Search

Cystic Fibrosis (CF) is caused by mutations on the CF transmembrane conductance regulator (CFTR) gene and is associated with chronic infection and inflammation. Recently, it has been demonstrated that LPS-induced CFTR dysfunction in airway epithelial cells is due to an early oxidative stress. Dimethyl fumarate (DMF) is an approved anti-inflammatory and anti-oxidant drug for auto-immune and inflammatory diseases, but its role in the CF has never been investigated. In this study, we examined the effect of DMF on CF-related cytokines expression, ROS measurements and CFTR channel function. We found that DMF reduced the inflammatory response to LPS stimulation in both CF and non-CF bronchial epithelial cells, both as co-treatment and therapy, and restored LPS-mediated decrease of Trikafta™-mediated CFTR function in CF cells bearing the most common mutation, c.1521_1523delCTT (F508del). DMF also inhibited the inflammatory response induced by IL-1β/H 2 O 2 and IL-1β/TNFα, mimicking the inflammatory status of CF patients. Finally, we also demonstrated that DMF exhibited an anti-oxidant effect on CF cells after different inflammatory stimulations. Since DMF is an approved drug, it could be further investigated as a novel anti-inflammatory molecule to ameliorate lung inflammation in CF and improve the CFTR modulators efficacy.

Wildfires represent a natural phenomenon with detrimental effects on natural resources and human health. A better knowledge, perception, and awareness of wildfire risk may help communities at risk of exposure to prevent future events and safeguard their own lives. The aim of this study is to explore differences between individuals with and without previous wildfire experience, in terms of (1) subjective and advanced wildfire knowledge, (2) self-reported perceptions, (3) level of information, (4) self-protection measures, and (5) importance of community involvement. As a second step, we investigated differences in the same variables, focusing more deeply on a group of individuals with previous wildfire experience, classifying them according to fire-related employment (fire-related workers vs. non-workers) and wildland-urban interface (WUI) proximity (WUI residents vs. non-WUI residents). The Kruskal-Wallis test was applied to establish differences between the pairs of subsamples. Our results partially confirmed our hypothesis, that direct experience leads individuals to have a greater preparedness on the topic of wildfires. Perception of knowledge is reflected only at a shallow level of expertise, and, therefore, no relevant within-group differences related to fire-related employment or to WUI proximity were detected. Moreover, available information was perceived to be insufficient, thus we report a strong need for developing effective communication to high-risk groups, such as homeowners and fire-related workers.

Unprecedented in the literature, levulinic acid (LA), one of the top value-added intermediates of chemical industry, is obtained from cigarette butts as cellulose feedstock by means of a one-pot hydrothermal process carried out at 200 °C for 2 h and catalysed by phosphoric acid. The protocol avoids the use of more aggressive and toxic H 2 SO 4 and HCl, that are generally employed on several cellulose sources (e.g. sludge paper), thus minimizing corrosion phenomena of plants. Neither chemical pre-treatment of butts nor specific purification procedure of LA are required. Notably, by simply modifying acid catalyst (e.g. using CH 3 COOH), another top value-added fine chemical such as 5-hydroxymethylfuraldehyde (HMF) is obtained, thus widening the scope of the method. Being cigarette filters a waste available in quantities of megatonnes per year, they represent an unlimited at no cost source of cellulose, thus enabling the up-scale to an industrial level of LA production., (© 2021. The Author(s).)

Background: Microscopically positive margins (R1) negatively impact survival in pancreatic ductal adenocarcinoma (PDAC). For patients with close/positive margins, intraoperative radiotherapy (IORT) can improve local control. The prognostic impact of an R1 resection in patients who receive total neoadjuvant therapy (TNT; FOLFIRINOX with chemoradiation) and IORT is unknown., Methods: Clinicopathologic data were retrospectively collected for borderline/locally advanced (BR/LA) PDAC patients who received TNT and underwent resection between 2011 and 2019. Disease-free (DFS) and overall survival (OS) measured from time of diagnosis were compared between groups., Results: Two hundred one patients received TNT and were resected, with a median DFS and OS of 24 months and 47 months, respectively. Eighty-eight patients (44%) received IORT; of these, 69 (78%) underwent an R0 and 19 (22%) an R1 resection. There was no significant difference in clinicopathologic factors between the IORT and no-IORT groups, except for resectability status (LA: IORT 69%, no-IORT 53%, p = 0.021) and surgeons' concern for a positive/close margin. R1 resection was associated with worse DFS and OS in the no-IORT population. However, among patients who received IORT, there was no difference in DFS (R0: 29 months, IQR 14-47 vs R1: 20 months, IQR 15-28; p = 0.114) or OS (R0: 48 months, IQR 25-not reached vs R1: 37 months, IQR 30-47; p = 0.307) between patients who underwent R0 vs R1 resection. In multivariate analysis, within the IORT group, R1 resection was not associated with DFS or OS., Conclusion: IORT may mitigate the adverse effect of an R1 resection on DFS and OS in BR/LA PDAC patients receiving TNT.

Background: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU., Methods: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders., Results: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30-41%]. 26% [21-30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36-54%]. 23% [15-32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65-78%]. Oxygenation on admission was the main source of between-study heterogeneity., Conclusions: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance., Registration: PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020., (© 2021. The Author(s).)

Background: The COVID-19 pandemic has led to new approaches to manage patients outside the ICU, including prone positioning in non-intubated patients. Objectives: To report the use of prolonged active prone positioning in spontaneously breathing patients with COVID-19-associated acute respiratory failure. Spontaneously breathing vs non-invasive respiratory support for COVID19 associated acute respiratory failure. Methods: Patients with PaO 2 /FiO 2 > 150, with lung posterior consolidations as assessed by means of lung ultrasound, and chest x-ray were studied. Under continuous pulse oximetry (SpO 2 ) monitoring, patients maintained active prone position. A PaO 2 /FiO 2 < 150 was considered as treatment failure and patients had to be switched to non-invasive respiratory support. Retrospectively, data of 16 patients undergoing who refused proning and underwent non-invasive respiratory support were used as controls. The primary outcome was the proportion of patients maintaining prolonged prone position and discharged home. Secondary outcomes included improvement in oxygenation, hospital length of stay, and 6-month survival. Results: Three out of 16 (18.7%) patients did not tolerate the procedure. Three more patients showed a worsening in PaO 2 /FiO 2 to <150 and required non-invasive support, two of whom finally needing endotracheal intubation. After 72 h, 10 out of 16 (62.5%) patients improved oxygenation [PaO 2 /FiO 2 : from 194.6 (42.1) to 304.7 (79.3.2) ( p < 0.001)] and were discharged home. In the control group, three out of 16 failed, required invasive ventilatory support, and died within 1 month in ICU. Thirteen were successful and discharged home. Conclusion: In non-intubated spontaneously breathing COVID-19 patients with PaO 2 /FiO 2 >150, active prolonged prone positioning was feasible and tolerated with significant improvement in oxygenation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pierucci, Ambrosino, Di Lecce, Dimitri, Battaglia, Boniello, Portacci, Resta and Carpagnano.)

Background: The survival benefit of negative margins for hepatocellular carcinoma (HCC) has been demonstrated. However, there is no consensus regarding the optimal resection margin width. We assessed the impact of hepatic resection margin width for solitary HCC on overall (OS), recurrence-free (RFS), and liver-specific recurrence-free survival (LSRFS)., Methods: Clinicopathologic data were retrospectively collected for solitary HCC patients who underwent a negative margin hepatectomy (1992-2015). Margin width was categorized in tertiles as "narrow" (≤ 0.3 cm), "intermediate" (0.31-1.0 cm), or "wide" (> 1.0 cm). Survival was compared among groups., Results: Of the 178 included patients, most were male (76%); median age, MELD score, and tumor size were 63 years, 8, and 5.2 cm, respectively; 93% were Child-Pugh class A. Median margin width was 0.5 cm. Median follow-up and OS were 47.8 months and 76.7 months, respectively. There was no significant survival difference among narrow, intermediate, and wide margin groups with a median OS of 53 months (IQR 21-not reached [NR]), 74 months (IQR 14-138), and 97 months (IQR 37-142) (p = 0.87), respectively. Median RFS was 33.0 months; again, there was no difference among narrow, intermediate, and wide margin groups with a median of 31 months (IQR 18-NR), 45 months (IQR 14-NR), and 27 months (IQR 11-NR), respectively (p = 0.66). Median LSRFS was 63.0 months (IQR 14-NR) with no difference among groups (p = 0.87). In multivariate analyses, margin width was not associated with OS (p = 0.77), RFS (p = 0.74), or LSRFS (p = 0.92). Findings were similar in all subgroups analyzed (≤ 5 cm, > 5 cm, microvascular invasion, T1, T2/T3, anatomical or non-anatomical resection, major or minor hepatectomy)., Conclusions: Narrow margins appear to be oncologically safe and the feasibility of achieving wide margins should not determine resectability., (© 2020. The Society for Surgery of the Alimentary Tract.)

To date, there is still a lack of unanimity regarding the definition of exacerbation of asthma and COPD and about objective measurements in the currently used criteria. The aim of our study was to conduct a survey among general practitioners (GPs) and pulmonologists regarding the clinical criteria arbitrarily considered as important to start a course of systemic corticoids and/or antibiotics in asthma and COPD. We conducted a survey enrolling 50 general practitioners (GPs) and 50 pulmonologists, that evaluated the clinical criteria arbitrated as essential to start a course of systemic corticosteroids or antibiotics during asthma and/or COPD exacerbations. Our results demonstrated incongruities between GPs and pulmonologist and within the same professional category concerning systemic corticosteroids. Conversely, we showed higher consensus between and within the groups about criteria to prescribe antibiotics.

Background: There are no studies investigating populations of patients with both pulmonary embolism and chronic obstructive pulmonary disease (PE-COPD) with and without deep venous thrombosis (DVT)., Aim of the Study: To define prevalence of DVT in COPD with PE and to compare characteristics of COPD patients who develop PE, with and without DVT. Secondly, we aimed to assess differences in the localization of PE among study groups.  METHODS. 116 patients with PE were enrolled in a retrospective study. Clinical data as well as echocardiographic and lower limb ultrasonography records were collected for all subjects. Subjects were divided into two groups according to the presence of COPD: Group 1, 54 patients with diagnosis of PE without COPD and Group 2, 66 patients diagnosed of PE with  COPD. Then, individuals of Group 2 were subdivided in two subgroups according to the presence (n=21) or absence (n=45) of DVT., Results: 33% of patients with COPD and PE showed DVT.  These subjects had higher PaCO2 and ejection fraction (p<0.05 for all) and higher percentage of chronic renal failure and diabetes mellitus compared to those without DVT (p<0.05 for all). Moreover, in COPD-PE patients with DVT, the most frequent localization was proximal (54% of total), whereas COPD-PE patients without DVT showed a more frequent segmental localization (60% of total). No difference was found in clinical presentation and blood-chemistry tests., Conclusions: DVT was non-common in PE-COPD patients. Chronic renal failure, and type 2 diabetes mellitus are more frequent in PE-COPD patients with DVT, that showed a higher frequency of proximal localization, thereby indicating a greater risk of more severe clinical implications. Conversely, PE- COPD subjects without DVT showed a more frequent segmental localization and were less hypercapnic. PE should be taken into account in COPD with worsening of respiratory symptoms, also in absence of DVT.

Positive results in pre-clinical studies of the triple combination of elexacaftor, tezacaftor and ivacaftor, performed in airway epithelial cell cultures obtained from patients harbouring the class II cystic fibrosis transmembrane conductance regulator (CFTR) mutation F508del-CFTR, translated to impressive clinical outcomes for subjects carrying this mutation in clinical trials and approval of Trikafta.Encouraged by this correlation, we were prompted to evaluate the effect of the elexacaftor, tezacaftor and ivacaftor triple combination on primary nasal epithelial cultures obtained from individuals with rare class II CF-causing mutations (G85E, M1101K and N1303K) for which Trikafta is not approved.Cultures from individuals homozygous for M1101K responded better than cultures harbouring G85E and N1303K after treatment with the triple combination with respect to improvement in regulated channel function and protein processing. A similar genotype-specific effect of the triple combination was observed when the different mutations were expressed in HEK293 cells, supporting the hypothesis that these modulators may act directly on the mutant proteins. Detailed studies in nasal cultures and HEK293 cells showed that the corrector, elexacaftor, exhibited dual activity as both corrector and potentiator, and suggested that the potentiator activity contributes to its pharmacological activity.These pre-clinical studies using nasal epithelial cultures identified mutation genotypes for which elexacaftor, tezacaftor and ivacaftor may produce clinical responses that are comparable to, or inferior to, those observed for F508del-CFTR., Competing Interests: Conflict of interest: O. Laselva has nothing to disclose. Conflict of interest: C. Bartlett has nothing to disclose. Conflict of interest: T.N.A. Gunawardena has nothing to disclose. Conflict of interest: H. Ouyang has nothing to disclose. Conflict of interest: P.D.W. Eckford has nothing to disclose. Conflict of interest: T.J. Moraes has nothing to disclose. Conflict of interest: C.E. Bear reports grants from CF Canada and Canadian Institutes of Health, during the conduct of the study; a philanthropic donation to the author's host institution from Jagle Bash, outside the submitted work. Conflict of interest: T. Gonska reports grants from CF Canada/SickKids Foundation, during the conduct of the study; travel reimbursement for lectures and for participation on an advisory board from Vertex Pharmaceutical Inc., outside the submitted work., (Copyright ©ERS 2021.)

Objectives : In the present single-centered, retrospective, observational study, we reported findings from 78 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS) hospitalized in an intermediate Respiratory Intensive Care Unit, subdividing the patients into two groups according to their clinical outcome, dead patients and discharged patients. Methods : We further subdivided patients depending on the noninvasive respiratory support used during hospitalization. Results : In those patients who died, we found significant older age and higher multimorbidity and higher values of serum lactate dehydrogenase, C-reactive protein, and D-dimer. Among patients who were submitted to bilevel positive airway pressure (BPAP), those who died had a significant shorter number of days in overall length of stay and lower values of arterial oxygen partial pressure to fractional inspired oxygen ratio (PaO2/FiO2 ratio) compared to those who survived. No difference in all-cause mortality was observed between the two different noninvasive respiratory support groups [48% for continuous positive airway pressure (CPAP) and 52% for BPAP]. Conclusion : In COVID-19 patients with moderate-to-severe ARDS using BPAP in an intermediate level of hospital care had more factors associated to all-cause mortality (shorter length of stay and lower baseline PaO2/FiO2 ratio) compared to those who underwent CPAP.

Background: Galectin-3, considered as a new inflammatory marker; it is increased in cardiovascular disease. We investigated Galectin-3 in relation to heart damage in patients with OSA and its role in inflammation, based on the Neutrophil-to-Lymphocyte Ratio (NLR)., Methods: Sixty-three consecutive patients (45 males, 18 females, 58.60 ± 12.28 years old) were studied. According to the Apnoea-Hypopnoea Index (AHI) patients were divided into Group 1 - non-severe (AHI <30) (17 males and 10 females, 59.89 ± 10.62 years old) and Group 2 - severe (AHI ≥30) (29 males and 6 females, aged 57.53 ± 13.30 years old) OSA. All patients underwent morning blood gas analysis, laboratory tests, nocturnal polygraphy, and echocardiography., Results: Galectin-3 was significantly increased in Group 2 (p = 0.027) patients. Moreover, it was directly related to left ventricle (LV) mass, left ventricle hypertrophy and LV posterior wall diameter. Tissue Doppler septal velocity (e'), that measures wall motion, was inversely correlated to Galectin-3. Furthermore, a direct association to diastolic dysfunction, evaluated as E/e' ratio, was observed. In line with these data, a direct correlation between Galectin-3 and left atrium volume was also found. Galectin-3 and percentage of total registration time with nocturnal oxygen saturation <90% (TST90) were directly correlated (p = 0.0003), while Galectin-3 and mean nocturnal SpO 2  were negatively correlated (p = 0.0045). We found a direct correlation between Galectin-3 and NLR (p = 0.011). Finally, Galectin-3 was able to predict 3-yr mortality with a specificity of 83.33% and a sensitivity of 91.84%., Conclusion: Galectin-3 showed a direct association to nocturnal respiratory indices and to cardiac remodelling in patients with OSA. OSA-induced inflammation may play an important role in the pathogenesis of heart damage., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ivacaftor (VX-770) was the first cystic fibrosis transmembrane conductance regulator (CFTR) modulatory drug approved for the treatment of patients with cystic fibrosis. Electron cryomicroscopy (cryo-EM) studies of detergent-solubilized CFTR indicated that VX-770 bound to a site at the interface between solvent and a hinge region in the CFTR protein conferred by transmembrane (tm) helices: tm4, tm5, and tm8. We re-evaluated VX-770 binding to CFTR in biological membranes using photoactivatable VX-770 probes. One such probe covalently labeled CFTR at two sites as determined following trypsin digestion and analysis by tandem-mass spectrometry. One labeled peptide resides in the cytosolic loop 4 of CFTR and the other is located in tm8, proximal to the site identified by cryo-EM. Complementary data from functional and molecular dynamic simulation studies support a model, where VX-770 mediates potentiation via multiple sites in the CFTR protein., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

The rare Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations, c.1826A > G (H609R) and c.3067&#95;3072delATAGTG (I1023&#95;V1024del), are associated with severe lung disease. Despite the existence of four CFTR targeted therapies, none have been approved for individuals with these mutations because the associated molecular defects were not known. In this study we examined the consequences of these mutations on protein processing and channel function in HEK293 cells. We found that, similar to F508del, H609R and I1023&#95;V1024del-CFTR exhibited reduced protein processing and altered channel function. Because the I1023&#95;V1024del mutation can be linked with the mutation, I148T, we also examined the protein conferred by transfection of a plasmid bearing both mutations. Interestingly, together with I148T, there was no further reduction in channel function exhibited by I1023-V1024del. Both H609R and I1023&#95;V1024del failed to exhibit significant correction of their functional expression with lumacaftor and ivacaftor. In contrast, the triple modulator combination found in TRIKAFTA TM , i.e., tezacaftor, elexacaftor and ivacaftor rescued trafficking and function of both of these mutants. These in-vitro findings suggest that patients harbouring H609R or I1023&#95;V1024del, alone or with I148T, may benefit clinically from treatment with TRIKAFTA TM .

During the COVID-19 lockdown, individuals were forced to remain at home, hence severely limiting the interaction within environmental stimuli, reducing the cognitive load placed on spatial competences. The effects of the behavioral restriction on cognition have been little examined. The present study is aimed at analyzing the effects of lockdown on executive function prominently involved in adapting behavior to new environmental demands. We analyze non-verbal fluency abilities, as indirectly providing a measure of cognitive flexibility to react to spatial changes. Sixteen students (mean age 20.75; SD 1.34), evaluated before the start of the lockdown (T1) in a battery of psychological tasks exploring different cognitive domains, have been reassessed during lockdown (T2). The assessment included the modified Five-Point Test (m-FPT) to analyze non-verbal fluency abilities. At T2, the students were also administered the Toronto Alexithymia Scale (TAS-20). The restriction of behaviors following a lockdown determines increased non-verbal fluency, evidenced by the significant increase of the number of new drawings. We found worsened verbal span, while phonemic verbal fluency remained unchanged. Interestingly, we observed a significant tendency to use the left part of each box in the m-FPT correlated with TAS-20 and with the subscales that assess difficulty in describing and identifying feelings. Although our data were collected from a small sample, they evidence that the restriction of behaviors determines a leftward bias, suggesting a greater activation of the right hemisphere, intrinsically connected with the processing of non-verbal information and with the need to manage an emotional situation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lardone, Turriziani, Sorrentino, Gigliotta, Chirico, Lucidi and Mandolesi.)

Tubular biological structures consisting of extracellular matrix (ECM) proteins and cells are basic functional units of all organs in animals and humans. ECM protein solutions at low concentrations (5-10 milligrams per milliliter) are abundantly used in 3D cell culture. However, their poor "printability" and minute-long gelation time have made the direct extrusion of tubular structures in bioprinting applications challenging. Here, this limitation is overcome and the continuous, template-free conversion of low-concentration collagen, elastin, and fibrinogen solutions into tubular structures of tailored size and radial, circumferential and axial organization is demonstrated. The approach is enabled by a microfabricated printhead for the consistent circumferential distribution of ECM protein solutions and lends itself to scalable manufacture. The attached confinement accommodates minute-long residence times for pH, temperature, light, ionic and enzymatic gelation. Chip hosted ECM tubular structures are amenable to perfusion with aqueous solutions and air, and cyclic stretching. Predictive collapse and reopening in a crossed-tube configuration promote all-ECM valves and pumps. Tissue level function is demonstrated by factors secreted from cells embedded within the tube wall, as well as endothelial or epithelial barriers lining the lumen. The described approaches are anticipated to find applications in ECM-based organ-on-chip and biohybrid structures, hydraulic actuators, and soft machines., (© 2021 Wiley-VCH GmbH.)

Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS), which worsen patients' health and increase healthcare spending. The aim of this study was to assess the clinical and economic impact of switching from omalizumab (OMA) to mepolizumab (MEP) in patients eligible for both biologics, but not optimally controlled by omalizumab. We retrospectively enrolled uncontrolled severe asthmatic patients who switched from OMA to MEP during the last two years. Information included blood eosinophil count, asthma control test (ACT), spirometry, serum IgE, fractional exhaled nitric oxide (FeNO), OCS intake, drugs, exacerbations/hospitalizations, visits and diagnostic exams. Within the perspective of Italian National Health System, a pre- and post-MEP 12-month standardized total cost per patient was calculated. 33 patients were enrolled: five males, mean age 57 years, disease onset 24 years. At OMA discontinuation, 88% were OCS-dependent with annual mean rate of 4.0 clinically significant exacerbations, 0.30 exacerbations needing emergency room visits or hospitalization; absenteeism due to disease was 10.4 days per patient. Switch to MEP improved all clinical outcomes, reducing total exacerbation rate (RR = 0.06, 95% CI 0.03-0.14), OCS-dependent patients (OR = 0.02, 95% CI 0.005-0.08), and number of lost working days (Δ = - 7.9, 95% CI - 11.2 to - 4.6). Pulmonary function improved, serum IgE, FeNO and eosinophils decreased. Mean annual costs were €12,239 for OMA and €12,639 for MEP (Δ = €400, 95% CI - 1588-2389); the increment due to drug therapy (+ €1,581) was almost offset by savings regarding all other cost items (- €1,181). Patients with severe eosinophilic asthma, not controlled by OMA, experienced comprehensive benefits by switching to MEP with only slight increases in economic costs.

Micellization is a phenomenon of central importance in surfactant solutions. Here, we demonstrate that the diffusion-based spreading of the free boundary between a micellar aqueous solution and pure water yields a one-dimensional spatial profile of surfactant concentration that can be used to identify the critical micelle concentration, here denoted as C *. This can be achieved because dilution of micelles into water leads to their dissociation at a well-defined position along the concentration profile and an abrupt increase in the diffusion coefficient. Rayleigh interferometry was successfully employed to determine C * values for three well-known surfactants in water at 25 °C: Triton X-100 (TX-100), sodium dodecyl sulfate (SDS), and poly(oxyethylene)(4)Lauryl Ether (Brij-30). The dependence of C * on salt concentration was also characterized for TX-100 in the presence of Na 2 SO 4 , NaCl, and NaSCN. Accurate values of C * can be directly identified by visual inspection of the corresponding concentration-gradient profiles. To apply the method of least squares to experimental concentration profiles, a mathematical expression was derived from Fick's law and the pseudophase separation model of micellization with the inclusion of appropriate modifications. While Rayleigh interferometry was employed in our experiments, this approach can be extended to any experimental technique that yields one-dimensional profiles of surfactant concentration. Moreover, diffusion-driven surfactant disaggregation is precise, noninvasive, requires single-sample preparation, and applies to both nonionic and ionic surfactants. Thus, this work provides the foundation of diffusion-driven dilution methods, thereby representing a valuable addition to existing techniques for the determination of C *.

Positron emission tomography (PET) using fluorodeoxyglucose ( 18 F-FDG) combined with magnetic resonance imaging (MR) is an emerging hybrid modality that has shown utility in evaluating abdominal and pelvic disease entities. Together, the high soft tissue contrast and metabolic/functional imaging capabilities make this modality ideal for oncologic imaging in many organ systems. Its clinical utility continues to evolve and future research will help solidify its role in oncologic imaging. In this manuscript, we aim to (1) provide an overview of the various PET/MR systems, describing the strengths and weaknesses of each system, and (2) review the oncologic applications for 18 F-FDG PET/MR in the abdomen and pelvis.

Background: The measures taken to contain the coronavirus disease 2019 (COVID-19) pandemic, such as the lockdown in Italy, do impact psychological health; yet, less is known about their effect on cognitive functioning. The transactional theory of stress predicts reciprocal influences between perceived stress and cognitive performance. However, the effects of a period of stress due to social isolation on spatial cognition and exploration have been little examined. The aim of the present study was to investigate the possible effects and impact of the COVID-19 pandemic on spatial cognition tasks, particularly those concerning spatial exploration, and the physiological leftward bias known as pseudoneglect. A right-hemisphere asymmetry for spatial attention processes crucially contributes to pseudoneglect. Other evidence indicates a predominantly right-hemisphere activity in stressful situations. We also analyzed the effects of lockdown on coping strategies, which typically show an opposite pattern of hemispheric asymmetry, favoring the left hemisphere. If so, then pseudoneglect should increase during the lockdown and be negatively correlated with the efficacy of coping strategies., Methods: One week before the start of the lockdown due to COVID-19 in Italy (T1), we had collected data from a battery of behavioral tests including tasks of peri-personal spatial cognition. During the quarantine period, from late April to early May 2020 (T2), we repeated the testing sessions with a subgroup of the same participants (47 right-handed students, mean age = 20, SD = 1.33). At both testing sessions, participants performed digitized neuropsychological tests, including a Cancellation task, Radial Arm Maze task, and Raven's Advanced Progressive Matrices. Participants also completed a newly developed COVID-19 Student Stress Scale, based on transactional models of stress, and the Coping Orientation to Problems Experienced-New Italian Version (COPE-NIV) to assess coping orientation., Results: The tendency to start cancelation from a left-sided item, to explore first a left-sided arm of the maze, and to choose erroneous response items on the left side of the page on Raven's matrices increased from T1 to T2. The degree of pseudoneglect increment positively correlated with perceived stress and negatively correlated with Positive Attitude and Problem-Solving COPE-NIV subscales., Conclusion: Lockdown-related stress may have contributed to increase leftward bias during quarantine through a greater activation of the right hemisphere. On the other hand, pseudoneglect was decreased for better coping participants, perhaps as a consequence of a more balanced hemispheric activity in these individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Somma, Bartolomeo, Vallone, Argiuolo, Cerrato, Miglino, Mandolesi, Zurlo and Gigliotta.)

Several studies showed that products made with ancient wheat genotypes have beneficial health properties compared to those obtained with modern wheat varieties, even though the mechanisms responsible for the positive effects are not clear. Ancient durum wheat genotypes are being currently used for the production of pasta, bread and other typical bakery products but the consumption is strictly local. In this work 15 genotypes of Triticum turgidum subsp. durum, including 10 ancient and 5 modern, were characterized for their technological traits through the determination of different parameters: protein content, dry gluten, gluten index, yellow index, ash, P/L, W and G. In addition, the baking aptitude of all genotypes was evaluated. All semolinas were subjected to leavening by commercial baker's yeast and the experimental breads were subjected to the qualitative characterization (weight loss, height, firmness, colour, volatile organic compounds, image and sensory analysis). The results obtained showed that protein content of grains and semolinas was higher in ancient rather than modern genotypes. Dry gluten ranged from 6.7% of the modern variety Simeto to 13.6% of the ancient genotype Scorsonera. Great differences were found for the yellow index which reached the highest value in Saragolla variety. The P/L and W ratios were significantly higher for the modern genotypes. On average, weight loss was about 14 g, while bread height varied significantly between the trials. Bread consistency varied between 12.6 and 31.3 N. Differences were observed for the yellow of the crumb (higher for modern genotypes) and for the redness of the crust (higher for ancient genotypes). The sensory evaluation displayed a high variability among the breads from the 10 ancient genotypes, while the control breads received scores closed to those of the modern genotypes. This study revealed that the modern durum wheat varieties showed a certain uniformity of behaviour, while the ancient genotypes exhibited a great variability of the final attributes of breads., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Some studies investigated epidemiological and clinical features of laboratory-confirmed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus causing coronavirus disease 2019 (COVID-19), but limited attention has been paid to the follow-up of hospitalized patients on the basis of clinical setting and the expertise of clinical management., Methods: In the present single-centered, retrospective, observational study, we reported findings from 87 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory syndrome hospitalized in an intermediate Respiratory Intensive Care Unit (RICU), subdividing the patients in two groups according to the admission date (before and after March 29, 2020)., Results: With improved skills in the clinical management of COVID-19, we observed a significant lower mortality in the T2 group compared with the T1 group and a significantly difference in terms of mortality among the patients transferred in Intensive Care Unit (ICU) from our intermediate RICU (100% in T1 group vs. 33.3% in T2 group). The average length of stay in intermediate RICU of ICU-transferred patients who survived in T1 and T2 was significantly longer than those who died (who died 3.3 ± 2.8 days vs. who survived 6.4 ± 3.3 days)., T Conclusions: The present findings suggested that an intermediate level of hospital care may have the potential to modify survival in COVID-19 patients, particularly in the present phase of a more skilled clinical management of the pandemic.

Background: F508del is prototypical of Class 2 CFTR mutations associated with protein misprocessing and reduced function. Corrector compounds like lumacaftor partially rescue the processing defect of F508del-CFTR whereas potentiators like ivacaftor, enhance its channel activity once trafficked to the cell surface. We asked if emerging modulators developed for F508del-CFTR can rescue Class 2 mutations previously shown to be poorly responsive to lumacaftor and ivacaftor., Methods: Rescue of mutant CFTRs by the correctors: AC1, AC2-1 or AC2-2 and the potentiator, AP2, was studied in HEK-293 cells and in primary human nasal epithelial (HNE) cultures, using a membrane potential assay and Ussing chamber, respectively., Results: In HEK-293 cells, we found that a particular combination of corrector molecules (AC1 plus AC2-1) and a potentiator (AP2) was effective in rescuing both the misprocessing and reduced function of M1101K and G85E respectively. These findings were recapitulated in patient-derived nasal cultures, although another corrector combination, AC1 plus AC2-2 also improved misprocessing in these primary tissues. Interestingly, while this corrector combination only led to a modest increase in the abundance of mature N1303K-CFTR it did enable its functional expression in the presence of the potentiator, AP2, in part, because the nominal corrector, AC2-2 also exhibits potentiator activity., Conclusions: Strategic combinations of novel modulators can potentially rescue Class 2 mutants thought to be relatively unresponsive to lumacaftor and ivacaftor., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020. Published by Elsevier B.V.)

It is widely recognized that the longer the ageing, the more valuable Parmigiano Reggiano (PR) cheese becomes, due to the improvement of its sensorial and nutritional properties. Up to now, the evaluation of PR properties has been performed on samples mainly aged up to 40 months. For this reason, this study was aimed at collecting information about the chemical-physical characteristics of PR cheeses after ageing at 24, 48 and 84 months. The basic analyses on water amount, protein content and volatile organic compounds (VOC) revealed that PR ageing is associated to the decomposition of the organic components into smaller units. This drives water molecules closer to the aforementioned units, thereby leading to a reduction of water activity. Moreover, it appears, from VOC investigation, that either the total amount of long chain fatty acids (LCFA) or the sole 9Z-octadecenoic acid considerably increased with PR aging, thereby making these molecular systems good fingerprint to monitor PR ripening. Fast field cycling (FFC) NMR relaxometry revealed different components of the molecular dynamics in the complex PR cheese samples, which were attributed to water trapped in casein micelles, water bound to polar groups in organic components, proteins, and fats. In particular, the reduction of the correlation times associated to the organic components was explained by the molecular size decrement following degradation processes. The ageing-independent component of the motion was assigned to water molecules bound to polar groups in organic moieties. Finally, the ageing-independent contribution to the overall relaxation rate was assigned to water molecules in casein micelles. This study revealed that FFC NMR relaxometry can be a promising technique to monitor the chemical physical changes during Parmigiano Reggiano cheese ripening., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cystic fibrosis (CF) is a genetic disorder affecting multiple organs, including the pancreas, hepatobiliary system and reproductive organs; however, lung disease is responsible for the majority of morbidity and mortality. Management of CF involves CF transmembrane conductance regulator (CFTR) modulator agents including corrector drugs to augment cellular trafficking of mutant CFTR as well as potentiators that open defective CFTR channels. These therapies are poised to help most individuals with CF, with the notable exception of individuals with class I mutations where full-length CFTR protein is not produced. For these mutations, gene replacement has been suggested as a potential solution.In this work, we used a helper-dependent adenoviral vector (HD-CFTR) to express CFTR in nasal epithelial cell cultures derived from CF subjects with class I CFTR mutations.CFTR function was significantly restored in CF cells by HD-CFTR and reached healthy control functional levels as detected by Ussing chamber and membrane potential (FLIPR) assay. A dose-response relationship was observed between the amount of vector used and subsequent functional outcomes; small amounts of HD-CFTR were sufficient to correct CFTR function. At higher doses, HD-CFTR did not increase CFTR function in healthy control cells above baseline values. This latter observation allowed us to use this vector to benchmark in vitro efficacy testing of CFTR-modulator drugs.In summary, we demonstrate the potential for HD-CFTR to inform in vitro testing and to restore CFTR function to healthy control levels in airway cells with class I or CFTR nonsense mutations., Competing Interests: Conflict of interest: H. Cao has nothing to disclose. Conflict of interest: H. Ouyang has nothing to disclose. Conflict of interest: O. Laselva has nothing to disclose. Conflict of interest: C. Bartlett has nothing to disclose. Conflict of interest: Z.P. Zhou has nothing to disclose. Conflict of interest: C. Duan has nothing to disclose. Conflict of interest: T. Gunawardena has nothing to disclose. Conflict of interest: J. Avolio has nothing to disclose. Conflict of interest: C.E. Bear reports grants from Cystic Fibrosis Canada CIHR and SickKids Foundation, during the conduct of the study. Conflict of interest: T. Gonska has received consultation fees and reimbursement of travel costs from Vertex Pharmaceutical Inc. Conflict of interest: J. Hu has nothing to disclose. Conflict of interest: T.J. Moraes has nothing to disclose., (Copyright ©ERS 2020.)

Introdution. In order to prevent or slow down the transmission of COVID-19, various public health measures have been introduced, including social distancing, environmental disinfection and the use of personal protective equipment (PPE). In this perspective, the clinical practice of healthcare professionals has changed dramatically. As a matter of fact, the use of surgical masks and N95 has significantly worsened the job performance of workers who deal directly with COVID-19 disease., Methods: The study included 116 health workers employed in the pulmonology, intensive care and infectious diseases departments of Bari and Foggia Hospital, directly involved in the healthcare of patients affected by COVID-19. Between May 1, 2020 and May 31, 2020, each participant completed an online questionnaire aimed to investigate the impact of the COVID-19 pandemic on workers' lifestyle changes and job performances. We compared the results based on the type of mask used by each participant (surgical mask vs N95)., Results: Although disturbances related to the use of the mask arose earlier in subjects who wore the N95 (p = 0.0094), healthcare workers that wore surgical masks reported a statistically higher average score for a greater number of disorders., Conclusions: This is the first study that compares the effects of the two most used PPE on the quality of life of health workers and which highlights the greater discomfort caused by surgical masks. This result brings to light a serious social problem, being surgical masks widely used in everyday life by ordinary people and non-healthcare workers.

The recent Coronavirus disease 19 (COVID-19) pandemic, first in China and then also in Italy, brought to the attention the problem of the saturation of Intensive Care Units (ICUs). Almost all previous reports showed that in ICU less than half of patients were treated with invasive mechanical ventilation (IMV) and the rest of them with non-invasive respiratory support. This highlighted the role of respiratory intensive care units (RICUs), where patients with moderate to severe respiratory failure can be treated with non-invasive respiratory support, avoiding ICU admission. In this report, we describe baseline characteristics and clinical outcomes of 97 patients with moderate to severe respiratory failure due to COVID-19 admitted to the RICU of the Policlinico of Bari from March 11 th to May 31 st 2020. In our population, most of the subjects were male (72%), non-smokers (76%), with a mean age of 69.65±14 years. Ninety-one percent of patients presented at least one comorbidity and 60% had more than two comorbidities. At admission, 40% of patients showed PaO 2 /FiO 2 ratio between 100 and 200 and 17% showed Pa0 2 /FiO 2 ratio <100. Mean Pa0 2 /FiO 2 ratio at admission was 186.4±80. These patients were treated with non-invasive respiratory support 40% with CPAP, 38% with BPAP, 3% with HFNC, 11% with standard oxygen therapy or with IMV through tracheostomy (patients in step down from ICU, 8%). Patients discharged to general ward (GW) were 51%, 30% were transferred to ICU and 19% died. To the best of our knowledge, this is one of the few described experiences of patients with respiratory failure due to COVID-19 treated outside the ICU, in a RICU. Outcomes of our patients, characterized by several risk factors for disease progression, were satisfactory compared with other experiences regarding patients treated with non-invasive respiratory support in ICU. The strategical allocation of our RICU, between ED and ICU, might have positively influenced clinical outcomes of our patients., (©Copyright: the Author(s).)

The combination therapies ORKAMBI TM and TRIKAFTA TM are approved for people who have the F508del mutation on at least one allele. In this study we examine the effects of potentiator and corrector combinations on the rare mutation c.3700A>G. This mutation produces a cryptic splice site that deletes six amino acids in NBD2 (I1234-R1239del). Like F508del it causes protein misprocessing and reduced chloride channel function. We show that a novel cystic fibrosis transmembrane conductance regulator CFTR modulator triple combination (AC1, corrector, AC2-2, co-potentiator and AP2, potentiator), rescued I1234-R1239del-CFTR activity to WT-CFTR level in HEK293 cells. Moreover, we show that although the response to ORKAMBI was modest in nasal epithelial cells from two individuals homozygous for I1234-R1239del-CFTR, a substantial functional rescue was achieved with the novel triple combination. Interestingly, while both the novel CFTR triple combination and TRIKAFTA TM treatment showed functional rescue in gene-edited I1234-R1239del-CFTR-expressing HBE cells and in nasal cells from two CF patients heterozygous for I1234-R1239del/W1282X, nasal cells homozygous for I1234-R1239del-CFTR showed no significant response to the TRIKAFTA TM combination. These data suggest a potential benefit of CFTR modulators on the functional rescue of I1234-R1239del -CFTR, which arises from the rare CF-causing mutation c.3700A>G, and highlight that patient tissues are crucial to our full understanding of functional rescue in rare CFTR mutations.

The aim of this research was to study the evolution of carotenoid compounds, antioxidant β-ctivity, volatiles and sensory quality in two mango cultivars dried at 50, 60 and 70 °C. Total carotenoids in fresh samples were about 12 and 6 mg/100 g (dry basis) in Keitt and Osteen samples, respectively. β-carotene was the main carotenoid, representing about 50% of total carotenoids. In both cultivars, carotenoids were more susceptible to drying at 60 °C. Total phenols and metal reduction activity were higher in Osteen than in Keitt, which had higher values in radical scavenging capacity. The antioxidant activities were best preserved with drying temperatures at 50 °C in Keitt and 60 °C in Osteen fruits. Fresh Osteen mango fruits had a volatile compound content of about 37.1, while Keitt of about 5.2 mg/kg (dry basis). All the compounds with odorous impact were significantly reduced after drying. As regards organoleptic characteristics through sensory analysis, Keitt dried mangoes were quite similar to the fresh product, compared to Osteen.

Background Angiotensin-converting enzyme 2, a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrates its highest surface expression in the lung, small bowel, and vasculature, suggesting abdominal viscera may be susceptible to injury. Purpose To report abdominal imaging findings in patients with coronavirus disease 2019. Materials and Methods In this retrospective cross-sectional study, patients consecutively admitted to a single quaternary care center from March 27 to April 10, 2020, who tested positive for SARS-CoV-2 were included. Abdominal imaging studies performed in these patients were reviewed, and salient findings were recorded. Medical records were reviewed for clinical data. Univariable analysis and logistic regression were performed. Results A total of 412 patients (average age, 57 years; range, 18 to >90 years; 241 men, 171 women) were evaluated. A total of 224 abdominal imaging studies were performed (radiography, n = 137; US, n = 44; CT, n = 42; MRI, n = 1) in 134 patients (33%). Abdominal imaging was associated with age (odds ratio [OR], 1.03 per year of increase; P = .001) and intensive care unit (ICU) admission (OR, 17.3; P < .001). Bowel-wall abnormalities were seen on 31% of CT images (13 of 42) and were associated with ICU admission (OR, 15.5; P = .01). Bowel findings included pneumatosis or portal venous gas, seen on 20% of CT images obtained in patients in the ICU (four of 20). Surgical correlation ( n = 4) revealed unusual yellow discoloration of the bowel ( n = 3) and bowel infarction ( n = 2). Pathologic findings revealed ischemic enteritis with patchy necrosis and fibrin thrombi in arterioles ( n = 2). Right upper quadrant US examinations were mostly performed because of liver laboratory findings (87%, 32 of 37), and 54% (20 of 37) revealed a dilated sludge-filled gallbladder, suggestive of bile stasis. Patients with a cholecystostomy tube placed ( n = 4) had negative bacterial cultures. Conclusion Bowel abnormalities and gallbladder bile stasis were common findings on abdominal images of patients with coronavirus disease 2019. Patients who underwent laparotomy often had ischemia, possibly due to small-vessel thrombosis. © RSNA, 2020.

Inflammatory bowel disease (IBD) is defined by a chronic relapsing and remitting inflammation of the gastrointestinal tract, with intestinal fibrosis being a major complication. The etiology of IBD remains unknown, but it is thought to arise from a dysregulated and excessive immune response to gut luminal microbes triggered by genetic and environmental factors. To date, IBD has no cure, and treatments are currently directed at relieving symptoms and treating inflammation. The current diagnostic of IBD relies on endoscopy, which is invasive and does not provide information on the presence of extraluminal complications and molecular aspect of the disease. Cross-sectional imaging modalities such as computed tomography enterography (CTE), magnetic resonance enterography (MRE), positron emission tomography (PET), single photon emission computed tomography (SPECT), and hybrid modalities have demonstrated high accuracy for the diagnosis of IBD and can provide both functional and morphological information when combined with the use of molecular imaging probes. This review presents the state-of-the-art imaging techniques and molecular imaging approaches in the field of IBD and points out future directions that could help improve our understanding of IBD pathological processes, along with the development of efficient treatments., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Oregano is-probably-the most appreciated and widespread aromatic plant in Sicily. With the aim of evaluating the modifications of oregano's essential oil composition over time, between 2013 and 2015 six weekly samplings of three different oregano plantations were carried out, from the beginning of flowering (early May) until the traditional harvest moment (end of June). Samples were hydrodistilled and the obtained essential oils (EOs) were evaluated by means of a combination of GC-FID and GC-MS. The Origanum plants under study were demonstrated to belong to the high-yielding, thymol-type biotypes, with thymol, γ-terpinene and p -cymene as three main components, among the total of about 50 of the evaluated EOs. In each location, EO yields were found to increase throughout survey dates. Significant variations were found in many EO components, both across years and throughout harvest dates within locations. The choice of the harvest moment was confirmed to be crucial in assessing quality aspects of oregano.

Background: The nonsense mutation, c.3846G>A (aka: W1282X-CFTR) leads to a truncated transcript that is susceptible to nonsense-mediated decay (NMD) and produces a shorter protein that is unstable and lacks normal channel activity in patient-derived tissues. However, if overexpressed in a heterologous expression system, the truncated mutant protein has been shown to mediate CFTR channel function following the addition of potentiators. In this study, we asked if a quadruple combination of small molecules that together inhibit nonsense mediated decay, stabilize both halves of the mutant protein and potentiate CFTR channel activity could rescue the functional expression of W1282X-CFTR in patient derived nasal cultures., Methods: We identified the CFTR domains stabilized by corrector compounds supplied from AbbVie using a fragment based, biochemical approach. Rescue of the channel function of W1282X.-CFTR protein by NMD inhibition and small molecule protein modulators was studied using a bronchial cell line engineered to express W1282X and in primary nasal epithelial cultures derived from four patients homozygous for this mutation., Results: We confirmed previous studies showing that inhibition of NMD using the inhibitor: SMG1i, led to an increased abundance of the shorter transcript in a bronchial cell line. Interestingly, on top of SMG1i, treatment with a combination of two new correctors developed by Galapagos/AbbVie (AC1 and AC2-2, separately targeting either the first or second half of CFTR and promoting assembly, significantly increased the potentiated channel activity by the mutant in the bronchial epithelial cell line and in patient-derived nasal epithelial cultures. The average rescue effect in primary cultures was approximately 50% of the regulated chloride conductance measured in non-CF cultures., Conclusions: These studies provide the first in-vitro evidence in patient derived airway cultures that the functional defects incurred by W1282X, has the potential to be effectively repaired pharmacologically., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2019. Published by Elsevier B.V.)

Objective : Sniff nasal inspiratory pressure (SNIP), a useful tool for the assessment of diaphragm function in patients with Amyotrophic Lateral Sclerosis (ALS), is usually performed together with lung function tests. The aim of this study was to evaluate whether SNIP results are influenced by the order of performance of the tests. Methods : 103 consecutive patients (65% males, 80% spinal onset) were recruited. The highest value of up to 10 sniffs, was recorded before (SNIPT0) and after (SNIPT1) the assessment of lung function, peak cough (PCF), and peak expiratory flow (PEF). Results : Mean and median values were respectively 31.10 and 26.00 cm H 2 O for SNIPT0 and 28.93 and 25.00 cm H 2 O for SNIPT1 ( p  < 0.001). The median value of (SNIPT1 - SNIPT0)/SNIPT0% was -7.10. Patients showing post lung function SNIP values above the median were included in Group 1 (51%), the others in group 2 (49%). Group 2 showed more severe baseline ventilatory restriction and reduction in PCF than Group 1. Positive direct relationships were found between SNIPT0 and SNIPT1 (coefficient β  = 0.95, p  < 0.001), and forced vital capacity and forced expiratory volume at one second. Conclusions : 50/103(49%) patients with ALS show a significant reduction in SNIP when assessed shortly after the performance of lung function tests. These patients suffer from more severe ventilatory restriction than patients not showing the reduction. Our findings suggest standardizing the order of respiratory tests during the follow up in order to avoid to misestimate the real strength of inspiratory muscles.

Objectives: The aim of this study was to compare PET/MR enterography with ileocolonoscopy regarding patients' acceptance and their future preference., Methods: Between October 2014 and February 2018 one-hundred-eleven patients underwent PET/MR enterography and ileocolonoscopy within 2 weeks. Overall acceptance of each modality was rated using a 10-point Likert scale with higher score indicating worse experience. Wilcoxon test was used to assess difference. Patients' acceptance of bowel cleansing and oral intake of contrast agent was analyzed in the same way. Furthermore, to find out if diagnosis, gender and age might influence patients' acceptance and future preference, Mann-Whitney U test for ordinal and Chi-squared test for categorical parameters were applied., Results: 77 patients (47 females) with a mean age of 44.5 years and diagnosed ulcerative colitis (UC; n = 46) and Crohn's disease (CD; n = 31), were included in the analysis. Overall, ileocolonoscopy was significantly better rated than PET/MR enterography (p < 0.001). Bowel cleansing was worse tolerated than oral intake of liquid (p < 0.001). Patients with CD preferred PET/MR enterography as future screening method, while UC patients favored ileocolonoscopy (p = 0.012). PET/MR enterography tended to be better accepted by CD patients (p = 0.08). Females tolerated both bowel cleansing and oral contrast agent worse than males (p = 0.05 and 0.047). No significant difference between different age groups was found., Conclusions: Ileocolonoscopy was rated as better tolerable than PET/MR and the overall rate for future preference was very similar. Optimization of both modalities might enhance patients' acceptance., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Cystic Fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The most common mutation, F508del , induces protein misprocessing and loss of CFTR function. The discovery through in vitro studies of the CFTR correctors (i.e. lumacaftor, tezacaftor) that partially rescue the misprocessing of F508del-CFTR with the potentiator ivacaftor is promising in giving an unprecedented clinical benefit in affected patients., Areas Covered: Online databases were searched using key phrases for CF and CFTR modulators. Tezacaftor-ivacaftor treatment has proved to be safer than lumacaftor-ivacaftor, although clinical efficacy is similar. Further clinical efficacy has ensued with the introduction of triple therapy, i.e. applying second-generation correctors, such as VX-569 and VX-445 (elexacaftor) to tezacaftor-ivacaftor. The triple combinations will herald the availability of etiologic therapies for patients for whom no CFTR modulators are currently applied (i.e. F508del /minimal function mutations) and enhance CFTR modulator therapy for patients homozygous for F508del ., Expert Opinion: CF patient-derived tissue models are being explored to determine donor-specific response to current approved and future novel CFTR modulators for F508del and other rare mutations. The discovery and validation of biomarkers of CFTR modulation will complement these studies in the long term and in real-life world.

The current diagnostic work-up and monitoring of idiopathic pulmonary fibrosis (IPF) is often invasive and time consuming. Breath analysis by e-nose technology has shown potential in the diagnosis of numerous respiratory diseases. In this pilot study, we investigated whether exhaled breath analysis by an e-nose could discriminate among patients with IPF, healthy controls and COPD. Second, we verified whether these classification could be repeated in a set of newly recruited patients as external validation. Third, we evaluated any significant relationships between exhaled VOCs and Bronchoalveolar lavage fluid (BALF) in IPF patients. We enrolled 32 patients with well-characterized IPF, 33 individuals with COPD and 36 healthy controls. An electronic nose (Cyranose 320) was used to analyze exhaled breath samples. Raw data were processed by Principal component reduction and linear discriminant analysis. External validation in newly recruited patients (10 IPF, 10 COPD and 10 controls) was tested using the previous training set. Exhaled VOC-profiles of patients with IPF were distinct from those of healthy controls (CVA  = 98.5%) as well as those with COPD (CVA  = 80.0%). External validation confirmed the above findings (IPF vs COPD vs healthy controls, CVA 96.7%). Moreover, a significant inversely proportional correlation was shown between BALF total cell count and both Principal Components 1 and 2 (r = 0.543, r 2 = 0.295, p < 0.01; r = 0.501, r 2 = 0.251; p < 0.01, respectively). The exhaled breath Volatile Organic Compounds- profile of patients with IPF can be detected by an electronic nose. This suggests that breath analysis has potential for diagnosis and/or monitoring of IPF.

In recent years, high flow nasal cannula is being increasingly used. Most studies showed positive results when used in hypoxaemic respiratory failure. Its use in a patient with a large endobronchial mass has not yet being described. We report a patient who presented with hemoptysis and hypoxaemic respiratory failure second to a large mass obstructing the right main bronchus. High flow oxygen via nasal cannula was initiated with a quick improvement of the hemoptysis and the oxygen saturation. Thus, allowing the patient to be rapidly stabilized.

The use of continuous positive airway pressure (CPAP) in asthma has been a point of debate over the past several years. Various studies, including those on animals and humans have attempted to understand the role and pathophysiology of CPAP in patients with either well controlled or poorly controlled asthma. The aim of this manuscript is to review the currently available literature on the physiologic and clinical effects of CPAP in animal models of asthma and on humans with stable asthma.

Electrochemical processes are considered very effective methods for the treatment of wastewater contaminated by organics resistant to conventional biological processes and various inorganic pollutants. Large sites that treat wastewaters usually deal with a large number of waters often characterized by different salinity contents, that could be potentially used to provide the energy necessary for the electrochemical remediation. Hence, in this work a reverse electrodialysis (RED) process for the treatment of synthetic wastewaters contaminated by organics, without energy inputs, using the salinity gradient of different wastewaters, was studied, for the first time. It was found that two synthetic wastewaters with different NaCl content can be effectively used in a RED system to drive anodic and cathodic processes for the removal of their organic contents without external energy supplies. The effects of salinity gradient, external resistance and set-up of the process was evaluated. Under optimized operating conditions, a fast and high removal of TOC (about 70% every hour) in the anodic compartment and a good stability of operating conditions for all the monitored time (10 h) were achieved. In addition, about 67% of the solution with high salinity used in the stack to provide the salinity gradient was effectively treated in the anodic compartment of the stack., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The consumption of loquat fruits is highly appreciated for their carotenoid content and valuable sensory notes, but it is limited due to the low shelf-life. An on-line temperature controlled microwave system based on infrared thermography was used to dry three different loquat cultivar at 60 °C. The time to reach the target value of 23% moisture content was about 105 min in Claudia fruits and 162 min in Virticchiara and Peluche. Seven carotenoids were identified in loquat fruits, among these the major were all-trans-β-carotene in Virticchiara and Claudia. Virticchiara had the major total carotenoid content (206 μg/g dry basis), followed by Peluche (158 μg/g d.b.) and Claudia (41 μg/g d.b.). The loss of carotenoids after drying ranged between 24% (Peluche) and 41% (Claudia). Carotenoids that showed a higher loss were on average: lutein (70%) and zeaxhantin (51%). Thirty-five volatile compounds were identified in fresh and dried loquats: the aldehydes were the most abundant class. After drying, aldehydes declined slightly, with alcohols falling more sharply. The shortened times by using temperature-controlled microwave heating with infrared thermography have guaranteed a fair quality of the dried loquats from the nutritional and sensory point of view, variable among the three cultivars.

Objectives : Few 'real-life' studies were conducted on the relationship between functional and clinical features in chronic obstructive pulmonary disease (COPD). We described the correlation between clinical and functional respiratory parameters in one-year follow-up observational study during stable phase COPD and regular inhalation therapy. Methods : In 237 patients, the impact of respiratory symptoms was evaluated using the modified Medical Research Council (mMRC) dyspnea scale, the COPD assessment test (CAT), and a self-assessment of patient's perceived COPD severity (Mapel scale) at baseline (T0) and after one year (T1). Results : Mean CAT and mMRC scores at T0 were 10.55 and 1.2, respectively. The majority of patients pointed out mild symptoms (values between 1 and 2 at Mapel scale). Mean CAT score at T0 did not differ after subdividing our population in the four spirometry GOLD stages. In the year of follow-up, FEV1 and hyperinflation indexes improved. CAT score was significantly associated with mMRC (p < 0.001), residual volume (RV) (p = 0.023), and RV/total lung capacity % (p = 0.011). Conclusion : The impact of symptoms in COPD stable patients was related to hyperinflation indexes and mMRC. There was no correlation between significant changes in CAT score and other symptom evaluation scores after one year.

The entry into the clinic of CFTR modulators such as TRIKAFTA has significantly improved life for ∼90% CF patients carrying one or two F508del mutations but challenges remain for rare CFTR mutations and the management of lung infections @SaraOcana1 https://bit.ly/3aRafQF., Competing Interests: Conflict of interest: S. Cuevas-Ocaña has nothing to disclose. Conflict of interest: O. Laselva has nothing to disclose. Conflict of interest: J. Avolio has nothing to disclose. Conflict of interest: R. Nenna has nothing to disclose., (Copyright ©ERS 2020.)

A dehydration experiment was carried out on Vitis vinifera L. cv Muscat of Alexandria (synonym Zibibbo) following the process for the production of renowned special dessert wines produced on Pantelleria island (Sicily, Italy). Harvested berries were pre-treated in a sodium hydroxide dipping solution (45 g/L, dipped for 185 s, 25 °C) to accelerate the drying process, rinsed, and dehydrated in simulated conditions (relative humidity 30%, 30 °C temperature, air speed 0.9 m/s). Three dehydration levels were achieved, corresponding to " Passolata ", " Bionda ", and " Malaga " stages (35%, 50%, and 65% of weight loss, respectively) of the Pantelleria denomination of origin (DOC). Grape skin mechanical properties, technological parameters, phenolics, and aroma profile varied considerably during dehydration. The most important aroma compounds for their olfactory impact, such as linalool, geraniol, nerol, and citronellol, especially in glycosylated forms, significantly increased in dried grapes compared to fresh ones, even if aroma profile modification occurred. A decrease in break skin force could have induced higher release of flavonoids. The findings showed relevant changes, allowing winemakers to better select the ratio of fresh and dehydrated grapes in the function of the final desired wine.