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1.
J Cell Immunol ; 6(2): 64-75, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873035

RESUMO

Background: Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes arthralgias and arthritis that may last for years. The objective of this study was to describe the arthritis progression and T cell immunology over a two-year period. Methods: A cohort of 40 cases of serologically confirmed CHIKV from Magdalena and Atlántico, Colombia were followed in 2019 and again in 2021. Arthritis disease severity, disability, pain, stiffness, physical function, mobility, fatigue, anxiety, sleep disturbances and depression were assessed. Serum cytokines and T-cell subsets were measured and tested for change. Correlations within each of the 2 time periods for laboratory parameters were also examined. Results: Although, arthritis disease severity, as measured by the Disease Activity Score-28 (DAS-28) did not change significantly over a two-year period, a new metric- the Chikungunya Disease Activity Score (CHIK-DAS)- was more sensitive to detect changes in disease severity than the Disease Activity Score-28 (DAS-28) and showed some improvement in average disease severity from moderate to mild over two years. Cases were characterized by moderate disability, pain, and stiffness with mild alterations of physical function, mobility, fatigue, anxiety, sleep disturbances and depression that did not change significantly over time. Small joints including the fingers and wrists were most affected without significant change over time. The percentage of effector T cells (Teffs) and regulatory T cells (Tregs) of CD4+ T cells both decreased over time. Teff percentages decreased more significantly resulting in a halving of the Teff/Treg ratio two years later. Furthermore, markers of Treg immunosuppressive function such as CTLA4, Helios, CD28, CD45RA and 41bb decreased over time. Cytokines did not change significantly over time. Conclusions: The presented data suggest that arthritis persists almost seven years after chikungunya infection in some patients with waning Teff and Treg numbers and activation markers over time. Treg activation may be a promising therapeutic target for further investigation.

2.
Mar Biotechnol (NY) ; 26(3): 447-459, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38691271

RESUMO

Marine environments harbor a plethora of microorganisms that represent a valuable source of new biomolecules of biotechnological interest. In particular, enzymes from marine bacteria exhibit unique properties due to their high catalytic activity under various stressful and fluctuating conditions, such as temperature, pH, and salinity, fluctuations which are common during several industrial processes. In this study, we report a new esterase (EstGoM) from a marine Pseudomonas sp. isolated at a depth of 1000 m in the Gulf of Mexico. Bioinformatic analyses revealed that EstGoM is an autotransporter esterase (type Va) and belongs to the lipolytic family II, forming a new subgroup. The purified recombinant EstGoM, with a molecular mass of 67.4 kDa, showed the highest hydrolytic activity with p-nitrophenyl octanoate (p-NP C8), although it was also active against p-NP C4, C5, C10, and C12. The optimum pH and temperature for EstGoM were 9 and 60 °C, respectively, but it retained more than 50% of its activity over the pH range of 7-11 and temperature range of 10-75 °C. In addition, EstGoM was tolerant of up to 1 M NaCl and resistant to the presence of several metal ions, detergents, and chemical reagents, such as EDTA and ß-mercaptoethanol. The enzymatic properties of EstGoM make it a potential candidate for several industrial applications.


Assuntos
Esterases , Pseudomonas , Pseudomonas/enzimologia , Pseudomonas/genética , Especificidade por Substrato , Esterases/metabolismo , Esterases/genética , Esterases/química , Concentração de Íons de Hidrogênio , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Temperatura , Estabilidade Enzimática , Filogenia , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Água do Mar/microbiologia
3.
Gac Med Mex ; 160(1): 62-67, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753542

RESUMO

BACKGROUND: The quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) is a score that has been proposed to quickly identify patients at higher risk of death. OBJECTIVE: To describe the usefulness of the qSOFA score to predict in-hospital mortality in cancer patients. MATERIAL AND METHODS: Cross-sectional study carried out between January 2021 and December 2022. Hospital mortality was the dependent variable. The area under the ROC curve (AUC) was calculated to determine the discriminative ability of qSOFA to predict in-hospital mortality. RESULTS: A total of 587 cancer patients were included. A qSOFA score higher than 1 obtained a sensitivity of 57.2%, specificity of 78.5%, a positive predictive value of 55.4% and negative predictive value of 79.7%. The AUC of qSOFA for predicting in-hospital mortality was 0.70. In-hospital mortality of patients with qSOFA scores of 2 and 3 points was 52.7 and 64.4%, respectively. In-hospital mortality was 31.9% (187/587). CONCLUSION: qSOFA showed acceptable discriminative ability for predicting in-hospital mortality in cancer patients.


ANTECEDENTES: El quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) es una puntuación propuesta para identificar de forma rápida a pacientes con mayor probabilidad de morir. OBJETIVO: Describir la utilidad de la puntuación qSOFA para predecir mortalidad hospitalaria en pacientes con cáncer. MATERIAL Y MÉTODOS: Estudio transversal realizado entre enero de 2021 y diciembre de 2022. La mortalidad hospitalaria fue la variable dependiente. Se calculó el área bajo la curva ROC (ABC) para determinar la capacidad discriminativa de qSOFA para predecir mortalidad hospitalaria. RESULTADOS: Se incluyeron 587 pacientes con cáncer. La puntuación qSOFA < 1 obtuvo una sensibilidad de 57.2 %, una especificidad de 78.5 %, un valor predictivo positivo de 55.4 % y un valor predictivo negativo de 79.7 %. El ABC de qSOFA para predecir mortalidad hospitalaria fue de 0.70. La mortalidad hospitalaria de los pacientes con qSOFA de 2 y 3 puntos fue de 52.7 y 64.4 %, respectivamente. La mortalidad hospitalaria fue de 31.9 % (187/587). CONCLUSIÓN: qSOFA mostró capacidad discriminativa aceptable para predecir mortalidad hospitalaria en pacientes con cáncer.


Assuntos
Mortalidade Hospitalar , Neoplasias , Escores de Disfunção Orgânica , Humanos , Neoplasias/mortalidade , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Sensibilidade e Especificidade , Curva ROC , Sepse/mortalidade , Sepse/diagnóstico , Valor Preditivo dos Testes , Área Sob a Curva , Adulto , Idoso de 80 Anos ou mais
4.
PLoS One ; 19(3): e0299521, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38507338

RESUMO

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.


Assuntos
Artrite Infecciosa , Febre de Chikungunya , Humanos , Citocinas/metabolismo , Interleucina-10/metabolismo , Estudos Transversais , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Febre de Chikungunya/complicações , Linfócitos T Reguladores/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Imunossupressores
5.
Gac. méd. Méx ; 160(1): 67-72, ene.-feb. 2024. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1557805

RESUMO

Resumen Antecedentes: El quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) es una puntuación propuesta para identificar de forma rápida a pacientes con mayor probabilidad de morir. Objetivo: Describir la utilidad de la puntuación qSOFA para predecir mortalidad hospitalaria en pacientes con cáncer. Material y métodos: Estudio transversal realizado entre enero de 2021 y diciembre de 2022. La mortalidad hospitalaria fue la variable dependiente. Se calculó el área bajo la curva ROC (ABC) para determinar la capacidad discriminativa de qSOFA para predecir mortalidad hospitalaria. Resultados: Se incluyeron 587 pacientes con cáncer. La puntuación qSOFA < 1 obtuvo una sensibilidad de 57.2 %, una especificidad de 78.5 %, un valor predictivo positivo de 55.4 % y un valor predictivo negativo de 79.7 %. El ABC de qSOFA para predecir mortalidad hospitalaria fue de 0.70. La mortalidad hospitalaria de los pacientes con qSOFA de 2 y 3 puntos fue de 52.7 y 64.4 %, respectivamente. La mortalidad hospitalaria fue de 31.9 % (187/587). Conclusión: qSOFA mostró capacidad discriminativa aceptable para predecir mortalidad hospitalaria en pacientes con cáncer.


Abstract Background: The quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) is a score that has been proposed to quickly identify patients at higher risk of death. Objective: To describe the usefulness of the qSOFA score to predict in-hospital mortality in cancer patients. Material and methods: Cross-sectional study carried out between January 2021 and December 2022. Hospital mortality was the dependent variable. The area under the ROC curve (AUC) was calculated to determine the discriminative ability of qSOFA to predict in-hospital mortality. Results: A total of 587 cancer patients were included. A qSOFA score higher than 1 obtained a sensitivity of 57.2 %, specificity of 78.5 %, a positive predictive value of 55.4 % and negative predictive value of 79.7 %. The AUC of qSOFA for predicting in-hospital mortality was 0.70. In-hospital mortality of patients with qSOFA scores of 2 and 3 points was 52.7 and 64.4 %, respectively. In-hospital mortality was 31.9 % (187/587). Conclusions: qSOFA showed acceptable discriminative ability for predicting in-hospital mortality in cancer patients.

6.
Int J Mol Sci ; 24(19)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37834225

RESUMO

Breast cancer remains the most frequently diagnosed cancer in women worldwide. Tumors that express hormone receptors account for 75% of all cases. Understanding alternative signaling cascades is important for finding new therapeutic targets for hormone receptor-positive breast cancer patients. JAK-STAT signaling is commonly activated in hormone receptor-positive breast tumors, inducing inflammation, proliferation, migration, and treatment resistance in cancer cells. In hormone receptor-positive breast cancer, the JAK-STAT cascade is stimulated by hormones and cytokines, such as prolactin and IL-6. In normal cells, JAK-STAT is inhibited by the action of the adaptor protein, LNK. However, the role of LNK in breast tumors is not fully understood. This review compiles published reports on the expression and activation of the JAK-STAT pathway by IL-6 and prolactin and potential inhibition of the cascade by LNK in hormone receptor-positive breast cancer. Additionally, it includes analyses of available datasets to determine the level of expression of LNK and various members of the JAK-STAT family for the purpose of establishing associations between expression and clinical outcomes. Together, experimental evidence and in silico studies provide a better understanding of the potential implications of the JAK-STAT-LNK loop in hormone receptor-positive breast cancer progression.


Assuntos
Neoplasias da Mama , Transdução de Sinais , Humanos , Feminino , Transdução de Sinais/fisiologia , Janus Quinases/metabolismo , Prolactina/metabolismo , Interleucina-6/metabolismo , Fatores de Transcrição STAT/metabolismo
7.
Biol Sex Differ ; 14(1): 60, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723501

RESUMO

BACKGROUND: Human endosomal Toll-like receptors TLR7 and TLR8 recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. TLR7 and TLR8 are, respectively, encoded by adjacent X-linked genes. We previously established that TLR7 evades X chromosome inactivation (XCI) in female immune cells. Whether TLR8 also evades XCI, however, has not yet been explored. METHOD: In the current study, we used RNA fluorescence in situ hybridization (RNA FISH) to directly visualize, on a single-cell basis, primary transcripts of TLR7 and TLR8 relative to X chromosome territories in CD14+ monocytes and CD4+ T lymphocytes from women, Klinefelter syndrome (KS) men, and euploid men. To assign X chromosome territories in cells lacking robust expression of a XIST compartment, we designed probes specific for X-linked genes that do not escape XCI and therefore robustly label the active X chromosome. We also assessed whether XCI escape of TLR8 was associated with sexual dimorphism in TLR8 protein expression by western blot and flow cytometry. RESULTS: Using RNA FISH, we show that TLR8, like TLR7, evades XCI in immune cells, and that cells harboring simultaneously TLR7 and TLR8 transcript foci are more frequent in women and KS men than in euploid men, resulting in a sevenfold difference in frequency. This transcriptional bias was again observable when comparing the single X of XY males with the active X of cells from females or KS males. Interestingly, TLR8 protein expression was significantly higher in female mononuclear blood cells, including all monocyte subsets, than in male cells. CONCLUSIONS: TLR8, mirroring TLR7, escapes XCI in human monocytes and CD4+ T cells. Co-dependent transcription from the active X chromosome and escape from XCI could both contribute to higher TLR8 protein abundance in female cells, which may have implications for the response to viruses and bacteria, and the risk of developing inflammatory and autoimmune diseases.


Human endosomal Toll-like receptors TLR7 and TLR8, encoded by two adjacent X-linked genes, recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. We previously reported that TLR7 evades X chromosome inactivation (XCI) in female immune cells, correlating with enhanced functional properties in B cells harboring biallelic expression of this gene. Here, we conducted a comprehensive single-cell resolution analysis of the transcriptional regulation of both TLR7 and TLR8, in CD14+ monocytes and CD4+ T lymphocytes. We unequivocally demonstrated that TLR8, like TLR7, escapes XCI in immune cells from female and Klinefelter syndrome males. When we analyzed TLR7 and TLR8 transcripts together, cells from women and KS men exhibited higher frequencies of cells co-transcribing the two genes. Surprisingly, these differences were attributable not only to the ability of TLR7 and TLR8 to be expressed on the Xi, but also to the joint transcriptional behavior of the TLR7­TLR8 gene pair on the active X chromosome specifically. This contrasted with a striking pattern of mutually exclusive transcription on the single X of euploid men. Corroborating our RNA FISH results, we found higher TLR8 protein expression in female than in male leukocytes, including all monocyte subpopulations. In summary, our data suggest that sex-biased co-regulation of the Toll-like receptor locus and XCI escape of TLR8 contribute to the sexual dimorphism in TLR8 expression, which may have important consequences for the functional make-up of monocyte and T cell populations.


Assuntos
Monócitos , Inativação do Cromossomo X , Humanos , Feminino , Masculino , Receptor 8 Toll-Like/genética , Linfócitos T , Hibridização in Situ Fluorescente , Receptor 7 Toll-Like/genética , Linfócitos T CD4-Positivos
8.
Cureus ; 15(8): e43240, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37692624

RESUMO

Adrenal myelolipoma is considered a benign neoplasm that accounts for 6% to 16% of adrenal incidentalomas, and it is the second most common incidental adrenal tumor after adrenal adenomas. They are usually asymptomatic; however, in the presence of symptoms, significant growth, or complications, open surgical resection is indicated. We present the case of a 46-year-old woman with obesity and diabetes who experienced five years of left hemiabdominal pain, which was unsuccessfully treated symptomatically. A computed tomography scan revealed findings suggestive of pancreatic lipoma and a suggestive image of left adrenal myelolipoma. Resection of the tumor was performed using an anterior midline approach, and histopathological examination confirmed left adrenal myelolipoma. The presented case represents the typical presentation of these tumors in a patient in the fifth decade of life with obesity, diabetes, and nonspecific abdominal pain possibly related to the size of the lesion found. Surgical intervention was indicated due to the presence of symptoms, lesion size, contiguity with abdominal organs, and the absence of a precise diagnosis. An anterior midline approach was chosen, and histopathological examination provided a definitive diagnosis. Adrenal myelolipoma is a rare entity that is often asymptomatic and incidentally diagnosed through imaging studies. However, they should be resected when symptomatic to prevent complications. Open surgical resection is the preferred approach.

9.
Sci Rep ; 13(1): 9014, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37268706

RESUMO

The adaptive filtering theory has been extensively developed, and most of the proposed algorithms work under the assumption of Euclidean space. However, in many applications, the data to be processed comes from a non-linear manifold. In this article, we propose an alternative adaptive filter that works on a manifold, thus generalizing the filtering task to non-Euclidean spaces. To this end, we generalized the least-mean-squared algorithm to work on a manifold using an exponential map. Our experiments showed that the proposed method outperforms other state-of-the-art algorithms in several filtering tasks.

10.
Cureus ; 15(5): e38760, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37303318

RESUMO

Evidence-based medicine has demonstrated an extensive list of etiologies for exocrine pancreatic insufficiency (EPI). EPI is defined as inadequate pancreatic enzyme efficacy in digestion due to insufficient enzyme production, activation, or early enzyme degradation. Among the etiologies, acute pancreatitis secondary to chronic and excessive consumption of alcohol has been found to be one of the most common causes. In 2022, a 43-year-old male patient with a past medical history of polysubstance abuse, acute on chronic pancreatitis, alcohol dependence, pulmonary embolism, hypertension, hyperlipidemia and diabetes mellitus type 2 presented to the Emergency Department with three days of epigastric abdominal pain, nausea and non-bloody, non-bilious vomiting. Proper imaging confirmed the diagnosis of acute pancreatitis. The key to treatment and surveillance relies on proper identification of risk factors, pertinent imaging for diagnostic evaluation and appropriate treatment with electrolyte repletion. The patient developed persistent electrolyte deficiencies despite appropriate repletion, indicating high suspicion of pancreatic insufficiency. The treatment most importantly relies on a combination of repletion of electrolytes as well as pancreatic enzymes with a clear patient understanding of their chronic condition, the importance of reducing modifiable risk factors and compliance with medical therapy.

12.
Cureus ; 14(11): e31092, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36475164

RESUMO

Amyloidosis is characterized by depositing insoluble fibrillar proteins that misfold into beta-pleated sheets. This phenomenon occurs on a systemic or local level and may interfere with the function of various organs, including the heart, kidneys, and liver. Among those presenting with amyloidosis, hepatic, gastrointestinal, renal, cardiac, vitreous, and immunological involvement may occur. These manifestations are linked to several clinical presentations, varying from abdominal pain and hepatomegaly to restrictive cardiomyopathy and chronic renal failure. The two most common types of amyloid proteins are amyloid light chain (AL) and serum amyloid A (AA) proteins. AL produced by immunoglobulin light chains kappa and lambda (κ, λ) circulate systemically and accumulate in organs. At the same time, serum AA proteins are acute-phase reactants seen in infectious, chronic inflammatory states. In an immune-mediated infection such as COVID-19, serum AA levels may be a predictive factor of disease severity and a valuable biomarker to monitor the clinical course of COVID-19 patients. This report highlights a case in which infection with COVID-19 provoked an effective immune response that may have contributed to the accelerated progression of systemic amyloidosis with hepatic involvement. The study further investigates the involvement of AL and AA proteins in COVID-19 infections, including their role in synergistically exacerbating an already grueling clinical course.

13.
Sci Rep ; 12(1): 17196, 2022 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-36229644

RESUMO

Cuffless blood pressure measurement enables unobtrusive and continuous monitoring that can be integrated with wearable devices to extend healthcare to non-hospital settings. Most of the current research has focused on the estimation of blood pressure based on pulse transit time or pulse arrival time using ECG or peripheral cardiac pulse signals as proximal time references. This study proposed the use of a phonocardiogram (PCG) and ballistocardiogram (BCG), two signals detected noninvasively, to estimate systolic blood pressure (SBP). For this, the PCG and the BCG were simultaneously measured in 21 volunteers in the rest, activity, and post-activity conditions. Different features were considered based on the relationships between these signals. The intervals between S1 and S2 of the PCG and the I, J, and K waves of the BCG were statistically analyzed. The IJ and JK slopes were also estimated as additional features to train the machine-learning algorithm. The intervals S1-J, S1-K, S1-I, J-S2, and I-S2 were negatively correlated with changes in SBP (p-val < 0.01). The features were used as explanatory variables for a regressor based on the Random Forest. It was possible to estimate the systolic blood pressure with a mean error of 3.3 mmHg with a standard deviation of ± 5 mmHg. Therefore, we foresee that this proposal has potential applications for wearable devices that use low-cost embedded systems.


Assuntos
Balistocardiografia , Ruídos Cardíacos , Humanos , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial , Análise de Onda de Pulso
14.
World J Clin Cases ; 10(21): 7553-7564, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-36157992

RESUMO

BACKGROUND: Urticaria is one of the most common causes of emergency room visits. It is defined as an acute inflammatory dermatosis, characterized by localized degranulation of mast cells, with consequent dermal microvascular and formation of edematous and pruritic plaques called hives. Urticaria affects the skin and tissues of the superficial mucosa. Sometimes it is accompanied by angioedema, which is characterized by deeper edema of the dermis and subcutaneous cellular tissue known as the urticarial-angioedema syndrome. About 15%-25% of the general population has suffered at least one type of urticaria at some point during their lifetime and hyperpermeability estimated at 7.6%-16% and has experienced acute urticaria that is usually self-limited and spontaneously resolves without requiring medical attention. CASE SUMMARY: We present the case of a young male patient who was referred to our department with a clinical picture of 4 mo of pruritus associated with hives of variable sizes, irregular borders, with interlesional confluence, that were non-painful, without involvement of the palms and soles of the feet but with a tendency to progression in a generalized manner. He had multiple emergency room visits and poor response to antihistamines and systemic corticosteroids. Imaging studies demonstrated nodules in the lower lingula segment, at the level of the greater fissure and in the anterior contour of the left anterior basal segment associated with parahiliar adenopathies in the absence of findings suggestive of infectious or autoimmune etiology. Segmental lobectomy was performed by thoracoscopy with resection of a lung nodule in the lingula and biopsy of the para-aortic mediastinal ganglion. The histopathological report showed the presence of poorly differentiated invasive adenocarcinoma with a solid morphological and acinar pattern with immunohistochemical description of lung tissue that expresses strong positive and diffuse reaction for thyroid transcription factor 1 (TTF-1) with negativity to P40 for a histopathological diagnosis of malignant epithelial neoplasia with expression of infiltrating adenocarcinoma. Spontaneous chronic urticaria is considered possibly secondary to lung adenocarcinoma. CONCLUSION: Chronic spontaneous urticaria is considered a paraneoplastic dermatosis with a controversial association in the literature. In the presented case, a young patient presented with chronic refractory urticaria and after an exhaustive clinical work-up was found to have a diagnosis of poorly differentiated lung adenocarcinoma with high expression of TTF-1. According to the Curth criteria, the urticaria presented by the patient is related to the oncological diagnosis. In addition, the high expression of TTF-1 documented in this case could be acting as an autoantigen that would cause chronic spontaneous urticaria. Further research evaluating a causal relationship between the TFF-1 protein and urticaria in lung cancer is needed.

15.
Int J Mol Sci ; 23(15)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35955836

RESUMO

Triple-negative breast cancer (TNBC) is associated with a poor prognosis and the absence of targeted therapy. c-Kit, a receptor tyrosine kinase (RTK), is considered a molecular target for anticancer drugs. Tyrosine kinase inhibitors (TKIs) recognizing c-Kit are used for the treatment of c-Kit-expressing tumors. However, the expression, function, and therapeutic potential of c-Kit have been little explored in TNBC. Here, we studied the expression and effects of c-Kit in TNBC through in vitro and in silico analysis, and evaluated the response to TKIs targeting c-Kit. Analysis of TNBC cells showed the expression of functional c-Kit at the cell membrane. The stimulation of c-Kit with its ligand induced the activation of STAT3, Akt, and ERK1/2, increasing cell migration, but had no effect on cell proliferation or response to Doxorubicin. Analysis of public datasets showed that the expression of c-Kit in tumors was not associated with patient survival. Finally, TNBC cells were susceptible to TKIs, in particular the effect of Nilotinib was stronger than Doxorubicin in all cell lines. In conclusion, TNBC cells express functional c-Kit, which is a targetable molecule, and show a strong response to Nilotinib that may be considered a candidate drug for the treatment of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Proliferação de Células , Doxorrubicina/farmacologia , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Receptores Proteína Tirosina Quinases , Neoplasias de Mama Triplo Negativas/patologia
16.
Rev. esp. nutr. comunitaria ; 28(2): 1-12, Abril-Junio, 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-205814

RESUMO

Fundamentos: La adaptación a la vida universitaria puede generar problemas cronobiológicos en losestudiantes. Los objetivos del estudio fueron estimar el índice de masa corporal (IMC), nivel de actividad físicay aspectos cronobiológicos en relación con el rendimiento académico de los estudiantes residentes en elcampus de una universidad internacional ubicada en Honduras.Métodos: El estudio fue transversal, aplicándose encuestas de autopercepción relacionadas con ritmos desueño, actividad física e índice de calidad de sueño; además, se tomaron medidas antropométricas. Lamuestra fue representativa (87) y los estudiantes fueron seleccionados al azar. Se realizaron test de análisisde frecuencias, ANDEVA, prueba Duncan (p<0,05) y Chi cuadrado.Resultados: Los resultados se compararon por rendimiento académico (< y > 88%). Se estimó que enpromedio la población estudiantil se encuentra en un rango normal de IMC, con actividad física alta ycronotipos intermedio-vespertino e intermedio-matutino. Estudiantes con menos del 88% de rendimientoacadémico presentaron un IMC promedio de sobrepeso (25,4 kg/m2). Con respecto al rendimientoacadémico, no se encontraron diferencias en horas, déficit, patrón y cronotipos de sueño.Conclusiones: Se encontraron diferencias en la calidad de sueño y el rendimiento académico. No sedeterminó relación directa entre el rendimiento académico, cronotipos y patrón de sueño. (AU)


Background: Adapting to university life can generate chronobiological problems in students. The objectivesof the study were to estimate the body mass index (BMI), level of physical activity and chronobiologicalaspects in relation to academic performance of students residing on the campus of an international universitylocated in Honduras.Methods: The study was cross-sectional, applying self-perception surveys related to sleep rhythms, physicalactivity, sleep quality index; in addition, anthropometric measurements. The sample was representative (87)and the students were randomly selected. Frequency analysis, ANDEVA, Duncan test (p<0,05) and Chi-squaretest were performed.Results: Results were compared by academic performance (< and > 88%). It was estimated that, on average,the student population was in a normal BMI range, with high physical activity and intermediate-afternoon andintermediate-matutine chronotypes. Students with < 88% of academic performance presented an averageoverweight BMI (25,4 kg/m2). With respect to academic performance, no differences were found in hours,deficit, pattern and chronotypes of sleep.Conclusions: Differences were found in sleep quality and academic performance. No direct relationship wasdetermined between academic performance, chronotypes and sleep pattern. (AU)


Assuntos
Humanos , Adulto Jovem , Higiene do Sono , Índice de Massa Corporal , Atividade Motora , Estudos Transversais , Saúde do Estudante
17.
Allergy ; 77(2): 525-539, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34181765

RESUMO

BACKGROUND: Voltage-gated calcium (Cav 1) channels contribute to T-lymphocyte activation. Cav 1.2 and Cav 1.3 channels are expressed in Th2 cells but their respective roles are unknown, which is investigated herein. METHODS: We generated mice deleted for Cav 1.2 in T cells or Cav 1.3 and analyzed TCR-driven signaling. In this line, we developed original fast calcium imaging to measure early elementary calcium events (ECE). We also tested the impact of Cav 1.2 or Cav 1.3 deletion in models of type 2 airway inflammation. Finally, we checked whether the expression of both Cav 1.2 and Cav 1.3 in T cells from asthmatic children correlates with Th2-cytokine expression. RESULTS: We demonstrated non-redundant and synergistic functions of Cav 1.2 and Cav 1.3 in Th2 cells. Indeed, the deficiency of only one channel in Th2 cells triggers TCR-driven hyporesponsiveness with weakened tyrosine phosphorylation profile, a strong decrease in initial ECE and subsequent reduction in the global calcium response. Moreover, Cav 1.3 has a particular role in calcium homeostasis. In accordance with the singular roles of Cav 1.2 and Cav 1.3 in Th2 cells, deficiency in either one of these channels was sufficient to inhibit cardinal features of type 2 airway inflammation. Furthermore, Cav 1.2 and Cav 1.3 must be co-expressed within the same CD4+ T cell to trigger allergic airway inflammation. Accordingly with the concerted roles of Cav 1.2 and Cav 1.3, the expression of both channels by activated CD4+ T cells from asthmatic children was associated with increased Th2-cytokine transcription. CONCLUSIONS: Thus, Cav 1.2 and Cav 1.3 act as a duo, and targeting only one of these channels would be efficient in allergy treatment.


Assuntos
Asma , Canais de Cálcio , Animais , Asma/metabolismo , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Citocinas/metabolismo , Humanos , Inflamação/metabolismo , Camundongos , Receptores de Antígenos de Linfócitos T/metabolismo , Células Th2/metabolismo
18.
Immunol Lett ; 233: 97-103, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33811941

RESUMO

The human immune system is in continuous interaction with environmental factors (pathogens, exercise, stress, pollutants, diet, vaccines, and therapeutics) that condition its efficiency by promoting or moderating multiple immune mechanisms. While the deleterious impact of external factors can be avoided or limited, the immune system itself grows weaker with age. Immune cells persist in the elderly, and the observed decline of cellular immunity is related to cellular senescence. Immunosenescence, which affects both T and B cells, erodes lymphocyte-dependent responses to vaccines and pathogens. Germinal centers (GCs), the organized lymphoid structures where B cells engage in affinity maturation, are regulated by follicular helper (Tfh) and follicular regulatory (Tfr) T cells, the major T cell components of GCs. This review discusses how age-related changes affect Tfh and Tfr cells as key components of B cell immunity, and how they ultimately shape the response of the ageing immune system to vaccines and infectious challenges.


Assuntos
Envelhecimento/imunologia , Linfócitos B/imunologia , Comunicação Celular , Linfócitos T/imunologia , Fatores Etários , Animais , Linfócitos B/metabolismo , Comunicação Celular/genética , Comunicação Celular/imunologia , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunomodulação , Linfócitos T/metabolismo
19.
Data Brief ; 35: 106813, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33604430

RESUMO

This data article describes the dataset of the International COVID-19 Impact on Parental Engagement Study (ICIPES). ICIPES is a collaborative effort of more than 20 institutions to investigate the ways in which, parents and caregivers built capacity engaged with children's learning during the period of social distancing arising from global COVID-19 pandemic. A series of data were collected using an online survey conducted in 23 countries and had a total sample of 4,658 parents/caregivers. The description of the data contained in this article is divided into two main parts. The first part is a descriptive analysis of all the items included in the survey and was performed using tables and figures. The second part refers to the construction of scales. Three scales were constructed and included in the dataset: 'parental acceptance and confidence in the use of technology', 'parental engagement in children's learning' and 'socioeconomic status'. The scales were created using Confirmatory Factor Analysis (CFA) and Multi-Group Confirmatory Analysis (MG-CFA) and were adopted to evaluate their cross-cultural comparability (i.e., measurement invariance) across countries and within sub-groups. This dataset will be relevant for researchers in different fields, particularly for those interested in international comparative education.

20.
Infectio ; 24(4): 248-254, oct.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1114877

RESUMO

Resumen Introducción: las infecciones causadas por Enterococcus resistente a Vancomicina (EVR) presentan mayor mortalidad en pacientes críticos, asociado a un aumento gradual en este patrón de resistencia, especialmente en el continente americano, por lo cual la adecuada terapia antimicrobiana empírica es fundamental para mejorar los desenlaces. Objetivo: determinar los factores de riesgo asociados al desarrollo de infección por EVR en pacientes sépticos en la Unidad de Cuidados Intensivos (UCI) del Hospital San José en Bogotá, Colombia. Métodos: Estudio descriptivo de casos y controles en pacientes sépticos ingresados a la UCI durante 2016 y 2017. Los casos se definieron como pacientes con infección por EVR y los controles los pacientes con infección por otro germen. Resultados: se incluyeron 32 pacientes con aislamiento de EVR y 96 controles. Los factores de riesgo asociados a infección por EVR fueron: nutrición parenteral (OR 15,7 IC 4,2-71,4), lavado peritoneal (OR 8,9 IC 3,2-24,8), cultivo polimicrobiano (OR 19,9 IC 6,0-83,4). La mortalidad fue 56,2% en casos y 33,3% en controles. Conclusiones: Los factores de riesgo hallados con mayor frecuencia fueron: múltiples lavados peritoneales, nutrición parenteral y cultivos polimicrobianos. Encontramos una correlación significativa en el uso de antibiótico empírico adecuado y la reducción en la mortalidad.


Summary Introduction: infections caused by Vancomycin-resistant Enterococcus (VRE) have higher mortality in critically ill patients, associated with increase in this pattern of resistance, especially in the Americas, which is why adequate empirical antimicrobial therapy is essential to improve outcomes Objective: to determine the risk factors associated with the development of infection by VRE in septic patients in the Intensive Care Unit (ICU) of San José Hospital in Bogotá, Colombia. Methods: Case-control study in septic patients admitted to the ICU during 2016 and 2017. The cases were defined as patients with VRE infection and the controls were patients with infection by another germ. Results: 32 patients with EVR isolation and 96 controls were included. The risk factors associated with infection by EVR were: parenteral nutrition (OR 15.7 IC 4.2-71.4), peritoneal lavage (OR 8.9 IC 3.2-24.8), polymicrobial culture (OR 19,9 IC 6.0-83.4). Mortality was 56.2% in cases and 33.3% in controls. Conclusions: The risk factors found most frequently were: multiple peritoneal lavage, parenteral nutrition and polymicrobial cultures. We found a significant correlation in the use of adequate empirical antibiotic and the reduction in mortality


Assuntos
Humanos , Masculino , Feminino , Vancomicina , Mortalidade , Enterococcus , Sepse , Infecções , Unidades de Terapia Intensiva , Antibacterianos
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