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INTRODUCTION: Egg allergy usually manifests during the initial 2 years of life, a period in which most vaccinations are administered. This often leads to delays in the application of some vaccines in patients with egg allergies, exposing them to a risk of contracting preventable infections. The aim of the study was to describe the frequency of reactions after applying the yellow fever vaccine (YFV) within a population with egg allergy. METHODS: This was a cohort study with retrospective, multicenter data (2014-2023). Patient records diagnosed with egg allergy were gathered from their initial egg-related reactions until their YFV administration. Information was also collected about hypersensitivity tests conducted for egg and YFV such as the skin prick test (SPT) and intradermal test (IDT). RESULTS: Among the 171 records analyzed, 23.9% of patients had a history of egg anaphylaxis. Out of these, 5 patients had a positive SPT and 21 IDT with the YFV. All patients tolerated the application of YFV without developing hypersensitivity reactions, regardless of the results of the YFV tests, the severity of egg reactions, the number of egg reactions, or the time since the last egg reaction. Out of the total patient cohort, 46.1% (79 individuals) encountered delays in receiving the YFV, and in this subset, 14% faced delays lasting longer than 12 months. CONCLUSION: The risk of allergic reactions with the YFV remains low. YFV tests generate delays in the vaccine application without providing high diagnostic accuracy. YFV should not be deferred even in patients with a history of severe egg reactions.
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Oxidative stress has long been postulated to play an essential role in aging mechanisms, and numerous forms of molecular damage associated with oxidative stress have been well documented. However, the extent to which changes in gene expression in direct response to oxidative stress are related to actual cellular aging, senescence, and age-related functional decline remains unclear. Here, we ask whether H2O2-induced oxidative stress and resulting gene expression alterations in prostate epithelial cells in vitro reveal gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease. While a broad range of significant changes observed in the expression of non-coding transcripts implicated in senescence-related responses, we also note an overrepresentation of gene-splicing events among differentially expressed protein-coding genes induced by H2O2. Additionally, the collective expression of these H2O2-induced DEGs is linked to age-related pathological dysfunction, with their protein products exhibiting a dense network of protein-protein interactions. In contrast, co-expression analysis of available gene expression data reveals a naturally occurring highly coordinated expression of H2O2-induced DEGs in normally aging prostate tissue. Furthermore, we find that oxidative stress-induced DEGs statistically overrepresent well-known senescence-related signatures. Our results show that oxidative stress-induced gene expression in prostate epithelial cells in vitro reveals gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease.
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HIV stigma is a social determinant of health that can influence multiple health outcomes, including adherence to antiretroviral therapy (ART), engagement in HIV care, and viral suppression levels in people with HIV (PWH). In Peru, where the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW), stigma may play an important role in healthcare engagement. To understand the relationship between stigma and two outcome variables, ART adherence and engagement in HIV care in 400 MSM and TGW, we assessed factors from the Behavioral Model for Vulnerable Populations at two HIV clinics that tailor services for sexual and gender minorities. While some predisposing, need, and enabling resource factors were associated with optimal (≥ 90%) ART adherence or engagement in HIV care, none of the stigma subscales were correlated, suggesting that when LGBTQ-affirming care is provided to MSM/TGW, stigma may not influence HIV-related outcomes.
RESUMEN: El estigma hacia el VIH es un determinante social de la salud que puede influir en múltiples desenlaces, incluyendo la adherencia a la terapia antirretroviral (TAR), el compromiso con la atención del VIH y los niveles de supresión viral en personas viviendo con VIH (PVV). En el Perú, donde la epidemia del VIH se concentra en hombres que tienen sexo con hombres (HSH) y mujeres transgénero (MT), el estigma puede desempeñar un papel importante en el compromiso con la atención médica. Para comprender la relación entre el estigma y dos variables de resultado, la adherencia al TAR y el compromiso con la atención del VIH en 400 HSH y MT, evaluamos factores del Modelo de Comportamiento para Poblaciones Vulnerables en dos clínicas de VIH que adaptan sus servicios para minorías sexuales y de género. Si bien algunos factores predisponentes, de necesidad y de recursos habilitantes se asociaron con una adherencia óptima (≥ 90%) al TAR o al compromiso con la atención del VIH, ninguna de las sub-escalas de estigma estuvieron correlacionadas, sugiriendo que cuando se brinda atención que afirma a la comunidad LGBTQ a HSH/MT, el estigma puede no influir en los desenlaces relacionados con el VIH.
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Infecções por HIV , Homossexualidade Masculina , Adesão à Medicação , Estigma Social , Pessoas Transgênero , Humanos , Masculino , Peru/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Pessoas Transgênero/psicologia , Pessoas Transgênero/estatística & dados numéricos , Feminino , Adulto , Homossexualidade Masculina/psicologia , Homossexualidade Masculina/estatística & dados numéricos , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Fármacos Anti-HIV/uso terapêutico , Pessoa de Meia-Idade , Estudos Transversais , Adulto Jovem , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricosRESUMO
OBJECTIVES: This study explores the hypothesis that COVID-19 patients are at a heightened risk of healthcare-associated infections (HAIs) associated with medical device usage compared to non-COVID-19 patients. Our primary objective was to investigate the correlation between COVID-19 infection in ICU patients and subsequent HAIs following invasive medical device insertion. Additionally, we aim to assess the impact of SARS-CoV-2 infection on onset times concerning specific microorganisms and the type of medical device, providing valuable insights into this intricate relationship in intensive care settings. METHODOLOGY: A retrospective cohort study was conducted using ICU patient records at our hospital from 2020 to 2022. This investigation entailed evaluating the timing of HAIs while distinguishing between patients with and without SARS-CoV-2 infection. We identified and analyzed the type of isolation and infection attributed to the medical device while controlling for ICU duration and ventilator days using Cox regression. RESULTS: Our study included 127 patients without SARS-CoV-2 infection and 140 patients with SARS-CoV-2 infection. The findings indicated a higher incidence of HAI caused by various microorganisms associated with any medical device in patients with SARS-CoV-2 (HR = 6.86; 95% CI-95%: 3.26-14.43; p < 0.01). After adjusting for ICU duration and ventilator days, a heightened frequency of HAIs persisted in SARS-CoV-2-infected individuals. However, a detailed examination of HAIs revealed that only ventilation-associated pneumonia (VAP) displayed a significant association (HR = 6.69; 95% CI: 2.59-17.31; p < 0.01). A statistically significant correlation between SARS-CoV-2 infection and the isolation of S. aureus was also observed (p = 0.034). The prevalence of S. aureus infection was notably higher in patients with SARS-CoV-2 (RR = 8.080; 95% CI: 1.052-62.068; p < 0.01). CONCLUSIONS: The frequency of pathogen isolates in invasive medical devices exhibited an association with SARS-CoV-2 infection. Critically ill patients with SARS-CoV-2 are more prone to developing early-onset VAP than those without SARS-CoV-2 infection.
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COVID-19 , Infecção Hospitalar , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Staphylococcus aureus , Cuidados Críticos , Infecção Hospitalar/epidemiologiaRESUMO
Bacillus thuringiensis (Bt) produces crystals composed mainly of Cry pesticidal proteins with insecticidal activity against pests but are highly susceptible to degradation by abiotic factors. In this sense, encapsulation techniques are designed to improve their performance and lifetime. However, the effects of polymeric matrix encapsulation such as gum arabic and maltodextrin by spray-dryer in the mechanisms of action of Bt kurstaki and Bt aizawai are unknown. We analyzed crystal solubilization, protoxin activation, and receptor binding after microencapsulation and compared them with commercial non-encapsulated products. Microencapsulation did not alter protein crystal solubilization, providing 130 kDa (Cry1 protoxin) and 70 kDa (Cry2 protoxin). Activation with trypsin, chymotrypsin, and larval midgut juice was analyzed, showing that this step is highly efficient, and the protoxins were cleaved producing similar ~ 55 to 65 kDa activated proteins for both formulations. Binding assays with brush border membrane vesicles of Manduca sexta and Spodoptera frugiperda larvae provided a similar binding for both formulations. LC50 bioassays showed no significant differences between treatments but the microencapsulated treatment provided higher mortality against S. frugiperda when subjected to UV radiation. Microencapsulation did not affect the mechanism of action of Cry pesticidal proteins while enhancing protection against UV radiation. These data will contribute to the development of more efficient Bt biopesticide formulations. KEY POINTS: ⢠Microencapsulation did not affect the mechanisms of action of Cry pesticidal proteins produced by Bt. ⢠Microencapsulation provided protection against UV radiation for Bt-based biopesticides. ⢠The study's findings can contribute to the development of more efficient Bt biopesticide formulations.
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Bacillus thuringiensis , Praguicidas , Polissacarídeos , Animais , Praguicidas/farmacologia , Goma Arábica , Agentes de Controle Biológico , Larva , Controle de PragasRESUMO
Distinct lesions are derived from notochordal cells (NCDL), ranging from benign to malignant ones. This study presents fifty NCDL cases diagnosed in a tertiary hospital of reference from the past 55 years: forty-two conventional chordomas, including one chondroid chordoma subtype, four benign notochordal cell tumors (BNCT), two conventional chordomas with BNCT foci, and two dedifferentiated chordomas. All patients were adults. Three BNCT were incidentally diagnosed, and one case presented local pain. Chordomas began with local pain and/or neurological symptoms. BNCT were well-defined intraosseous lesions, hypointense on T1-weighted images (WI) and hyperintense on T2-WI, without enhancement in the contrast. Conventional chordomas, including its chondroid subtype, were lobulated masses with cortical disruption and soft tissue extension, hypointense on T1-WI and hyperintense on T2-WI, with variable contrast enhancement. BNCT were histologically composed of solid sheets of vacuolated cells with clear cytoplasm and round and central nuclei. No atypia, lobular growth pattern, myxoid matrix, or bone infiltration were seen. Conventional chordomas were histologically composed of physaliphorous cells in a myxoid stroma with lobulated and infiltrating growth patterns. Observational follow-up using radiological controls was decided on for the BNCT cases. None of these cases presented local recurrence or metastasis. En-bloc resection and adjuvant radiotherapy were selected for sacral and vertebral chordoma cases. Sixteen patients died due to tumor-related factors; twenty-eight presented local recurrence, and four developed distant metastases. New therapeutic options are being studied for chordoma cases. Clinical, radiological, and histopathological data are necessary to properly diagnose and follow up of NCDL.
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Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.
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Dengue , Interleucina-6 , Interleucina-8 , Organização Mundial da Saúde , Humanos , Dengue/imunologia , Dengue/diagnóstico , Criança , Masculino , Feminino , Interleucina-6/sangue , Pré-Escolar , Interleucina-8/sangue , Dengue Grave/diagnóstico , Dengue Grave/imunologia , Dengue Grave/sangue , Adolescente , Índice de Gravidade de Doença , Biomarcadores/sangue , Vírus da Dengue/imunologia , Guias de Prática Clínica como Assunto , Citometria de Fluxo , Lactente , Citocinas/sangueRESUMO
Asthma is a chronic immunological disease related to oxidative stress and chronic inflammation; both processes promote airway remodeling with collagen deposition and matrix thickening, causing pulmonary damage and lost function. This study investigates the immunomodulation of C-phycocyanin (CPC), a natural blue pigment purified from cyanobacteria, as a potential alternative treatment to prevent the remodeling process against asthma. We conducted experiments using ovalbumin (OVA) to induce asthma in Sprague Dawley rats. Animals were divided into five groups: (1) sham + vehicle, (2) sham + CPC, (3) asthma + vehicle, (4) asthma + CPC, and (5) asthma + methylprednisolone (MP). Our findings reveal that asthma promotes hypoxemia, leukocytosis, and pulmonary myeloperoxidase (MPO) activity by increasing lipid peroxidation, reactive oxygen and nitrogen species, inflammation associated with Th2 response, and airway remodeling in the lungs. CPC and MP treatment partially prevented these physiological processes with similar action on the biomarkers evaluated. In conclusion, CPC treatment enhanced the antioxidant defense system, thereby preventing oxidative stress and reducing airway inflammation by regulating pro-inflammatory and anti-inflammatory cytokines, consequently avoiding asthma-induced airway remodeling.
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Remodelação das Vias Aéreas , Asma , Modelos Animais de Doenças , Ovalbumina , Estresse Oxidativo , Ficocianina , Ratos Sprague-Dawley , Animais , Ficocianina/farmacologia , Ficocianina/uso terapêutico , Asma/tratamento farmacológico , Asma/metabolismo , Asma/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Ovalbumina/efeitos adversos , Ratos , Remodelação das Vias Aéreas/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Masculino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Citocinas/metabolismoRESUMO
BACKGROUND: Mandibular third molar (MTM) extraction is one of the most frequently performed surgeries in the oral cavity. Establishing the level of surgical difficulty pre-operatively is an essential step to ensure correct treatment planning. In Spain, MTM extraction - especially in cases presenting greater difficulty - is normally performed by doctors specializing in oral and maxillofacial surgery, or by dentists with postgraduate qualifications in oral surgery. The present work set out to analyze the extent to which perceptions of surgical difficulty of the said intervention vary in relation to professional training. MATERIAL AND METHODS: This cross-sectional, descriptive, observational study took the form of a survey. Using a visual analog scale (VAS), participants evaluated both the perceived difficulty of 30 cases of MTM extraction described by means of digital panoramic radiographs and the perceived difficulty deriving from a series of factors conditioning MTM extraction. The results underwent statistical analysis with SPSS Statistics 28.0 software. Non-parametric tests (Mann Whitney test for independent samples and the Kruskal-Wallis test) were applied. RESULTS: A total of 213 surveys were available for analysis. Both groups awarded the greatest importance to clinical experience, followed by anatomical and radiographic factors, root morphology obtaining the highest score among anatomical factors (9.01±1.42), while proximity of the MTM to the inferior alveolar nerve was regarded as the least important anatomical factor (8.11±2.54). Significant differences were only found for patient age, whereby maxillofacial surgeons awarded this factor more importance than dentists. CONCLUSIONS: The different training received by dentists specialized in oral surgery and maxillofacial surgeons did not influence either perceptions of surgical difficulty of MTM extraction, or opinions as to the factors influencing surgical difficulty.
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Cirurgiões Bucomaxilofaciais , Cirurgia Bucal , Humanos , Estudos Transversais , Dente Serotino/cirurgia , Extração DentáriaRESUMO
Particle detector systems require data acquisition systems (DAQs) as their back-end. This paper presents a new edge-computing DAQ that is capable of handling multiple pixel detectors simultaneously and was designed for particle-tracking experiments. The system was designed for the ROC4SENS readout chip, but its control logic can be adapted for other pixel detectors. The DAQ was based on a system-on-chip FPGA (SoC FPGA), which includes an embedded microprocessor running a fully functional Linux system. An application using a client-server architecture was developed to facilitate remote control and data visualization. The comprehensive DAQ is very compact, thus reducing the typical hardware load in particle tracking experiments, especially during the obligatory characterization of particle telescopes.
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BACKGROUND: Chronic inducible urticaria (CIndU) management often follows chronic spontaneous urticaria (CSU) guidelines, but a step-by-step evaluation of their effectiveness in CIndU is lacking. OBJECTIVE: To assess the clinical impact of adapting CSU international guidelines for CIndU management. METHODS: We conducted a prospective cohort study involving patients diagnosed with CIndU based on challenge tests and a Urticaria Control Test (UCT) score of ≤11 points. Following the guidelines, a stepwise approach was used: avoidance measures, antihistamines, omalizumab, and cyclosporine. Treatment steps were added based on individual response, with control defined as UCT ≥12 points. Pharmacological steps were evaluated for at least 1 month, with the next step initiated in case of a UCT score ≤11 points. RESULTS: We enrolled 194 patients with CIndU. Of them, 134 patients had CIndU with concomitant CSU and 60 had CIndU only. Following the step-by-step approach outlined in the guidelines, a total of 159 (81.9%) patients reach a UCT ≥12 points, with avoidance measures 23 (11.8%) patients, antihistamines 84 (43.2%), omalizumab 35 (18%), and cyclosporine 17 (8.7%). CONCLUSIONS: This study supports the use of a stepwise approach based on CSU guidelines for CIndU management. However, a significant proportion of patients, particularly those with CIndU only, did not achieve adequate control. This highlights the heterogeneity within CIndU and the need for further research to develop new therapies for patients with CIndU who remain uncontrolled.
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Antialérgicos , Urticária Crônica , Ciclosporina , Antagonistas dos Receptores Histamínicos , Omalizumab , Guias de Prática Clínica como Assunto , Humanos , Feminino , Masculino , Adulto , Urticária Crônica/tratamento farmacológico , Pessoa de Meia-Idade , Omalizumab/uso terapêutico , Estudos Prospectivos , Ciclosporina/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antialérgicos/uso terapêutico , Resultado do Tratamento , Urticária/tratamento farmacológicoRESUMO
Early detection of CSU patients with low probability of a clinical response with antihistamines could undergo prompt initiation of therapeutic alternatives. The aim of the study was to develop and internally validate a model for predicting the clinical response to antihistamines in adult patients with chronic spontaneous urticaria (CSU), who consult allergology and dermatology care centers. A cohort of CSU patients, recruited from four participating centers, were followed up for 12 months. Fifteen candidate variables were selected to be included in the multivariate model and then internal validation was done with bootstrap analysis with 1000 simulations. The outcome variable, clinical response to antihistamines, was evaluated with the UAS (Urticaria Activity Score) scale for seven days: "No response to antihistamines" was defined as UAS7 ≥7 points after at least one month with a maximum dose of antihistamines, while "Response to antiH1" was defined as UAS7 ≤6 points for at least three months with the use of antiH1. A total of 790 patients were included. Among the different models analyzed, the model that included age, angioedema, anxiety/depression, time with the disease, NSAIDs (Non-steroidal anti-inflammatory drugs) intolerance, and UAS7 baseline was considered the one with the best performance (accuracy 0.675, HL 0.87, AUC 0.727). The internal validation analyses demonstrated good consistency of the model. In conclusion, this prediction model identifies the probability of response to antihistamines in patients with chronic spontaneous urticaria. The model could be useful for a personalized therapeutic approach according to individual patient risk.
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Antialérgicos , Urticária Crônica , Urticária , Adulto , Humanos , Doença Crônica , Urticária Crônica/tratamento farmacológico , Urticária/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H1 , Anti-Inflamatórios não Esteroides/uso terapêutico , Omalizumab/uso terapêutico , Antialérgicos/uso terapêutico , Resultado do TratamentoRESUMO
Thermal lens spectroscopy (TLS) is a high-sensitivity method to determine the concentration of light-absorbing species in samples. Here, we implemented a transient configuration of the technique, with a focused pump and a collimated probe beam coaxially propagating. A Fabry-Perot optical resonator is incorporated allowing multi-passing of the probe beam through the sample to enhance sensitivity. We show how the low detection limit of the method can be reduced approximately by half by making differential measurements of the signal at a far field in the center point of the probe beam spot and that obtained by spatial filtering of the same beam, the so-called eclipsed signal. Measurements were performed in test samples of Deyman's organic dye, Strawberry 2143 v.7, dissolved in ethanol. The thermal lens signal measured as a function of the dye concentration in water at the center of the beam was compared with the differential signal resulting from this and the eclipsed beam.
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Vaccines are biological preparations widely used to provide acquired immunity against various life-threatening organisms and prevent severe complications of different infections. Vaccines typically demonstrate a high level of safety with minimal adverse effects. Nevertheless, it is crucial to enhance awareness when a potential new side effect emerges, as exemplified in the case discussed ahead. Despite the rarity of independent third nerve palsy occurrences, its association with the zoster vaccine remains unprecedented.
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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
The Aedes aegypti cadherin-like protein (Aae-Cad) and the membrane-bound alkaline phosphatase (Aae-mALP) are membrane proteins identified as putative receptors for the larvicidal Cry toxins produced by Bacillus thuringiensis subsp. israelensis bacteria. Cry toxins are the most used toxins in the control of different agricultural pest and mosquitos. Despite the relevance of Aae-Cad and Aae-mALP as possible toxin-receptors in mosquitoes, previous efforts to establish a clear functional connection among them and Cry toxins activity have been relatively limited. In this study, we used CRISPR-Cas9 to generate knockout (KO) mutations of Aae-Cad and Aae-mALP. The Aae-mALP KO was successfully generated, in contrast to the Aae-Cad KO which was obtained only in females. The female-linked genotype was due to the proximity of aae-cad gene to the sex-determining loci (M:m). Both A. aegypti KO mutant populations were viable and their insect-development was not affected, although a tendency on lower egg hatching rate was observed. Bioassays were performed to assess the effects of these KO mutations on the susceptibility of A. aegypti to Cry toxins, showing that the Aae-Cad female KO or Aae-mALP KO mutations did not significantly alter the susceptibility of A. aegypti larvae to the mosquitocidal Cry toxins, including Cry11Aa, Cry11Ba, Cry4Ba, and Cry4Aa. These findings suggest that besides the potential participation of Aae-Cad and Aae-mALP as Cry toxin receptors in A. aegypti, additional midgut membrane proteins are involved in the mode of action of these insecticidal toxins.
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Aedes , Fosfatase Alcalina , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias , Sistemas CRISPR-Cas , Caderinas , Endotoxinas , Proteínas Hemolisinas , Animais , Aedes/genética , Aedes/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/genética , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Endotoxinas/genética , Endotoxinas/metabolismo , Feminino , Caderinas/genética , Caderinas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Resistência a Inseticidas/genética , Técnicas de Inativação de Genes , Larva/genética , Larva/crescimento & desenvolvimento , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Masculino , Inseticidas/farmacologiaRESUMO
Synovial sarcomas are uncommon and highly aggressive sarcomas. Typically, they start in the soft tissues of the extremities, although they may develop in the head and neck region in rare cases. When they do, they usually present with localized symptoms in the affected area. Our patient is a 20-year-old man without a medical history who complained of a three-month history of submental swelling of the left side with a non-tender, palpable 5 cm mass. Initially believed to be a plunging ranula, the patient underwent transoral excision of the left submandibular soft tissue mass in the neck by the ear, nose, and throat (ENT) specialist. The pathological analysis of the mass confirmed the presence of a poorly differentiated synovial sarcoma. A postoperative neck imaging was performed, which showed a significant decrease in mass size compared to the previous imaging; however, the mass was still present. This is one of the few described cases of a poorly differentiated synovial sarcoma located on the floor of the mouth. Therefore, it highlights the importance of considering it as a possible differential diagnosis of head and neck pathologies.
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INTRODUCTION: Amidst the routine utilization of protocolized sedation in ventilated ICU patients, existing management guidelines exhibit a lack of unanimous recommendations for its widespread adoption. This study endeavors to comprehensively assess the effectiveness and safety of protocolized sedation in critically ill ventilated patients. OBJECTIVE: The primary objective of this study was to systematically review and conduct a meta-analysis of clinical trials comparing protocolized sedation with standard management in critically ill ventilated patients. Key outcomes under scrutiny include ICU and hospital mortality, ventilation days, duration of ICU stay, and incidents of self-extubation. The evaluation incorporates the Risk of Bias 2 (RoB2) tool to assess the quality of included studies. Data analysis utilizes a random-effects model for relative risk (RR) and mean differences. Subgroup analysis categorizes sedation protocols into algorithmic or daily interruption, addressing potential heterogeneity. Additionally, a GRADE evaluation is performed to ascertain the overall certainty of the evidence. RESULTS: From an initial pool of 1504 records, 10 studies met the inclusion criteria. Protocolized sedation demonstrated a reduced RR for mortality (RR: 0.80, 95% CI 0.68-0.93, p < 0.01, I2 = 0%) and a decrease in ventilation days (mean difference: - 1.12, 95% CI - 2.11 to - 0.14, p = 0.03, I2 = 84%). Furthermore, there was a notable reduction in ICU stay (mean difference: - 2.24, 95% CI - 3.59 to - 0.89, p < 0.01, I2 = 81%). However, incidents of self-extubation did not exhibit a significant difference (RR: 1.20, 95% CI 0.49-2.94, p = 0.69, I2 = 35%). Subgroup analyses effectively eliminated heterogeneity (I2 = 0%), and the GRADE evaluation yielded moderate results for mortality, ventilation days, and ICU duration. CONCLUSION: Protocolized sedation, whether implemented algorithmically or through daily interruption, emerges as a safe and effective approach when compared to standard management in ventilated ICU patients. The findings from this study contribute valuable insights to inform evidence-based practices in sedation management for this critical patient population.
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Hipnóticos e Sedativos , Unidades de Terapia Intensiva , Respiração Artificial , Humanos , Respiração Artificial/métodos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Cuidados Críticos/métodos , Cuidados Críticos/normas , Estado Terminal/mortalidade , Estado Terminal/terapia , Sedação Consciente/métodos , Mortalidade Hospitalar , Tempo de Internação , Protocolos ClínicosRESUMO
Commercial swine producers are responsible for implementing changes in their production systems to ensure animal welfare. The objective of this study is to evaluate the levels of animal welfare on rearing and fattening farms certified in good animal husbandry practices using the Welfare Quality® protocol. Eighty-one certified commercial farms (n = 2,150 pigs), distributed in six geographical areas of Colombia, were evaluatedby six trained veterinarians. . A multilevel analysis was performed to identify variables associated with the animal welfare/farm rating and to identify behavioral variables. Farms evaluated had an enhanced (n = 68, 83.9%), followed by excellent (n = 7, 8.7%) and acceptable (n = 6, 7.4%) level of animal welfare. Variables significantly associated with the overall protocol rating (R2 = 0.37) were temperature comfort (OR: 1.05, p = 0.008), absence of disease (OR: 1.06, p = 0.02) and absence of pain (OR: 1.06, p = 0.0001). Significant differences in behavioral measures were observed across farms (P < 0.05). The high animal welfare scores of certified farms suggest changes in producers' understanding and attitudes towards production and animal welfare.