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Renal involvement is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The present study included patients with recently diagnosed Class III and Class IV lupus nephritis (LN) treated by Rheumatology who, upon the detection of alterations in their kidney function, were referred to Nephrology for the joint management of both medical specialties. The purpose of this study was to compare the plasma expression of Toll-Like Receptor 7 (TLR7) and TLR9 in healthy control (HC) subjects and newly diagnosed Class III and Class IV LN patients with 12-month follow-ups. The plasma expression of TLR7 and TLR9 proteins was determined by the ELISA method. A significant increase in the expression of TLR7 protein was found in Class III LN in the basal determination compared to the expression in the HC (p = 0.002) and at 12 months of follow-up (p = 0.03) vs. HC. The expression of TLR9 showed a behavior opposite to that of TLR7. TLR9 showed decreased protein expression in LN Class III patients' baseline and final measurements. The result was similar in the basal and final determinations of LN Class IV compared to the expression in HC. A significant decrease in SLEDAI -2K was observed at 12 months of follow-up in patients in Class III (p = 0.01) and Class IV (p = 0.0001) of LN. Complement C3 levels improved significantly at 12-month follow-up in Class IV patients (p = 0.0001). Complement C4 levels decreased significantly at 12-month follow-up in LN Class III compared to baseline (p = 0.01). Anti-DNA antibodies decreased significantly at 12 months of follow-up in Class IV LN (p = 0.01). A significant increase in proteinuria was found at 12 months of follow-up in Class III LN, compared to the baseline determination (p = 0.02). In LN Class IV, proteinuria decreased at 12 months of follow-up compared to baseline (p = 0.0001). Albuminuria decreased at 12 months of follow-up in LN Class IV (p = 0.006). Class IV LN, albuminuria also decreased at 12 months of follow-up (p = 0.009). Hematuria persisted in all patients and the glomerular filtration rate did not change. Three Class IV patients died before 12 months of follow-up from various causes. In conclusion, although the rheumatologic data appeared to improve, the renal function data remained inconsistent. Decreased expression of TLR9 and increased expression of TLR7 could be useful in the early diagnosis of Class III and Class IV LN is correct.
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Nefrite Lúpica , Receptor 7 Toll-Like , Receptor Toll-Like 9 , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/sangue , Nefrite Lúpica/metabolismo , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/genética , Receptor Toll-Like 9/metabolismo , Feminino , Adulto , Masculino , Seguimentos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto JovemRESUMO
Objective: To determine gender gaps in Emeritus researchers in Colombia. Methods: Oaxaca-Blinder-Kitakagwa decomposition model, correcting the sample selection bias with the inclusion of Mills' inverse ratio (Heckman's Lambda) through an ordered probit model. Data: Information available in the ScienTI Platform - Colombia during the period 2015-2021. Results: The results show that the gender gap between female and male researchers is 5.8%. To achieve Emeritus status, one must be over 65 years old, and the possibility of achieving Emeritus status is 5.1% higher for female researchers than for their male counterparts. These differences can be explained by the time constraints that female researchers face in being productive, as they spend more time than male researchers on caregiving responsibilities, either due to motherhood or the care of other dependent family members. Conclusions: The results obtained allow us to affirm that there is a gender gap in scientific research in Colombia in the Emeritus research category in the calls for proposals for the period 2015-2021. Moreover, the existing gap cannot be explained by factors associated with attributes of education and academic productivity that are part of the regulatory requirements, insofar as not being explained by them, it evidences the existence of discrimination against women researchers to access the highest research category.
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Pesquisadores , Colômbia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Fatores SexuaisRESUMO
OBJECTIVES: To evaluate the influence of dentin moisture on the clinical behavior of a universal adhesive on posterior teeth after 36 months of follow-up. METHODS: Forty-five patients participated in this study. Following a split-mouth design, three operators placed 90 Class I/Class II restorations over moist dentin (MD) or dry (DD) (n = 45) with resin composite (Filtek Bulk Fill) and a universal adhesive used in the etch-and-rinse mode (Single Bond Universal). Each restoration was evaluated according to the FDI and USPHS criteria (postoperative sensitivity, fracture and retention, marginal staining, marginal adaptation, and recurrence of caries) at baseline and after 6-, 12-, and 36 months. For statistical analysis, Kruskal Wallis analysis of variance rank (α = 0.05) and Kaplan-Meier survival analysis were used. RESULTS: No significant difference between groups was observed in each FDI criterion after 36 months of clinical evaluation (p > 0.05). The retention rates (confidence interval 95 %) were 97.37 % (86.5 - 99.5) for both MD and DD without significant difference between them (p > 0.05). Eight restorations (MD = 4; DD = 4) showed minimal marginal staining defects (p > 0.05). Two restorations were lost (MD = 1; DD = 1). Fifteen restorations (MD = 8; DD = 7) presented minor marginal discrepancies according to the FDI criteria (p > 0.05). CONCLUSION: The clinical performance of the universal adhesive when applied in etch-and-rinse mode was not influenced by dentin moisture in posterior bulk-fill composite restorations. CLINICAL SIGNIFICANCE: The level of dentin moisture appears not to influence the clinical efficacy of a universal adhesive when applied using the etch-and-rinse technique in posterior composite resin restorations.
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Bis-Fenol A-Glicidil Metacrilato , Resinas Compostas , Cárie Dentária , Adaptação Marginal Dentária , Falha de Restauração Dentária , Restauração Dentária Permanente , Sensibilidade da Dentina , Adesivos Dentinários , Dentina , Cimentos de Resina , Humanos , Restauração Dentária Permanente/métodos , Resinas Compostas/química , Resinas Compostas/uso terapêutico , Feminino , Masculino , Método Duplo-Cego , Adulto , Cimentos de Resina/química , Pessoa de Meia-Idade , Bis-Fenol A-Glicidil Metacrilato/química , Bis-Fenol A-Glicidil Metacrilato/uso terapêutico , Cárie Dentária/terapia , Adesivos Dentinários/química , Adesivos Dentinários/uso terapêutico , Seguimentos , Adulto Jovem , Resultado do Tratamento , Colagem Dentária/métodos , Condicionamento Ácido do DenteRESUMO
BACKGROUND: Snakebite envenomation inflicts a high burden of mortality and morbidity in sub-Saharan Africa. Antivenoms are the mainstay in the therapy of envenomation, and there is an urgent need to develop antivenoms of broad neutralizing efficacy for this region. The venoms used as immunogens to manufacture snake antivenoms are normally selected considering their medical importance and availability. Additionally, their ability to induce antibody responses with high neutralizing capability should be considered, an issue that involves the immunization scheme and the animal species being immunized. METHODOLOGY/PRINCIPAL FINDINGS: Using the lethality neutralization assay in mice, we compared the intrageneric neutralization scope of antisera generated by immunization of horses with monospecific, bispecific/monogeneric, and polyspecific/monogeneric immunogens formulated with venoms of Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp. or non-spitting Naja spp. It was found that the antisera raised by all the immunogens were able to neutralize the homologous venoms and, with a single exception, the heterologous congeneric venoms (considering spitting and non-spitting Naja separately). In general, the polyspecific antisera of Bitis spp, Echis spp, and Dendroaspis spp gave the best neutralization profile against venoms of these genera. For spitting Naja venoms, there were no significant differences in the neutralizing ability between monospecific, bispecific and polyspecific antisera. A similar result was obtained in the case of non-spitting Naja venoms, except that polyspecific antiserum was more effective against the venoms of N. melanoleuca and N. nivea as compared to the monospecific antiserum. CONCLUSIONS/SIGNIFICANCE: The use of polyspecific immunogens is the best alternative to produce monogeneric antivenoms with wide neutralizing coverage against venoms of sub-Saharan African snakes of the Bitis, Echis, Naja (non-spitting) and Dendroaspis genera. On the other hand, a monospecific immunogen composed of venom of Naja nigricollis is suitable to produce a monogeneric antivenom with wide neutralizing coverage against venoms of spitting Naja spp. These findings can be used in the design of antivenoms of wide neutralizing scope for sub-Saharan Africa.
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Antivenenos , Testes de Neutralização , Animais , Cavalos/imunologia , Antivenenos/imunologia , Antivenenos/administração & dosagem , Camundongos , África Subsaariana , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Venenos de Serpentes/imunologia , Soros Imunes/imunologia , Venenos Elapídicos/imunologia , Mordeduras de Serpentes/imunologiaRESUMO
OBJECTIVE: Identify molecular mimicry between TPO, eosinophil peroxidase (EPX), thyroglobulin and IL24 and microorganism antigens. METHODS: Through in silico analysis, we performed local alignments between human and microorganism antigens with PSI-BLAST. Proteins that did not present a 3D structure were modeled by homology through the Swiss Modeller server and epitope prediction was performed through Ellipro. Epitopes were located in the 3D models using PYMOL software. RESULTS: A total of 38 microorganism antigens (parasites, bacteria) had identities between 30% and 45%, being the highest with Anisakis simplex. The alignment between 2 candidate proteins from A. simplex and EPX presented significant values, with identities of 43 and 44%. In bacteria, Campylobacter jejuni presented the highest identity with thyroglobulin (35%). 220 linear and conformational epitopes of microorganism antigens were predicted. Peroxidasin-like proteins from Toxocara canis and Trichinella pseudospiralis presented 10 epitopes similar to TPO and EPX, as possible molecules triggering cross-reactivity. No virus presented identity with the human proteins studied. CONCLUSION: TPO and EPX antigens shared potential cross-reactive epitopes with bacterial and nematode proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between infections and urticaria/hypothyroidism. In vitro work is needed to demonstrate the results obtained in the in silico analysis.
OBJETIVO: Identificar mimetismo molecular entre TPO, eosinofil peroxidasa (EPX), tiroglobulina e IL24 y antígenos de microorganismos. MÉTODOS: A través de análisis in silico, realizamos los alineamientos locales entre los antígenos humanos y de microorganismos con PSI-BLAST. Las proteínas que no presentaban estructura 3D, fueron modeladas por homología a través del servidor Swiss Modeller y se realizó una predicción de epítopes a través de Ellipro. Los epítopes se localizaron en los modelos 3D utilizando el software PYMOL. RESULTADOS: Un total de 38 antígenos de microorganismos (parásitos y bacterias), tuvieron identidades entre 30 y 45%, siendo los más altos con Anisakis simplex. El alineamiento entre dos proteínas candidatas de A. simplex y EPX presentaron valores importantes, con identidades de 43 y 44%. En las bacterias, Campylobacter jejuni presentó la mayor identidad con tiroglobulina (35%). Se predijeron 220 epítopes lineales y conformacionales de antígenos de microorganismos. Las proteínas similares a la peroxidasina de Toxocara canis y Trichinella pseudospiralis presentaron diez epítopes similares a TPO y EPX, como posibles moléculas desencadenantes de una reactividad cruzada. Ningún virus presentó identidad con las proteínas humanas estudiadas. CONCLUSIÓN: Los antígenos TPO y EPX compartieron potenciales epítopes de reacción cruzada con proteínas bacterianas y nematodos, lo que sugiere que el mimetismo molecular podría ser un mecanismo que explique la relación entre infecciones y la urticaria/hipotiroidismo. Se necesitan trabajos in vitro que demuestren los resultados obtenidos en el análisis in silico.
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Autoantígenos , Iodeto Peroxidase , Mimetismo Molecular , Tireoglobulina , Mimetismo Molecular/imunologia , Humanos , Tireoglobulina/imunologia , Iodeto Peroxidase/imunologia , Peroxidase de Eosinófilo/imunologia , Animais , Antígenos de Bactérias/imunologia , Reações Cruzadas , Proteínas de Ligação ao Ferro/imunologia , Epitopos/imunologiaRESUMO
OBJECTIVE: Analyze the molecular mimicry between Plasmodium spp. and autoantigens associated with GBS, identifying possible antigenic epitopes. METHODS: PSI-Blast, Praline, Emboss, Protein Data Bank, Swiss Model Server, AlphaFold 2, Ellipro and PyMol 2.3 were used to search for homologies, perform alignments, obtain protein structures, and predict epitopes. RESULTS: 17 autoantigens and seven immunological targets of the peripheral nervous system were included, identifying 72 possible epitopes associated with GBS. From the proteome of Plasmodium spp. (298 proteins), only two showed similarities close to 30% with TRIM21 and BACE1, generating seven possible epitopes. CONCLUSION: No significant homologies were observed between the proteome of GBS and Plasmodium spp. The exploration of other mechanisms such as immune-mediated capillary damage, Epitope Spreading or Bystander Activation is suggested to explain the mentioned association. These findings underscore the need to clarify the etiology of autoimmune diseases and the role of pathogens. The need for experimental studies to validate these results is emphasized.
OBJETIVO: Analizar el mimetismo molecular entre Plasmodium spp. y autoantígenos asociados al SGB, identificando posibles epítopos antigénicos. MÉTODOS: Se emplearon PSI-Blast, Praline, Emboss, Protein Data Bank, Swiss Model Server, AlphaFold 2, Ellipro y PyMol 2.3 para buscar homologías, realizar alineamientos, obtener estructuras proteicas y predecir epítopos. RESULTADOS: Se incluyeron 17 autoantígenos y siete objetivos inmunológicos del sistema nervioso periférico, identificándose 72 posibles epítopos asociados al SGB. Del proteoma de Plasmodium spp. (298 proteínas), solo dos mostraron similitud cercana al 30% con TRIM21 y BACE1, generando siete posibles epítopos. CONCLUSIÓN: No se observaron homologías significativas entre el proteoma de SGB y Plasmodium spp. Se sugiere la exploración de otros mecanismos como el daño capilar inmunomediado, Epitope Spreading o Bystander Activation para explicar la asociación mencionada. Estos hallazgos subrayan la necesidad de aclarar la etiología de las enfermedades autoinmunes y el papel de los patógenos. Se enfatiza la necesidad de estudios experimentales para validar estos resultados.
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Síndrome de Guillain-Barré , Mimetismo Molecular , Mimetismo Molecular/imunologia , Síndrome de Guillain-Barré/imunologia , Humanos , Plasmodium/imunologia , Autoantígenos/imunologia , Epitopos/imunologiaRESUMO
OBJECTIVE: Conduct an in-silico assessment of potential molecular mimicry between human aquaporins, A. fumigatus, and diverse allergenic sources. METHODS: Amino acid sequences of human AQP3 and A. fumigatus aquaporin were compared through multiple alignments with 25 aquaporins from diverse allergenic sources. Phylogenetic analysis and homology-based modeling were executed, and the ElliPro server predicted conserved antigenic regions on 3D structures. RESULTS: Global identity among studied aquaporins was 32.6%, with a specific conserved local region at 71.4%. Five monophyletic clades (A-E) were formed, and Group B displayed the highest identity (95%), including 6 mammalian aquaporins, notably AQP3. A. fumigatus aquaporin exhibited the highest identity with Malassezia sympodialis (35%). Three linear and three discontinuous epitopes were identified in both human and A. fumigatus aquaporins. The Root Mean Square Deviation (RMSD) from overlapping aquaporin structures was 1.006. CONCLUSION: Identification of potential linear and conformational epitopes on human AQP3 suggests likely molecular mimicry with A. fumigatus aquaporins. High identity in a specific antigenic region indicates potential autoreactivity and a probable antigenic site involved in cross-reactivity. Validation through in vitro and in vivo studies is essential for further understanding and confirmation.
OBJETIVO: Realizar una evaluación in silico del posible mimetismo molecular entre las acuaporinas humanas, A. fumigatus y diversas fuentes alergénicas. MÉTODOS: Se compararon secuencias de aminoácidos de AQP3 humana y acuaporina de A. fumigatus mediante alineamientos múltiples con 25 acuaporinas de diversas fuentes alergénicas. Se ejecutaron análisis filogenéticos y modelos basados en homología, y el servidor ElliPro predijo regiones antigénicas preservadas en estructuras 3D. RESULTADOS: La identidad global entre las acuaporinas estudiadas fue del 32.6%, con una región local específica preservada en el 71.4%. Se formaron cinco clados monofiléticos (A-E), y el grupo B mostró la identidad más alta (95%), incluidas 6 acuaporinas de mamíferos, en particular AQP3. A. fumigatus aquaporin exhibió la mayor identidad con Malassezia sympodialis (35%). Se identificaron tres epítopos lineales y tres discontinuos en acuaporinas tanto humanas como de A. fumigatus. La desviación cuadrática media (RMSD) de las estructuras de acuaporinas superpuestas fue de 1,006. CONCLUSIÓN: La identificación de posibles epítopos lineales y conformacionales en AQP3 humano sugiere un probable mimetismo molecular con acuaporinas de A. fumigatus. La identidad alta en una región antigénica específica indica autorreactividad potencial y un sitio antigénico probable implicado en la reactividad cruzada. La validación mediante estudios in vitro e in vivo es desicivo para una mayor comprensión y confirmación.
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Alérgenos , Aquaporina 3 , Aquaporinas , Aspergillus fumigatus , Simulação por Computador , Mimetismo Molecular , Aspergillus fumigatus/imunologia , Humanos , Aquaporinas/química , Aquaporinas/genética , Aquaporinas/metabolismo , Aquaporinas/imunologia , Aquaporina 3/metabolismo , Aquaporina 3/genética , Alérgenos/imunologia , Hipersensibilidade/imunologia , Proteínas Fúngicas/química , Proteínas Fúngicas/imunologia , Proteínas Fúngicas/genética , Sequência de Aminoácidos , Filogenia , Epitopos/imunologiaRESUMO
OBJECTIVES: To evaluate the clinical performance of posterior restorations over wet and dry dentin with an etch-and-rinse adhesive after 36 months of clinical service. METHODS: Forty-five participants were recruited, each one had at least two posterior teeth that needed restoration. Ninety restorations were placed on Class I or Class II cavities. For the restoration protocol, a simplified etch-and-rinse adhesive (Adper Single Bond 2) was applied over wet (WD) or dry dentin (DD) and later restored with a bulk-fill composite (Filtek Bulk Fill) under rubber dam isolation. Each restoration was evaluated using the World Dental Federation (FDI) criteria after 6, 12, and 36 months of clinical service, regarding the following principal restoration characteristics: postoperative sensitivity, marginal discoloration, marginal adaptation, fracture of material and retention, and recurrence of caries. Kruskal Wallis analysis of variance rank (α = 0.05) and Kaplan-Meier survival analysis were used for statistical analysis. RESULTS: After 36 months of clinical evaluation, no significant difference between groups was observed in each FDI criterion (p > 0.05). Twenty restorations (WD=10, DD=10) showed minor marginal staining, and twenty-two restorations (WD=11, DD=11) presented small marginal adaptation defects (p > 0.05). Four restorations were lost (WD = 2, DD = 2) and the fracture rates (95% confidence interval) were 94.9% for each one, without significant difference between wet and dry dentin (p > 0.05). SIGNIFICANCE: The degree of dentin moisture does not seem to affect the clinical performance of a simplified etch-and-rinse adhesive in posterior restorations when the adhesive is applied vigorously over the dentine surface.
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Cárie Dentária , Cimentos Dentários , Humanos , Adesivos Dentinários/química , Cimentos de Resina , Restauração Dentária Permanente/métodos , Resinas Compostas/química , Cárie Dentária/terapia , Dentina , Adaptação Marginal DentáriaRESUMO
Snakebite envenomation is a neglected tropical disease posing a high toll of mortality and morbidity in sub-Saharan Africa. Polyspecific antivenoms of broad effectiveness and specially designed for this region require a detailed understanding of the immunological features of the mamba snake (Dendroaspis spp.) venoms for the selection of the most appropriate antigen combination to produce antivenoms of wide neutralizing scope. Monospecific antisera were generated in rabbits against the venoms of the four species of mambas. The toxic effects of the immunization scheme in the animals were evaluated, antibody titers were estimated using immunochemical assays, and neutralization of lethal activity was assessed. By the end of the immunization schedule, rabbits showed normal values of the majority of hematological parameters tested. No muscle tissue damage was noticed, and no alterations in most serum chemical parameters were observed. Immunological analyses revealed a variable extent of cross-reactivity of the monospecific antisera against the heterologous venoms. The venoms of D. jamesoni and D. viridis generated the antisera with broader cross-reactivity by immunochemical parameters. The venoms of D. polylepis and D. viridis generated the antisera with better cross-neutralization of lethality, although the neutralizing ability of all antisera was lower than 0.16 mg venom/mL antiserum against either homologous or heterologous venoms. These experimental results must be scaled to large animal models used in antivenom manufacture at industrial level to assess whether these predictions are reproducible.
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This study analyzes the clinical characteristics of patients diagnosed with White Piedra through a systematic review of cases in the literature. A sample of 131 subjects was considered, of which 91.6% were female and most were 18 years of age or younger. Most studies were conducted in Brazil, followed by India, and Mexico. The most common etiologic agent found was Trichosporon spp (34.3%). Most affected patients were asymptomatic (94.6%) and predisposing factors included long hair, use of a hair band or hair accessories, and wet hair. The most common clinical feature was the presence of nodules. The evaluation of treatment effectiveness was hindered by the scarcity of follow-up information in the majority of the studies. It is concluded that White Piedra infection is more common in young women and is associated with hair-related factors.
Assuntos
Piedra , Trichosporon , Humanos , Feminino , Masculino , Piedra/diagnóstico , Piedra/tratamento farmacológico , Piedra/etiologia , Cabelo , Brasil/epidemiologia , México/epidemiologiaRESUMO
En el pasado mes mayo, realizamos el Foro: Integridad Científica, Buenas Prácticas en Publicación y Ciencia Abierta. Este evento fue una ocasión importante en la que abordamos temas actuales en el ámbito de la investigación científica, coincidiendo con la conmemoración de los 20 años de nuestra Revista Investigaciones Andina y el 90 aniversario del nacimiento del gran divulgador científico Carl Sagan. Recordando sus palabras: "La ciencia no es perfecta, con frecuencia se utiliza mal, no es más que una herramienta, pero es la mejor herramienta que tenemos. Se corrige a sí misma, está siempre evolucionando y se puede aplicar a todo. Con esta herramienta conquistamos lo imposible", reflexionamos sobre la importancia de la integridad en la ciencia, así como los retos que enfrentamos en su defensa. Sagan también nos recordó que "los humanos se comportan como humanos", haciendo referencia a la complejidad y desafíos que pueden surgir en el comportamiento ético
Last May, we held the Forum: Scientific Integrity, Best Practices in Publication and Open Science. This event was an important occasion in which we addressed current issues in the field of scientific research, coinciding with the commemoration of the 20th anniversary of our journal Investigaciones Andina and the 90th anniversary of the birth of the great science popularizer Carl Sagan. Recalling his words: "Science is not perfect, it is often misused, it is only a tool, but it is the best tool we have. It corrects itself, it is always evolving and can be applied to everything. With this tool we conquer the impossible," we reflected on the importance of integrity in science, as well as the challenges we face in its defense. Sagan also reminded us that "humans behave like humans," referring to the complexity and challenges that can arise in ethical behavior.
No passado mês de maio, realizámos o Fórum: Integridade Científica, Boas Práticas de Publicação e Ciência Aberta. Este evento foi uma ocasião importante em que abordámos questões actuais no campo da investigação científica, coincidindo com a comemoração do 20º aniversário da nossa revista Investigaciones Andina e o 90º aniversário do nascimento do grande divulgador da ciência Carl Sagan. Recordando as suas palavras: "A ciência não é perfeita, é muitas vezes mal utilizada, é apenas uma ferramenta, mas é a melhor ferramenta que temos. Corrige-se a si própria, está sempre a evoluir e pode ser aplicada a tudo. Com esta ferramenta conquistamos o impossível", reflectimos sobre a importância da integridade na ciência, bem como sobre os desafios que enfrentamos para a defender. Sagan lembrou-nos também que "os humanos comportam-se como humanos", referindo-se à complexidade e aos desafios que podem surgir no comportamento ético.
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Humanos , Revisão de Integridade CientíficaRESUMO
BACKGROUND: Infections are a major cause of morbidity and mortality in patients with pemphigus vulgaris (PV). One of the most common infections in these patients is candidiasis. This is probably due to the use of systemic immunosuppressants, including oral and intravenous corticosteroids, mainly in megadoses (pulse therapy), although it is unknown if there are other associated factors, in addition to immunosuppressive treatment. We determine the factors associated with candidiasis in PV patients in two second-care level hospitals in Mexico. METHODS: We reviewed 100 cases with PV. Cases were randomly selected from the databases of two second-care level hospitals between January 2010 and December 2019 (10 years). The primary endpoint was the incidence of candidiasis in patients with PV. RESULTS: One hundred patients with PV were enrolled in this retrospective study. Candidiasis was observed in 79 patients (79%). A maximum corticosteroid dose of 55 mg/day during the last year (p = 0.001) and a higher neutrophil/lymphocyte ratio were associated with candidiasis in patients with PV (p = 0.001). CONCLUSION: Risk factors favoring candidiasis in patients with PV are not only related to the use of corticosteroids, but also to demographic factors, the activity of the disease, and the systemic inflammation associated with autoimmunity.
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Lupus nephritis (LN) is the most frequent and severe complication of systemic lupus erythematosus (SLE). A prospective cohort with a six-month follow-up was performed. Twelve SLE patients diagnosed with LN Class III, twelve NL Class IV patients, and twelve healthy control subjects (HC) were included. SLE data, renal function, oxidants, antioxidants, and inflammation were determined at baseline and six-month follow-up. During the six-month follow-up, the SLE Disease Activity Index (SLEDAI-2K) decreased in both LN Class III (20.08 ± 6.92 vs. 11.92 ± 5.87, p < 0.001) and LN Class IV (25.33 ± 6.01 vs. 13.83 ± 5.52, p < 0.001) patients. Furthermore, the values of the C4 component also increased during follow-up for LN Class III (25.36 ± 6.34 vs. 30.91 ± 9.22, p = 0.027) and LN Class IV (12.18 ± 3.90 vs. 20.33 ± 8.95, p = 0.008) groups. Regarding inflammation markers, both groups presented decreased C-reactive protein (CRP), but this was only significant for patients with LN class III (7.93 ± 1.77 vs. 4.72 ± 3.23, p = 0.006). Renal function remained stable in both groups, with no changes in eGFR. Patients with LN Class III and Class IV showed higher baseline levels for lipoperoxides (Class III p < 0.01, Class IV p < 0.1) and carbonyl groups in proteins (Class III p < 0.01, Class IV p < 0.1) compared to HC. Moreover, both groups presented lower baseline values of total antioxidant capacity (Class III p < 0.01, Class IV p < 0.1) and catalase (Class III p < 0.01, Class IV p < 0.1) compared to HCs. However, antioxidant and oxidant markers did not show significant differences between baseline values and at six months for either of the two study groups. In conclusion, patients show an imbalance in the oxidative state characterized by the increase in the oxidants LPO and protein carbonyl groups and the decrease in the activity of the antioxidant enzymes TAC and CAT compared to HC. However, the patients did not present an increase in disease activity and renal function improvement. The glomerular filtration rate did not change during the length of the study, and SLEDAI -2K, C3, and C4 improved. The early co-management between Rheumatologists and Nephrologists is essential to prevent the rapid progression of LN. It would be interesting to administer antioxidant supplements to patients with a recent diagnosis of LN and evaluate its effect in a follow-up study.
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Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immune-pathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the roles of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing roles of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/metabolismo , Receptor Toll-Like 9/metabolismo , Receptor 7 Toll-Like/genética , Imunidade Inata , OxirreduçãoRESUMO
BACKGROUND: Envenomations by African snakes represent a high burden in the sub-Sahara region. The design and fabrication of polyspecific antivenoms with a broader effectiveness, specially tailored for its use in sub-Saharan Africa, require a better understanding of the immunological features of different Naja spp. venoms of highest medical impact in Africa; and to select the most appropriate antigen combinations to generate antivenoms of wider neutralizing scope. METHODOLOGY/PRINCIPAL FINDINGS: Rabbit-derived monospecific antisera were raised against the venoms of five spitting cobras and six non-spitting cobras. The effects of immunization in the animal model were assessed, as well as the development of antibody titers, as proved by immunochemical assays and neutralization of lethal, phospholipase A2 and dermonecrotic activities. By the end of the immunization schedule, the immunized rabbits showed normal values of all hematological parameters, and no muscle tissue damage was evidenced, although alterations in aspartate aminotransferase (AST) and alkaline phosphatase (ALP) suggested a degree of hepatic damage caused mainly by spitting cobra venoms. Immunologic analyses revealed a considerable extent of cross-reactivity of monospecific antisera against heterologous venoms within the spitting and no-spitting cobras, yet some antisera showed more extensive cross-reactivity than others. The antisera with the widest coverage were those of anti-Naja ashei and anti-N. nigricollis for the spitting cobras, and anti-N. haje and anti-N. senegalensis for the non-spitting cobras. CONCLUSIONS/SIGNIFICANCE: The methods and study design followed provide a rationale for the selection of the best combination of venoms for generating antivenoms of high cross-reactivity against cobra venoms in sub-Saharan Africa. Results suggest that venoms from N. ashei, N. nigricollis within the spitting cobras, and N. haje and N. senegalensis within the non-spitting cobras, generate antisera with a broader cross-reactivity. These experimental results should be translated to larger animal models used in antivenom elaboration to assess whether these predictions are reproduced.
Assuntos
Lagomorpha , Naja , Animais , Coelhos , Elapidae , Antivenenos/farmacologia , Soros Imunes , Venenos ElapídicosRESUMO
During the production of snake antivenoms, the animals used as immunoglobulin source are subjected to processes that could deteriorate their physical condition. Therefore, these conditions must be carefully designed and validated. In this work, the immunization and bleeding protocols applied to horses used to produce the African polyspecific antivenom EchiTAb-plus-ICP were evaluated regarding their effects on the horses' health. The study focused on horses that had been previously immunized with venoms and then received periodic booster venom injections for antivenom production. It was found that the periodic immunization with 5 mg of a mixture of venoms of Bitis arietans, Echis ocellatus, Dendroaspis polylepis, and Naja nigricollis did not induce systemic signs of envenomation, and only caused mild swelling at the injection site, which did not evolve to abscesses, fistulas, or fibrosis. Three consecutive days of bleeding, collecting 6-8 L of blood per day, and self-transfusing the red blood cells (RBC) in the second and third days, did not induce evident cardiorespiratory alterations. However, this procedure caused significant reductions in RBC, hematocrit, hemoglobin, and total plasma protein values. Seven weeks after bleeding, these parameters were recovered, and horses were ready for the next immunization/bleeding cycle. The intravenous administration of equine albumin, at a dose of 2 g/kg body weight, increased the apparent plasma volume and the albumin concentration. However, this procedure induced early adverse reactions and transient alterations of the serum levels of the enzyme gamma-glutamyl transferase (GGT), thus suggesting some degree of hepatic injury. It was concluded that immunization and bleeding as described in this work do not cause significant clinical alterations in the horse's health, except for a transient drop in some hematological parameters. The albumin-based fluid therapy used does not hasten the recovery after bleeding but instead induces adverse events in the animals.
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Resumen Esta investigación tiene como objetivo capturar la segregación ocupacional y la discriminación salarial por género en la Universidad del Cauca, ubicada en el suroccidente colombiano, durante cuatro momentos en el tiempo (2005, 2010, 2015 y 2020). La metodología es cuantitativa e implementa en el primer caso el Índice de Karmel y MacLachlan (KM) y la descomposición de Kitagawa-Oaxaca-Blinder (KOB) en el segundo. Se utiliza información de datos panel en la descomposición KOB, lo que permite evaluar la evolución de la segregación en el tiempo. Las variables incluyen el género, el salario, la edad, los años de experiencia, el nivel de formación, los cargos administrativos, la unidad académica, entre otros. La información fue suministrada por la Vicerrectoría académica de la Universidad de forma totalmente anonimizada. Los resultados muestran evidencia de segregación ocupacional y discriminación salarial por género; a pesar de que en los últimos años ambas brechas se están cerrando levemente, el problema permanece. La segregación ocupacional ocurre aún en ocupaciones beta tradicionalmente ocupadas por las mujeres pese a la baja percepción de discriminación laboral por parte de las profesoras universitarias. En cuanto a las ocupaciones alfa, estas mantienen la hegemonía masculina. Las características observables hacen que existan diferencias en la modificación salarial entre profesores y profesoras, pero estas cada vez se hacen menos fuertes por el aumento en el nivel de formación y la disminución en el número de hijos e hijas. Existen factores discriminatorios no observados que mantienen la discriminación salarial femenina en respuesta a factores culturales arraigados en el patriarcado y tradicionalismo de la región donde se encuentra la universidad.
Abstract This research aims to capture occupational segregation and wage discrimination by gender in the University of Cauca, located in southwestern Colombia, during four periods (2005, 2010, 2015 y 2020). There are few studies in this direction, and the existing ones do not address it in depth, at least in emerging countries. In this sense, it is the first time it has been done for Colombian higher education institutions. The methodology is quantitative and it implements the Karmel and MacLachlan Index (KM) in the first case and the Kitagawa-Oaxaca-Blinder (KOB) decomposition in the second one. To deepen the analysis panel data information was used for the first time in the KOB decomposition for these issues, which allows evaluating the evolution of segregation over time. The variables analysed include gender, wage, age, years of experience, education level, administrative charges, and academic departments of origin, among others. The information used comes from the official data provided by the Administrative Office of the University of Cauca. This is characterized by being totally anonymous and by exclusively comprising full-time teachers, that is, those with an indefinite term contract. Temporal teachers and/or professors with a defined term contract are excluded, due to the volatility in the employment relationship, which would otherwise introduce noise into the analysis. In general, the information shows that alpha professions (better paid, with greater projection and public recognition) have been dominated in the last five years by professors; while beta professions (that is those with lower salaries, little projection and recognition) have been led by women. This preliminary result leads to consider that there is labor and/or wage segregation within this university. The estimates of the KM index showed, firstly, that all professions, both alpha and beta, have at least some segregation in the period analysed, since this is greater than zero. Second, segregation has been low and slightly decreasing over time for beta professions. In fact, it was 0.09 in 2005 and 0.072 in 2020. Third, for alpha professions, the index has been markedly increasing over time, which suggests that the proportion of female teachers who must change professions so that segregation from men was zero is increasing. Regarding wage discrimination, all the differences were negative, which shows that the average salaries of female teachers are lower than those of male teachers and therefore their difference is less than zero. Although the results are only statistically significant for the years 2011, 2014 and 2020, it can be highlighted that these differentials have been decreasing over time. In effect, it was -0.24 log-wage in 2005 and -0.051 log-wage in 2020. These results are partially in line with those obtained in the KM index. Occupational and salary segregation seems to have decreased slightly in recent years in this university, but it still exists. In the case of decomposition change, all the variations in the endowment are positive and significant but are characterized as decreasing, which indicates that changes in average wage differentials have been narrowing over time. The empirical evidence suggest that occupational segregation still occurs in beta professions traditionally occupied by women despite the low perception of job discrimination by university professors. As for alpha occupations, they maintain male hegemony. The observable characteristics mean that there are differences in the wage modification between male and female teachers, but this is becoming less strong due to the increase in the education level and the decrease in the number of children. There are unobserved discriminatory factors that maintain female wage discrimination in response to cultural factors rooted in the patriarchy and traditionalism of the region where the university is located.
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RESUMEN INTRODUCCIÓN: La COVID-19 se acompaña de eventos tromboembólicos venosos y arteriales en pacientes con historia de hipertensión y aterosclerosis. Se reporta el caso de una paciente joven y sin factores de riesgo cardiovascular que adquirió la infección por el SARS-COV2 y luego presentó un accidente cerebrovascular isquémico. CASO: Paciente de 44 años hospitalizada por la covid-19 en tratamiento protocolario con anticoagulación, esteroide y oxígeno suplementario. Al día 7 del inicio de los síntomas respiratorios presentó infarto cerebral por trombosis de arteria carótida derecha, arteria cerebral media derecha e izquierda y edema cerebral hemisférico derecho, tras lo cual fue diagnosticada con muerte encefálica. El estudio vascular no documentó una etiología diferente a la covid-19. DISCUSIÓN: Se plantea que la infección condiciona un estado inflamatorio sistémico, endotelialitis, ulceración de placas ateroscleróticas preexistentes e hipercoagulabilidad. Lo anterior facilita la aparición de trombosis vascular. Es frecuente encontrar elevación de reactantes de fase aguda y de los productos del metabolismo de la fibrina. El accidente cerebrovascular (ACV) isquémico se ha descrito en el 1 al 5 % de los pacientes con la covid-19. En pacientes con factores de riesgo cardiovascular, durante las primeras 2 semanas desde el inicio de los síntomas respiratorios, el compromiso isquémico suele afectar a múltiples territorios vasculares. CONCLUSIÓN: La covid-19 por sí sola es un factor de riesgo para trombosis arterial secundaria a la inflamación sistémica y estados de hipercoagulabilidad, por lo que debe ser tenida en cuenta en el estudio de ACV isquémico en pacientes jóvenes.
ABSTRACT INTRODUCTION: It is known that COVID-19 is associated with venous and arterial thromboembolic events in patients with history of hypertension and atherosclerosis. Herein, it is presented a case of a young woman without known cardiovascular risk, who was infected by SARS-COV 2 and then an ischemic stroke. CASE: 44 years-old woman with moderate COVID-19 in protocolary treatment with anticoagulants, steroid and oxygen. In the seventh day since symptoms onset, she presented acute ischemic stroke due to acute thrombosis of right carotid artery, and right and left medial cerebral arteries, then rapidly developed malignant cerebral edema and brain death. Vascular study failed to report and etiology other than COVID-19. DISCUSSION: It is suggested that the infection produces a systemic inflammatory state, endothelialitis, ulceration of preexisting atherosclerotic plaques, and hypercoagulability that facilitate thrombosis. Ischemic stroke is described in 1 to 5% of COVID-19, it is common to find an elevation of acute phase reactants and products of fibrin metabolism. Multiple vascular territories are usually compromised in patients with known cardiovascular risk factors and 12 days after the onset of symptoms. CONCLUSION: COVID-19 by itself is a risk factor for arterial thrombosis secondary to systemic infection and hypercoagulability states and it should be taken into account in the study of ischemic stroke in young patients.