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Ultrahot giant exoplanets receive thousands of times Earth's insolation1,2. Their high-temperature atmospheres (greater than 2,000 kelvin) are ideal laboratories for studying extreme planetary climates and chemistry3-5. Daysides are predicted to be cloud-free, dominated by atomic species6 and much hotter than nightsides5,7,8. Atoms are expected to recombine into molecules over the nightside9, resulting in different day and night chemistries. Although metallic elements and a large temperature contrast have been observed10-14, no chemical gradient has been measured across the surface of such an exoplanet. Different atmospheric chemistry between the day-to-night ('evening') and night-to-day ('morning') terminators could, however, be revealed as an asymmetric absorption signature during transit4,7,15. Here we report the detection of an asymmetric atmospheric signature in the ultrahot exoplanet WASP-76b. We spectrally and temporally resolve this signature using a combination of high-dispersion spectroscopy with a large photon-collecting area. The absorption signal, attributed to neutral iron, is blueshifted by -11 ± 0.7 kilometres per second on the trailing limb, which can be explained by a combination of planetary rotation and wind blowing from the hot dayside16. In contrast, no signal arises from the nightside close to the morning terminator, showing that atomic iron is not absorbing starlight there. We conclude that iron must therefore condense during its journey across the nightside.
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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive lung disease of unknown aetiology, characterized by the relentless deposition of fibrotic tissue. Biomarkers may play a pivotal role as indicators of disease presence, progression, and treatment response. Sirtuins, a family of enzymes with ADP ribosyltransferase or deacetylase activity, have been implicated in several diseases, including pulmonary fibrosis. METHODS: A cross-sectional, prospective, observational single-center study was conducted to investigate the potential role of serum SIRTs levels as biomarkers in patients with IPF. Demographic, clinical, and functional data and serological samples were collected from 34 patients with IPF followed at the Interstital Lung and Rare Diseases Outpatient Clinic of the Vanvitelli Pneumology Clinic, Monaldi Hospital, Naples, Italy and from 19 age-matched controls. RESULTS: Serum SIRT-1 levels were significantly reduced in IPF patients compared to controls (median IPF 667 [435-858] pg/mL versus controls 925 [794-1173] pg/mL; p < 0.001 ). In contrast, serum SIRT-3 levels were significantly increased in IPF patients compared to controls (median IPF 338 [230-500] pg/mL versus controls 154 [99.8-246] pg/mL; p < 0.001). There were no statistically significant differences in serum SIRT-6 and SIRT-7 levels between IPF and controls. In addition, we found a significant positive correlation between SIRT-1 and lung function parameters such as FEV1% (ϱ=0.417;p = 0.016), FVC% (ϱ=0.449;p = 0.009) and DLCO% (ϱ=0.393;p = 0.024), while a significant negative correlation was demonstrated between SIR-1 and GAP score, demonstrating a significant reduction in SIRT-1 in advanced Gender-Age-Physiology (GAP) stages 2-3 compared to GAP stage 1 (p = 0.008). CONCLUSIONS: This prospective, cross-sectional study showed that SIRT-1 was associated with lung function and IPF severity and that both SIRT-1 and SIRT-3 could be considered as potential biomarkers of IPF, whereas SIRT-6 and SIRT-7 were not associated with IPF.
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Biomarcadores , Fibrose Pulmonar Idiopática , Sirtuína 1 , Sirtuína 3 , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/sangue , Masculino , Feminino , Biomarcadores/sangue , Estudos Transversais , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Sirtuína 3/sangue , Sirtuína 1/sangue , PrognósticoRESUMO
Idiopathic Interstitial Pneumonias (IIPs) are a heterogeneous group of the broader category of Interstitial Lung Diseases (ILDs), pathologically characterized by the distortion of lung parenchyma by interstitial inflammation and/or fibrosis. The American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary consensus classification of the IIPs was published in 2002 and then updated in 2013, with the authors emphasizing the need for a multidisciplinary approach to the diagnosis of IIPs. The histological evaluation of IIPs is challenging, and different types of IIPs are classically associated with specific histopathological patterns. However, morphological overlaps can be observed, and the same histopathological features can be seen in totally different clinical settings. Therefore, the pathologist's aim is to recognize the pathologic-morphologic pattern of disease in this clinical setting, and only after multi-disciplinary evaluation, if there is concordance between clinical and radiological findings, a definitive diagnosis of specific IIP can be established, allowing the optimal clinical-therapeutic management of the patient.
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Pneumonias Intersticiais Idiopáticas , Patologistas , Humanos , Consenso , Estudos Interdisciplinares , Taxa Respiratória , Pneumonias Intersticiais Idiopáticas/diagnósticoRESUMO
The characterization of modifications of microbial proteins is of primary importance to dissect pathogen lifecycle mechanisms and could be useful in identifying therapeutic targets. Attempts to solve this issue yielded only partial and non-exhaustive results. We developed a multidisciplinary approach by coupling in vitro infection assay, mass spectrometry (MS), protein 3D modelling, and surface plasma resonance (SPR). As a proof of concept, the effect of low UV-C (273 nm) irradiation on SARS-CoV-2 spike (S) protein was investigated. Following UV-C exposure, MS analysis identified, among other modifications, the disruption of a disulphide bond within the conserved S2 subunit of S protein. Computational analyses revealed that this bond breakage associates with an allosteric effect resulting in the generation of a closed conformation with a reduced ability to bind the ACE2 receptor. The UV-C-induced reduced affinity of S protein for ACE2 was further confirmed by SPR analyses and in vitro infection assays. This comprehensive approach pinpoints the S2 domain of S protein as a potential therapeutic target to prevent SARS-CoV-2 infection. Notably, this workflow could be used to screen a wide variety of microbial protein domains, resulting in a precise molecular fingerprint and providing new insights to adequately address future epidemics.
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COVID-19 , Humanos , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Ligação ProteicaRESUMO
OBJECTIVES: Sars-CoV-2 acute infection is clinically heterogeneous, ranging from asymptomatic cases to patients with a severe, systemic clinical course. Among the involved factors age and preexisting morbidities play a major role; genetic host susceptibility contributes to modulating the clinical expression and outcome of the disease. Mannose-binding lectin is an acute-phase protein that activates the lectin-complement pathway, promotes opsonophagocytosis and modulates inflammation, and is involved in several bacterial and viral infections in humans. Understanding its role in Sars-CoV-2 infection could help select a better therapy. METHODS: We studied MBL2 haplotypes in 419 patients with acute COVID-19 in comparison to the general population and related the haplotypes to clinical and laboratory markers of severity. RESULTS: We recorded an enhanced frequency of MBL2 null alleles in patients with severe acute COVID-19. The homozygous null genotypes were significantly more frequent in patients with advanced WHO score 4-7 (OR of about 4) and related to more severe inflammation, neutrophilia, and lymphopenia. CONCLUSIONS: Subjects with a defective MBL2 genotype (i.e., 0/0) are predisposed to a more severe acute Sars-CoV-2 infection; they may benefit from early replacement therapy with recombinant MBL. Furthermore, a subset of subjects with the A/A MBL genotype develop a relevant increase of serum MBL during the early phases of the disease and develop a more severe pulmonary disease; in these patients, the targeting of the complement may help. Therefore, COVID-19 patients should be tested at hospitalization with serum MBL analysis and MBL2 genotype, to define the optimal therapy.
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COVID-19 , Lectina de Ligação a Manose , Humanos , COVID-19/genética , SARS-CoV-2 , Genótipo , Predisposição Genética para Doença , Lectina de Ligação a Manose/genética , InflamaçãoRESUMO
Once thought to be a sterile environment, it is now established that lungs are populated by various microorganisms that participate in maintaining lung function and play an important role in shaping lung immune surveillance. Although our comprehension of the molecular and metabolic interactions between microbes and lung cells is still in its infancy, any event causing a persistent qualitative or quantitative variation in the composition of lung microbiome, termed "dysbiosis", has been virtually associated with many respiratory diseases. A deep understanding of the composition and function of the "healthy" lung microbiota and how dysbiosis can cause or participate in disease progression will be pivotal in finding specific therapies aimed at preventing diseases and restoring lung function. Here, we review lung microbiome dysbiosis in different lung pathologies and the mechanisms by which these bacteria can cause or contribute to the severity of the disease. Furthermore, we describe how different respiratory disorders can be caused by the same pathogen, and that the real pathogenetic mechanism is not only dependent by the presence and amount of the main pathogen but can be shaped by the interaction it can build with other bacteria, fungi, and viruses present in the lung. Understanding the nature of this bacteria crosstalk could further our understanding of each respiratory disease leading to the development of new therapeutic strategies.
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Disbiose , Microbiota , Humanos , Pulmão/microbiologia , Progressão da Doença , BactériasRESUMO
Obesity, through adipose tissue (AT) inflammation and dysregulation, represents a critical factor for COVID-19; here, we investigated whether serum levels of adiponectin, HMW oligomers, leptin, and resistin are modulated and/or correlated with clinical and biochemical parameters of severe COVID-19 patients. This study included 62 severe COVID-19 patients; 62 age and sex-matched healthy subjects were recruited as a control group. Anthropometric and biochemical parameters were obtained and compared. Adiponectin, HMW oligomers, leptin, and resistin were analyzed by ELISA. The adiponectin oligomerization state was visualized by Western blotting. When compared to healthy subjects, total adiponectin levels were statistically lower in severe COVID-19 while, in contrast, the levels of leptin and resistin were statistically higher. Interestingly, HMW adiponectin oligomers negatively correlated with leptin and were positively associated with LUS scores. Resistin showed a positive association with IL-6, IL-2R, and KL-6. Our data strongly support that adipose tissue might play a functional role in COVID-19. Although it needs to be confirmed in larger cohorts, adiponectin HMW oligomers might represent a laboratory resource to predict patient seriousness. Whether adipokines can be integrated as a potential additional tool in the evolving landscape of biomarkers for the COVID-19 disease is still a matter of debate. Other studies are needed to understand the molecular mechanisms behind adipokine's involvement in COVID-19.
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Adiponectina , COVID-19 , Humanos , Leptina , Resistina , SARS-CoV-2RESUMO
Herein, we investigate the structure-property relationships in a new series of benzothiazole based unsymmetrical hexafluorocyclopentene dithienylethenes (DTEs) and compare the results with the known facts for symmetric diarylethenes (DAEs). We reveal high photocyclization efficiency resulting from a significant shift of ground state equilibrium to the antiparallel conformation and a barrierless excited state pathway to conical intersection, which remains unperturbed even in polar solvents for most of the prepared DTEs. Furthermore, we uncover that the rate of back thermal cycloreversion correlates clearly more with the central C-C bond-length in the transition state than with the central C-C bond-length in the ground state of the cyclic form. Finally, our detailed vibrational spectral analysis of studied DTEs points out significant changes in Raman and infrared spectra during photoswitching cycles which pave the way for a non-destructive readout of stored information.
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Propofol-based sedation provides faster recovery than midazolam-based regimens with similar safety and comfort during video flexible bronchoscope (VFB) procedures. Pulmonologist-administered propofol "balanced" analgosedation (PAP-BAS) is still debated in Italy. In this real-life study, PAP-BAS safety and comfort during VFB procedures were investigated. We analysed prospectively the subjects undergoing elective VFB procedures in the Pulmonology and RICU of Arezzo Hospital between February and July 2019. PAP-BAS combined low propofol and meperidine doses titrated to achieve an RASS score between 0 and -3. The primary end-point was the complications' rate. Secondary end-points were as follows: the relation between propofol's dose and a subject's comfort assessed with a VAS, recovery time according to a modified Aldrete score ≥9, RASS, and subjects' will of undergoing the procedure again. We collected postprocedure symptoms' intensity too. Our 158 study patients (67 years; SD ± 14; 64% males) incurred in 25% of complication, fully resolved with medical therapy. Neither recourse to ventilator support nor death was reported. Intraprocedural comfort was good (94% of VAS score ≤2). Among postprocedural symptoms, cough was the most frequently reported, in 36% of the cases. Although half of subjects remembered the procedure, 90% of them would have repeated it, if necessary. 85% of them recovered from procedures within 10 minutes. Complications, VAS, and recovery time were not correlated with propofol dose. To our knowledge, this is the first Italian study showing that PAP-BAS to perform a VFB procedure is safe, well tolerated with a quick recovery. Randomised controlled trials are warranted to confirm these preliminary results.
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Propofol , Sedação Consciente/métodos , Feminino , Humanos , Hipnóticos e Sedativos , Masculino , Meperidina , Midazolam/efeitos adversos , Propofol/efeitos adversos , PneumologistasRESUMO
COVID-19 is an infective disease resulting in widespread respiratory and non-respiratory symptoms prompted by SARS-CoV-2 infection. Interaction between SARS-CoV-2 and host cell receptors prompts activation of pro-inflammatory pathways which are involved in epithelial and endothelial damage mechanisms even after viral clearance. Since inflammation has been recognized as a critical step in COVID-19, anti-inflammatory therapies, including both steroids and non-steroids as well as cytokine inhibitors, have been proposed. Early treatment of COVID-19 has the potential to affect the clinical course of the disease regardless of underlying comorbid conditions. Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for symptomatic relief of upper airway infections, became the mainstay of early phase treatment of COVID-19. In this review, we discuss the current evidence for using NSAIDs in early phases of SARS-CoV-2 infection with focus on ketoprofen lysine salt based on its pharmacodynamic and pharmacokinetic features.
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COVID-19 , Humanos , SARS-CoV-2 , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Replicação Viral , Cloreto de Sódio , Cloreto de Sódio na DietaRESUMO
Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancer cases. Stage III NSCLC represents a highly heterogenous stage characterized by different disease presentations and a wide range of treatment options. For patients with good performance status and unresectable-stage III NSCLC with programmed death-ligands 1 (PD-L1) tumor proportion score (TPS) ≥1%, durvalumab consolidation immunotherapy after a platinum-based chemo-radiotherapy is strongly recommended. However, age, poor performance status, underlying comorbidities may represent contraindications for chemotherapy to be used in a subgroup of patients. Herein, we report a case of an 80-year-old male affected by a stage IIIB lung adenocarcinoma with overexpression of PD-L1 (TPS 90%) treated with pembrolizumab, an immune checkpoint inhibitor targeting PD-1/PD-L1 pathways, which shows a complete resolution of lung lesion after four cycles of treatment. Although randomized controlled trials are required, this case report may suggest the potential role of pembrolizumab for chemotherapy unsuitable patients with overexpressing PD-L1 unresectable-stage III NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
Asthma is a chronic respiratory disease in which airway inflammation is a key feature, even in the milder expressions of the disease. The conventional pharmacological approach to mild asthma has long relied on reliever therapy with as-needed short-acting beta-agonists (SABAs), while anti-inflammatory maintenance with inhaled corticosteroids (ICSs) has been reserved for patients with more persistent asthma. Poor adherence to maintenance treatment is an important issue in asthma management, and can partly explain suboptimal symptom control. Over-reliance on SABA bronchodilators for rapid symptom relief is common in real life and potentially leads to an increased risk of asthma morbidity and mortality. Combined anti-inflammatory and reliever medications in a single inhaler have the potential to overcome these limitations. Recent studies in patients with mild asthma have shown that anti-inflammatory reliever therapy with budesonide-formoterol, given on an as-needed basis, is superior to SABA in ensuring asthma control and non-inferior to budesonide maintenance therapy in preventing exacerbations. To address the implications of these important findings for the management of patients with asthma, Italian specialists convened at a series of meetings held during the second half of 2018 across Italy. This article presents their position on these topics and includes a review of the evidence supporting the use of anti-inflammatory reliever therapy in mild asthma and the implementation of this novel approach in clinical practice.
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Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , HumanosRESUMO
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world since December 2019 to become a global public health emergency for the elevated deaths and hospitalizations in Intensive Care Units. The severity spectrum of SARS-CoV-2 pneumonia ranges from mild to severe clinical conditions. The clinical course of SARS-CoV-2 disease is correlated with multiple factors including host characteristics (genetics, immune status, age, and general health), viral load and, above all, the host distribution of the airways and lungs of the viral receptor cells. In this review, we will briefly summarize the current knowledge of the characteristics and management of coronavirus disease 2019-pneumonia. However, other studies are needed to better understand the pathogenetic mechanisms induced by SARS-Cov-2 infection, and to evaluate the long-term consequences of the virus on the lungs.
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Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Pneumonia Viral/tratamento farmacológico , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/fisiopatologia , COVID-19/patologia , COVID-19/fisiopatologia , Gerenciamento Clínico , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologiaRESUMO
The transmission of airborne pathogens represents a major threat to worldwide public health. Ultraviolet light irradiation can contribute to the sanification of air to reduce the pathogen transmission. We have designed a compact filter for airborne pathogen inactivation by means of UVC LED sources, whose effective irradiance is enhanced thanks to high reflective surfaces. We used ray-tracing and computational fluid dynamic simulations to model the device and to maximize the performance inside the filter volume. Simulations also show the inhibition of SARS-Cov-2 in the case of high air fluxes. This study demonstrates that current available LED technology is effective for air sanification purposes.
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Microbiologia do Ar , COVID-19/prevenção & controle , Desinfecção/instrumentação , Desenho de Equipamento , Controle de Infecções/métodos , SARS-CoV-2 , Raios Ultravioleta , Desinfecção/métodos , Humanos , Exposição por Inalação/prevenção & controle , Pneumonia Viral/prevenção & controleRESUMO
Photochromic hydrazones are attracting the attention in the field of photochromic systems especially due to their P-type character. To understand the structural features and their correlation with the spectroscopic data, UV-Vis, vibrational and ellipsometry spectroscopic techniques are employed with the support of density functional theory (DFT) calculations to three hydrazone derivatives based on benzoylpyridine. Interestingly, analysis of the structure shows the presence of two distinct rotamers around the pyridine ring with different energy and the well-defined conjugation path that changes due to E to Z isomerization especially in the hydrazone -C=N-NH part of the skeleton. IR and Raman spectra are analyzed, showing a higher selectivity in the Z form; moreover, the comparison with the normal modes proves the effect of the reaction on the backbone structure. The experimental results are in good agreement with the theoretical predictions, especially in the case of the Raman spectrum. The molecular polarization also changes from E to Z forms as predicted by DFT calculations. Spectroscopic ellipsometry on thin films of TOPAS doped with 10 %wt of the dimethylamino hydrazone derivative is used to prove such change at the molecular level. A modulation of the refractive index is observed, and it is correlated with the concentration of the active moiety and the calculated electronic polarizabilities.
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BACKGROUND: UltraViolet-C (UV-C) lamps may be used to supplement current hospital cleaning and disinfection of surfaces contaminated by SARS-CoV-2. Our aim is to provide some practical indications for the correct use of UV-C lamps. METHODS: We studied three UV-C lamps, measuring their spatial irradiance and emission over time. We quantify the error that is committed by calculating the irradiation time based exclusively on the technical data of the lamps or by making direct irradiance measurements. Finally, we tested specific dosimeters for UV-C. RESULTS: Our results show that the spatial emission of UV-C lamps is strongly dependent on the power of the lamps and on the design of their reflectors. Only by optimizing the positioning and calculating the exposure time correctly, is it possible to dispense the dose necessary to obtain SARS-CoV-2 inactivation. In the absence of suitable equipment for measuring irradiance, the calculated irradiation time can be underestimated. We therefore consider it precautionary to increase the calculated times by at least 20%. CONCLUSION: To use UV-C lamps effectively, it is necessary to follow a few simple precepts when choosing, positioning and verifying the lamps. In the absence of instruments dedicated to direct verification of irradiance, photochromic UV-C dosimeters may represent a useful tool for easily verifying that a proper UV-C dose has been delivered.
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COVID-19/prevenção & controle , Desinfecção/métodos , SARS-CoV-2/efeitos dos fármacos , Raios Ultravioleta , Hospitais , Humanos , Inativação de Vírus/efeitos da radiaçãoRESUMO
INTRODUCTION: Medulloblastoma (MB) is the most common primary malignant intracranial tumor in childhood, but it is very rare in adults, and for this reason, the optimal treatment has not yet been defined. We designed a multicentric study in order to define relevant outcome measures for future prospective studies. MATERIALS AND METHODS: The project involved 10 Italian centers. The database shared among the centers contains epidemiological, diagnostic (radiological and histological/molecular), therapeutic, recurrence information, and survival data. RESULTS: A total of 152 patients (102 males and 50 females, median age 32) were included in the study. Twenty-three of 152 patients had a diagnosis of classic medulloblastoma, 52/152 had desmoplastic/extensive nodularity, 2/152 had large-cell anaplastic medulloblastoma, and the remaining had diagnoses not otherwise specified. Almost all patients underwent craniospinal irradiation after surgery; in 85.5% of patients, adjuvant chemotherapy, mainly platinum- and etoposide-based chemotherapy, was performed immediately after RT. Upon recurrence, most patients were retreated with various chemotherapy regimens, including intrathecal chemotherapy in patients with leptomeningeal dissemination. The overall survival (OS) rate at 5 years was 73.3% (95% CI, 65.0-80.0%). The median OS for the whole group of patients was 112 months. CONCLUSIONS: The data collected were mainly consistent with the literature. A limitation of this study was the large number of patients lost to follow-up and the lack of molecular data for most patients diagnosed until 2010. An important challenge for the future will be MB biologic characterization in adults, with the identification of specific genetic patterns. It will be important to have more national and international collaborations to provide evidence-based management strategies that attempt to obtain a standard of care.
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Neoplasias Cerebelares , Meduloblastoma , Neurologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/epidemiologia , Neoplasias Cerebelares/terapia , Terapia Combinada , Feminino , Humanos , Itália/epidemiologia , Masculino , Meduloblastoma/diagnóstico , Meduloblastoma/epidemiologia , Meduloblastoma/terapia , Recidiva Local de Neoplasia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Disproportionate systemic inflammation in chronic obstructive pulmonary disease (COPD) is associated with declining lung functions and comorbidities. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have emerged as valuable markers of the systemic inflammation in COPD. Adiponectin (Acpr30) circulates in serum as complexes of different molecular weight (HMW, MMW, LMW) with multifaceted metabolic and anti-inflammatory properties implicated in airway pathophysiology. We aimed to investigate the association between Acpr30 and its oligomers and the NLR and PLR in COPD patients. Seventy stable COPD patients were enrolled. Acrp30 serum levels and the HMW oligomers as well as hematological parameters and their ratio were evaluated. Both NLR and PLR are associated with lower BMI. Interestingly, total Acpr30 is negatively associated with NLR but not with PLR; after adjusting for age, BMI and FEV1, Acpr30 was independently associated with NLR. Conversely, HMW Acpr30 and HMW/Acpr30 ratio were positively correlated to NLR. The association of Acpr30, HMW Acpr30 and HMW/totalAcpr30 ratio with NLR but not with PLR in COPD patients indicates that Acrp30 oligomerization could represent a biological mechanism interfering with systemic inflammation in COPD. Further studies in larger cohorts of patients are required to confirm these results.
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Doença Pulmonar Obstrutiva Crônica , Adiponectina , Humanos , Inflamação , Linfócitos , Neutrófilos , Estudos RetrospectivosRESUMO
Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration; after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration; interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel's formation, to candidate them as therapeutic targets.
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Adiponectina/farmacologia , Movimento Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Leptina/farmacologia , Neovascularização Fisiológica/fisiologia , Células Cultivadas , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Identification of risk factors for severe outcome of SARS-CoV-2 infection is an important issue in COVID-19 management. Much attention has been focused on comorbidities as well as drugs taken by patients. Usage of proton pump inhibitors (PPIs) appears to potentially influence disease course. These drugs are known to reduce stomach acid and also modulate the immune system. Their use, prior to and during COVID-19 infection, seems to predispose to the development of more severe pneumonia and therefore to a greater risk of mortality. Instead, the use of histamine receptor 2 antagonists (H2RAs) seems to be associated with a better outcome in patients with COVID-19, in terms of symptoms, risk of intubation and death. As PPIs are essential for treatment of many disorders, usage of these drugs should be balanced considering the benefits and risk ratio, in order to guarantee their correct use for the necessary time. It remains to be clarified whether the detrimental effects, in terms of COVID-19 severe outcome, are due to PPIs or to the underlying disease for which they are administered. New controlled-randomized trials are required to better understand their impact in SARS-CoV-2 infections. *Vanvitelli/Monaldi COVID Group: Adriano Cristinziano, Carolina Delle Donne, Cecilia Calabrese, Fabio Perrotta, Filippo Scialò, Francesco Lassandro, Gennaro Mazzarella, Giorgio Paoli, Leonardo De Luca, Maria Galdo, Miriam Buonincontro, Roberta Cianci, Rosalba Donizzetti, Stefano Sanduzzi Zamparelli, Tullio Valente, Vito D'Agnano, Vittorio Bisogni.