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1.
Tech Coloproctol ; 26(11): 893-900, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35986806

RESUMO

BACKGROUND: High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell cancer (ASCC) precursors. Although it is superior to other diagnostic methods, particularly cytology, the visual identification of areas suspected of having high-grade squamous intraepithelial lesions remains difficult. Convolutional neural networks (CNNs) have shown great potential for assessing endoscopic images. The aim of the present study was to develop a CNN-based system for automatic detection and differentiation of HSIL versus LSIL in HRA images. METHODS: A CNN was developed based on 78 HRA exams from a total of 71 patients who underwent HRA at a single high-volume center (GH Paris Saint-Joseph, Paris, France) between January 2021 and January 2022. A total of 5026 images were included, 1517 images containing HSIL and 3509 LSIL. A training dataset comprising 90% of the total pool of images was defined for the development of the network. The performance of the CNN was evaluated using an independent testing dataset comprising the remaining 10%. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve (AUC) were calculated. RESULTS: The algorithm was optimized for the automatic detection of HSIL and its differentiation from LSIL. Our model had an overall accuracy of 90.3%. The CNN had sensitivity, specificity, positive and negative predictive values of 91.4%, 89.7%, 80.9%, and 95.6%, respectively. The area under the curve was 0.97. CONCLUSIONS: The CNN architecture for application to HRA accurately detected precursors of squamous anal cancer. Further development and implementation of these tools in clinical practice may significantly modify the management of these patients.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Lesões Intraepiteliais Escamosas , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/patologia , Inteligência Artificial , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Humanos , Redes Neurais de Computação
2.
Tech Coloproctol ; 25(11): 1243-1248, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34499277

RESUMO

BACKGROUND: Colon capsule endoscopy (CCE) is a minimally invasive alternative for patients unwilling to undergo conventional colonoscopy, or for whom the latter exam is contraindicated. This is particularly important in the setting of colorectal cancer screening. Nevertheless, these exams produce large numbers of images, and reading them is a monotonous and time-consuming task, with the risk of overlooking important lesions. The development of automated tools based on artificial intelligence (AI) technology may improve some of the drawbacks of this diagnostic instrument. METHODS: A database of CCE images was used for development of a Convolutional Neural Network (CNN) model. This database included anonymized images of patients with protruding lesions in the colon or patients with normal colonic mucosa or with other pathologic findings. A total of 3,387,259 frames from 24 CCE exams were retrospectively reviewed. For CNN development, 3640 images (860 protruding lesions and 2780 with normal mucosa or other findings) were ultimately extracted. Training and validation datasets were constructed for the development and testing of the CNN. RESULTS: The CNN detected protruding lesions with a sensitivity, specificity, positive and negative predictive values of 90.7, 92.6, 79.2 and 96.9%, respectively. The area under the receiver operating characteristic curve for detection of protruding lesions was 0.97. CONCLUSIONS: The deep learning algorithm we developed is capable of accurately detecting protruding lesions. The application of AI technology to CCE may increase its diagnostic accuracy and acceptance for screening of colorectal neoplasia.


Assuntos
Endoscopia por Cápsula , Neoplasias Colorretais , Inteligência Artificial , Colo/diagnóstico por imagem , Colonoscopia , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Estudos Retrospectivos
3.
Dig Dis Sci ; 63(3): 746-754, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29349693

RESUMO

BACKGROUND/AIMS: The broader use of anti-tumor necrosis factor (TNF) agents in inflammatory bowel disease (IBD) has been associated with a high rate of adverse reactions. Dermatological complications are among the most common adverse events. We assessed the incidence, risk factors, management, and outcome of anti-TNF-induced dermatological complications in a large cohort of IBD patients. METHODS: This was an observational retrospective study at a single tertiary referral center. All consecutive adult IBD patients treated with anti-TNF agents between 2005 and 2015 were identified. Patients who developed at least one dermatological complication while on anti-TNF therapy were included. RESULTS: From the 732 patients treated with anti-TNF agents, 211 (29%) developed at least one dermatological complication: 52% women (mean age of 42 ± 13 years), 85% with Crohn's disease, 67% were under infliximab. Median follow-up time under anti-TNF therapy was 53 (27-77) months. Dermatological complications recorded were: infections (13.5%), psoriasiform lesions (5.3%), injection/infusion reactions (3.8%), skin cancer (0.5%), and miscellaneous (5.6%). Overall, female gender (OR = 1.658, p = 0.029), smoking (OR = 2.021, p = 0.003), and treatment with an infliximab dose of 10 mg/kg (OR = 2.012, p = 0.007) were independent risk factors for dermatological complications in multivariable analysis. Female gender (OR = 3.63, p = 0.017), smoking (OR = 2.846, p = 0.041), and treatment with adalimumab (OR = 8.894, p < 0.001) were independently associated with development of psoriasiform lesions. Three (3%) patients with infectious complications and 12 (31%) patients with psoriasiform lesions discontinued anti-TNF therapy definitively. CONCLUSIONS: Dermatological manifestations occurred in almost one-third of our population. Infections were the most common complication, but anti-TNF-induced psoriasiform lesions were the most common cause for anti-TNF therapy definitive discontinuation.


Assuntos
Anti-Inflamatórios/efeitos adversos , Toxidermias/epidemiologia , Fármacos Gastrointestinais/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/efeitos adversos , Adulto , Toxidermias/patologia , Toxidermias/terapia , Feminino , Humanos , Incidência , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
4.
Dis Esophagus ; 30(3): 1-6, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27629280

RESUMO

Self-expanding metal stents (SEMS) are the treatment of choice for advanced esophageal cancers. Literature is scarce on risk factors predictors for adverse events after SEMS placement. Assess risk factors for adverse events after SEMS placement in advanced esophageal cancer and evaluate survival after SEMS placement. Cross-sectional study of patients with advanced esophageal cancer referred for SEMS placement, during a period of 3 years. Ninety-seven patients with advanced esophageal cancer placed SEMS. Adverse events were more common when tumors were located at the level of the distal esophagus/cardia (47% vs 23%, P = 0.011, OR 3.1), with statistical significance being kept in the multivariate analysis (OR 3.1, P = 0.018). Time until adverse events was lower in the tumors located at the level of the distal esophagus/cardia (P = 0.036). Survival was higher in patients who placed SEMS with curative intent (327 days [126-528] vs. 119 days [91-147], P = 0.002) and in patients submitted subsequently to surgery compared with those who did just chemo/radiotherapy or who did not do further treatment (563 days [378-748] vs. 154 days [133-175] vs. 46 days [20-72], P < 0.001). Subsequent treatment kept statistical significance in the multivariate analysis (HR 3.4, P < 0.001). SEMS allow palliation of dysphagia in advanced esophageal cancer and are associated with an increased out-of-hospital survival, as long as there are conditions for further treatments. Tumors located at the level of the distal esophagus/cardia are associated with a greater number of adverse events, which also occur earlier.


Assuntos
Transtornos de Deglutição/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagoscopia/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Stents Metálicos Autoexpansíveis/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cárdia/patologia , Cárdia/cirurgia , Terapia Combinada , Estudos Transversais , Transtornos de Deglutição/etiologia , Intervalo Livre de Doença , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/patologia , Esofagoscopia/instrumentação , Esofagoscopia/métodos , Esôfago/patologia , Esôfago/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cuidados Paliativos/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
5.
Rapid Commun Mass Spectrom ; 29(9): 821-9, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-26377010

RESUMO

RATIONALE: Individual foraging behavior is an important variable of predators commonly studied at the population level. Some hammerhead shark species play a significant role in the marine ecosystem as top consumers. In this context, stable isotope analysis allows us to infer some ecological metrics and patterns that cannot usually be obtained using traditional methods. METHODS: We determined the isotopic composition (δ(13)C and δ(15)N values) of dorsal muscle and vertebrae of Sphyrna lewini and Sphyrna zygaena using a continuous-flow system consisting of an elemental analyzer combined with a Delta Plus XL mass spectrometer. Foraging variability by sex and by individual was inferred from the isotopic values. RESULTS: There were no significant differences in the isotopic values of muscle samples between sexes, but there were differences between species. The trophic niche breadth of the two species was similar and overlap was low. A low niche overlap was observed between S. lewini individual vertebrae. We found differences in the δ(15)N values of S. zygaena vertebrae, with lower values in the first group of samples. CONCLUSIONS: Despite these hammerhead shark species inhabiting the same area, there was low trophic niche overlap between species and individuals, due to different individual foraging strategies, according to the carbon and nitrogen isotopic profiles obtained. The use of tissues that retain lifetime isotopic information is useful to complement studies on trophic ecology.

6.
Antonie Van Leeuwenhoek ; 107(2): 575-88, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25527391

RESUMO

Plants interact with a myriad of microbial cells in the rhizosphere, an environment that is considered to be important for plant development. However, the differential structuring of rhizosphere microbial communities due to plant cultivation under differential agricultural practices remains to be described for most plant species. Here we describe the rhizosphere microbiome of grapevine cultivated under conventional and organic practices, using a combination of cultivation-independent approaches. The quantification of bacterial 16S rRNA and nifH genes, by quantitative PCR (qPCR), revealed similar amounts of these genes in the rhizosphere in both vineyards. PCR-DGGE was used to detect differences in the structure of bacterial communities, including both the complete whole communities and specific fractions, such as Alphaproteobacteria, Betaproteobacteria, Actinobacteria, and those harboring the nitrogen-fixing related gene nifH. When analyzed by a multivariate approach (redundancy analysis), the shifts observed in the bacterial communities were poorly explained by variations in the physical and chemical characteristics of the rhizosphere. These approaches were complemented by high-throughput sequencing (67,830 sequences) based on the V6 region of the 16S rRNA gene, identifying the major bacterial groups present in the rhizosphere of grapevines: Proteobacteria, Actinobacteria, Firmicutes, Bacteriodetes, Acidobacteria, Cloroflexi, Verrucomicrobia and Planctomycetes, which occur in distinct proportions in the rhizosphere from each vineyard. The differences might be related to the selection of plant metabolism upon distinct reservoirs of microbial cells found in each vineyard. The results fill a gap in the knowledge of the rhizosphere of grapevines and also show distinctions in these bacterial communities due to agricultural practices.


Assuntos
Agricultura/métodos , Biota , Microbiologia do Solo , Argentina , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Eletroforese em Gel de Gradiente Desnaturante , Oxirredutases/genética , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real , Rizosfera , Análise de Sequência de DNA , Vitis/crescimento & desenvolvimento
7.
Transgenic Res ; 23(6): 1043-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24659218

RESUMO

The Brazilian National Biosafety Committee approved in 2011 a new post release monitoring system for environmental releases of genetically modified organisms. It has a number of novel features in comparison with other established or proposed systems. The new system also allows the proponent to ask for monitoring exemption. General surveillance forms the basis of the monitoring system, similar to the European model, but differs markedly in the way it operates. While the European proposal is based on monitoring measurable variables extracted from environmental observations, from baselines previously established for multiple protection targets, the Brazilian system uses direct alerts of damage, without the aid of baseline values. The strength of the Brazilian form of monitoring is the possibility of generating an information network with the effective participation of many actors from the monitored area. A network constituted by highly qualified members, as proposed elsewhere, is too complex and unrealistic in Brazil and in many other countries. In conclusion, the Brazilian monitoring system is flexible and can be adjusted to the Brazilian reality over the next years, as a response to the ever growing experience in monitoring. It also meets the demands of the Brazilian society for transparency, rational use of resources, opportunity for national companies, and food and environmental biosafety.


Assuntos
Exposição Ambiental/prevenção & controle , Monitoramento Ambiental/métodos , Plantas Geneticamente Modificadas/efeitos adversos , Medição de Risco/métodos , Brasil , Humanos
8.
Parasite Immunol ; 36(7): 313-23, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24606067

RESUMO

Serodiagnosis of visceral leishmaniasis is often hindered by cross-reactions to other parasitic diseases. Identifying specific B-cell epitopes in proteins is therefore important for immunodiagnostics, as well as for disease control by vaccines. This study aimed to identify linear and conformational B-cell epitopes and to evaluate the secondary structure of antigen proteins in Leishmania infantum using in silico analysis. Linear epitopes were predicted using the Immune Epitope Database and Analysis Resource (IEDB), BepiPred and BcePred programs. The conformational B-cell epitopes were identified using the CBTOPE server. The combination of the predictions using IEDB, BepiPred and BcePred generated 148 linear epitopes from the calpain-like cysteine peptidase (CP), thiol-dependent reductase 1 (TDR1) and HSP70 proteins. In total, 164 conformational epitopes were predicted, mostly located in the linear epitope region. The predicted epitopes are located in α helix and random coil regions in the thiol-dependent reductase 1 and HSP70 proteins. New linear and conformational B-cell epitopes of L. infantum proteins were identified in silico, and the prediction using various programs ensures greater accuracy of the results, as suggested by confirmation of previously identified HSP70 epitopes.


Assuntos
Antígenos de Protozoários/imunologia , Epitopos de Linfócito B/imunologia , Leishmania infantum/imunologia , Leishmaniose Visceral/imunologia , Sequência de Aminoácidos , Antígenos de Protozoários/química , Biologia Computacional/métodos , Cisteína Endopeptidases/química , Cisteína Endopeptidases/imunologia , Proteínas de Choque Térmico HSP70/química , Proteínas de Choque Térmico HSP70/imunologia , Humanos , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/parasitologia , Dados de Sequência Molecular , Oxirredutases/química , Oxirredutases/imunologia
9.
Braz J Biol ; 84: e278069, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865564

RESUMO

Products derived from medicinal plants with antimicrobial activity are considered a promising alternative in the treatment of fungal infections. In this perspective, this study proposed to evaluate the antifungal activity of the dichloromethane fraction of Annona crassiflora Mart. against C. albicans strains. Tests were carried out to determine Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC), microbial growth kinetics, fungal cell wall and membrane mechanisms of action, antifungal biofilm activity, and cytotoxic effects on human erythrocytes. The extract presented MIC and MFC values that ranged from 256 µg/mL to 1,024 µg/mL, with fungicidal activity in the microbial growth kinetics assay. The mechanism of action did not occur through damage to the cell wall or via binding to ergosterol in the membrane, though the fraction presents activity against biofilm and is not cytotoxic in human erythrocytes. The dichloromethane fraction of Annona crassiflora Mart. presented antifungal activity and reduced biofilm growth, without toxicity against human erythrocytes; however, further studies are needed to define its mechanism of action.


Assuntos
Annona , Antifúngicos , Biofilmes , Candida albicans , Cloreto de Metileno , Testes de Sensibilidade Microbiana , Extratos Vegetais , Annona/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Humanos , Extratos Vegetais/farmacologia , Biofilmes/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos
10.
Reprod Fertil Dev ; 25(6): 955-65, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23050662

RESUMO

The aim of the present study was to evaluate the effects of growth differentiation factor 9 (GDF-9) and FSH on the in vitro development of caprine preantral follicles cultured for 16 days. Ovarian fragments were cultured in αMEM⁺ (α-minimum essential medium, pH 7.2-7.4, 10 µg mL⁻¹ insulin, 5.5 µg mL⁻¹ transferrin, 5.0 ng mL⁻¹ selenium, 2 mM glutamine, 2 mM hypoxanthine and 1.25 mg mL⁻¹ bovine serum albumin) in the absence or presence of 200 ng mL⁻¹ GDF-9 and/or 50 ng mL⁻¹ FSH added during the first (Days 0-8) and/or second (Days 8-16) half of the culture period. Non-cultured and cultured fragments were processed for histological and ultrastructural analyses. After 16 days, all treatments using GDF-9 or FSH showed higher rates of follicular survival compared with αMEM⁺ alone. Compared with non-cultured control, sequential culture media containing GDF-9 and/or FSH significantly increased the percentage of developing follicles and follicle diameter. Moreover, a progressive increase in oocyte diameter was observed only with sequential culture medium containing GDF-9 until Day 8 followed by FSH (GDF-9/FSH) in the second half of the culture period. After 16 days of culture, ultrastructural analysis confirmed the integrity of follicles cultured in the presence of GDF-9/FSH. In conclusion, a dynamic medium containing GDF-9 and FSH (GDF-9/FSH) maintained follicular integrity and promoted activation of primordial follicles and growth during long-term in vitro culture of goat preantral follicles.


Assuntos
Fármacos para a Fertilidade Feminina/farmacologia , Hormônio Foliculoestimulante/farmacologia , Cabras/fisiologia , Fator 9 de Diferenciação de Crescimento/farmacologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Folículo Ovariano/efeitos dos fármacos , Matadouros , Animais , Brasil , Bovinos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cruzamentos Genéticos , Feminino , Hormônio Foliculoestimulante/genética , Fator 9 de Diferenciação de Crescimento/genética , Humanos , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Oócitos/ultraestrutura , Oogênese/efeitos dos fármacos , Folículo Ovariano/fisiologia , Folículo Ovariano/ultraestrutura , Proteínas Recombinantes/farmacologia , Fatores de Tempo , Técnicas de Cultura de Tecidos/veterinária
11.
Genet Mol Res ; 12(4): 4459-67, 2013 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-24222225

RESUMO

Period-3 oscillations in genome composition can be detected through correlation functions. Since these oscillations are closely related to the genetic code structure, we developed methods for quantitative comparison of genomic and exonic oscillation amplitudes and decay. In contrast to genomic correlations, exonic period-3 oscillation amplitudes are persistent. A model postulating an uncorrelated distribution of exons in the genome has been applied to the analysis of Escherichia coli K12, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens genomic decay, allowing for a quantitative discussion of genome organization.


Assuntos
Éxons , Modelos Genéticos , Algoritmos , Animais , Caenorhabditis elegans/genética , Drosophila melanogaster/genética , Escherichia coli K12/genética , Código Genético , Genoma Bacteriano , Genoma Fúngico , Genoma Helmíntico , Genoma Humano , Genoma de Inseto , Humanos , Saccharomyces cerevisiae/genética , Análise de Sequência de DNA
12.
Braz J Anesthesiol ; 73(2): 132-137, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34626754

RESUMO

BACKGROUND: Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during anesthesia, but also by day-to-day symptoms, such as exercise intolerance, that may alert the health professional. OBJECTIVE: The study aimed to analyze the incidence of fatigue in MH susceptible patients and the variables that can impact perception of fatigue, such as the level of routine physical activity and depression. METHODS: A cross-sectional observational study was carried out with three groups ... 22 patients susceptible to MH (positive in vitro muscle contracture test), 13 non-susceptible to MH (negative in vitro muscle contracture test) and 22 controls (no history of MH). Groups were assessed by a demographic/clinical questionnaire, a fatigue severity scale (intensity, specific situations, psychological consequences, rest/sleep response), and the Beck depression scale. Subgroups were re-assessed with the Baecke habitual physical exercise questionnaire (occupational physical activity, leisure physical exercise, leisure/locomotion physical activity). RESULTS: There were no significant differences among the three groups regarding fatigue intensity, fatigue related to specific situations, psychological consequences of fatigue, fatigue response to resting/sleeping, depression, number of active/sedentary participants, and the mean time and characteristics of habitual physical activity. Nevertheless, unlike the control sub-group, the physically active MH-susceptible subgroup had a higher fatigue response to resting/sleeping than the sedentary MH susceptible subgroup (respectively, 5.9.ß...ß1.9 vs. 3.9.ß...ß2, t-test unpaired, p.ß<.ß0.05). CONCLUSION: We did not detect subjective fatigue in MH susceptible patients, although we reported protracted recovery after physical activity, which may alert us to further investigation requirements.


Assuntos
Contratura , Hipertermia Maligna , Humanos , Hipertermia Maligna/epidemiologia , Hipertermia Maligna/diagnóstico , Halotano , Estudos Transversais , Depressão , Exercício Físico , Suscetibilidade a Doenças/diagnóstico
13.
Braz J Biol ; 83: e274070, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37937628

RESUMO

Coffea sp. is cultivated in many tropical countries. Brazil has always adopted intensive agricultural practices, but organic coffee farming is an alternative system based on the non-use of agrochemicals and the rational management of soils. Metabarcoding 16S analysis using next-generation sequencing has been developed to identify and compare the diversity of the Coffea arabica L. rhizospheric bacterial community in two farming areas in São Paulo, Brazil. Dourado uses conventional farming, while Ribeirão Corrente uses organic. We found broad taxonomic composition, with sequences from 24 phyla, 55 classes, 61 orders, 146 families, and 337genus. The three most abundant phyla were Proteobacteria (38.27%), Actinobacteria (15.56%), and Acidobacteria (16.10%). In organic farming, the top 3 were the family Sphingomonadaceae, order Rhizobiales, genus Nocardioides, and Gp6. The genus Gp2 and the phylum Candidatus Saccharibacteria were the most abundant OTUs exclusively present in conventional farming. In the organic farming practice, Proteobacteria, Actinobacteria, and Acidobacteria were also present among the exclusive OTUs; we also found OTUs belonging to Bacteroidetes, Firmicutes, and Verrucomicrobia. Our study indicates a positive effect of organic farming on microbial communities. Fertilization may directly affect soil microbiota, suggesting that a large and active microbial community low in functional diversity might not adapt to new climatic conditions. A diverse community could provide better resilience to environmental changes, improving the productivity of this important crop.


Assuntos
Coffea , Humanos , Brasil , Bactérias/genética , Agricultura , Proteobactérias/genética , Solo/química , Microbiologia do Solo , RNA Ribossômico 16S/genética
14.
Clin Genet ; 82(1): 56-63, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21534946

RESUMO

Mutations in the TMPRSS3 gene are known to cause autosomal recessive non-syndromic hearing impairment (ARNSHI). After undergoing a genome scan, 10 consanguineous Pakistani families with ARNSHI were found to have significant or suggestive evidence of linkage to the TMPRSS3 region. In order to elucidate if the TMPRSS3 gene is responsible for ARNSHI in these families, the gene was sequenced using DNA samples from these families. Six TMPRSS3 variants were found to cosegregate in 10 families. None of these variants were detected in 500 control chromosomes. Four novel variants, three of which are missense [c.310G>A (p.Glu104Lys), c.767C>T (p.Ala256Val) and c.1273T>C (p.Cys425Arg)] and one nonsense [c.310G>T (p.Glu104Stop)], were identified. The pathogenicity of novel missense variants was investigated through bioinformatics analyses. Additionally, the previously reported deletion c.208delC (p.His70ThrfsX19) was identified in one family and the known mutation c.1219T>C (p.Cys407Arg) was found in five families, which makes c.1219T>C (p.Cys407Arg) as the most common TMPRSS3 mutation within the Pakistani population. Identification of these novel variants lends support to the importance of elements within the low-density lipoprotein receptor A (LDLRA) and serine protease domains in structural stability, ligand binding and proteolytic activity for proper TMPRSS3 function within the inner ear.


Assuntos
Orelha Interna/patologia , Perda Auditiva/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Serina Endopeptidases/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 21 , Consanguinidade , Orelha Interna/enzimologia , Éxons , Feminino , Genes Recessivos , Ligação Genética , Loci Gênicos , Perda Auditiva/enzimologia , Perda Auditiva/patologia , Humanos , Masculino , Modelos Moleculares , Mutação , Linhagem , Fenótipo , Estrutura Terciária de Proteína
15.
Clin Oncol (R Coll Radiol) ; 34(9): 608-616, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35667940

RESUMO

AIMS: In recent years, major improvements in breast cancer treatments have led to a significant increase in survival. Despite that, this population's quality of life (QoL) information is lacking, especially real-world data. MATERIALS AND METHODS: This was a prospective, multicentre, observational study of female breast cancer patients, without prior systemic treatment, treated between 2012 and 2019 in private health care in Brazil. QoL was assessed by two questionnaires, the EQ-5D-5L and the EORTC-QLQ-BR23. Additional data were retrospectively collected. RESULTS: The study comprised 1372 patients, most with early-stage disease (80.2% stages 0-II). At a median follow-up of 25.6 months, the estimated 3-year overall survival was 93.6%. Patients with locally advanced and metastatic breast cancer had the lowest visual analogue scale scores and the highest symptom burden in all dimensions of EQ-5D-5L, but with the most significant improvement after treatment. With the EORTC-QLQ-BR23 questionnaire, patients undergoing lumpectomy had a better perception of body image. Axillary dissection led to greater arm symptoms after 12 months, radiotherapy enhanced breast symptoms and patients treated with chemotherapy had significant worsening in the effects of systemic therapy compared with endocrine or HER2 therapy. Staging and immunohistochemical subtype correlated with survival and with several QoL parameters, but overall survival was not independently affected by patient-reported outcomes in this cohort. CONCLUSION: Our results show that early diagnosis and access to treatments with fewer side-effects, such as endocrine or targeted therapy, and less aggressive surgeries are the best strategies to achieve a better QoL for breast cancer patients.


Assuntos
Neoplasias da Mama , Qualidade de Vida , Neoplasias da Mama/terapia , Feminino , Humanos , Assistência Centrada no Paciente , Estudos Prospectivos , Estudos Retrospectivos , Inquéritos e Questionários
16.
Genet Mol Res ; 10(3): 1393-402, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21823088

RESUMO

The chelonians are, in general, important for the economy of the traditional populations of the Amazon region, especially as a source of animal protein. Furthermore, sub-products, such as eggs and fat, are utilized in the manufacture of cosmetics, and the plastron and carapace are used in the manufacture of adornments. The freshwater turtle species Podocnemis sextuberculata, locally known as "iaçá" or "pitiú", is widely distributed in the Amazon Basin in Brazil and also in Colombia and Peru. This species is on the International Union for Conservation of Nature Red List in the category of vulnerable species. We examined the genetic variability and population structure of three populations represented by 64 individuals sampled from Reserva Federal de Abufari, Tapauá, Amazonas State; Reserva de Desenvolvimento Sustentável Mamirauá, Tefé, Amazonas State, and Terra Santa, Pará State. All of these are over 1000 km from each other. A partial 415-bp sequence of the mitochondrial gene ND1 was utilized as a molecular marker. Seven haplotypes were observed; the most common haplotype was shared by all the areas sampled, while the rarest haplotypes were represented by a single individual and were thus restricted to a single locality. The sharing of the most common haplotype, the high number of migrants (Nm) and the AMOVA results indicate a lack of genetic structure among the sampling localities. The levels of genetic variability observed were homogeneous among the sampling localities. These results (Ó¨(ST) and Nm) are compatible with what is known about the ecology of this species, which has a great migratory capacity.


Assuntos
Genética Populacional/métodos , Animais , Brasil , Colômbia , DNA Mitocondrial/genética , Haplótipos/genética , Peru , Tartarugas/classificação , Tartarugas/genética
17.
Acta Gastroenterol Belg ; 84(4): 669-671, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34965051

RESUMO

Whipple's disease is a rare chronic systemic infection caused by Tropheryma whipplei. The widespread infection by this rod is responsible for the protean clinical manifestations of the disease, although its classical form is notable for the prevalence of abdominal symptoms such as chronic diarrhea and abdominal pain. Whitish-yellow patches, suggestive of lymphangiectasia, are typically observed in the duodenum during upper endoscopy. The diagnosis of this condition is supported by the identification in duodenal biopsies of Periodic acid-Schiff staining within lamina propria macrophages. Nevertheless, a significant portion of patients do not have lesions within the range of conventional upper endoscopy. Therefore, other endoscopic procedures such as video capsule endoscopy and enteroscopy may be useful to detect more distal lesions. The authors describe a case where the combined used of both techniques allowed the unmasking of this disease.


Assuntos
Doença de Whipple , Antibacterianos/uso terapêutico , Duodeno/diagnóstico por imagem , Endoscopia Gastrointestinal , Humanos , Tropheryma , Doença de Whipple/diagnóstico , Doença de Whipple/tratamento farmacológico
19.
Dermatol Online J ; 16(9): 5, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20875326

RESUMO

We report the case of a 30-year-old woman presenting with a single, deep, asymptomatic frontal ulcer that had developed in the previous two months without preceding trauma. Blood tests revealed reactive Rapid Plasma Reagin and Treponema pallidum hemagglutination assays. The diagnosis of syphilitic gumma was confirmed after histological analysis of the ulcer border. No other manifestations of late syphilis were detected. Ulcer healing was observed after treatment with benzathine penicillin and there was progressive reduction of follow-up serum RPR titers. The relevance of this case arises from its unusual presentation in a previously healthy immunocompetent individual.


Assuntos
Úlcera Cutânea/microbiologia , Sífilis/diagnóstico , Adulto , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Penicilina G Benzatina/uso terapêutico , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/tratamento farmacológico , Sífilis/tratamento farmacológico , Treponema pallidum
20.
Dermatol Online J ; 16(12): 11, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-21199637

RESUMO

We report the case of a 64-year-old male presenting with a rapidly enlarging painful violaceous plaque in the left buttock and posterior thigh, following a gluteal intramuscular injection of benzathine penicillin. Associated urinary incontinence and lower left limb paresis were consistent with sciatic and lower sacral nerve damage, as confirmed by electromyography. Additional underlying muscular damage was observed in ultrasound and computer tomodensitometry scans and supported by high serum levels of creatine kinase and lactate dehydrogenase. Aggressive treatment was performed with fluid expansion, intravenous steroid bolus, vasodilators and anticoagulation, resulting in slow improvement of cutaneous and muscular lesions. However, no significant effect was observed on neurologic dysfunction after 6 months of regular neuromuscular rehabilitation. Nicolau Livedoid Dermatitis is a rare and potentially fatal condition showing variable levels of tissue impairment and unpredictable course and prognosis. Specific treatment is not consensual and the efficacy of any particular treatment remains to be established.


Assuntos
Antibacterianos/efeitos adversos , Artérias/lesões , Injeções Intramusculares/efeitos adversos , Isquemia/induzido quimicamente , Plexo Lombossacral/lesões , Doenças Musculares/induzido quimicamente , Paresia/etiologia , Penicilina G Benzatina/efeitos adversos , Nervo Isquiático/lesões , Pele/irrigação sanguínea , Incontinência Urinária/etiologia , Antibacterianos/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Artérias/efeitos dos fármacos , Nádegas , Humanos , Isquemia/tratamento farmacológico , Plexo Lombossacral/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Paresia/induzido quimicamente , Paresia/terapia , Penicilina G Benzatina/administração & dosagem , Púrpura/induzido quimicamente , Nervo Isquiático/irrigação sanguínea , Sífilis/complicações , Sífilis/tratamento farmacológico , Coxa da Perna , Incontinência Urinária/induzido quimicamente , Incontinência Urinária/terapia
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