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BACKGROUND: High positive end-expiratory pressure (PEEP>10 cmH2O) is commonly used in mechanically ventilated hypoxemic patients with COVID-19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH2O on lung hyperinflation and collapse in mechanically ventilated patients with COVID-19. METHODS: Twenty mechanically ventilated patients with COVID-19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH2O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over-aerated (density below -900 HU) and non-aerated (density above -100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative. RESULTS: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO2:FiO2) in the overall study population was 137 (119-162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over-aerated lung volume decreased by 159 (98-186) mL, while the non-aerated lung volume increased by only 58 (31-91) mL. In nine (45%) patients, the net response was negative. Their over-aerated lung volume decreased by 46 (18-72) mL, but their non-aerated lung volume increased by 107 (44-121) mL. CONCLUSION: In 20 patients with COVID-19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse.
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COVID-19 , Síndrome do Desconforto Respiratório , Choque , Humanos , Complacência Pulmonar/fisiologia , COVID-19/terapia , Pulmão/diagnóstico por imagem , Respiração com Pressão Positiva/métodos , Tomografia Computadorizada por Raios XRESUMO
Anthocyanins protect plants against various biotic and abiotic stresses, and anthocyanin-rich foods exert benefits on human health due to their antioxidant activity. Nevertheless, little information is available on the influence of genetic and environmental factors on the anthocyanin content in olive fruits. Based on this consideration, the total anthocyanin content, the genes involved in anthocyanin biosynthesis, and three putative R2R3-MYB transcription factors were evaluated at different ripening stages in the drupes of the Carolea and Tondina cultivars, sampled at different altitudes in the Calabria region, Italy. During drupe ripening, the total anthocyanin content and the transcript levels of analyzed genes gradually increased. In line with the anthocyanin content, a different level of expression of anthocyanin structural genes was observed in 'Carolea' compared to 'Tondina', and in relation to the cultivation area. Furthermore, we identified Oeu050989.1 as a putative R2R3-MYB involved in the regulation of anthocyanin structural genes correlated with the environmental temperature change response. We conclude that anthocyanin accumulation is strongly regulated by development, genotype, and also by environmental factors such as temperature, associated with the altitude gradient. The obtained results contribute to reducing the current information gap regarding the molecular mechanisms on anthocyanin biosynthesis regulation related to the environmental conditions in Olea europaea.
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Antocianinas , Olea , Humanos , Antocianinas/metabolismo , Olea/genética , Olea/metabolismo , Fatores de Transcrição/metabolismo , Genótipo , Antioxidantes/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Frutas/metabolismoRESUMO
The interaction of hydrophobic silicon dioxide particles (fumed silicon dioxide), as model air pollutants, and Langmuir monolayers of a porcine lung surfactant extract has been studied in order to try to shed light on the physicochemical bases underlying the potential adverse effects associated with pollutant inhalation. The surface pressure-area isotherms of lung surfactant (LS) films including increasing amounts of particles revealed that particle incorporation into LS monolayers modifies the organization of the molecules at the water/vapor interface, which alters the mechanical resistance of the interfacial films, hindering the ability of LS layers for reducing the surface tension, and reestablishing the interface upon compression. This influences the normal physiological function of LS as is inferred from the analysis of the response of the Langmuir films upon the incorporation of particles against harmonic changes of the interfacial area (successive compression-expansion cycles). These experiments evidenced that particles alter the relaxation mechanisms of LS films, which may be correlated to a modification of the transport of material within the interface and between the interface and the adjacent fluid during the respiratory cycle.
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Surfactantes Pulmonares , Dióxido de Silício , Animais , Pulmão , Pressão , Surfactantes Pulmonares/química , Surfactantes Pulmonares/metabolismo , Propriedades de Superfície , Tensão Superficial , Tensoativos/metabolismo , SuínosRESUMO
BACKGROUND: Prone positioning improves survival in moderate-to-severe acute respiratory distress syndrome (ARDS) unrelated to the novel coronavirus disease (COVID-19). This benefit is probably mediated by a decrease in alveolar collapse and hyperinflation and a more homogeneous distribution of lung aeration, with fewer harms from mechanical ventilation. In this preliminary physiological study we aimed to verify whether prone positioning causes analogue changes in lung aeration in COVID-19. A positive result would support prone positioning even in this other population. METHODS: Fifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography in the supine and prone position with a constant positive end-expiratory pressure (PEEP) within three days of endotracheal intubation. Using quantitative analysis, we measured the volume of the non-aerated, poorly-aerated, well-aerated, and over-aerated compartments and the gas-to-tissue ratio of the ten vertical levels of the lung. In addition, we expressed the heterogeneity of lung aeration with the standardized median absolute deviation of the ten vertical gas-to-tissue ratios, with lower values indicating less heterogeneity. RESULTS: By the time of the study, PEEP was 12 (10-14) cmH2O and the PaO2:FiO2 107 (84-173) mmHg in the supine position. With prone positioning, the volume of the non-aerated compartment decreased by 82 (26-147) ml, of the poorly-aerated compartment increased by 82 (53-174) ml, of the normally-aerated compartment did not significantly change, and of the over-aerated compartment decreased by 28 (11-186) ml. In eight (53%) patients, the volume of the over-aerated compartment decreased more than the volume of the non-aerated compartment. The gas-to-tissue ratio of the ten vertical levels of the lung decreased by 0.34 (0.25-0.49) ml/g per level in the supine position and by 0.03 (- 0.11 to 0.14) ml/g in the prone position (p < 0.001). The standardized median absolute deviation of the gas-to-tissue ratios of those ten levels decreased in all patients, from 0.55 (0.50-0.71) to 0.20 (0.14-0.27) (p < 0.001). CONCLUSIONS: In fifteen patients with COVID-19, prone positioning decreased alveolar collapse, hyperinflation, and homogenized lung aeration. A similar response has been observed in other ARDS, where prone positioning improves outcome. Therefore, our data provide a pathophysiological rationale to support prone positioning even in COVID-19.
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COVID-19 , Síndrome do Desconforto Respiratório , COVID-19/terapia , Humanos , Pulmão/diagnóstico por imagem , Decúbito Ventral/fisiologia , Respiração Artificial , Síndrome do Desconforto Respiratório/terapiaRESUMO
Three-dimensional cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions. The surface hydrophobicity strongly influences the promotion of cell aggregate formation. In particular, for spheroid formation, highly water-repellent coatings seem to be required for the significant effects of the process. In this work, surfaces at different wettability have been compared to observe their influence on the growth and promotion of aggregates of representative mammalian cell lines, both tumoral and non-tumoral (3T3, HaCat and MCF-7 cell lines). The effect of increased hydrophobicity from TCPS to agarose hydrogel to mixed organic-inorganic superhydrophobic (SH) coating has been investigated by optical and fluorescence microscopy, and by 3D confocal profilometry, in a time scale of 24 h. The results show the role of less wettable substrates in inducing the formation of spheroid-like cell aggregates at a higher degree of sphericity for the studied cell lines.
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Técnicas de Cultura de Células , Proliferação de Células , Hidrogéis/química , Esferoides Celulares/metabolismo , Células 3T3 , Animais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Camundongos , Esferoides Celulares/citologiaRESUMO
Rationale: Acidemia is a severe condition among critically ill patients. Despite lack of evidence, sodium bicarbonate is frequently used to correct pH; however, its administration is burdened by several side effects. We hypothesized that the reduction of plasma chloride concentration could be an alternative strategy to correct acidemia.Objectives: To evaluate feasibility, safety, and effectiveness of a novel strategy to correct acidemia through extracorporeal chloride removal by electrodialysis.Methods: Ten swine (six treated and four control animals) were sedated, mechanically ventilated and connected to an extracorporeal electrodialysis device capable of selectively removing chloride. In random order, an arterial pH of 7.15 was induced either through reduction of ventilation (respiratory acidosis) or through lactic acid infusion (metabolic acidosis). Acidosis was subsequently sustained for 12-14 hours. In treatment pigs, soon after reaching target acidemia, electrodialysis was started to restore pH.Measurements and Main Results: During respiratory acidosis, electrodialysis reduced plasma chloride concentration by 26 ± 5 mEq/L within 6 hours (final pH = 7.36 ± 0.04). Control animals exhibited incomplete and slower compensatory response to respiratory acidosis (final pH = 7.29 ± 0.03; P < 0.001). During metabolic acidosis, electrodialysis reduced plasma chloride concentration by 15 ± 3 mEq/L within 4 hours (final pH = 7.34 ± 0.07). No effective compensatory response occurred in control animals (final pH = 7.11 ± 0.08; P < 0.001). No complications occurred.Conclusions: We described the first in vivo application of an extracorporeal system targeted to correct severe acidemia by lowering plasma chloride concentration. Extracorporeal chloride removal by electrodialysis proved to be feasible, safe, and effective. Further studies are warranted to assess its performance in the presence of impaired respiratory and renal functions.
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Acidose/sangue , Acidose/terapia , Cloretos/sangue , Diálise Renal/métodos , Animais , Eletricidade , Circulação Extracorpórea , SuínosRESUMO
The most common pediatric mitochondrial disease is Leigh syndrome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that continuously breathing normobaric 11% O2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated survival curves and organ pathology in Ndufs4 KO mice exposed to hypoxia or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as continuous normobaric 17% O2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O2 in mice with late-stage encephalopathy reverses their established neurological disease, evidenced by improved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hypoxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.
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Complexo I de Transporte de Elétrons/genética , Hipóxia/metabolismo , Doença de Leigh/patologia , Doença de Leigh/terapia , Mitocôndrias/patologia , Doenças Neurodegenerativas/terapia , Animais , Modelos Animais de Doenças , Doença de Leigh/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doenças Neurodegenerativas/patologia , Oxigênio/uso terapêutico , RespiraçãoRESUMO
Hypoxic pulmonary vasoconstriction (HPV) is a physiological vasomotor response that maintains systemic oxygenation by matching perfusion to ventilation during alveolar hypoxia. Although mitochondria appear to play an essential role in HPV, the impact of mitochondrial dysfunction on HPV remains incompletely defined. Mice lacking the mitochondrial complex I (CI) subunit Ndufs4 ( Ndufs4-/-) develop a fatal progressive encephalopathy and serve as a model for Leigh syndrome, the most common mitochondrial disease in children. Breathing normobaric 11% O2 prevents neurological disease and improves survival in Ndufs4-/- mice. In this study, we found that either genetic Ndufs4 deficiency or pharmacological inhibition of CI using piericidin A impaired the ability of left mainstem bronchus occlusion (LMBO) to induce HPV. In mice breathing air, the partial pressure of arterial oxygen during LMBO was lower in Ndufs4-/- and in piericidin A-treated Ndufs4+/+ mice than in respective controls. Impairment of HPV in Ndufs4-/- mice was not a result of nonspecific dysfunction of the pulmonary vascular contractile apparatus or pulmonary inflammation. In Ndufs4-deficient mice, 3 wk of breathing 11% O2 restored HPV in response to LMBO. When compared with Ndufs4-/- mice breathing air, chronic hypoxia improved systemic oxygenation during LMBO. The results of this study show that, when breathing air, mice with a congenital Ndufs4 deficiency or chemically inhibited CI function have impaired HPV. Our study raises the possibility that patients with inborn errors of mitochondrial function may also have defects in HPV.
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Complexo I de Transporte de Elétrons/deficiência , Hipóxia/fisiopatologia , Doença de Leigh/fisiopatologia , Vasoconstrição/fisiologia , Animais , Brônquios/metabolismo , Modelos Animais de Doenças , Hipóxia/metabolismo , Pulmão/metabolismo , Pulmão/fisiopatologia , Camundongos Transgênicos , Mitocôndrias/metabolismo , Artéria Pulmonar/metabolismo , Circulação Pulmonar/fisiologiaRESUMO
Sickle cell disease is an inherited disorder of hemoglobin (Hb). During a sickle cell crisis, deoxygenated sickle hemoglobin (deoxyHbS) polymerizes to form fibers in red blood cells (RBCs), causing the cells to adopt "sickled" shapes. Using small molecules to increase the affinity of Hb for oxygen is a potential approach to treating sickle cell disease, because oxygenated Hb interferes with the polymerization of deoxyHbS. We have identified a triazole disulfide compound (4,4'-di(1,2,3-triazolyl)disulfide, designated TD-3), which increases the affinity of Hb for oxygen. The crystal structures of carboxy- and deoxy-forms of human adult Hb (HbA), each complexed with TD-3, revealed that one molecule of the monomeric thiol form of TD-3 (5-mercapto-1H-1,2,3-triazole, designated MT-3) forms a disulfide bond with ß-Cys93, which inhibits the salt-bridge formation between ß-Asp94 and ß-His146. This inhibition of salt bridge formation stabilizes the R-state and destabilizes the T-state of Hb, resulting in reduced magnitude of the Bohr effect and increased affinity of Hb for oxygen. Intravenous administration of TD-3 (100 mg/kg) to C57BL/6 mice increased the affinity of murine Hb for oxygen, and the mice did not appear to be adversely affected by the drug. TD-3 reduced in vitro hypoxia-induced sickling of human sickle RBCs. The percentage of sickled RBCs and the P50 of human SS RBCs by TD-3 were inversely correlated with the fraction of Hb modified by TD-3. Our study shows that TD-3, and possibly other triazole disulfide compounds that bind to Hb ß-Cys93, may provide new treatment options for patients with sickle cell disease.
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Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/farmacologia , Dissulfetos/farmacologia , Eritrócitos/efeitos dos fármacos , Hemoglobinas/metabolismo , Oxigênio/metabolismo , Triazóis/farmacologia , Anemia Falciforme/metabolismo , Animais , Eritrócitos/metabolismo , Hemoglobina Falciforme/metabolismo , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Metalotioneína 3 , Camundongos , Camundongos Endogâmicos C57BL , Polimerização/efeitos dos fármacos , Ligação ProteicaRESUMO
OBJECTIVES: To test the safety of a novel miniaturized device that produces nitric oxide (NO) from air by pulsed electrical discharge, and to demonstrate that the generated NO can be used to vasodilate the pulmonary vasculature in rabbits with chemically-induced pulmonary hypertension. STUDY DESIGN: A miniature NO (mini-NO) generator was tested for its ability to produce therapeutic levels (20-80â¯parts per million (ppm)) of NO, while removing potentially toxic gases and metal particles. We studied healthy 6-month-old New Zealand rabbits weighing 3.4⯱â¯0.4â¯kg (mean⯱â¯SD, nâ¯=â¯8). Pulmonary hypertension was induced by chemically increasing right ventricular systolic pressure to 28-30â¯mmHg. The mini-NO generator was placed near the endotracheal tube. Production of NO was triggered by a pediatric airway flowmeter during the first 0.5â¯s of inspiration. RESULTS: In rabbits with acute pulmonary hypertension, the mini-NO generator produced sufficient NO to induce pulmonary vasodilation. Potentially toxic nitrogen dioxide (NO2) and ozone (O3) were removed by the Ca(OH)2 scavenger. Metallic particles, released from the electrodes by the electric plasma, were removed by a 0.22⯵m filter. While producing 40â¯ppm NO, the mini-NO generator was cooled by a flow of air (70â¯ml/min) and the external temperature of the housing did not exceed 31⯰C. CONCLUSIONS: The mini-NO generator safely produced therapeutic levels of NO from air. The mini-NO generator is an effective and economical approach to producing NO for treating neonatal pulmonary hypertension and will increase the accessibility and therapeutic uses of life-saving NO therapy worldwide.
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Hidróxido de Cálcio/administração & dosagem , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico/administração & dosagem , Terapia Respiratória/instrumentação , Administração por Inalação , Animais , Desenho de Equipamento , Feminino , Masculino , Metais/isolamento & purificação , Óxido Nítrico/uso terapêutico , Coelhos , Temperatura , Pressão Ventricular/efeitos dos fármacosRESUMO
The effect of the incorporation of hydrophilic titanium dioxide (TiO2) nanoparticles on the interfacial properties of Langmuir monolayers of 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) has been evaluated combining interfacial thermodynamic studies, dilatational rheology, and Brewster angle microscopy (BAM). The results show that the TiO2 nanoparticles are able to penetrate DPPC layers, modifying the organization of the molecules and, consequently, the phase behavior and viscoelastic properties of the systems. Measurements of dilational viscoelasticity against the frequency have been performed, using the oscillatory barrier method, at different values of the surface pressure corresponding to different degrees of compression of the monolayer. The presence of TiO2 nanoparticles also affects the dynamic response of the monolayer modifying both the quasi-equilibrium dilatational elasticity and the high frequency limit of the viscoelastic modulus. The principal aim of this work is to understand the fundamental physicochemical bases related to the incorporation of specific nanoparticles of technological interest into the interfacial layer with biological relevance such as phospholipid layers. This can provide information on potential adverse effects of nanoparticles for health and the environment.
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Phytochelatins (PCs) are small cysteine-rich peptides involved in metal detoxification, not genetically encoded but enzymatically synthesized by phytochelatin synthases (PCSs) starting from glutathione. The constitutive PCS expression even in the absence of metal contamination, the wide phylogenetic distribution and the similarity between PCSs and the papain-type cysteine protease catalytic domain suggest a wide range of functions for PCSs. These proteins, widely studied in land plants, have not been fully analyzed in algae and cyanobacteria, although these organisms are the first to cope with heavy-metal stress in aquatic environments and can be exploited for phytoremediation. To fill this gap, we compared the features of the PCS proteins of different cyanobacterial and algal taxa by phylogenetic linkage. The analyzed sequences fall into two main, already known groups of PCS-like proteins. Contrary to previous assumptions, they are not classed as prokaryotic and eukaryotic sequences, but rather as sequences characterized by the alternative presence of asparagine and aspartic/glutamic acid residues in proximity of the catalytic cysteine. The presence of these enzymes with peculiar features suggests differences in their post-translational regulation related to cell/environmental requirements or different cell functions rather than to differences due to their belonging to different phylogenetic taxa.
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The interaction of biomaterials with the immune system is ruled by the action of macrophages. The surface features of these biomaterials, like wettability, which is an expression of chemical composition, texture, and geometry, can affect macrophages response. Such surface parameters can be then efficiently exploited to improve biocompatibility by lowering undesired immunological reactions and at the same time creating the substrate for positive interactions. In this work, the preparation and physicochemical characterization of highly water-repellent surfaces to develop and characterize 3D spheroids derived from monocyte-macrophages (RAW 264.7 cell line) has been carried out. As a measure of cell viability over time, the obtained aggregates have been transferred under standard 2D cell culture conditions. Significant changes on the morphology-associated polarization of the derived cellular entities have been evaluated at the nanoscale through 3D profilometry. The results suggested that the spheroid formation using highly repellent substrates induced the activation of M2-type cells. This simple and cost-effective approach can be used for preparing M2-based macrophages for regenerative purposes.
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Hydrophobicity, olephobicity, hemophobicity, amphiphobicity, omniphobicity, icephobicity [...].
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Microplastics, particles under 5 mm, pervade aquatic environments, notably in Tarragona's coastal region (NE Iberian Peninsula), hosting a major plastic production complex. To investigate weathering and yellowness impact on plastic pellets toxicity, sea-urchin embryo tests were conducted with pellets from three locations-near the source and at increasing distances. Strikingly, distant samples showed toxicity to invertebrate early stages, contrasting with innocuous results near the production site. Follow-up experiments highlighted the significance of weathering and yellowing in elevated pellet toxicity, with more weathered and colored pellets exhibiting toxicity. This research underscores the overlooked realm of plastic leachate impact on marine organisms while proposes that prolonged exposure of plastic pellets in the environment may lead to toxicity. Despite shedding light on potential chemical sorption as a toxicity source, further investigations are imperative to comprehend weathering, yellowing, and chemical accumulation in plastic particles.
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Larva , Microplásticos , Poluentes Químicos da Água , Animais , Microplásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Larva/efeitos dos fármacos , Ouriços-do-Mar/efeitos dos fármacos , Plásticos/toxicidade , Plásticos/química , Monitoramento Ambiental/métodosRESUMO
OBJECTIVES: to date, no consensus has been reached on the surgical gold-standard in pleural mesothelioma (PM). We retrospectively reviewed our experience as a tertiary referral centre, to compare short- and long-term survival of PM patients undergoing different types of surgery. METHODS: in retrospective, observational, single-centre study, we analysed all the patients histologically diagnosed with PM undergoing surgical procedures with palliative or curative intent at IRCCS Istituto Nazionale dei Tumori of Milan, Italy, from January 2003 to December 2020. The primary study endpoint was 10-year overall survival (OS) in three different types of resections: extra-pleural-pneumonectomy (EPP), pleurectomy/decortication (P/D), partial-pleurectomy/pleural-biopsy (PP/B). Secondary endpoints were postoperative hospital stay and postoperative 30-day and 90-day mortality rates. The survival function was estimated using Kaplan-Meier, and the Log-rank test was used for testing differences. Univariable and Multivariable Cox regression models were implemented to estimate Hazard Ratio (HR) for all variables of interest. RESULTS: 243 consecutive patients were enrolled, EPP was performed in 49 (20.2%), P/D in 58 (23.8%), PP/B in 136 (56.0%) patients. The median follow-up time was 19.8 months. 10-year OS was significantly better for P/D group (16%, Log-Rank test p<0.0001) compared to PP/B (1.8%) and EPP (0%). No statistically significant differences were found among the 3 surgical groups in 30- and 90-day mortality rates. At multivariable analysis, gender (male, HR=1.58), type of resection (P/D, HR=0.55) and surgery date (recent years, HR=0.61) were found to be independent prognostic factors for OS. CONCLUSIONS: in PM, lung-sparing curative approach (e.g. P/D) should be preferred in highly selected patients and in highly experienced centres, whenever appropriate. Anyway, when P/D is not indicated, adopting palliative/conservative management (e.g. PP/B) could ensure comparable results as extremely aggressive surgeries (e.g. EPP). The aim of surgery in PM should not be reaching complete resection, but rather accomplishing significant resection allowing to complete the multimodality treatment in highly selected patients in experienced centers.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária , Neoplasias Pulmonares/patologia , Resultado do Tratamento , Mesotelioma Maligno/cirurgia , Neoplasias Pleurais/patologia , Pneumonectomia/métodos , Modelos de Riscos ProporcionaisRESUMO
Background: Stage III lung cancer (LC) represents a heterogeneous group of diseases, and the optimal management is still a matter of debate. To date, only a few studies have assessed the role of multidisciplinary team (MDT) discussion in impacting survival of stage III LC. Hence, we aimed to reported the impact of the implementation of MDT discussion on long-term survival of stage III LC patients. Methods: This is a retrospective, observational, single-centre cohort study evaluating data of consecutive patients with a clinical and pathological diagnosis of stage III LC treated before [2005-2011] and after [2012-2020] the implementation of MDT. The primary outcome was 5-year overall survival (OS). Results: A total of 983 patients were enrolled with stage III LC, 411 (41.8%) pre-MDT and 572 (58.2%) post-MDT. The 5-year OS rates were 25.3% for the pre-MDT cohort and 33.9% for the post-MDT cohort (P=0.0008). Resected patients (n=670), who underwent trimodality therapy achieved a higher 5-year OS in both pre-MDT and post-MDT groups. An increased 5-year OS was observed in patients who underwent systemic therapy, from 28.2% in pre-MDT to 40.2% in post-MDT cohorts. In non-resected patients, there was an increased in 5-year OS in both systemic and chemoradiotherapy groups. Conclusions: The implementation of an MDT increased the 5-year OS in both resected and non-resected stage III LC patients. Implementing MDT might be useful in improving the management of therapy with less invasive local and surgical strategies personalized for each LC patient.
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The large and necessary diffusion of huge solar plants in extra urban areas implies the adoption of maintenance strategies especially where human intervention would require high costs and logistic problems. Animal dejections like bird droppings and agricultural sprays are environmental agents able to significantly decrease light absorption and, in some cases, cause serious damage to the electric conversion systems in a photovoltaic panel. In this work, the performance of a superhydrophobic (SH) coating in terms of durable self-cleaning properties and transparency has been studied in the presence of commercial and simulated contaminants on glass reference and solar panel surfaces. Wettability studies have been carried out both in static and dynamic conditions in order to compare the compositional effect of commercial liquids used as fertilizers or pesticides and molecules like pancreatin as model substances simulating bird droppings. From these studies, it can be observed that the superhydrophobic coating, independently from the surface where it is applied, is able to repel water and substances used such as fertilizers or pesticides and substances simulating bird droppings, maintaining its properties and transparency. This kind of approach can provide information to design suitable spray formulations without the above-mentioned drawbacks to be used in natural environment areas and agrosolar plants.
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Epigenetics, referring to heritable gene regulatory information that is independent of changes in DNA sequences, is an important mechanism involved both in organism development and in the response to environmental events. About the epigenetic marks, DNA methylation is one of the most conserved mechanisms, playing a pivotal role in organism response to several biotic and abiotic stressors. Indeed, stress can induce changes in gene expression through hypo- or hyper-methylation of DNA at specific loci and/or in DNA methylation at the genome-wide level, which has an adaptive significance and can direct genome evolution. Exploring DNA methylation in responses to abiotic stress could have important implications for improving stress tolerance in algae. This article summarises the DNA methylation pattern in algae and its impact on abiotic stress, such as heavy metals, nutrients and temperature. Our discussion provides information for further research in algae for a better comprehension of the epigenetic response under abiotic stress, which could favour important implications to sustain algae growth under abiotic stress conditions, often related to high biosynthesis of interesting metabolites.
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Cell therapies commonly pursue tissue stimulation for regenerative purposes by replacing cell numbers or supplying for functional deficiencies. To this aim, monodispersed cells are usually transplanted for incorporation by local injection. The limitations of this strategy include poor success associated with cell death, insufficient retention, or cell damage due to shear forces associated with the injection. Spheroids have recently emerged as a model that mimics an in vivo environment with more representative cell-to-cell interactions and better intercellular communication. Nevertheless, cost-effective and lab friendly fabrication and effectively performed recovery are challenges that restrict the broad application of spheroids. In this work, glass surfaces were modified with an environmentally friendly superhydrophobic coating. The superhydrophobic surfaces were used for the 3D spheroid preparation of fibroblasts (3T3 cell line) and keratinocytes (HaCaT cell line). The effectiveness of the spheroids to be recovered and grown under 2D culture conditions was evaluated. The morphology of the migrated cells from the 3D spheroids was characterized at the nano-microscale through 3D profilometry. The results demonstrated improved adhesion and proliferation in the migrated cells, both advanced properties for regenerative applications.