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Poly(lactic-acid) (PLA) is a biodegradable polymer widely used as a packaging material. Its monomer, lactic acid, and its derivatives have been used in the food, cosmetic, and chemical industries. The accumulation of PLA residues leads to the development of green degrading methodologies, such as enzymatic degradation. This work evaluates the potential use of three cutinolytic enzymes codified in the Aspergillus nidulans genome to achieve this goal. The results are compared with those obtained with proteinase K from Tritirachium album, which has been reported as a PLA-hydrolyzing enzyme. The results show that all three cutinases act on the polymer, but ANCUT 1 releases the highest amount of lactic acid (25.86 mM). Different reaction conditions assayed later led to double the released lactic acid. A decrease in weight (45.96%) was also observed. The enzyme showed activity both on poly L lactic acid and on poly D lactic acid. Therefore, this cutinase offers the potential to rapidly degrade these package residues, and preliminary data show that this is feasible.
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INTRODUCTION: Cancer is an individual disease and its formation and development are specific to each host. Conventional treatments are ineffective in complex cases, such as metastasis, and have severe adverse side effects. New strategies are needed to address the problem, and the use of immunogenic cell death (ICD) as a trigger or booster of the immune system through the exposure of damage-associated molecular patterns, along with tumor antigens, by cancerous cells is presented as an immunization approach in this work. METHODS: For this purpose, 4T1 cells were exposed to doxorubicin (DOX) for 24 hours and then, these cells undergoing ICD were subcutaneously administered to mice. The ICD induction by DOX on 4T1 was assessed by flow cytometry and image analysis. This immunization process was performed three times and after the last administration, the immunized mice were challenged with a subcutaneous xenograft of live cancer cells. RESULTS: The results demonstrate that the mice immunized with cells undergoing ICD after exposure to DOX presented no primary tumor or indications of distant metastatic lesion development. CONCLUSION: In summary, our findings indicate that the immunization process utilizing ICD is indeed efficacious in managing this aggressive form of pre-clinical breast cancer.
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AIM: To evaluate the agreement between the bedside ultrasound in a single epigastric window and the plain X-ray to confirm the positioning of the enteral catheter in critically ill patients. MATERIAL AND METHODS: This was an observational, cross-sectional study conducted in two Intensive Care Units of a university hospital. The ultrasound exams were carried out immediately after the introduction of the enteral catheter, using only the epigastric window, with an injection of 5 ml of air associated with 5 ml of saline solution. In all cases, the plain radiography was taken to confirm the positioning of the enteral catheter and to define the beginning of nutritional therapy. RESULTS: This study included 83 patients, the positioning of the enteral catheter was confirmed by plain radiography in all cases and by ultrasound in 81 (97.6%) patients. The median duration of the ultrasound exam was 2 (2-3) minutes, while the time spent between the request for the X-ray and the release of the exam for a doctor's appointment was 225 (120-330) minutes. CONCLUSION: Bedside ultrasound proved to be an effective, quick, and safe method to confirm the position of the enteral catheter in critically ill patients.
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Estado Terminal , Humanos , Estudos Transversais , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Ultrassonografia/métodos , Nutrição Enteral/instrumentação , Nutrição Enteral/métodos , Reprodutibilidade dos Testes , Adulto , Unidades de Terapia Intensiva , Sistemas Automatizados de Assistência Junto ao Leito , Intubação Gastrointestinal/métodos , Intubação Gastrointestinal/instrumentaçãoRESUMO
INTRODUCTION: Scorpionism is a public health problem, especially in tropical regions. In Brazil, the prevalence of envenomation by scorpions is high, and the average national lethality is around 0.16 percent. The Tityus serrulatus scorpion is the primary species of medical importance. However, objective tools to predict and define the severity of these envenomations are lacking. MATERIALS AND METHODS: This was an observational study conducted among patients aged 0-19 years with scorpionism. Patients were admitted to a reference hospital between December 2020 and May 2022. Point-of-care ultrasound was performed within 24 hours of the scorpion sting. RESULTS: Forty-nine patients were included, with a median age of 3.6 (interquartile range 2.3-5.3) years and a predominance of females (51 percent). Fifteen patients (30.6 percent) presented major life-threatening signs, 32 (65.3 percent) minor systemic manifestations, and two (4.1 percent) only local manifestations. Left ventricular dysfunction was identified in 13 patients (26.5 percent). Ten patients (20.4 percent) presented pattern B (visualization of three or more B lines in the evaluated quadrant) in at least one lung window. The sensitivity and specificity of cardiac and pulmonary ultrasound to identify the most severely ill patients were 86 percent and 94 percent, respectively. DISCUSSION: The changes found on point-of-care ultrasound were associated with life-threatening signs. All patients with class III envenomation were referred to the intensive care unit, showing the importance of early identification of this subgroup. The main limitations were the small sample size and the fact that admission to intensive care was not based on systematic criteria. CONCLUSIONS: Point-of-care ultrasound is able to identify early signs of pulmonary congestion and heart failure in scorpionism. It can be useful for the objective selection of patients who are at a higher risk of complications and death and who require intensive support; it may also be valuable for periodic reassessments. Point-of-care ultrasound is a valuable tool for identifying and monitoring severe cases of scorpionism.
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Sistemas Automatizados de Assistência Junto ao Leito , Picadas de Escorpião , Índice de Gravidade de Doença , Ultrassonografia , Humanos , Feminino , Masculino , Pré-Escolar , Criança , Lactente , Adolescente , Brasil/epidemiologia , Adulto Jovem , Escorpiões , Hospitalização , AnimaisRESUMO
INTRODUCTION: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team. OBJECTIVE: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP. METHODS: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes. RESULTS: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up. CONCLUSIONS: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice.
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Carcinoma Pulmonar de Células não Pequenas , Consenso , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Espanha , Equipe de Assistência ao Paciente , Técnica Delphi , Estadiamento de NeoplasiasRESUMO
OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.
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Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Masculino , Feminino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Espanha , Anticorpos Monoclonais/uso terapêutico , Adulto , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Quimioterapia de Consolidação , Antígeno B7-H1/antagonistas & inibidoresRESUMO
Breast cancer is the most prevalent neoplasia among women worldwide. For the estrogen receptor-positive (ER+) phenotype, tamoxifen is the standard hormonal therapy; however, it carries the risk of promoting endometrial carcinoma. Hence, we aimed to evaluate the antiproliferative effect of the phytochemical α-mangostin (AM) as a co-adjuvant alongside tamoxifen on breast cancer cells to improve its efficacy while reducing its adverse effects on endometrium. For this, ER+ breast cancer cells (MCF-7 and T-47D) and endometrial cells (N30) were treated with AM, 4-hydroxytamoxifen (4-OH-TMX), and their combination. Cell proliferation was evaluated using sulforhodamine B assay, and the pharmacological interaction was determined through the combination index and the dose reduction index calculation. The genes KCNH1, CCDN1, MKI67, and BIRC5 were amplified by real-time PCR as indicators of oncogenesis, cell cycle progression, cell proliferation, and apoptosis, respectively. Additionally, genes involved in ER signaling were analyzed. In breast cancer cells, the combination of AM with 4-OH-TMX showed a synergistic antiproliferative effect and favorable dose reduction. AM and 4-OH-TMX decreased KCNH1, CCND1, and BIRC5 gene expression. In endometrial cells, AM decreased MKI-67 gene expression, while it reverted the 4-OH-TMX-dependent CCND1 upregulation. This study establishes the benefits of incorporating AM as a co-adjuvant for first-line ER+ breast cancer therapy.
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Critical COVID-19 has been associated with altered patterns of cytokines. Distinct inflammatory processes in systemic and pulmonary sites have been reported, but studies comparing these two sites are still scarce. We aimed to evaluate the profile of pulmonary and systemic cytokines and chemokines in critically ill COVID-19 patients. Levels of cytokines and chemokines were measured in plasma samples and minibronchoalveolar lavage of critical COVID-19 patients within 48 h and 5-8 days after intubation. Distinct inflammatory processes were observed in the lungs and blood, which were regulated separately. Survivor patients showed higher lung cytokine levels including IFN-γ, IL-2, IL-4, G-CSF, and CCL4, while nonsurvivors displayed higher levels in the blood, which included IL-6, CXCL8, CXCL10, CCL2, and CCL4. Furthermore, our findings indicate that high TNF and CXCL8 levels in the mini-BAL were associated with better lung oxygen exchange capacity, whereas high levels of IFN-γ in plasma were associated with worse lung function, as measured using the PaO2/FiO2 ratio. These results suggest that a robust and localized inflammatory response in the lungs is protective and associated with survival, whereas a systemic inflammatory response is detrimental and associated with mortality in critical COVID-19.
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COVID-19 , Humanos , Citocinas , Plasma , Inflamação , PulmãoRESUMO
This study analyzes the effect of lockdown due to COVID-19 on the spatiotemporal variability of ozone (O3), sulfur dioxide (SO2), and nitrogen dioxide (NO2) concentrations in different provinces of continental Ecuador using satellite information from Sentinel - 5P. The statistical analysis includes data from 2018 to March 2021 and was performed based on three periods defined a priori: before, during, and after lockdown due to COVID-19, focusing on the provinces with the highest concentrations of the studied gases (hotspots). The results showed a significant decrease in NO2 concentrations during the COVID-19 lockdown period in all the study areas: the Metropolitan District of Quito (DMQ) and the provinces of Guayas and Santo Domingo de los Tsáchilas. In the period after lockdown, NO2 concentrations increased by over 20% when compared to the pre-lockdown period, which may be attributable to a shift towards private transportation due to health concerns. On the other hand, SO2 concentrations during the lockdown period showed irregular, non-significant variations; however, increases were observed in the provinces of Chimborazo, Guayas, Santa Elena, and Morona Santiago, which could be partly attributed to the eruptive activity of the Sangay volcano during 2019-2020. Conversely, O3 concentrations increased by 2-3% in the study areas; this anomalous behavior could be attributed to decreased levels of NOx, which react with ozone, reducing its concentration. Finally, satellite data validation using the corresponding data from monitoring stations in the DMQ showed correlation values of 0.9 for O3 data and 0.7 for NO2 data, while no significant correlation was found for SO2.
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Quando pensamos no Estudo Multicêntrico, pensamos no científico e no popular (de povo, de tradição, de memória e experiência), em diálogo nos territórios da Atenção Básica em Saúde do país. Como prevenir e promover saúde em meio a uma doença que ocupou quase todos os espaços da vida social? A covid-19 estava nas conversas sérias da ciência, no jornal das televisões, nas mensagens de Whatsapp™, nas orientações dos profissionais da saúde, nas trocas de receitas caseiras, no debate político. Assim, iniciamos com a pergunta: como a população está "traduzindo" as orientações médico-científicas, como estão se prevenindo e, ao mesmo tempo, estão se informando sobre a pandemia? Foram convidados a fazer parte do estudo os alunos, docentes e coordenadores do Mestrado Profissional em Saúde da Família PROFSAÚDE, sendo um projeto estruturante do Programa, que deu origem ao grupo de pesquisa do CNPq "Territórios, Modelagens e Práticas em Saúde da Família". O estudo envolveu 21 instituições da Rede, de todas as regiões do país, com a aplicação em 128 Unidades Básicas de Saúde, nos 88 municípios de atuação dos mestrandos no país. Assim, participaram mais de 200 alunos e, pelo menos, 100 docentes e orientadores, tendo sido entrevistadas 7.085 famílias. Foi um verdadeiro mutirão nacional, enriquecido com as nuances locais e regionais. Os resultados da pesquisa mostram que a dinâmica territorial que aproxima as ações de saúde à vida das pessoas foi fundamental no enfrentamento e na mitigação de impactos de emergências sanitárias como a pandemia da covid-19. O estudo multicêntrico desenvolvido pelo Programa reitera a grande capilaridade da Rede PROFSÁUDE no território nacional, na produção de conhecimento técnico e científico para o aprimoramento da Estratégia de Saúde da Família e confirma seu compromisso com a formação de profissionais de saúde e com o fortalecimento do Sistema Único de Saúde.