The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell-mediated resistance to metastasis.

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.

Properties and Processing of Aviation Exhaust Aerosol at Cruise Altitude Observed from the IAGOS-CARIBIC Flying Laboratory.

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.

Oral cancer diagnosis communication: Impact of an educational intervention using the SPIKES protocol.

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.

Unusual Presentation of Lymphangioma Circumscriptum of the Vulva: In Association With Crohn Disease.

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.

Management of infantile hemangiomas-experience of a tertiary hospital.

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.

Use of Deep Neural Networks in the Detection and Automated Classification of Lesions Using Clinical Images in Ophthalmology, Dermatology, and Oral Medicine-A Systematic Review.

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.

A systematic review on recurrent cardioinhibitory vasovagal syncope: Does pacing therapy break the fall?

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.

Randomised short-term trial of high-span versus low-span APAP for treating sleep apnoea.

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.

The Stomatological Complications of Diamond-Blackfan Anemia: A Case Report.

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.

Metabolic regulation of the host-fungus interaction: from biological principles to therapeutic opportunities.

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.

Drug-Related Adverse Reactions in Pediatric Inflammatory Bowel Disease.

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.

Convolutional neural network misclassification analysis in oral lesions: an error evaluation criterion by image characteristics.

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.

Domiciliary High-Flow Nasal Therapy in Primary Ciliary Dyskinesia.

We report the case of an adolescent with severe primary ciliary dyskinesia (PCD) phenotype associated with a rare genotype. His clinical condition deteriorated, with daily cough and breathlessness, hypoxemia, and lung function decline. Despite being started on home noninvasive ventilation (NIV), the symptoms progressed to dyspnea at rest and thoracic pain. High-flow nasal cannula (HFNC) was started during the daytime as an adjuvant to NIV, and he was started on regular oral opioids for pain and dyspnea control. There was a clear improvement in comfort and dyspnea and breathing work relief. Additionally, better exercise tolerance was also noted. He is currently on the lung transplant waiting list. We aim to emphasize the benefits of HFNC as an add-on therapy for the management of chronic breathlessness since our patient experienced an improvement in breathing and exercise tolerance. However, there is a paucity of studies regarding domiciliary HFNC, particularly in pediatric age. Therefore, further studies are needed to achieve optimal and personalized care. Close monitoring and frequent reassessment in a specialized center are key to adequate management.