatic exercise program and low-level laser therapy (LLLT) (associated or not) on degenerative modifications and inflammatory mediators on the articular cartilage using an experimental model of knee OA. METHOD: Forty male Wistar rats were divided into 4 groups: knee OA - without treatment (OA); OA plus exercise program group (OAE); OA plus LLLT (OAL); OA plus exercise program associated with LLLT (OAEL). Trained rats performed a water-jumping program carrying a load equivalent to 50-80 % of their body mass strapped to their chest. The laser irradiation was used either as the only method or after the exercise training had been performed, at 2 points contact mode (medial and lateral side of the left joint). The treatments started 4 weeks after the surgery, 3 days/week for 8 weeks. RESULTS: The results revealed that all treated groups (irradiated or not) exhibited a better pattern of tissue organization, with less fibrillation and irregularities along the articular surface and improved chondrocytes organization. Also, a lower cellular density and structural damage (OARSI score) and higher thickness values were observed in all treated groups. Additionally, OAE and OAEL showed a reduced expression in IL-1ß and caspase-3 as compared with OA. Furthermore, a statistically lower MMP-13 expression was only observed in OAEL as compared with OA. CONCLUSION: These results suggest that aquatic exercise program and LLLT were effective in preventing cartilage degeneration. Also, physical exercise program presented anti-inflammatory effects in the knees in OA rats.

A comparison of pre and post-operative vedaprofen with ketoprofen for pain control in dogs.

BACKGROUND: This prospective randomized blinded clinical study aimed to investigate the potential of vedaprofen for preventive analgesia, comparing its analgesic effects with ketoprofen administered post-operatively in dogs undergoing maxillectomy or mandibulectomy. RESULTS: Pain control was effective and rescue analgesia was not necessary in any group. Pain scores were not significantly different between groups. The respiratory rate and rectal temperature were decreased in all groups at extubation until 6 hours post-extubation compared to baseline. Cortisol and epinephrine levels were increased only at 0.5 hours after extubation in all groups compared to baseline. CONCLUSIONS: Vedaprofen did not present any preventive analgesic effect. Pre- and postoperative vedaprofen were as effective as ketoprofen for postoperative pain control.

Metal-contaminated sediment toxicity in a highly impacted Neotropical river: Insights from zebrafish embryo toxicity assays.

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.

FOXO3a deregulation in uterine smooth muscle tumors.

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.

Association of CD133, ALDH1, CD117 and OCT4 expression with prognosis of patients with cervical cancer.

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.