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The plasma membrane tetraspan molecule MS4A4A is selectively expressed by macrophage-lineage cells, but its function is unknown. Here we report that MS4A4A was restricted to murine and human mononuclear phagocytes and was induced during monocyte-to-macrophage differentiation in the presence of interleukin 4 or dexamethasone. Human MS4A4A was co-expressed with M2/M2-like molecules in subsets of normal tissue-resident macrophages, infiltrating macrophages from inflamed synovium and tumor-associated macrophages. MS4A4A interacted and colocalized with the ß-glucan receptor dectin-1 in lipid rafts. In response to dectin-1 ligands, Ms4a4a-deficient macrophages showed defective signaling and defective production of effector molecules. In experimental models of tumor progression and metastasis, Ms4a4a deficiency in macrophages had no impact on primary tumor growth, but was essential for dectin-1-mediated activation of macrophages and natural killer (NK) cell-mediated metastasis control. Thus, MS4A4A is a tetraspan molecule selectively expressed in macrophages during differentiation and polarization, essential for dectin-1-dependent activation of NK cell-mediated resistance to metastasis.
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Células Matadoras Naturais/imunologia , Lectinas Tipo C/metabolismo , Macrófagos/imunologia , Proteínas de Membrana/metabolismo , Metástase Neoplásica/imunologia , Neoplasias/imunologia , Animais , Diferenciação Celular/imunologia , Linhagem da Célula , Dexametasona/farmacologia , Humanos , Interleucina-4/metabolismo , Ativação Linfocitária/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Metástase Neoplásica/prevenção & controle , Neoplasias/patologiaRESUMO
The characteristics of aviation-induced aerosol, its processing, and effects on cirrus clouds and climate are still associated with large uncertainties. Properties of aviation-induced aerosol, however, are crucially needed for the assessment of aviation's climate impacts today and in the future. We identified more than 1100 aircraft plume encounters during passenger aircraft flights of the IAGOS-CARIBIC Flying Laboratory from July 2018 to March 2020. The aerosol properties inside aircraft plumes were similar, independent of the altitude (i.e., upper troposphere, tropopause region, and lowermost stratosphere). The exhaust aerosol was found to be mostly externally mixed compared to the internally mixed background aerosol, even at a plume age of 1 to 3 h. No enhancement of accumulation mode particles (diameter >250 nm) could be detected inside the aircraft plumes. Particle number emission indices (EIs) deduced from the observations in aged plumes are in the same range as values reported from engine certifications. This finding, together with the observed external mixing state inside the plumes, indicates that the aviation exhaust aerosol almost remains in its emission state during plume expansion. It also reveals that the particle number EIs used in global models are within the range of the EIs measured in aged plumes.
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OBJECTIVE: This study evaluated the influence of a single educational intervention on the perception and knowledge of strategies for communicating oral cancer diagnoses. METHODS: A educational intervention, 72 dentists and 41 dental undergraduates participated in the 'Maio Vermelho Project', a continuing education activity. Participants completed a 14-question online questionnaire concerning their experiences and perceptions of delivering difficult news. The educational intervention featured an interview illustrating the SPIKES protocol, broadcast on YouTube. RESULTS: Participants had a mean age of 40 years. A minority (21.2%) had encountered or experienced communicating an oral cancer diagnosis. Exposure to lectures on this topic during their education was uncommon (22.1%) but more prevalent among students. After the intervention, confidence in communicating a cancer diagnosis (29.2%) and addressing the patient's family (30.1%) in line with the SPIKES protocol increased. CONCLUSION: A training deficit persists in delivering cancer diagnoses, highlighting the need for educational interventions to empower students and professionals in this critical procedure. Integration of this topic into the dental undergraduate curriculum is imperative. CLINICAL RELEVANCE: Effectively communicating a cancer diagnosis poses challenges to healthcare professionals, impacting treatment outcomes. Implementing educational interventions ensures that professionals are well prepared to navigate this complex task, ultimately improving patient care.
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ABSTRACT: Lymphangioma circumscriptum (LC) is a rare benign condition, with marked dilation of surface lymphatic vessels in the deep and subcutaneous layers. Vulvar LC can become a highly disabling condition with vulvar discomfort, itching, burning and lymph seeping being the dominant symptoms. Biopsy is mandatory for the diagnosis. There is no consensus on the standard treatment for vulvar LC and recurrence is frequent. In complex cases with wide disease location, combination of different treatment options, such as abrasive methods and surgery, may lead to the best clinical and aesthetical result, with extended disease-free periods. We present a patient with a long history of Crohn disease with multiple pelvic surgeries who developed an extensive vulvar LC.
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Doença de Crohn , Linfangioma , Neoplasias Vulvares , Vulvodinia , Feminino , Humanos , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/cirurgia , Neoplasias Vulvares/patologia , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Vulva/patologia , Linfangioma/diagnóstico , Linfangioma/cirurgia , Linfangioma/patologia , Vulvodinia/patologiaRESUMO
Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during coronary artery bypass grafting (CABG) from two MI cohorts, patients with non-ST-segment elevation MI (NSTEMI) and patients with ST-segment elevation MI (STEMI), and a control group composed of patients with stable angina and without previous history of MI. The PF miR content was analyzed by small RNA sequencing, and its biological effect was assessed on human cardiac fibroblasts. PF accumulates fibrotic and inflammatory molecules in STEMI patients, namely causing the soluble suppression of tumorigenicity 2 (ST-2), which inversely correlates with the left ventricle ejection fraction. Although the PF of the three patient groups induce similar levels of fibroblast-to-myofibroblast activation in vitro, RNA sequencing revealed that PF from STEMI patients is particularly enriched not only in pro-fibrotic miRs but also anti-fibrotic miRs. Among those, miR-22-3p was herein found to inhibit TGF-ß-induced human cardiac fibroblast activation in vitro. PF constitutes an attractive source for screening diagnostic/prognostic miRs and for unveiling novel therapeutic targets in cardiac fibrosis.
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Fibrose , MicroRNAs , Infarto do Miocárdio , Líquido Pericárdico , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Masculino , Líquido Pericárdico/metabolismo , Feminino , Miocárdio/metabolismo , Miocárdio/patologia , Pessoa de Meia-Idade , Fibroblastos/metabolismo , Idoso , Fator de Crescimento Transformador beta/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genéticaRESUMO
The purpose of the study is to describe the experience of a multidisciplinary team in a tertiary hospital regarding the management of Infantile Hemangiomas (IH). The method employed is a retrospective analysis of patients with IH followed in a tertiary pediatric hospital between January 2010 and May 2022. A total of 393 IH were diagnosed (56.7% female), with a median age of 5 months (interquartile range (IQR), 3-10). Imaging investigation was necessary for diagnosis and for exclusion of other IH in 9.2% and 14.3%, respectively. Focal (74.0%) and superficial (59.7%) lesions were more frequent as was facial location (35.9%). Pre-treatment ulceration or hemorrhage occurred in 6.6%. At follow-up, 87.4% regressed partially and 12.6% completely; 2.7% relapsed. Propranolol was started in 30.0% of cases for a median period of 9 months (IQR, 6-12), mainly due to esthetic concerns (41.9%). Side effects occurred in 8.3% (sleep disturbance in 5.1%). Only 1.7% were refractory and 5.9% had a rebound effect. Eleven patients were treated with topical timolol and 41 underwent surgery. Patients that were treated with propranolol had more risk factors (p = 0.016) and presented deeper lesions (p < 0.001) with a larger diameter (p < 0.001); total IH regression was less frequent (p < 0.001). Since 2020, twice-daily dosage was more frequently prescribed than three times daily (p = 0.007) and inpatient initiation of propranolol decreased (p = 0.750), without significant difference in the incidence of adverse reactions, duration of treatment, and lesion evolution. Conclusions: Our protocol proved to be safe and feasible in an outpatient setting and twice daily administration of propranolol was effective. The majority of IH showed at least partial regression. Early detection of high-risk IH is paramount and a multidisciplinary assessment by a specialized team is essential for adequate management. What is Known: ⢠IH are the most common vascular tumors in childhood. Although the majority evolves favorably, treatment may be warranted in selected cases. ⢠Early detection of high-risk IH is paramount, and a multidisciplinary assessment by a specialized team is essential for adequate management. What is New: ⢠One-third of our sample was treated with propranolol. These patients had more risk factors and presented deeper lesions with a larger diameter, and tumor total regression was less frequent. ⢠Our results reinforce safety and feasibility of propranolol initiation in an outpatient setting, including twice daily dosage.
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Hemangioma , Neoplasias Cutâneas , Humanos , Feminino , Criança , Lactente , Masculino , Propranolol/uso terapêutico , Hemangioma/diagnóstico , Hemangioma/tratamento farmacológico , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Administração Oral , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêuticoRESUMO
Artificial neural networks (ANN) are artificial intelligence (AI) techniques used in the automated recognition and classification of pathological changes from clinical images in areas such as ophthalmology, dermatology, and oral medicine. The combination of enterprise imaging and AI is gaining notoriety for its potential benefits in healthcare areas such as cardiology, dermatology, ophthalmology, pathology, physiatry, radiation oncology, radiology, and endoscopic. The present study aimed to analyze, through a systematic literature review, the application of performance of ANN and deep learning in the recognition and automated classification of lesions from clinical images, when comparing to the human performance. The PRISMA 2020 approach (Preferred Reporting Items for Systematic Reviews and Meta-analyses) was used by searching four databases of studies that reference the use of IA to define the diagnosis of lesions in ophthalmology, dermatology, and oral medicine areas. A quantitative and qualitative analyses of the articles that met the inclusion criteria were performed. The search yielded the inclusion of 60 studies. It was found that the interest in the topic has increased, especially in the last 3 years. We observed that the performance of IA models is promising, with high accuracy, sensitivity, and specificity, most of them had outcomes equivalent to human comparators. The reproducibility of the performance of models in real-life practice has been reported as a critical point. Study designs and results have been progressively improved. IA resources have the potential to contribute to several areas of health. In the coming years, it is likely to be incorporated into everyday life, contributing to the precision and reducing the time required by the diagnostic process.
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Dermatologia , Oftalmologia , Humanos , Inteligência Artificial , Reprodutibilidade dos Testes , Redes Neurais de ComputaçãoRESUMO
Vasovagal reflex is the most common cause of syncope. Pacemaker with rate drop response (RDR) or closed-loop stimulation (CLS) anti-syncope algorithms have been studied in recurrent vasovagal syncope (VVS), with conflicting results. We aim to investigate the role of pacemaker therapy and anti-syncope pacing mode in cardioinhibitory recurrent VVS. MEDLINE, Cochrane Library and registered clinical trials were searched for single or double-blind randomized controlled trials on pacing as a treatment for recurrent VVS. Five studies were eligible, overall enrolling 228 patients. After pooling data from all trials, pacemaker therapy showed a 63% reduction in syncope recurrence compared to control [Risk Ratio (RR): 0.37; 95% CI: 0.14-0.98; I2 = 67%)]. Subgroup analyses suggested that the effect was greater in single-blind studies (RR: 0.07; 95% CI: 0.01-0.52, I2 = 0%). When comparing pacing algorithms, the results from RDR versus no pacing trials (n = 2) did not show a significant reduction in syncope recurrence (RR: 0.73; 95% CI: 0.25-2.16, I2 60 = 75%). In contrast, the data from the CLS versus standard pacing trials (n = 3) evidenced a statistically meaningful reduction in syncopal burden (RR: 0.18; 95% CI: 0.07-0.47, I2 = 0%). It is unclear whether pacemaker therapy reduces syncopal burden in cardioinhibitory recurrent VVS. However, our results suggest effectiveness of CLS pacing mode.
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Estimulação Cardíaca Artificial/métodos , Síncope Vasovagal/terapia , Algoritmos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Síncope Vasovagal/fisiopatologiaAssuntos
COVID-19 , SARS-CoV-2 , Humanos , Pandemias , Pessoal de Saúde/psicologia , Atenção à SaúdeRESUMO
PURPOSE: Auto-titrating continuous positive airway pressure (APAP) devices were developed to improve treatment efficacy and compliance in patients with obstructive sleep apnoea syndrome (OSAS). Since there are insufficient data on the optimal pressure range setting, we aimed to compare the adherence, efficacy and tolerability of treatment with high-span versus low-span APAP. METHODS: Seventy-six newly diagnosed OSAS patients fulfilling the treatment criteria were randomised to receive high-span (HS, range 4-15cmH2O, n = 38) or low-span (LS, range 8-12cmH2O, n = 38) APAP. Patients were assessed at 1 and 3 months. RESULTS: Median Epworth sleepiness scale (ESS) was 13 (IQR, 6-16) and median apnoea-hypopnoea index (AHI) was 35.9 (IQR, 27.6-56.3). There were no significant differences in baseline demographic and clinical characteristics between groups. Overall, no significant differences were found at the first month assessment. After 3 months of therapy, we found again no differences in residual AHI or ESS. However, the group HS proved less adherent than group LS, respectively, with median 87 % (IQR, 60.5-97.5) versus 94 % (IQR, 80.0-98.3) of the nights using ≥4 h (P = 0.014) and mean (±SD) usage 5.7 ± 1.6 versus 6.4 ± 1.2 h/night (P = 0.049). The group HS reported more frequently nasal congestion, excessive oronasal dryness and nocturnal awakenings of at least moderate intensity, the latter with statistical significance (P = 0.005). CONCLUSIONS: Both pressure ranges appear to be equally effective to correct AHI and to improve symptoms. Though, patients with high-span APAP were less compliant to treatment, raising issues about the tolerability of wide pressure range settings of these devices.
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Pressão Positiva Contínua nas Vias Aéreas/métodos , Apneia Obstrutiva do Sono/terapia , Adulto , Idoso , Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/terapia , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Inquéritos e QuestionáriosRESUMO
Diamond-Blackfan Anemia (DBA) is a rare heterogeneous genetic disease characterized by severe anemia, reduction or absence of erythroid progenitors, and pro-apoptoptic hematopoiesis, which culminates in bone marrow failure. The disease generally manifests in infancy, as craniofacial, cardiac, genitourinary, and upper limb congenital anomalies. Therapy with corticoids is the treatment of choice, while blood transfusion is adopted during diagnosis and as a chronic approach if the patient does not respond to corticoids. This case report describes DBA in a patient that presented with lesions on the oral mucosa caused by secondary neutropenia. The stomatologist plays an important role in a transdisciplinary team and must remain attentive to the general health conditions of patients, since some oral lesions may be associated with systemic events.
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Anemia de Diamond-Blackfan/sangue , Anemia de Diamond-Blackfan/complicações , Neutropenia/diagnóstico por imagem , Corticosteroides/uso terapêutico , Negro ou Afro-Americano , Anemia de Diamond-Blackfan/diagnóstico , Anemia de Diamond-Blackfan/etnologia , Apoptose , Transfusão de Sangue , Brasil , Comorbidade , Feminino , Hematopoese/fisiologia , Hemodinâmica , Hospitalização , Humanos , Inflamação , Mucosa Bucal/patologia , Neutropenia/complicações , Adulto JovemAssuntos
Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Simendana/uso terapêutico , Vasoconstritores/uso terapêutico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Pressão Arterial , Dobutamina/uso terapêutico , Dopamina/uso terapêutico , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Mortalidade Hospitalar , Humanos , Hipotensão/induzido quimicamente , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Taquicardia Supraventricular/induzido quimicamente , Resultado do TratamentoAssuntos
Compostos Benzidrílicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Glucosídeos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Sistemas de Liberação de Medicamentos/métodos , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Estudos ProspectivosRESUMO
Fungal infections present a significant global public health concern, impacting over one billion individuals worldwide and resulting in more than 3 million deaths annually. Despite considerable progress in recent years, the management of fungal infections remains challenging. The limited development of novel diagnostic and therapeutic approaches is largely attributed to our incomplete understanding of the pathogenetic mechanisms involved in these diseases. Recent research has highlighted the pivotal role of cellular metabolism in regulating the interaction between fungi and their hosts. In response to fungal infection, immune cells undergo complex metabolic adjustments to meet the energy demands necessary for an effective immune response. A comprehensive understanding of the metabolic circuits governing antifungal immunity, combined with the integration of individual host traits, holds the potential to inform novel medical interventions for fungal infections. This review explores recent insights into the immunometabolic regulation of host-fungal interactions and the infection outcome and discusses how the metabolic repurposing of immune cell function could be exploited in innovative and personalized therapeutic approaches.
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The therapeutic approach to inflammatory bowel disease (IBD) is complex, often involving multiple pharmacologic classes. We aimed to evaluate the prevalence of drug-related adverse reactions (ARs) associated with therapies used in pediatric IBD. We conducted a retrospective study of pediatric patients with IBD followed in a tertiary hospital from 2010 to 2022. Ninety-nine patients were included (62.6% were male), with a median age at diagnosis of 13 years (interquartile range [IQR] 11-15 years). The majority had Crohn's disease (69.7%), followed by ulcerative colitis (21.2%) and unclassified IBD (9.1%). The most prescribed therapies were: immunomodulators (n = 75, 75.8%), exclusive enteral nutrition (n = 61, 61.6%), and biologics (n = 58, 58.6%). During a median follow-up time of 31 months (IQR 11-51 months), the incidence of ARs was 16.2% (16 ARs occurred in 14 patients). The main drug involved was azathioprine (12/16) and the most frequent AR was hepatitis (5/16). Drug discontinuation was necessary in all but 1 case. Of the ARs recorded, 75% were mild to moderate and 81.3% did not require specific treatment; all patients had clinical and/or analytical normalization. There was a positive association between the cumulative number of prescribed drugs and the occurrence of ARs (P = .044). The incidence of ARs was similar to the rates reported in the few existing previous studies. The majority of ARs were mild, but implied the discontinuation of therapy or dose reduction, with a possible impact on disease control.
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Colite Ulcerativa , Doença de Crohn , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doenças Inflamatórias Intestinais , Humanos , Masculino , Criança , Adolescente , Feminino , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Azatioprina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologiaRESUMO
OBJECTIVE: This retrospective study analyzed the errors generated by a convolutional neural network (CNN) when performing automated classification of oral lesions according to their clinical characteristics, seeking to identify patterns in systemic errors in the intermediate layers of the CNN. STUDY DESIGN: A cross-sectional analysis nested in a previous trial in which automated classification by a CNN model of elementary lesions from clinical images of oral lesions was performed. The resulting CNN classification errors formed the dataset for this study. A total of 116 real outputs were identified that diverged from the estimated outputs, representing 7.6% of the total images analyzed by the CNN. RESULTS: The discrepancies between the real and estimated outputs were associated with problems relating to image sharpness, resolution, and focus; human errors; and the impact of data augmentation. CONCLUSIONS: From qualitative analysis of errors in the process of automated classification of clinical images, it was possible to confirm the impact of image quality, as well as identify the strong impact of the data augmentation process. Knowledge of the factors that models evaluate to make decisions can increase confidence in the high classification potential of CNNs.