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New generation hormone therapies (NGHT) is the gold standard treatment for metastatic prostate cancers and/or castration-resistant tumors. Four molecules have been approved: enzalutamide, abiraterone acetate, apalutamide and darolutamide. These treatments are oral therapies taken on a daily basis, which raise issues of adherence to treatment, adverse effects and drug interactions. Therapeutic educational programs for patients represent an emerging care activity that allows patients to acquire skills to better live with their disease and treatment. As of today, no such specific program to new generation hormone therapy in prostate cancer has been developed in France, which was the goal of our current study. This was conducted in three steps: i) identification of patients' educational needs through an exchange with a focus group of patients, ii) gathering of expert opinions on useful information to be given to patients on NGHT via a questionnaire submitted to GETUG members and iii) implementation of the program per se. Qualitative analysis of exchanges with the focus group of patients led to the identification of 7 meaning categories. Expert opinions regarding useful information to deliver to patients identified 13 key items. Based on these preliminary data concerning patients' educational needs, we set up the first french program dedicated to metastatic prostate cancer patients undergoing NGHT that included three therapeutic education workshops: "Experience of the disease", "Management of the treatment" and "Physical activity and diet".
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Neoplasias de Próstata Resistentes à Castração , Acetato de Abiraterona/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , França , Hormônios/uso terapêutico , Humanos , Masculino , Nitrilas/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológicoRESUMO
Patients with one form of cancer are at increased risk for another, and this is true for lung cancer, where synchronous primary lung cancers are an increasing multifaceted challenge.1,2 Here, we present the case of a middle age woman who was found to have bilateral lung masses. Biopsy and subsequent testing revealed unique synchronous lung adenocarcinomas, each with unique genetic signatures. Despite having two unique tumors, she was found to have CHEK2 mutations in both tumors and in germline testing. Because of this extensive testing that showed unique tumors, she was ultimately diagnosed with stage IIIb and IA2 lung cancers, and this changed her treatment options. Consideration of unique primary tumors leads to thorough diagnostics, which changed this patient's diagnosis, prognosis, and treatment. We hope this case raises awareness for multiple primary tumors, as well as CHEK2 as an important oncogene.
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Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Quinase do Ponto de Checagem 2/genética , Mutação em Linhagem Germinativa , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Feminino , Humanos , Neoplasias Pulmonares/terapia , Pessoa de Meia-IdadeRESUMO
Potato bacterial wilt is caused by the devastating bacterial pathogen Ralstonia solanacearum. Quantitative resistance to this disease has been and is currently introgressed from a number of wild relatives into cultivated varieties through laborious breeding programs. Here, we present two methods that we have developed to facilitate the screening for resistance to bacterial wilt in potato. The first one uses R. solanacearum reporter strains constitutively expressing the luxCDABE operon or the green fluorescent protein (gfp) to follow pathogen colonization in potato germplasm. Luminescent strains are used for nondestructive live imaging, while fluorescent ones enable precise pathogen visualization inside the plant tissues through confocal microscopy. The second method is a BIO-multiplex-PCR assay that is useful for sensitive and specific detection of viable R. solanacearum (IIB-1) cells in latently infected potato plants. This BIO-multiplex-PCR assay can specifically detect IIB-1 sequevar strains as well as strains belonging to all four R. solanacearum phylotypes and is sensitive enough to detect without DNA extraction ten bacterial cells per mL in complex samples.The described methods allow the detection of latent infections in roots and stems of asymptomatic plants and were shown to be efficient tools to assist potato breeding programs.
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Ralstonia solanacearum , Solanum tuberosum , Reação em Cadeia da Polimerase Multiplex , Óperon , Doenças das Plantas , Ralstonia solanacearum/genéticaRESUMO
Ralstonia pseudosolanacearum GMI1000 (Rpso GMI1000) is a soil-borne vascular phytopathogen that infects host plants through the root system causing wilting disease in a wide range of agro-economic interest crops, producing economical losses. Several features contribute to the full bacterial virulence. In this work we study the participation of light, an important environmental factor, in the regulation of the physiological attributes and infectivity of Rpso GMI1000. In silico analysis of the Rpso genome revealed the presence of a Rsp0254 gene, which encodes a putative blue light LOV-type photoreceptor. We constructed a mutant strain of Rpso lacking the LOV protein and found that the loss of this protein and light, influenced characteristics involved in the pathogenicity process such as motility, adhesion and the biofilms development, which allows the successful host plant colonization, rendering bacterial wilt. This protein could be involved in the adaptive responses to environmental changes. We demonstrated that light sensing and the LOV protein, would be used as a location signal in the host plant, to regulate the expression of several virulence factors, in a time and tissue dependent way. Consequently, bacteria could use an external signal and Rpsolov gene to know their location within plant tissue during the colonization process.
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Proteínas de Bactérias/genética , Interações Hospedeiro-Patógeno/fisiologia , Ralstonia/fisiologia , Solanum lycopersicum/microbiologia , Aderência Bacteriana/fisiologia , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Luz , Polissacarídeos Bacterianos/genética , Polissacarídeos Bacterianos/metabolismo , Ralstonia/patogenicidadeRESUMO
OBJECTIVE: To evaluate the seroprevalence of COVID-19 infection in pauci-symptomatic and asymptomatic people, the associated epidemiological factors, and IgG antibody kinetic over a 5-month period to get a better knowledge of the disease transmissibility and the rate of susceptible persons that might be infected. METHODS: Seroprevalence was evaluated by a cross-sectional study based on the general population of Santa Fe, Argentina (non-probabilistic sample) carried out between July and November 2020. A subgroup of 20 seropositive individuals was followed-up to analyze IgG persistence. For the IgG anti-SARS-CoV-2 antibodies detection, the COVID-AR IgG® ELISA kit was used. RESULTS: 3 000 individuals were included conforming asymptomatic and pauci-symptomatic groups (n=1 500 each). From the total sample, only 8.83% (n=265) presented reactivity for IgG anti-SARS-CoV-2. A significant association was observed between positive anti-SARS-CoV-2 IgG and a history of contact with a confirmed case; the transmission rate within households was approximately 30%. In the pauci-symptomatic group, among the seropositive ones, anosmia and fever presented an OR of 16.8 (95% CI 9.5-29.8) and 2.7 (95% CI 1.6-4.6), respectively (p <0.001). In asymptomatic patients, IgG levels were lower compared to pauci-symptomatic patients, tending to decline after 4 months since the symptoms onset. CONCLUSION: We observed a low seroprevalence, suggestive of a large population susceptible to the infection. Anosmia and fever were independent significant predictors for seropositivity. Asymptomatic patients showed lower levels of antibodies during the 5-month follow-up. IgG antibodies tended to decrease over the end of this period regardless of symptoms.
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BACKGROUND: Recent literature has identified significant benefit of consolidation durvalumab following chemoradiotherapy in patients with unresectable non-small cell lung cancer (NSCLC). However, immunotherapy has demonstrated modest benefit in patients harboring oncogene driver mutations. While standard of care in metastatic oncogenic driven tumors is targeted tyrosine kinase inhibitors (TKIs), there is little data to guide treatment for patients who present with earlier stage unresectable disease, receiving chemoradiotherapy and have both high PD-L1 expression as well as concomitant actionable driver mutations. CLINICAL PRESENTATION: We report a patient who presented with stage IIIB lung adenocarcinoma with high PD-L1 expression (80%) for which she received definitive concurrent chemoradiotherapy with consolidation durvalumab. The patient quickly progressed and was found to harbor a MET exon 14 splice site alteration for which she received crizotinib and had a good response. DISCUSSION: This case highlights the possibility that patients with non-metastatic, unresectable NSCLC with high PD-L1 expression and a concomitant driver mutation may benefit from targeted tyrosine kinase inhibitors rather than immune checkpoint inhibitor therapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Quimiorradioterapia , Quimioterapia de Consolidação , Éxons/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MutaçãoRESUMO
ABSTRACT Objective. To evaluate the seroprevalence of COVID-19 infection in pauci-symptomatic and asymptomatic people, the associated epidemiological factors, and IgG antibody kinetic over a 5-month period to get a better knowledge of the disease transmissibility and the rate of susceptible persons that might be infected. Methods. Seroprevalence was evaluated by a cross-sectional study based on the general population of Santa Fe, Argentina (non-probabilistic sample) carried out between July and November 2020. A subgroup of 20 seropositive individuals was followed-up to analyze IgG persistence. For the IgG anti-SARS-CoV-2 antibodies detection, the COVID-AR IgG® ELISA kit was used. Results. 3 000 individuals were included conforming asymptomatic and pauci-symptomatic groups (n=1 500 each). From the total sample, only 8.83% (n=265) presented reactivity for IgG anti-SARS-CoV-2. A significant association was observed between positive anti-SARS-CoV-2 IgG and a history of contact with a confirmed case; the transmission rate within households was approximately 30%. In the pauci-symptomatic group, among the seropositive ones, anosmia and fever presented an OR of 16.8 (95% CI 9.5-29.8) and 2.7 (95% CI 1.6-4.6), respectively (p <0.001). In asymptomatic patients, IgG levels were lower compared to pauci-symptomatic patients, tending to decline after 4 months since the symptoms onset. Conclusion. We observed a low seroprevalence, suggestive of a large population susceptible to the infection. Anosmia and fever were independent significant predictors for seropositivity. Asymptomatic patients showed lower levels of antibodies during the 5-month follow-up. IgG antibodies tended to decrease over the end of this period regardless of symptoms.
RESUMEN Objetivo. Evaluar la seroprevalencia de la infección por el virus causante de la COVID-19 en personas paucisintomáticas y asintomáticas, los factores epidemiológicos asociados y la cinética de los anticuerpos IgG durante un período de cinco meses para conocer mejor la transmisibilidad de la enfermedad y la tasa de personas susceptibles a estar infectadas. Métodos. Se evaluó la seroprevalencia mediante un estudio transversal basado en la población general de Santa Fe, Argentina (muestra no probabilística) llevado a cabo entre julio y noviembre del 2020. Se realizó un seguimiento de un subgrupo de 20 personas seropositivas para analizar la persistencia de los anticuerpos IgG. Para la detección de los anticuerpos IgG contra SARS-COV-2, se empleó el kit ELISA COVID-AR IgG®. Resultados. Hubo 3 000 participantes divididos en un grupo asintomático y un grupo paucisintomático (n=1 500 cada grupo). De la muestra total, solo 8,83% (n=265) presentó una reactividad de IgG contra el SARS-CoV-2. Se observó una asociación significativa entre anticuerpos IgG positivos contra el SARS-CoV-2 y antecedente de contacto con un caso confirmado. La tasa de transmisión en el hogar fue de 30% aproximadamente. En el grupo paucisintomático, entre las personas seropositivas, la anosmia y la fiebre presentaron un OR de 16,8 (IC 95% 9,5-29,8) y 2,7 (IC 95% 1,6-4,6), respectivamente (p <0,001). En los pacientes asintomáticos, los niveles de IgG fueron inferiores en comparación con los pacientes paucisintomáticos, con tendencia a la baja pasados cuatro meses desde la aparición de los síntomas. Conclusiones. Se observó una seroprevalencia baja, indicadora de una gran población susceptible a la infección. La anosmia y la fiebre fueron factores predictivos independientes de relevancia para la seropositividad. Los pacientes asintomáticos mostraron niveles inferiores de anticuerpos durante el seguimiento de cinco meses. Los anticuerpos IgG tendieron a disminuir hacia el final del período con independencia de los síntomas.
RESUMO Objetivo. Avaliar a soroprevalência de anticorpos contra a COVID-19 em indivíduos paucissintomáticos e assintomáticos, os fatores epidemiológicos associados e a cinética dos anticorpos da classe IgG em um período de 5 meses, visando aprimorar o conhecimento sobre a transmissibilidade da doença e a taxa de suscetíveis à infecção. Métodos. Inquérito transversal de soroprevalência realizado na população geral (amostra não probabilística) de Santa Fé, na Argentina, entre julho e novembro de 2020. Um subgrupo de 20 indivíduos soropositivos foi acompanhado para analisar a persistência de anticorpos IgG. O kit de ensaio imunoenzimático (ELISA) COVID-AR IgG® foi usado para a detecção de anticorpos IgG contra SARS-CoV-2. Resultados. A amostra compreendeu 3 000 indivíduos, divididos entre assintomáticos e paucissintomáticos (n = 1.500 por grupo). Deste total, somente 8,83% (n = 265) apresentaram reatividade, com a detecção de anticorpos IgG contra SARS-CoV-2. Observou-se uma associação significativa entre a presença de anticorpos IgG contra SARS-CoV-2 e histórico de contato com caso confirmado. A taxa de transmissão intradomiciliar foi de aproximadamente 30%. No grupo paucissintomático, entre os soropositivos, o odds ratio (OR) para anosmia foi de 16,8 (IC 95% 9,5-29,8), e para febre, 2,7 (IC 95% 1,6-4,6) (p <0,001). Os indivíduos assintomáticos apresentaram níveis de IgG mais baixos que os paucissintomáticos, com uma tendência de declínio após 4 meses do início dos sintomas. Conclusões. Observou-se uma soroprevalência baixa de anticorpos contra a COVID-19 na população estudada, o que indica um grande número de pessoas suscetíveis à infecção. Anosmia e febre foram preditores importantes independentes de soropositividade. Os assintomáticos apresentaram níveis mais baixos de anticorpos aos 5 meses de acompanhamento. Houve uma tendência de redução dos anticorpos IgG ao final deste período, independentemente da presença de sintomas.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Portador Sadio/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Argentina/epidemiologia , Imunoglobulina G/sangue , Ensaio de Imunoadsorção Enzimática , Estudos Soroepidemiológicos , Estudos Transversais , Teste Sorológico para COVID-19 , Anosmia/virologiaRESUMO
Objetivo: Cartografar o percurso de uma usuária-guia na Rede de Cuidado em Saúde Mental. Método: O estudo aconteceu em uma cidade de Minas Gerais, no ano de 2018. A produção dos dados se deu por meio da elaboração de narrativas e vivências da Rede de Atenção Psicossocial e das relações sociais da usuária-guia, denominada "Borracha". Resultados: A partir do acompanhamento da produção do cuidado para com a usuária, foi possível visualizar os platôs que permeiam seu caminho, relacionados ao seu quadro psiquiátrico, ao gênero e à cor da pele e que geram estigmas que dificultam o seu caminhar na rede. Mas, apesar dos obstáculos, tem-se o acolhimento desta nos serviços substitutivos. Outro fator que desponta como possibilidade de cuidado e de reinserção social é a produtividade e geração de renda, que propicia um sentimento de pertencimento social ao indivíduo. Conclusão: Nesse sentido, apesar das falhas existentes na rede, têm-se possibilidades e mecanismos, já endossados nas políticas públicas, para a efetivação da reinserção social, como a economia solidária, bastando que Estado, gestores e profissionais de saúde se empenhem em implementá-las.
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The Liberibacter genus comprises insect endosymbiont bacterial species that cause destructive plant diseases, including Huanglongbing in citrus and zebra chip in potato. To date, pathogenic 'Candidatus Liberibacter spp.' (CLs) remain uncultured, therefore the plant-associated Liberibacter crescens (Lcr), only cultured species of the genus, has been used as a biological model for in vitro studies. Biofilm formation by CLs has been observed on the outer midgut surface of insect vectors, but not in planta. However, the role of biofilm formation in the life cycle of these pathogens remains unclear. Here, a model system for studying CLs biofilms was developed using Lcr. By culture media modifications, bovine serum albumin (BSA) was identified as blocking initial cell-surface adhesion. Removal of BSA allowed for the first time observation of Lcr biofilms. After media optimization for biofilm formation, we demonstrated that Lcr attaches to surfaces, and form cell aggregates embedded in a polysaccharide matrix both in batch cultures and under flow conditions in microfluidic chambers. Biofilm structures may represent excellent adaptive advantages for CLs during insect vector colonization helping with host retention, immune system evasion, and transmission. Future studies using the Lcr model established here will help in the understanding of the biology of CLs.
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Biofilmes/crescimento & desenvolvimento , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Modelos Biológicos , Rhizobiaceae , Liberibacter , Rhizobiaceae/patogenicidade , Rhizobiaceae/fisiologia , Soroalbumina Bovina/químicaRESUMO
Nowadays, fertilization and pest control are carried out using chemical compounds that contaminate soil and deteriorate human health. Plant growth promoting bacteria endophytes (PGPBEs), are a well-studied group of bacteria that offers benefits to the host plant, such as phytostimulation, biofertilization, and protection against other microorganisms. The study of Gluconacetobacter diazotrophicus-which belongs to PGPBEs-aids the development of alternative strategies of an integrated approach for crop management practices. Ralstonia solanacearum is responsible for bacterial wilt disease. This phytopathogen is of great interest worldwide due to the enormous economic losses it causes. In this study the action of G. diazotrophicus as a growth promoting bacterium in Arabidopsis thaliana seedlings is analyzed, evaluating the antagonistic mechanisms of this beneficial endophytic bacterium during biotic stress produced by R. solanacearum. Effective colonization of G. diazotrophicus was determined through bacterial counting assays, evaluation of anatomical and growth parameters, and pigments quantification. Biocontrol assays were carried out with Ralstonia pseudosolanacearum GMI1000 model strain and R. solanacearum A21 a recently isolated strain. Inoculation of A. thaliana (Col 0) with G. diazotrophicus Pal 5 triggers a set of biochemical and structural changes in roots, stems, and leaves of seedlings. Discrete callose deposits as papillae were observed at specific sites of root hairs, trichomes, and leaf tissue. Upon R. pseudosolanacearum GMI1000 infection, endophyte-treated plants demonstrated being induced for defense through an augmented callose deposition at root hairs and leaves compared with the non-endophyte-treated controls. The endophytic bacterium appears to be able to prime callose response. Roots and stems cross sections showed that integrity of all tissues was preserved in endophyte-treated plants infected with R. solanacearum A21. The mechanisms of resistance elicited by the plant after inoculation with the endophyte would be greater lignification and sclerosis in tissues and reinforcement of the cell wall through the deposition of callose. As a consequence of this priming in plant defense response, viable phytopathogenic bacteria counting were considerably fewer in endophyte-inoculated plants than in not-inoculated controls. Our results indicate that G. diazotrophicus colonizes A. thaliana plants performing a protective role against the phytopathogenic bacterium R. solanacearum promoting the activation of plant defense system.
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Exquisite control of the electrodeposition of metal films and coatings is critical to a number of high technology and manufacturing industries, delivering functionality as diverse as anti-corrosion and anti-wear coatings, electronic device interconnects and energy storage. The frequent involvement of more than one metal motivates the capability to control, maintain and monitor spatial disposition of the component metals, whether as multilayers, alloys or composites. Here we investigate the deposition, evolution and dissolution of single and two-component metal layers involving Ag, Cu, and Sn on Au substrates immersed in the deep eutectic solvent (DES) Ethaline. During galvanostatically controlled stripping of the metals from two-component systems the potential signature in simultaneous thickness electrochemical potential (STEP) measurements provides identification of the dissolving metal; coulometric assay of deposition efficiency is an additional outcome. When combined with quartz crystal microbalance (QCM) frequency responses, the mass change : charge ratio provides oxidation state data; this is significant for Cu in the high chloride environment provided by Ethaline. The spatial distribution (solvent penetration and external roughness) of multiple components in bilayer systems is provided by specular neutron reflectivity (NR). Significantly, the use of the recently established event mode capability shortens the observational timescale of the NR measurements by an order of magnitude, permitting dynamic in situ observations on practically useful timescales. Ag,Cu bilayers of both spatial configurations give identical STEP signatures indicating that, despite the extremely low layer porosity, thermodynamic constraints (rather than spatial accessibility) dictate reactivity; thus, surprisingly, Cu dissolves first in both instances. Sn penetrates the Au electrode on the timescale of deposition; this can be prevented by interposing a layer of either Ag or Cu.
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Bacterial wilt (BW) caused by Ralstonia solanacearum is responsible for substantial losses in cultivated potato (Solanum tuberosum) crops worldwide. Resistance genes have been identified in wild species; however, introduction of these through classical breeding has achieved only partial resistance, which has been linked to poor agronomic performance. The Arabidopsis thaliana (At) pattern recognition receptor elongation factor-Tu (EF-Tu) receptor (EFR) recognizes the bacterial pathogen-associated molecular pattern EF-Tu (and its derived peptide elf18) to confer anti-bacterial immunity. Previous work has shown that transfer of AtEFR into tomato confers increased resistance to R. solanacearum. Here, we evaluated whether the transgenic expression of AtEFR would similarly increase BW resistance in a commercial potato line (INIA Iporá), as well as in a breeding potato line (09509.6) in which quantitative resistance has been introgressed from the wild potato relative Solanum commersonii. Resistance to R. solanacearum was evaluated by damaged root inoculation under controlled conditions. Both INIA Iporá and 09509.6 potato lines expressing AtEFR showed greater resistance to R. solanacearum, with no detectable bacteria in tubers evaluated by multiplex-PCR and plate counting. Notably, AtEFR expression and the introgression of quantitative resistance from S. commersonii had a significant additive effect in 09509.6-AtEFR lines. These results show that the combination of heterologous expression of AtEFR with quantitative resistance introgressed from wild relatives is a promising strategy to develop BW resistance in potato.
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Potato (Solanum tuberosum L.) is one of the main hosts of Ralstonia solanacearum, the causative agent of bacterial wilt. This plant pathogen bacteria produce asymptomatic latent infections that promote its global spread, hindering disease control. A potato breeding program is conducted in Uruguay based on the introgression of resistance from the wild native species S. commersonii Dun. Currently, several backcrosses were generated exploiting the high genetic variability of this wild species resulting in advanced interspecific breeding lines with different levels of bacterial wilt resistance. The overall aim of this work was to characterize the interaction of the improved potato germplasm with R. solanacearum. Potato clones with different responses to R. solanacearum were selected, and colonization, dissemination and multiplication patterns after infection were evaluated. A R. solanacearum strain belonging to the phylotype IIB-sequevar 1, with high aggressiveness on potato was genetically modified to constitutively generate fluorescence and luminescence from either the green fluorescence protein gene or lux operon. These reporter strains were used to allow a direct and precise visualization of fluorescent and luminescent cells in plant tissues by confocal microscopy and luminometry. Based on wilting scoring and detection of latent infections, the selected clones were classified as susceptible or tolerant, while no immune-like resistance response was identified. Typical wilting symptoms in susceptible plants were correlated with high concentrations of bacteria in roots and along the stems. Tolerant clones showed a colonization pattern restricted to roots and a limited number of xylem vessels only in the stem base. Results indicate that resistance in potato is achieved through restriction of bacterial invasion and multiplication inside plant tissues, particularly in stems. Tolerant plants were also characterized by induction of anatomical and biochemical changes after R. solanacearum infection, including hyperplasic activity of conductor tissue, tylose production, callose and lignin deposition, and accumulation of reactive oxygen species. This study highlights the potential of the identified tolerant interspecific potato clones as valuable genetic resources for potato-breeding programs and leads to a better understanding of resistance against R. solanacearum in potato.
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The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood donors. Allelic frequencies, Global Linkage Disequilibrium (GLD), Linkage Disequilibrium (LD) for specific pairs of alleles and two-loci haplotype frequencies were estimated. We showed that HLA-A, HLA-H, HLA-F, HLA-G and HLA-G UTRs were all in highly significant pairwise GLD, in contrast to HLA-E. Moreover, HLA-A displayed restricted associations with HLA-G UTR and HLA-H. We also confirmed several associations that were previously found to have a negative impact on transplantation outcome. In summary, our results suggest complex functional and clinical implications of the HLA-A genetic region.
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Alelos , Antígenos HLA-A/genética , Antígenos de Histocompatibilidade Classe I/genética , França , Frequência do Gene , Loci Gênicos , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Several breeding programs are under way to introduce resistance to bacterial wilt caused by Ralstonia solanacearum in solanaceous crops. The lack of screening methods allowing easy measurement of pathogen colonization and the inability to detect latent (i.e., symptomless) infections are major limitations when evaluating resistance to this disease in plant germplasm. We describe a new method to study the interaction between R. solanacearum and potato germplasm that overcomes these restrictions. The R. solanacearum UY031 was genetically modified to constitutively generate light from a synthetic luxCDABE operon stably inserted in its chromosome. Colonization of this reporter strain on different potato accessions was followed using life imaging. Bacterial detection in planta by this nondisruptive system correlated with the development of wilting symptoms. In addition, we demonstrated that quantitative detection of the recombinant strain using a luminometer can identify latent infections on symptomless potato plants. We have developed a novel, unsophisticated, and accurate method for high-throughput evaluation of pathogen colonization in plant populations. We applied this method to compare the behavior of potato accessions with contrasting resistance to R. solanacearum. This new system will be especially useful to detect latency in symptomless parental lines before their inclusion in long-term breeding programs for disease resistance.
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Cromossomos Bacterianos/genética , Proteínas Luminescentes/genética , Organismos Geneticamente Modificados , Doenças das Plantas/microbiologia , Ralstonia solanacearum/genética , Solanum/microbiologia , Proteínas de Bactérias/genética , Cruzamento , Resistência à Doença , Genes Reporter , Genes Sintéticos , Interações Hospedeiro-Patógeno , Medições Luminescentes , Óperon , Raízes de Plantas/microbiologia , Caules de Planta/microbiologia , Regiões Promotoras Genéticas , Ralstonia solanacearum/isolamento & purificação , Ralstonia solanacearum/patogenicidade , Ralstonia solanacearum/fisiologia , Sensibilidade e Especificidade , Solanum tuberosum/microbiologia , VirulênciaRESUMO
Victims of massive bee attacks become extremely ill, presenting symptoms ranging from dizziness and headache to acute renal failure and multiple organ failure that can lead to death. Previous attempts to develop specific antivenom to treat these victims have been unsuccessful. We herein report a F(ab)(´)(2)-based antivenom raised in horse as a potential new treatment for victims of multiple bee stings. The final product contains high specific IgG titers and is effective in neutralizing toxic effects, such as hemolysis, cytotoxicity and myotoxicity. The assessment of neutralization was revised and hemolysis, the primary toxic effect of these stings, was fully neutralized in vivo for the first time.
Assuntos
Antivenenos/imunologia , Venenos de Abelha/imunologia , Abelhas/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Antivenenos/toxicidade , Relação Dose-Resposta Imunológica , Hemólise/imunologia , Cavalos , Imunização , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fab das Imunoglobulinas/isolamento & purificação , Imunoglobulina G/imunologia , Masculino , Camundongos , Testes de NeutralizaçãoRESUMO
Objetivo: Estimar a dose efetiva (E) e o detrimento associados aos exames de Tomografia Computadorizada de Feixe Cônico (TCFC), seguindo as últimas recomendações da International Comission on Radiological Protection (ICRP). Materiais e Métodos: A E foi calculada multiplicando-se as dosesabsorvidas/equivalentes pela medula óssea, tireóide, pele, superfície óssea, glândulas salivares, cérebro e órgãos remanescentes (região extra-torácica, linfonodos, músculo e mucosa oral), resultantes de diferentes equipamentos e protocolos de aquisição de imagens, pelo fator de peso desses tecidos. O detrimento foi estimado multiplicando-se o valor de E pelo coeficiente de probabilidade de efeitos estocásticos resultantes de baixas doses de radiação que é 5,7 x 10-2 eventos por Sievert (Sv). Os equipamentos e protocolos foram agrupados de acordo com o volume irradiado (campo de visão). A média, desvio padrão e coeficiente devariação de cada grupo foram calculados. Resultados: Protocolos que empregaram um campo de visãomaior resultaram em aumento da dose efetiva e do detrimento. As médias (desvio-padrão) das doses efetivaspara campos de visão pequeno, médio e grande foram 33,91 μSv (13,38), 82,85 μSv (74,26) e 107,99 μSv (43,82), respectivamente. O grupo de campo de visão pequeno apresentou menor coeficiente de variação (39%). Conclusão: A E resultante da TCFC é alta comparada a outros exames radiográficos convencionais,embora o detrimento seja relativamente pequeno. A indicação dos exames e a seleção dos protocolos devem ser criteriosamente justificadas de forma que os benefícios resultantes da exposição dos pacientes à radiaçãosuperem o potencial detrimento.
Assuntos
Medição de Risco , Tomografia Computadorizada de Feixe Cônico/efeitos adversos , Doses de RadiaçãoRESUMO
Na prática clínica, apesar dos avanços tecnológicosdecorrentes dos resultados de pesquisa, ainda é comum encontrarvários profissionais utilizando produtos no tratamento tópico de lesões sem evidência científica. Um produto muitoutilizado é o composto de ácidos graxos essenciais(AGE). No entanto, são observados alguns questionamentos quanto asua efetividade. Diante disso, optou)se por fazer uma revisão integrativa da literatura com objetivo de identificar aefetividade dos ácidos graxos essenciais no tratamento de lesão cutânea. Como resultado dessa revisão,pode)se concluirque publicações relevantes sobre o tema ainda são escassas e os estudos aqui analisados não se constituem referênciapara o uso do AGE, visto que os mesmos apresentam fragilidades metodológicas que inviabilizam o estabelecimento derecomendações.
In clinical practice, despite technological advances arising from research results, it is still commonto find manyprofessionals using products in the topical treatment of lesions without scientific evidence. A widelyused product iscomposed of essential fatty acids (AGE). However, some issues about its effectiveness can be observed.Thus, we decidedto make an integrative review of the literature toidentify the effectiveness of essential fatty acidsin the treatment ofskin lesion. As a result of this review, we can conclude that relevant publications on the subject arestill scarce and thestudies reviewed here do not represent a referenceto the use of the AGE, as they have methodologicalweaknesses thatprevent the establishment of recommendations.
En la práctica clínica, a pesar de los avances tecnológicos derivados de resultados de la investigación, aún es comúnencontrar muchos profesionales que utilizan productos en el tratamiento tópico de las lesiones, sin evidencia científica.Un producto ampliamente utilizado se compone de ácidos grasos esenciales (AGE). Sin embargo, se hacenalgunaspreguntas acerca de su eficacia. Por lo tanto, hemos decidido hacer una revisión bibliográfica integrada que tuvo comoobjetivo identificar la eficacia de los ácidos grasos esenciales en el tratamiento de lesiones en la piel. Como resultado deesta revisión, podemos concluir que las publicaciones relevantes sobre el tema son todavía escasas y los estudios revisadosaquí, no constituyen una referencia para el uso delAGE, ya que presentan deficiencias metodológicas que impiden elestablecimiento de recomendaciones.
Assuntos
Humanos , Cicatrização , Ácidos Graxos Essenciais , Ácidos LinolênicosRESUMO
Peptides constitute the largest group of Hymenoptera venom toxins; some of them interact with GPCR, being involved with the activation of different types of leukocytes, smooth muscle contraction and neurotoxicity. Most of these toxins vary from dodecapeptides to tetradecapeptides, amidated at their C-terminal amino acid residue. The venoms of social wasps can also contains some tetra-, penta-, hexa- and hepta-peptides, but just a few of them have been structurally and functionally characterized up to now. Protonectin (ILGTILGLLKGL-NH(2)) is a polyfunctional peptide, presenting mast cell degranulation, release of lactate dehydrogenase (LDH) from mast cells, antibiosis against Gram-positive and Gram-negative bacteria and chemotaxis for polymorphonucleated leukocytes (PMNL), while Protonectin (1-6) (ILGTIL-NH(2)) only presents chemotaxis for PMNL. However, the mixture of Protonectin (1-6) with Protonectin in the molar ratio of 1:1 seems to potentiate the biological activities dependent of the membrane perturbation caused by Protonectin, as observed in the increasing of the activities of mast cell degranulation, LDH releasing from mast cells, and antibiosis. Despite both peptides are able to induce PMNL chemotaxis, the mixture of them presents a reduced activity in comparison to the individual peptides. Apparently, when mixed both peptides seems to form a supra-molecular structure, which interact with the receptors responsible for PMNL chemotaxis, disturbing their individual docking with these receptors. In addition to this, a comparison of the sequences of both peptides suggests that the sequence ILGTIL is conserved, suggesting that it must constitute a linear motif for the structural recognition by the specific receptor which induces leukocytes migration.