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The most recent progress in reconstructive therapy for the management of periodontitis and peri-implantitis bone defects has relied on the development of highly porous biodegradable bioaerogels for guided bone regeneration. The objective of this work was to evaluate in vitro the osteoinduction of periodontal-originating cells (human dental follicle mesenchymal cells, DFMSCs) promoted by a nano-hydroxyapatite/chitosan (nHAp/CS) bioaerogel, which was purified and sterilized by a sustainable technique (supercritical CO2). Moreover, the in vivo bone regeneration capacity of the nHAp/CS bioaerogel was preliminarily assessed as a proof-of-concept on a rat calvaria bone defect model. The quantification of DNA content of DFMSCs seeded upon nHAp/CS and CS scaffolds (control material) showed a significant increase from the 14th to the 21st day of culture. These results were corroborated through confocal laser scanning microscopy analysis (CLSM). Furthermore, the alkaline phosphatase (ALP) activity increased significantly on the 21st day, similarly for both materials. Moreover, the presence of nHAp promoted a significantly higher expression of osteogenic genes after 21 days when compared to CS scaffolds and control. CLSM images of 21 days of culture also showed an increased deposition of OPN over the nHAp/CS surface. The in vivo bone formation was assessed by microCT and histological analysis. The in vivo evaluation showed a significant increase in bone volume in the nHAp/CS test group when compared to CS and the empty control, as well as higher new bone formation and calcium deposition within the nHAp/CS structure. Overall, the present study showed that the nHAp/CS bioaerogel could offer a potential solution for periodontal and peri-implant bone regeneration treatments since the in vitro results demonstrated that it provided favorable conditions for DFMSC proliferation and osteogenic differentiation, while the in vivo outcomes confirmed that it promoted higher bone ingrowth.
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Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.
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Citocinas , Modelos Animais de Doenças , Ratos Wistar , Receptores de Interleucina-6 , Crânio , Animais , Masculino , Citocinas/metabolismo , Receptores de Interleucina-6/antagonistas & inibidores , Crânio/efeitos dos fármacos , Ratos , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Microtomografia por Raio-X , Peptídeo Hidrolases/metabolismo , Imuno-Histoquímica , Distribuição AleatóriaRESUMO
BACKGROUND: Oral cancer (OC) and oral potentially malignant disorders (OPMD) pose significant challenges to public health in Brazil. This study aimed to estimate the prevalence of oral cancer (OC) and oral potentially malignant disorders (OPMD) among patients who would be treated by Brazilian dentists during their careers. MATERIAL AND METHODS: Data on the number of dentists in Brazil were extracted from the 2022 census data, while incidence rates for OC cases were sourced from the Brazilian National Cancer Institute (INCA). Population estimates for Brazil and data on dental check-up rates were obtained from relevant national sources. RESULTS: Our analysis indicates that a general dentist in Brazil can expect to encounter on average two to three OC patients and on average 675 patients with OPMDs over a 35-year career. Regional disparities were observed, with certain regions showing higher than the average number of encounters due to low density of dentists in some rural districts. CONCLUSIONS: Brazilian dentists are likely to confront a substantial number of OPMD cases during their professional tenure, emphasizing the need for public health policies aimed at enhancing dental surgeons' education in oral cancer prevention and early detection.
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BACKGROUND: This study aimed to explore the clinical, histopathologic, and immunohistochemical characteristics of myofibromas (MFs) affecting the head and neck region. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded tissue blocks of patients diagnosed with MFs in the head and neck were retrieved from the archives of three oral and maxillofacial pathology laboratories. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed, and follow-up status were retrieved from the patient's medical records or pathology reports. RESULTS: Sixteen cases were included in the study. Females were slightly more affected than males. The first and second decades of life were more prevalent. The most common locations were the alveolar ridge and cheek. Although rare, some of the patients were presented with intraosseous lesions. Microscopically, tumors consisted of plump, spindle-shaped myofibroblasts arranged in whorls or fascicles with varying degrees of differentiation. Immunohistochemically, diffuse positivity for vimentin and α-SMA was observed, while Ki-67 mostly showed low immunoreactivity (<5%). Treatment primarily involved complete excision. CONCLUSIONS: MFs in the head and neck region are rare and predominantly affect female patients during the second decade of life. Despite their rarity, central MFs should be considered in the differential diagnosis of intraosseous lesions in infants.
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Neoplasias Encefálicas , Deleção Cromossômica , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 1 , Glioma , Isocitrato Desidrogenase , Mutação , Humanos , Isocitrato Desidrogenase/genética , Glioma/genética , Glioma/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico por imagem , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 1/genéticaRESUMO
No comprehensive classification system that guides prognosis and therapy of pituitary adenomas exists. The 2022 WHO histopathology-based classification system can only be applied to lesions that are resected, which represent few clinically significant pituitary adenomas. Many factors independent of histopathology provide mechanistic insight into causation and influence prognosis and treatment of pituitary adenomas. We propose a new approach to guide prognosis and therapy of pituitary adenomas by integrating clinical, genetic, biochemical, radiological, pathological, and molecular information for all adenomas arising from anterior pituitary cell lineages. The system uses an evidence-based scoring of risk factors to yield a cumulative score that reflects disease severity and can be used at the bedside to guide pituitary adenoma management. Once validated in prospective studies, this simple manageable classification system could provide a standardised platform for assessing disease severity, prognosis, and effects of therapy on pituitary adenomas.
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Adenoma , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/terapia , Estudos Prospectivos , Prognóstico , Adenoma/diagnóstico , Adenoma/terapia , Fatores de RiscoRESUMO
BACKGROUND: The Latin American region represents a hotspot for oral cancer incidence and mortality. To reduce oral cancer mortality rates, screening for early detection of subjects with suspicious or innocuous oral lesions has been promoted. A systematic review was performed to assess the outcomes of oral cancer screening in the Latin American region. MATERIAL AND METHODS: An electronic search was conducted in eight databases and grey literature. The eligibility criteria included screening where adult participants underwent any screening test during an organized screening program. Screening programs were assessed to understand trends in oral cancer diagnosis. Rates of oral cancers diagnosed in screening programs were classified as increase, decrease, or stable based on each year assessed. RESULTS: Following our searches, twelve studies conducted in Brazil and Cuba were included. The screening tests reported were visual oral examination (VOE) and in one study in addition light-based fluorescence testing. 13,277,608 individuals were screened and a total of 1,516 oral cancers were detected (0.01%). Only two studies aimed to screen high-risk individuals (smokers and drinkers). Oral cancer cases diagnosed during screening programs were proportionately stable over the years 1997 to 2009 but increased from 2010 to 2021. The fluorescence-associated VOE test demonstrated a sensitivity of 100% and a specificity of 90%. Similarly, the VOE test alone exhibited a sensitivity of 100%, with specificity ranging from 75% to 90%. CONCLUSIONS: Screening studies conducted in Latin American countries had serious limitations both in methodology (lack of examiner training) and in reporting data (lack of description of clinical categories of screen positives). Capacitation of health workers to perform VOE in well-designed screening programs should be implemented.
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Detecção Precoce de Câncer , Neoplasias Bucais , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/epidemiologia , Brasil/epidemiologia , Cuba/epidemiologia , América Latina/epidemiologiaRESUMO
BACKGROUND: Ependymomas rarely disseminate to other central nervous system areas distant from the original site. Stereotactic radiosurgery (SRS) provides high control rates for recurring ependymomas. The treatment of optic nerve tumors carries high morbidity, but SRS is an acceptable option to manage these cases to reduce risks. OBSERVATIONS: The authors report the case of a 31-year-old male with a cervical spinal ependymoma who had a disseminated pattern of recurrence including the optic nerve after initial resection of the cervical lesion. The optic nerve tumor was treated with SRS, and the authors discuss the technical aspects of the treatment and its outcomes. At the last follow-up, the optic nerve tumor was controlled with SRS, and visual function was preserved. LESSONS: High-grade ependymomas such as the one in the presented case can have unpredictable patterns of recurrence. SRS provides excellent control of the distant recurring ependymoma with a low complication profile given the location of the tumor in this case.
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PURPOSE: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy. METHODS: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ. RESULTS: The highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009). CONCLUSION: Targeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM. CLINICALTRIALS: gov Identifier: NCT03344250.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapêutico , Leucócitos Mononucleares/patologia , Neoplasias Encefálicas/genética , Linfócitos T/patologia , Glioblastoma/tratamento farmacológico , Receptores ErbB , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Alquilantes/farmacologiaRESUMO
PURPOSE: The aim of this study was to analyze the relationship between adiposity, cardiometabolic risk and cardiorespiratory fitness (CRF) according to different groups of adiponectin concentration. METHODS: 255 adolescents of both sexes, aged 11-17 years old, participated. Anthropometric and biochemical parameters such as body mass, height, abdominal circumference (AC), waist circumference (WC), fat mass, fat-free mass, total cholesterol (TC), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), triglycerides (TG), glucose, insulin, adiponectin, blood pressure, peak oxygen consumption (VO2peak) were measured. Body mass index (BMI), z-score BMI (BMI-z), triponderal mass index (TMI), waist-to-height ratio (WHtR), homeostasis model to assessment insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were calculated. Adiponectin was categorized: low adiponectin concentration (LAC ≤ 5.18 µg/mL-1), intermediate (IAC = 5.18 and 7.63 µg/mL-1) and high (HAC ≥ 7.63 µg/ml-1). RESULTS: LAC showed higher BMI, BMI-z and TMI than the other groups (p < 0.05) and higher AC, WC and WHtR that the HAC (p < 0.05). IAC showed lower values of TC, LDL-c and TG, and the LAC presented the highest values of insulin, HOMA-IR and QUICKI (p < 0.05) to the IAC and HAC. HAC presented the lower VO2peak than the other groups (p < 0.01). BMI, TMI, glucose, insulin, HOMA-IR showed inverse, and QUICKI a direct and weak correlation with adiponectin (p < 0.05). No significant association was found between adiponectin and VO2peak (p > 0.05). CONCLUSION: The LAC group had higher means in the anthropometric variables and the worst results related to insulin resistance and sensitivity. Thus, adiponectin may play an important role in obesity and reduced concentration may be a factor in the development of obesity-associated morbidities.
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Aptidão Cardiorrespiratória , Resistência à Insulina , Adolescente , Criança , Feminino , Humanos , Masculino , Adiponectina , Antropometria/métodos , Índice de Massa Corporal , LDL-Colesterol , Glucose , Insulina , Obesidade , Fatores de Risco , Triglicerídeos , Circunferência da CinturaRESUMO
BACKGROUND: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs. MATERIAL AND METHODS: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. RESULTS: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cystic carcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. CONCLUSIONS: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST.
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Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Humanos , Carcinoma Adenoide Cístico/tratamento farmacológico , Neoplasias das Glândulas Salivares/tratamento farmacológico , Bases de Dados Factuais , Glândulas SalivaresRESUMO
Global environmental concerns drive research toward the development of new eco-friendly compounds to replace pollutant chemicals. This study focuses on optimizing the production of trehalose lipids (TLs), which are glycolipid biosurfactants (BS) with various applications like antimicrobial or surface tension reduction. New microorganism sources, growth conditions, medium composition, purification conditions, and physicochemical properties of TLs are studied. Addressing a microscale approach, TLs production was successfully achieved using Rhodotorula sp. and Rhodococcus erythropolis to compare, with different media compositions including glucose-based and salt media supplemented with glycerol, glucose, n-hexadecane, n-dodecane. Liquid-liquid extraction using ethyl acetate and methanol was employed for compound extraction, followed by characterization using analytical methods such as Thin layer chromatography (TLC), High performance liquid chromatography (HPLC), and UHPLC. The produced TLs exhibited a minimum surface tension of 47 mN/m and a critical micellar concentration of 4.4 mg/mL. This study also identified Rhodotorula sp. as a new sustainable producer of TLs with improved productivity.
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Rhodotorula , Trealose , Glicolipídeos , Micelas , Glucose , Tensoativos/químicaRESUMO
BACKGROUND: Frailty has emerged as one of the major risk factors of loss of autonomy and it can be reverted through early and appropriate interventions. A wide range of available frailty screening tools are administered, mainly in clinical settings. However, few frailty instruments are self-administered. OBJECTIVES: The aim of this study was to determine the diagnostic test accuracy of a modified self-administered questionnaire derived from the Study of Osteoporotic Fractures (SOF) index against the Fried frailty phenotype in identifying frailty. DESIGN: Observational, multicenter, diagnostic test accuracy study. PARTICIPANTS: Participants aged 70 and over, living at home or in community-dwelling (n=5134) in two centers in France were contacted. MEASUREMENTS: Participants were mailed self-administered questionnaires derived from the SOF index. Responders who accepted the home evaluation were assessed by trained nurses, blinded to results of the questionnaire, using the Fried frailty phenotype as the reference method. RESULTS: The questionnaire was sent to 5134 participants, of which 1878 (36.6%) met inclusion criteria and returned the questionnaire. Fried frailty assessments were obtained in 691 (35.4%) participants. A total of 639 subjects had a complete evaluation on both the self-administered questionnaire and the Fried phenotype. Mean age was 78.9 (standard deviation [SD]: 5.95) years and 359 (56.2%) participants were women. According to the questionnaire, 159 (24.9%) subjects were considered frail, 172 (26.9%) pre-frail, and 308 (48.2) robust. With the home evaluation, Fried frailty phenotype results were respectively, 114 (17.8%), 295 (46.2%) and 230 (36%). The self-administered questionnaire presented a sensitivity of 66.6% (95% CI: 57.2-75.2) and a specificity of 84.2% (95% CI: 80.8-87.2). CONCLUSIONS: A self-administered questionnaire can be used in elders and represents an opportunity for empowering them in the management of their health in the context of frailty.
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Fragilidade , Humanos , Feminino , Idoso , Masculino , Fragilidade/diagnóstico , Fragilidade/prevenção & controle , Idoso Fragilizado , Valor Preditivo dos Testes , Serviços Postais , Avaliação Geriátrica/métodos , Vida IndependenteRESUMO
BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS: All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS: From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS: Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.
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Carcinoma de Células Escamosas , Neoplasias Gengivais , Úlceras Orais , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Feminino , Neoplasias Gengivais/patologia , Brasil/epidemiologia , Úlcera/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Diagnóstico Diferencial , Estudos RetrospectivosRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) usually invades peripheral nerves through a process known as perineural invasion (PNI), recognized as an adverse factor considered for the administration of postoperative adjuvant therapy. The aim of this study was to assess the impact of PNI on survival and cervical lymph node metastasis in a cohort of OSCC patients. MATERIAL AND METHODS: Presence, location and extension of PNI were assessed in a cohort of 57 paraffin-embedded OSCC resections. Clinico-pathological variables were obtained from each case. Five-year overall survival (OS) and 5-year disease-specific survival (DSS) curves were constructed according to the Kaplan-Meier method and compared with log-rank test. The Cox proportional hazard model was used to assess the role of PNI as an independent risk factor related to poor survival, and a binary logistic regression was performed to estimate the predictive value of PNI for regional lymph node metastasis. RESULTS: PNI was observed in 49.1% of the cases, affecting only small nerves. Peritumoral PNI was the most common location, and multifocal PNI the most frequent extent. Most PNI positive cases had cervical metastasis (p=0.001), and PNI was more frequent in stages III-IV than in I-II (p=0.02). The five-year OS and the 5-year DSS decreased in PNI positive and peritumoral PNI cases. PNI was an independent risk factor for poor 5-year OS and poor 5-year DSS. The odds for cervical lymph node metastasis were of 6.076 (p=0.006) and 10.257 (p=0.007) for PNI and Tumor budding (TB) positive cases, respectively. CONCLUSIONS: PNI is a frequent finding in OSCC and an independent risk factor for poor OS and DSS. PNI and TB are both risk factors associated to an increased likelihood for the development of lymph node metastasis. Therefore, we suggest further investigations to test the combined PNI-TB scoring system in risk stratification models for OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Metástase Linfática , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/patologia , Invasividade Neoplásica/patologia , Prognóstico , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common affected site, usually causing macroglossia. Biopsy is essential for the diagnosis and the occurrence of its systemic form is mandatory to be investigated. This systematic review evaluated the existing information in the literature on Amyloidosis in the oral cavity to allow a more comprehensive and updated analysis of its clinicopathological characteristics, as well as to explore the main forms of treatment and prognostic factors. MATERIAL AND METHODS: Electronic searches were undertaken in five databases supplemented by manual scrutiny. RESULTS: A total of 111 studies were included with 158 individuals. CONCLUSIONS: The disease had a higher prevalence in women, the tongue was the most affected site, as well as the systemic form of the disease. The worst prognosis was for cases of systemic amyloidosis associated with multiple myeloma.
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Amiloidose , Macroglossia , Mieloma Múltiplo , Doenças da Língua , Humanos , Feminino , Amiloidose/diagnóstico , Amiloidose/complicações , Amiloidose/patologia , Macroglossia/complicações , Macroglossia/diagnóstico , Doenças da Língua/patologia , Língua/patologiaRESUMO
Air pollution and climate change are the most important environmental issues for European citizens. Despite the air quality improvements achieved in recent years, with most pollutants' concentrations below the European Union legislated values, it is necessary to understand whether this will continue in the future due to expected climate changes impacts. In this context, this work tries to answer two main questions: (i) What is the relative contribution of emission source regions/activities to air quality, now and in the future, considering a climate change scenario?; and (ii) What additional policies are needed to support win-win strategies for air quality and climate mitigation and/or adaptation, at urban scale? For that, a climate and air quality modelling system, with source apportionment tools, was applied to the Aveiro Region, in Portugal. Main results show that in the future, due to the implementation of carbon neutrality measures, air quality in the Aveiro Region may improve, with reduction up to 4 µg.m-3 for particulate matter (PM) concentrations and 22 µg.m-3 for nitrogen dioxide (NO2), and consequently, the premature deaths due to air pollution exposure will also decrease. The expected air quality improvement will ensure that, in the future, the limit values of the European Union (EU) Air Quality Directive will not be exceeded, but the same will not happen if the proposed revision of the EU Air Quality Directive is approved. Results also shown that, in the future, industrial sector will be the one with higher relative contribution for PM concentrations and the second one for NO2. For that sector, additional emission abatement measures were tested, showing that, in the future, it is possible to comply with all the new limit values proposed by the EU.
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OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.