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1.
Foods ; 13(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39272476

RESUMO

In Chile, honey is produced from several native species with interesting biological properties. Accordingly, those attributes are present in Chilean honeys owing to the presence of phenolic compounds inherited from specific floral sources. In recent years, the exported volume of Chilean honeys has been increased, reaching new markets with demanding regulations directed toward the fulfilment of consumers' expectations. Accordingly, there are countries with special requirements referring to Paenibacillus larvae spore-free honeys. This microorganism is the pathogen responsible for American foulbrood disease in beehives; however, antibiotics are not allowed when an apiary tests positive for P. larvae. On the other hand, it is mandatory to have an accurate method to remove the potential presence of spores in bee products intended for export. Exposure to ionizing radiation can be an efficient way to achieve this goal. In this work, 54 honey samples harvested from northern, central and southern Chile were analyzed for physicochemical patterns, total phenols, antioxidant activity and antiradical activity. Honeys with and without spores were exposed to ionizing radiation at three levels of intensity. Afterwards, the presence of spores and the effect on phenol bioavailability, antiradical activity and antioxidant activity were measured again. This research presents results showing a positive correlation between the percentage of prevalence of native endemic species in the set of honeys analyzed and the capacity to resist this process, without altering their natural attributes determined before irradiation treatments.

2.
Foot Ankle Surg ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39164136

RESUMO

BACKGROUND: Various fixation methods have been described for Akin osteotomy, based on using metal implants or transosseous sutures. The aim of this study was to evaluate radiological outcomes and complications of closing wedge Akin osteotomy based on a crossed suture configuration of the joint capsule rather than using implants. The null hypothesis is that a crossed suture has comparable radiological results to other techniques, with no additional complications. METHODS: It's a retrospective study. Patients who underwent Akin osteotomy fixed either with implant or joint capsule suture between 2015 and 2018 were included. Distal articular set angle corrections in pre- and postoperative anteroposterior foot x-rays were calculated by 2 observers. Complications, such as pain, infection, non-union and need of surgery revision, was compared at 1 year follow-up. RESULTS: 89 patients, 30 in the implant group and 59 in the suture group. Mean distal articular set angle corrections were 6.43 (SD 5.54) and 7.36 (SD 5.48) degrees in the implant and suture groups, respectively, without statistically significant differences (p 0454). Complications were 2 local pain and 1 wound infection cases in the suture and implant groups, respectively (p 0138, p 0197). CONCLUSION: Akin osteotomy with suture fixation yields comparable radiological results to metal implant fixation methods without increasing the associated complications.

3.
Nat Commun ; 15(1): 3741, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702301

RESUMO

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Transdução de Sinais , Fatores de Transcrição , Proteínas de Sinalização YAP , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Sinalização YAP/metabolismo , Linhagem Celular Tumoral , Animais , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasia Residual , Camundongos , Quinase 1 de Adesão Focal/metabolismo , Quinase 1 de Adesão Focal/genética , Receptores ErbB/metabolismo , Receptores ErbB/genética , Quinase do Linfoma Anaplásico/metabolismo , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Eur J Obstet Gynecol Reprod Biol ; 298: 23-30, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38705010

RESUMO

OBJECTIVE: Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session. STUDY DESIGN: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. RESULTS: This analysis included 250 patients, of whom 208 were considered to be at high-intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8-8.3] and 7.8% at 5 years (95% CI 4.8-12.6). The 5-year OS rate was 86.2% (95% CI 80.6-90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1-82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. CONCLUSION: These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.


Assuntos
Braquiterapia , Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/radioterapia , Braquiterapia/métodos , Braquiterapia/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/efeitos adversos , Idoso de 80 Anos ou mais , Adulto , Recidiva Local de Neoplasia/radioterapia , Resultado do Tratamento , Histerectomia , Dosagem Radioterapêutica
5.
Rev Esp Enferm Dig ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38685898

RESUMO

33-year-old woman, previously hospitalized for self-limited migratory bile duct strictures, presented with jaundice three months after giving birth. Blood analysis revealed elevated levels of aspartate aminotransaminase 1064U/L, alanine aminotransaminase 1097U/L, gamma-glutamyl transferase 194U/L, alkaline phosphatase 284U/L, bilirubin 27mg/dL and prothrombin time of 19.3s. Magnetic resonance-cholangiopancreatography revealed intrahepatic bile duct dilation with a stenosis in the common hepatic duct, not detected on endoscopic retrograde cholangiopancreatography. Additionally, diffuse signal abnormalities were observed in the liver parenchyma on T2 sequences. An early liver biopsy showed moderate-severe interface hepatitis with IgG4-positive plasma cell infiltration (IgG4-PPC) of 8-20cells/HPF, hepatocellular ballooning and focal rosette formation, yielding 6 points of the simplified-score for autoimmune hepatitis and treatment with methylprednisolone was initiated. Despite treatment, there was no improvement after two weeks and the patient received rituximab as a rescue treatment, but three days later, developed candida sepsis with rapid progression to multiorgan failure, ultimately resulting in death.

6.
Front Oncol ; 14: 1347727, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567146

RESUMO

Background and purpose: Image-guided adapted brachytherapy (IGABT) is superior to other radiotherapy techniques in the treatment of locally advanced cervical cancer (LACC). We aimed to investigate the benefit of interstitial needles (IN) for a combined intracavitary/interstitial (IC/IS) approach using IGABT over the intracavitary approach (IC) alone in patients with LACC after concomitant external beam radiotherapy (EBRT) and chemotherapy. Materials and methods: We included consecutive patients with LACC who were treated with IC/IS IGABT after radiochemotherapy (RCT) in our retrospective, observational study. Dosimetric gain and sparing of organs at risk (OAR) were investigated by comparing the IC/IS IGABT plan with a simulated plan without needle use (IC IGABT plan) and the impact of other clinical factors on the benefit of IC/IS IGABT. Results: Ninety-nine patients were analyzed, with a mean EBRT dose of 45.5 ± 1.7 Gy; 97 patients received concurrent chemotherapy. A significant increase in median D90% High Risk Clinical target volume (HR-CTV) was found for IC/IS (82.8 Gy) vs IC (76.2 Gy) (p < 10-4). A significant decrease of the delivered dose for all OAR was found for IC/IS vs IC for median D2cc to the bladder (77.2 Gy), rectum (68 Gy), sigmoid (53.2 Gy), and small bowel (47 Gy) (all p < 10-4). Conclusion: HR-CTV coverage was higher with IC/IS IGABT than with IC IGABT, with lower doses to the OAR in patients managed for LACC after RCT. Interstitial brachytherapy in the management of LACC after radiotherapy provides better coverage of the target volumes, this could contribute to better local control and improved survival of patients.

7.
Chem Soc Rev ; 53(8): 3714-3773, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38456490

RESUMO

Self-assembled monolayers (SAMs) represent highly ordered molecular materials with versatile biochemical features and multidisciplinary applications. Research on SAMs has made much progress since the early begginings of Au substrates and alkanethiols, and numerous examples of peptide-displaying SAMs can be found in the literature. Peptides, presenting increasing structural complexity, stimuli-responsiveness, and biological relevance, represent versatile functional components in SAMs-based platforms. This review examines the major findings and progress made on the use of peptide building blocks displayed as part of SAMs with specific functions, such as selective cell adhesion, migration and differentiation, biomolecular binding, advanced biosensing, molecular electronics, antimicrobial, osteointegrative and antifouling surfaces, among others. Peptide selection and design, functionalisation strategies, as well as structural and functional characteristics from selected examples are discussed. Additionally, advanced fabrication methods for dynamic peptide spatiotemporal presentation are presented, as well as a number of characterisation techniques. All together, these features and approaches enable the preparation and use of increasingly complex peptide-based SAMs to mimic and study biological processes, and provide convergent platforms for high throughput screening discovery and validation of promising therapeutics and technologies.


Assuntos
Peptídeos , Propriedades de Superfície , Peptídeos/química , Humanos , Técnicas Biossensoriais , Adesão Celular/efeitos dos fármacos
8.
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
9.
Medisur ; 22(1)feb. 2024.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1558537

RESUMO

Fundamento: la infertilidad es un problema de salud, que afecta cada vez con mayor incidencia, a ambos sexos. La endometriosis es una de las afecciones ginecológicas más frecuentes y una de las principales causas de infertilidad femenina. Objetivo: determinar los conocimientos sobre endometritis crónica que poseen las féminas del cantón de Ambato, Ecuador. Método: se realizó un estudio descriptivo de corte transversal en mujeres con endometritis crónica, pertenecientes al cantón de Ambato, durante el período de julio a diciembre de 2022. La muestra fue de 30 pacientes seleccionadas mediante muestreo no probabilístico de bola de nieve. Se realizó un análisis de contenido temático y se empleó el método de Mapas Cognitivos Difusos. Para la recolección de la información se realizó una entrevista semiestructurada. Resultados: existió un predominio de pacientes entre 26 a 30 años de edad. El 76,7 % de las pacientes refirieron no poseer conocimientos sobre el tema, el 86,7 % no había recibido educación sexual y reproductiva formal y el 70 % había sido estigmatizado. El 83,3 % de las féminas refirieron no visitar periódicamente un profesional de salud reproductiva y el 76,7 % no había accedido a información sobre la temática. El 100 % de las pacientes consideraron necesario realizar talleres, charlas y realizar intervenciones comunitarias para sensibilizar sobre el impacto de la endometritis crónica en la fertilidad femenina. Conclusiones: la endometritis crónica estuvo presente en féminas en edad reproductiva, por lo que resulta necesario desarrollar estrategias de prevención de salud para minimizar su incidencia.


Foundation: infertility is a health problem that affects both sexes with increasing incidence. Endometriosis is one of the most common gynecological conditions and one of the main causes of female infertility. Objective: determine the knowledge about chronic endometritis that women in the canton of Ambato, Ecuador, have. Methods: a descriptive cross-sectional study was carried out in women with chronic endometritis, belonging to the canton of Ambato, during the period from July to December 2022. The sample was 30 patients selected through non-probabilistic snowball sampling. A thematic content analysis was carried out and the Fuzzy Cognitive Maps method was used. To collect the information, a semi-structured interview was carried out. Results: there was a predominance of patients between 26 and 30 years of age. 76,7 % of the patients reported not having knowledge on the subject, 86,7 % had not received formal sexual and reproductive education and 70 % had been stigmatized. 83,3 % of the women reported not periodically visiting a reproductive health professional and 76,7 % had not accessed information on the subject. 100 % of the patients considered it necessary to hold workshops, talks and carry out community interventions to raise awareness about the impact of chronic endometritis on female fertility. Conclusions: chronic endometritis was present in women of reproductive age, so it is necessary to develop health prevention strategies to minimize its incidence.

10.
Rev. estomatol. Hered ; 34(1): 27-35, ene.-mar. 2024. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1565541

RESUMO

RESUMEN Objetivo : Describir la asociación del desempeño docente percibido por una población de estudiantes y el nivel de satisfacción autorreportada por los profesores de la Licenciatura de Cirujano Dentista de la Facultad de Estudios Superiores Zaragoza de la Universidad Nacional Autónoma de México. Materiales y métodos: Estudio observacional, prolectivo, transversal, descriptivo, realizado en dos fases. En la primera se mostró la satisfacción laboral autorreportada por 123 académicos; en la segunda fase se encuestó a 120 estudiantes para que evaluaran a sus 6 docentes muy satisfechos, y a 140 para los 7 muy insatisfechos, para lo cual se les aplicó una encuesta adaptada del Departamento de Evaluación Docente de la facultad. Resultados : Al asociar el desempeño de los 6 docentes más satisfechos laboralmente con la percepción que de ellos tienen sus 120 estudiantes, los resultados muestran que el 2 % (n = 2) considera que los académicos tienen un mal desempeño vs. el 44 % (n = 53) que considera que tienen un desempeño excelente. En cuanto a los 7 docentes identificados como muy insatisfechos, desde la mirada de los estudiantes, el 10 % (n = 14) considera que el desempeño es malo; y para el 49 % (n = 68) es excelente. La satisfacción laboral autorreportada por los 13 académicos y el desempeño docente percibido por sus estudiantes no mostró diferencias estadísticamente significativas. Para los estudiantes, un docente tiene un excelente ejercicio de su actividad pese a su insatisfacción laboral, así como un mal desempeño aun cuando se autopercibe como muy satisfecho. Conclusiones : Los resultados de la investigación muestran que no hay una asociación entre el rendimiento docente y la satisfacción laboral según los estudiantes. La actitud de un profesor hacia los estudiantes no siempre coincide con su nivel de satisfacción laboral.


ABSTRACT Objective : To describe the association between the teaching performance perceived by a population of students and the level of satisfaction self-reported by the professors of the bachelor's degree program in Dental Surgery of the Facultad de Estudios Superiores Zaragoza of the Universidad Nacional Autónoma de México. Materials and methods : Observational, prolective, cross-sectional, descriptive study, conducted in two phases. The first phase showed the self-reported job satisfaction of 123 academics; in the second phase, 120 students were surveyed to evaluate their 6 very satisfied teachers and 140 for the 7 dissatisfied ones, for which a survey adapted from the Department of Teaching Evaluation of the faculty was applied. Results : When associating the performance of the 6 teachers most satisfied with their job with the perception that their 120 students have of them, the results show that 2 % (n = 2) consider that the academics have a poor performance vs. 44 % (n = 53) who consider that they have an excellent performance. As for the 7 teachers identified as very dissatisfied, from the students' point of view, 10 % (n = 14) consider the performance poor; and for 49 % (n = 68), it is excellent. The job satisfaction self-reported by the 13 academics and the teaching performance perceived by their students did not show statistically significant differences. For the students, a teacher has excellent performance despite job dissatisfaction and poor performance even when he or she perceives himself or herself as very satisfied. Conclusions : The research results show no association between teaching performance and job satisfaction according to students. A teacher's attitude towards students does not always coincide with his or her level of job satisfaction.


RESUMO Objetivo : Descrever a associação entre o desempenho docente percepcionado por uma população de estudantes e o nível de satisfação autoreportado pelos professores da Licenciatura em Cirurgia Dentária na Facultad de Estudios Superiores Zaragoza da Universidad Nacional Autónoma de México. Materiais e métodos : Estudo observacional, proletivo, transversal e descritivo realizado em duas fases. Na primeira fase, foi analisada a satisfação profissional autorreferida de 123 académicos; na segunda fase, 120 estudantes foram inquiridos para avaliar os seus 6 professores altamente satisfeitos e 140 para os 7 insatisfeitos, utilizando um inquérito adaptado do Departamento de Avaliação do Ensino da faculdade. Resultados : Ao associar o desempenho dos 6 professores mais satisfeitos com o seu trabalho à percepção que os seus 120 alunos têm deles, os resultados mostram que 2 % (n = 2) consideram que os académicos têm um mau desempenho contra 44 % (n = 53) que consideram que têm um excelente desempenho. Quanto aos 7 professores identificados como muito insatisfeitos, do ponto de vista dos estudantes, 10 % (n = 14) consideram que o seu desempenho é mau; e para 49 % (n = 68) é excelente. A satisfação profissional autorrelatada pelos 13 académicos e o desempenho docente percepcionado pelos seus estudantes não revelaram diferenças estatisticamente significativas. Para os estudantes, um professor tem um desempenho excelente apesar da sua insatisfação profissional e tem um desempenho fraco mesmo quando se considera muito satisfeito. Conclusões : Os resultados da investigação mostram que não existe uma associação entre o desempenho docente e a satisfação profissional, segundo os estudantes. A atitude de um professor em relação aos alunos nem sempre coincide com o seu nível de satisfação profissional.

11.
Am J Health Syst Pharm ; 81(4): 112-119, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-37675967

RESUMO

PURPOSE: Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat multiple hematologic malignancies and graft-versus-host disease. Though less myelosuppressive than cytotoxic chemotherapy, increased infections, including invasive fungal infections (IFIs), have been reported with ibrutinib use. This study aimed to determine the characteristics and risk factors for infection associated with ibrutinib at our institution. METHODS: Patients who received ibrutinib between June 2014 and August 2019 were included. Primary endpoints were the incidence of any infection and the incidence of serious infection (defined as hospitalization, parenteral antimicrobial therapy, or pneumonia regardless of hospitalization). Infection risk factors were assessed using logistic regression. RESULTS: One hundred thirty-two patients were identified (78% male; median age, 71 years). The most common indications for ibrutinib were chronic lymphocytic leukemia (67%) and mantle cell lymphoma (12%). Infection and serious infection occurred in 94 (71%) and 47 (36%) patients, respectively; when pneumonia was excluded as a criterion for serious infection, the serious infection rate was 27%. The median time from ibrutinib initiation to first infection was 125 days. Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) (odds ratio [OR], 4.60; 95% CI, 1.22-17.4) and corticosteroid use (OR, 5.55; 95% CI, 1.52-20.3) were significant risk factors for serious infection. IFIs were diagnosed in 7 patients (5%): 5 had Pneumocystis jirovecii pneumonia and 2 were infected with invasive molds. CONCLUSION: Serious infection and IFI rates are high but similar to those previously described. Risk factors for serious infection included allo-HSCT and corticosteroid use. Targeted antimicrobial prophylaxis should be evaluated in prospective studies in patients on ibrutinib to reduce serious infections and IFI.


Assuntos
Adenina/análogos & derivados , Anti-Infecciosos , Neoplasias Hematológicas , Leucemia Linfocítica Crônica de Células B , Piperidinas , Pneumonia , Humanos , Adulto , Masculino , Idoso , Feminino , Estudos Prospectivos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/epidemiologia , Anti-Infecciosos/uso terapêutico , Corticosteroides/uso terapêutico
12.
Nat Genet ; 56(1): 60-73, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38049664

RESUMO

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Regulação para Cima/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Citidina Desaminase/genética , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo
13.
Aten Primaria ; 56(2): 102782, 2024 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-37924621

RESUMO

OBJECTIVE: The objective was to develop a screening for heart disease detection in primary care, to identify pathological electrocardiographic changes and underlying heart disease in adolescents. DESIGN: The study was carried out for one year using multistage sampling. SITE: Primary care centers in a health area that had digital ECG equipment (12 centers) were selected. PARTICIPANTS: Initially, 718 (16.6%) 14-year-old adolescents were recruited and those with a previous diagnosis of heart disease were excluded. INTERVENTIONS: Screening consisted of including a health questionnaire in the mandatory 14-year-old check-up. MAIN MEASUREMENTS: Screening included a questionnaire, cardiac auscultation, ECG and echocardiography. Abnormality criteria were established to refer for a second evaluation by a cardiologist. RESULTS: Finally, the sample was made up of 698 adolescents, with a mean age of 13.7±0.5 years, and 354 (50.7%) were boys. A total of 149 (21.3%) were selected for a second review by cardiology: 88 (12.6%) due to a positive questionnaire, 11 (2.2%) due to abnormal cardiac auscultation, and 66 (9.5%) due to ECG findings. Adolescents with evidence of heart disease were 24 (3.4%). Of these, 14 (2.0%) had suggestive alterations and follow-up was recommended, 6 (0.9%) had a definitive diagnosis of heart disease, and 4 (0.6%) had other pathological findings related to the cardiovascular system. CONCLUSIONS: The screening allowed us to identify 1% of adolescents with heart disease and another 2% will remain in follow-up. The ECG detected more pathological cases than the questionnaire.


Assuntos
Morte Súbita Cardíaca , Cardiopatias , Masculino , Humanos , Adolescente , Feminino , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia , Cardiopatias/diagnóstico , Ecocardiografia , Programas de Rastreamento
14.
An. bras. dermatol ; 99(3): 414-424, Mar.-Apr. 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1556862

RESUMO

Abstract Background Acne is a chronic inflammatory disorder of the pilosebaceous unit that is associated with a negative impact on quality of life, causing anxiety, depression, and poor self-esteem. The treatment of acne is not simple and presents some new challenges. This article addresses important issues faced by dermatologists on their daily, some of them specific for Latin America. Objective To discuss daily practice recommendations when managing acne patients. Methods A literature review was conducted by a group of eight experts with extensive experience in the field of acne. The results of the data review were presented at an initial kick-off meeting to align the consensus topics. Two e-surveys using the Delphi methodology and an interim group webinar meeting were held. Results The expert panel reached a consensus on all proposed key statements, providing scientific support to help dermatologists and healthcare providers make acne management decisions on topics that can be challenging in the everyday practice of dermatology, such as the characteristics of Generation Z or the importance of the maintenance phase of adult acne treatment. Conclusion This article provides current recommendations for managing acne patients. The high level of agreement achieved based on the latest evidence supports the best acne therapeutic choices in both established topics and new important issues that have emerged in recent years, such as the impact of social media, Generation Z characteristics, and transgender male patient specifics.

15.
Braz. j. infect. dis ; 28(3): 103767, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1564149

RESUMO

Abstract Background C. difficile has been increasingly reported as a cause of gastrointestinal disease in children, ranging from mild self-limiting diarrhea to severe conditions such as pseudomembranous colitis and toxic megacolon. Only two pediatric research groups reported the presence of C. difficile infection in Brazilian children, but no previous research has examined C. difficile infection among children in northeastern Brazil. This prospective cross-sectional study investigated the molecular epidemiology and antimicrobial resistance of C. difficile strains isolated from children and adolescents with diarrhea referred to a tertiary pediatric hospital in Brazil while exploring the associated risk factors. Results Toxin positivity or C. difficile isolation was found in 30.4 % (17/56) samples. C. difficile was isolated from 35 % (6/17) samples. Four toxigenic strains were identified (tpi+, tcdA+, tcdB+, cdtB-, without tcdC deletions) belonging to PCR ribotypes and PFGE-pulsotypes: 046 (new pulsotype 1174), 106 (NAP11), 002 (new pulsotype 1274), 012 (new pulsotype NML-1235). Two of the six isolates belonging to ribotypes 143 and 133 were non-toxigenic. All toxigenic strains were sensitive to metronidazole and vancomycin. Regarding the clinical manifestation, diarrhea lasted an average of 11 days, ranging from 3 to 50 days and was often associated with mucus and/or blood. All six patients from whom the C. difficile was isolated had a chronic disease diagnosis, with these comorbidities as the main risk factors. Conclusion Our study enhances our understanding of the present epidemiological landscape of C. difficile-associated diarrhea (CDI) among children in northeastern Brazil, reveling a substantial CDI frequency of 30.4 %, with toxigenic strains detected in 76.4 % of cases, highlighting a higher prevalence compared to earlier Brazilian studies. In the globalized world, an understanding of disease-generating strains, the associated risk factors, clinical manifestation, and antimicrobial sensitivity has fundamental epidemiological importance and draws attention to preventive measures, allowing for more decisive action.

16.
Int J Mol Sci ; 24(23)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38069446

RESUMO

Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and ß-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from H2S and NH3. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Colite Ulcerativa/metabolismo , Doença de Crohn/metabolismo , Mucosa Intestinal/metabolismo , Mitocôndrias
17.
Exp Clin Endocrinol Diabetes ; 131(12): 631-638, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38056490

RESUMO

BACKGROUND: Little is known about the relationship between signal intensity patterns on T2-weighted magnetic resonance imaging (MRI) in non-functioning pituitary adenomas (NFPAs). OBJECTIVE: In this study, the clinical, hormonal, histological features, and therapeutic responses were evaluated according to the T2 signal intensity in NFPAs. METHODS: This retrospective and multicenter study included a group of 166 NFPA patients (93 men, 56%, mean age 58.5 ±14.8 yr). RESULTS: Approximately half of the tumors (n=84, 50.6%) were hyperintense, while 34.3% (n=57) and 15.1% (n=25) were iso- and hypointense, respectively. The median maximum tumor diameter of the isointense group [16 (13-25) mm] was significantly lower than that of the hyperintense [23 (16.6-29.7) mm] group (p=0.003). Similarly, the tumor volume of the isointense group [1,523 (618-5,226) mm3] was significantly lower than that of the hyperintense [4,012 (2,506-8,320) mm3] group (p=0.002). Chiasmatic compression occurred less frequently in tumors with isointense signal characteristics (38.6%) compared to tumors with hypointense (68%) and hyperintense (65.5%) signal characteristics (p=0.003). Invasive adenomas (p=0.001) and the degree of cavernous sinus invasion (p<0.001) were more frequent in the hyperintense adenoma group compared to the remaining groups. Plurihormonal tumors and silent lactotroph adenomas were more frequent in the isointense tumor group. CONCLUSION: In conclusion, hyperintensity on T2-weighted MRI in NFPAs is associated with larger and more invasive tumors compared to isointense NFPAs.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Adenoma/patologia , Relevância Clínica , Imageamento por Ressonância Magnética/métodos , Neoplasias Hipofisárias/tratamento farmacológico , Estudos Retrospectivos , Feminino
18.
Rev. argent. reumatolg. (En línea) ; 34(3): 99-104, dic. 2023. tab, graf
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1535526

RESUMO

La encefalitis autoinmune es un trastorno inmunomediado que compromete distintos territorios del parénquima cerebral, involucrando frecuentemente la materia gris profunda o la corteza, con o sin compromiso de la materia blanca, meninges o médula espinal. Se asocia frecuentemente con enfermedades autoinmunes o paraneoplásicas, y constituye un reto diagnóstico. Reportamos el caso de una mujer de 55 años con antecedente de síndrome de Sjögren que consultó a Emergencias por cefalea y confusión. El líquido cefalorraquídeo (LCR) presentaba leucocitosis con neutrofilia. En la resonancia magnética nuclear (RMN) cerebral se evidenciaron múltiples imágenes de comportamiento restrictivo, de señal hiperintensa en T2 y FLAIR, a predominio córtico-subcortical a nivel occipital bilateral, hemisferio cerebeloso derecho y parietal derecho. Se descartaron infecciones y neoplasias. El panel de anticuerpos para encefalitis autoinmune aquaporina-4 y anti-MOG en LCR fue negativo. Recibió metilprednisolona endovenosa con mejoría progresiva de los síntomas.


Autoimmune encephalitis is an immune-mediated disorder that affects different areas of the brain parenchyma, often involving deep gray matter or the cortex, with or without involvement of white matter, meninges, or spinal cord. It is frequently associated with autoimmune or paraneoplastic diseases and is a diagnostic challenge. We report the case of a 55-year-old woman with history of Sjögren's syndrome who presented to the emergency department with headache and episodes of confusion. Cerebrospinal fluid (CSF) analysis showed leukocytosis with neutrophilia. Brain MRI revealed multiple restricted diffusion lesions with hyperintense signal on T2 and FLAIR sequences, predominantly in the bilateral occipital region, right cerebellar hemisphere, and right parietal region. Infections and neoplasms were ruled out. The panel of antibodies for autoimmune encephalitis, including Aquaporin-4 and anti-MOG in CSF, was negative. She received intravenous methylprednisolone, leading to symptom improvement.


Assuntos
Feminino , Sistema Nervoso Central
19.
Transpl Infect Dis ; 25 Suppl 1: e14184, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37910586

RESUMO

Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/etiologia , Fatores de Risco , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Reação em Cadeia da Polimerase Multiplex , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/etiologia
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