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Background: Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection caused by John Cunningham virus (JCV) reactivation, potentially associated with natalizumab (NTZ) treatment for Multiple Sclerosis (MS). The anti-JCV antibodies titre (JCV index) increases during NTZ treatment; however, the effects of other disease-modifying therapies (DMTs) on the JCV index have not been fully explored. Objective: The aim of the study was to evaluate changes in the JCV index during treatment with several DMTs. Methods: This longitudinal study evaluated the JCV index before starting DMT (T0) and during treatment with DMT (T1). Results: A total of 260 participants (65.4 % females, mean age 43 ± 11.3 ) were enrolled: 68 (26.2 %) treated with fingolimod (FTY), 65 (25 %) rituximab or ocrelizumab (RTX/OCR), 37 (14.2 %) dimethyl-fumarate (DMF), 29 (11.2 %) cladribine (CLD), 23 (8.8 %) teriflunomide (TFM), 20 (7.7 %) interferon or glatiramer acetate (IFN/GA), and 18 (6.9 %) alemtuzumab (ALM). At T1, the percentage of patients with JCV index 1.51 was found to be significantly reduced in the RTX/OCR group (51.6 % versus 37.5 %, p = 0.04). In the FTY group, a significant reduction in the percentage of patients with JCV index Conclusion: DMTs with a T and/or B depleting mechanism of action induced a significant reduction in the JCV index. These results may suggest new possible sequencing strategies potentially maximizing disease control while reducing the PML risk.

Context Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. Objective Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed. Methods In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action. Results From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P < 0.0001; target 1.4-2.5 nmol/L). Body-weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P = 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P = 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported. Conclusions Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency.

Though membrane distillation (MD) has gained more and more attention in the field of desalination, the wetting phenomenon was still a non-negligible problem. In this work, a method combined dip-coating and UV in situ polymerization for preparing hydrophobic/hydrophilic perfluoropolyether (PFPE)/polyvinylidene fluoride composite membranes. This composite membrane consisted of a top thin hydrophobic coating layer and hydrophilic substrate membrane. In terms of anti-wetting properties, contact angle and liquid entry pressure of all composite membranes (except for those based on 0.45 μm) exceeded 160o and 0.3 MPa, respectively. In particular, the desalination performance was tested in vacuum membrane distillation tests by feeding 3.5% (mass) saline solution (NaCl) at 60 oC. The composite membranes with larger support pore size and lower PFPE content had higher membrane distillation flux. And for stability tests (testing the 0.22 μm membrane coated by 5% (mass) PFPE), the highest MD flux 29.08 kg·m–2·h–1 and stable salt rejection (over 99.99%) during the period. Except that, the effects of coating material concentration and pore sizes of substrate membrane were also investigated for surface morphology and topography, porosity, mechanical strength and pore size characteristics. This work provided a simple and effective alternative to prepare excellent hydrophobic composite membranes for MD applications.

The concept of Rh/Al2O3 catalyst pellets packed in highly conductive copper foams has been successfully tested in methane steam reforming showing the beneficial effects of thermal conductivity on the obtainment of gradient-less radial temperature profiles. In this work, the same concept is proposed as a strategy for the lab-scale kinetic investigation under concentrated conditions at ambient pressure; thanks to the homogeneous heating of the catalyst mass across the reactor section and the measurement of axial temperature profiles, well-controlled temperature conditions are obtained, and the experimental investigation can be extended to usually unfeasible conditions of high reactant concentrations, overcoming the typical challenges for the kinetic study. Here, steam reforming experiments were performed with CH4 and H2O feed molar fractions in the ranges of 10−20 % and 40–90 %, respectively. The co-feed of CO and H2 was also investigated. A kinetic scheme was developed that substantially confirmed the main results of previous kinetic investigations in annular micro-reactor, performed under diluted conditions; in particular, the first order dependence of the rate of steam reforming on methane partial pressure, the independence from H2O partial pressure, and the important inhibiting effect of CO were confirmed. The independence of the reaction rate from the H2 co-feed was here demonstrated for the first time. The new experimental campaign allowed to identify more clearly the kinetic dependencies of the water gas shift reaction, positively influenced by H2O partial pressure but scarcely affected by CO partial pressure, which could be also explained based on the inhibiting effect of surface CO coverage. Parameter estimates were obtained by model fit over a wide temperature range (400−850 °C), conveying robustness to the proposed kinetic scheme for future reactor design applications.

Background: Direct locoregional treatments were recently proposed for the local control of cervical and distant metastasis of thyroid cancer, but data on their use as part of a multimodality approach for primary thyroid tumors are poor. In this feasibility study, laser ablation (LTA) was successfully used for the initial debulking of unresectable radioiodine-refractory thyroid cancer in sequential therapy with Tyrosine-Kinase Inhibitors (TKI). Case Presentation: A 69-year-old woman underwent partial resection of papillary thyroid cancer with extensive tracheal infiltration. Post-treatment whole-body scan (131I, 8140 MBq) showed the absence of cervical thyroid uptake. The patient experienced a rapid increase in her cervical mass associated with dysphonia, dyspnea, and dysphagia. Due to a concomitant severe hypertensive state and cardiac failure, the patient was treated with LTA after a multidisciplinary consultation. After local anesthesia, two 300 nm optic fibers were inserted into the lesion through 21G spinal needles. Two illuminations with 4-watt output power and 3600 Joules energy delivery were performed with a diode-laser source. LTA resulted in rapid cancer debulking, and mass volume decreased from 23.9 to 7.5 mL resulting in significant improvement of pressure symptoms. Three months later, the patient was started on lenvatinib due to the initial regrowth of the tumor mass. The cervical tumor burden was controlled by TKI for 20 months when a rapid disease progression occurred, and the patient died. Discussion: Locally advanced, unresectable, and radioiodine-refractory thyroid tumors can be managed with a novel multimodality approach. The initial debulking with LTA of the locally aggressive disease results in rapid control of the tumor burden threatening patients’ life and is effectively followed by long-term control with TKI treatment. Conclusion: Based on this experience, sequential multimodality treatment with an initial locally directed laser ablation procedure followed by TKI therapy may be considered as a salvage option in patients with unresectable and rapidly progressive RR thyroid tumors.

Background Progressive multifocal leukoencephalopathy (PML) can rarely occur in Multiple Sclerosis (MS) patients undergoing dimethyl fumarate (DMF) treatment. Our case stresses the limits of current diagnostic and stratification risk criteria, highlighting the potential role of Magnetic Resonance Imaging (MRI) in advising clinical choices. Case presentation A 54 years old MS male patient treated with DMF, after 3 years of clinical stability developed a subacute clinical worsening. He had no severe lymphopenia but MRI signs suggestive of a coexistence of PML and MS activity. Although his viral title was negative, DMF was discontinued, with clinical and radiological improvement. Conclusions This case highlights the challenges behind PML diagnosis, especially in patients not fulfilling the risk stratification criteria and that might present with concurrent disease activity, stressing the potential role of MRI in informing therapeutic decisions.

A 3-year-old girl came to our attention for fever and upper respiratory tract infection associated with thrombocytopenia, non-immune hemolytic anemia, and acute kidney injury (AKI). Complete blood count and renal function slowly normalized, with no need for dialysis. She was always normotensive with valid diuresis; her neurological status also rapidly improved. Nasal swab turned out positive for influenza A H1N1; stool test was negative for Shiga toxin-producing Escherichia coli (STEC). The patient was treated with oseltamivir for 5 days with a favorable outcome. Association between hemolytic uremic syndrome (HUS) and H1N1 influenza is poorly reported in literature [1, 2, 3, 4]. The pathogenic role of the virus in causing HUS is still controversial and debated [1, 2, 3, 4]. In our patient, complement activity markers (serum C3 and C5b-9) alteration suggested a transient, virus-mediated complement activation.

Biomass gasification has acquired considerable interest as a sustainable and environmentally friendly way to produce heat, hydrogen or electricity from agro-industrial wastes or other kinds of biomass. A very effective solution for the achievement of high electrical efficiency (up to 55%) is the integration of biomass gasification with solid oxide fuel cell (SOFC) technology, including the necessary gas cleanup to avoid degradation of the SOFC. For this reason, this paper first shows in detail the risk and the impact of carbon deposition, exposure to tar, hydrogen sulphide, hydrogen chloride and alkali metals on SOFC anode and then, considering the tolerance limit for inorganic and organic contaminants (

Sphene (CaTiSiO5, i.e. CaO·TiO2·SiO2) ceramics were successfully developed via the polymer derived ceramics route, starting from a commercial silicone containing specific oxide fillers. The approach allowed the combination of synthesis, in conditions of high phase purity, and advanced manufacturing. In particular, the adopted starting materials enabled an easy preparation of pastes, to be used for direct ink writing (DIW) of three-dimensional reticulated scaffolds. Sphene scaffolds, after firing at 1300 °C, were always regular and crack-free, despite changes in the line spacing, resulting in variable porosity (from ≈ 59 to 74 %), and exhibited a compressive strength from 3.9 to 12.7 MPa. The porosity was actually hierarchical, considering the formation of ‘spongy’ struts. In vitro tests, with increasing immersion time in SBF solution, confirmed the bioactivity, combined with a quite slow ion release, useful to maintain the pH value at nearly physiological values. Additional biological tests, consisting of the seeding of scaffold with normal human adult dermal fibroblasts, showed adequate cell viability and no toxicity effect.

Antonella Potalivo,1,* Jonathan Montomoli,1,* Francesca Facondini,1 Gianfranco Sanson,2 Luigi Arcangelo Lazzari Agli,3,4 Tiziana Perin,5 Francesco Cristini,6 Enrico Cavagna,7 Raffaella De Giovanni,8 Carlo Biagetti,6 Ilaria Panzini,9 Cinzia Ravaioli,10 Maria Maddalena Bitondo,1 Daniela Guerra,1 Giovanni Giuliani,1 Elena Mosconi,1 Sonia Guarino,1 Elisa Marchionni,6 Gianfilippo Gangitano,5 Ilaria Valentini,3,4 Luca Giampaolo,8 Francesco Muratore,7 Giuseppe Nardi1 1Department of Anaesthesia and Intensive Care, Infermi Hospital, AUSL della Romagna, Rimini, Italy; 2Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 3Department of Pneumology, Infermi Hospital, Rimini, Italy; 4Ceccarini Hospital, AUSL della Romagna, Riccione, Italy; 5Department of Emergency Medicine, Infermi Hospital, AUSL Della Romagna, Rimini, Italy; 6Department of Infectious Diseases, Infermi Hospital, AUSL della Romagna, Rimini,Italy; 7Department of Radiology, Infermi Hospital, AUSL della Romagna, Rimini, Italy; 8Department of Internal Medicine, Cervesi Hospital, AUSL della Romagna, Cattolica, Italy; 9Department of Clinical Research, AUSL della Romagna, Ravenna, Italy; 10Ausl della Romagna Health Care Service Direction, Ravenna, Italy*These authors contributed equally to this workCorrespondence: Giuseppe NardiDepartment of Anaesthesia and Intensive Care, Infermi Hospital, AUSL della Romagna, Viale Settembrini 2, Rimini 47921, ItalyTel +39 0541-705254Fax +39 0541 705886Email 4doctornardi@gmail.comPurpose: Although the decision of which ventilation strategy to adopt in COVID-19 patients is crucial, yet the most appropriate means of carrying out this undertaking is not supported by strong evidence. We therefore described the organization of a province-level healthcare system during the occurrence of the COVID-19 epidemic and the 60-day outcomes of the hospitalized COVID-19 patients according to the respiratory strategy adopted given the limited available resources.Patients and Methods: All COVID-19 patients (26/02/2020– 18/04/2020) in the Rimini Province of Italy were included in this population-based cohort study. The hospitalized patients were classified according to the maximum level of respiratory support: oxygen supplementation (Oxygen group), non-invasive ventilation (NIV-only group), invasive mechanical ventilation (IMV-only group), and IMV after an NIV trial (IMV-after-NIV group). Sixty-day mortality risk was estimated with a Cox proportional hazard analysis adjusted by age, sex, and administration of steroids, canakinumab, and tocilizumab.Results: We identified a total of 1,424 symptomatic patients: 520 (36.5%) were hospitalized, while 904 (63.5%) were treated at home with no 60-day deaths. Based on the respiratory support, 408 (78.5%) were assigned to the Oxygen group, 46 (8.8%) to the NIV-only group, 25 (4.8%) to the IMV-after-NIV group, and 41 (7.9%) to the IMV-only group. There was no significant difference in the PaO2/FiO2 at IMV inception in the IMV-after-NIV and IMV-only groups (p=0.9). Overall 60-day mortality was 24.2% (Oxygen: 23.0%; NIV-only: 19.6%; IMV-after-NIV: 32.0%; IMV-only: 36.6%; p=0.165). Compared with the Oxygen group, the adjusted 60-day mortality risk significantly increased in the IMV-after-NIV (HR 2.776; p=0.024) and IMV-only groups (HR 2.966; p=0.001).Conclusion: This study provided a population-based estimate of the impact of the COVID-19 outbreak in a severely affected Italian province. A similar 60-day mortality risk was found for patients undergoing immediate IMV and those intubated after an NIV trial with favorable outcomes after prolonged IMV.Keywords: COVID-19, mechanical ventilation, mortality, noninvasive ventilation, multidisciplinary team approach, ARDS

Thanks to the use of small-angle neutron scattering (SANS), a detailed structural description of thermosensitive polymer-grafted cellulose nanocrystals (CNCs) was obtained and the behavior of aqueous suspensions of these derivatized biosourced particles upon temperature increase was revealed. Although literature data show that the surface grafting of thermosensitive polymers drastically enhances the colloidal properties of CNCs, direct space microscopic investigation techniques fail in providing sufficient structural information on these objects. In the case of CNCs decorated with temperature-sensitive polyetheramines following a peptide coupling reaction, a qualitative and quantitative analysis of SANS spectra shows that CNCs are homogeneously covered by a shell comprising polymer chains in a Gaussian conformation with a thickness equal to their radius of gyration in solution, thus revealing a mushroom regime. An increase of the temperature above the lower critical solution temperature (LCST) of the polyetheramine results in the formation of finite size bundles whose aggregation number depends on the particle concentration and suspension temperature deviation from the LCST. SANS analysis further reveals local changes at the CNC surface corresponding to a release of water molecules and a related denser polymer shell conformation. Noticeably, data show a full reversibility at all length scales when a sample was cooled down to below the LCST after being heated above it. Overall, the results obtained by SANS allow an in-depth structural investigation of derivatized CNCs, which is of high interest for the design of functional materials comprising these biosourced colloids.

Poultry litter is widely applied as a fertilizer even though it is one of the main antibiotic sources to agricultural soils. Long-term sublethal effects (56 days) on the antioxidant system of Eisenia andrei earthworms following exposure to fluoroquinolone-contaminated poultry litter (enrofloxacin + ciprofloxacin) at 5.0, 10, and 20 g kg-1 were evaluated. The following biomarkers were assessed: superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH), and a lipid peroxidation (LPO) proxy. Significant CAT and SOD increases, and a moderate positive correlation (ρ = 0.67, p < 0.05) between these enzymes was observed. Glutathione-S-transferase levels increased significantly at 10 g kg-1, while GSH exhibited a dose-dependent response at 5.0 mg kg-1 (4-106%), 10 mg kg-1 (28-330 %), and 20 mg kg-1 (45-472%). LPO levels exhibited a decreasing trend with increasing poultry litter concentrations of 8-170% (5.0 g kg-1), 7-104% (10 mg kg-1), and 3-6% (20 mg kg-1). A principal component analysis (PCA) highlighted increased SOD and CAT activities, possibly due to increased reactive oxygen species (ROS) concentrations. Biological health status assessments based on the biomarker response index indicate major alterations in the first month of exposure and becoming moderate in the second month. These findings indicate an antioxidant system attenuation trend. It is possible, however, that successive poultry litter applications may reduce the long-term recovery capacity of the evaluated biomarkers.

El uso de fertilizantes orgánicos en el Valle del Yaqui tiende a reducir la degradación del suelo en la producción de trigo, sin embargo, todavía no se han evaluado los impactos biológicos de esta práctica en el suelo. El objetivo de este experimento fue cuantificar el impacto del cambio en el manejo del cultivo de trigo, de convencional a orgánico, sobre la reducción de la degradación fúngica del suelo, por medio del análisis de sus poblaciones fúngicas cultivables y su diversidad. La hipótesis fue que la aportación de fertilizantes orgánicos al cultivo de trigo produce cambios positivos en las propiedades fisicoquímicas del suelo, lo cual beneficia a las poblaciones de hongos, y disminuye su degradación. Tres campos comerciales de trigo se seleccionaron con 1) fertilización sintética convencional (SF), 2) fertilización sintética más fertilización orgánica (SF+OF) y 3) sólo fertilización orgánica (OF). Los sitios de estudio bajo OF y SF+OF vs. SF mostraron mayores, contenidos de materia orgánica (1.5, 1.6 vs. 0.45%), población de hongos (1.7x105, 9.1x104 vs. 1.6x104 CFU g-1 de suelo seco) y diversidad (12, 12 vs. 2). Con base en el análisis filogenético, se aislaron 9, 11 y 2 géneros de hongos de los sitios de estudio bajo fertilización orgánica, sintética + orgánica y sintética, respectivamente. La diversidad metabólica de las cepas fúngicas obtenidas mostró que la producción de indoles osciló entre 0.5 y 65.4 μg mL-1; el hongo Stachybotrys sp. TSM35 fue el productor de indoles mayor. La solubilización de fosfatos mayor (21%) se observó en la cepa Talaromyces pinophilus TSO42 y la cepa con producción de sideróforos mayor (33.9%) fue Volutella ciliata TSM43. Además, el 60% de las cepas mostraron riesgos potenciales para la salud (α- o β-hemólisis). La rotación de convencional a orgánico en el cultivo del trigo logró cambios positivos en las propiedades fisicoquímicas del suelo, en la diversidad y características metabólicas de las poblaciones fúngicas cultivable. El control de la calidad microbiológica de los fertilizantes orgánicos se necesita para evitar riesgos microbiológicos en los sistemas agronómicos, causados por la introducción de cepas con potencial patogénico.

Introduction: This study aimed to analyze macular structure by using spectral-domain optical coherence tomography (SD-OCT) in a cohort of patients affected by autosomal recessive retinitis pigmentosa and Usher syndrome, due to genetic variants in USH2A gene, and to correlate optical coherence tomography (OCT) parameters with functional and genetic data. Methods: The subjects of this study were 92 patients, 46 syndromic (Usher syndrome type IIa [Ush2]) and 46 nonsyndromic (autosomal recessive RP [arRP]), with clinical and genetic diagnosis of USH2A-related retinal dystrophy, who underwent a complete ophthalmic examination and spectral-domain OCT analysis. The study focused on evaluating the differences between the 2 groups in the following parameters: best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, presence of epiretinal membrane (ERM), and cystic macular lesions (CMLs). Variants in USH2A gene were divided into 3 categories, according to the expected impact (low/high) at protein level of the different variants on each allele. Results: BCVA and EZ width were significantly lower in Ush2 than in arRP patients (p < 0.0001 and p = 0.001). ERM was detected in 34.8% (16/46) of arRP patients and in 65.2% (30/46) of Ush2 patients (p = 0.003). CML was detected in 17.4% (8/46) of arRP patients and 30.4% (14/46) of Ush2 patients (p = 0.14). The allelic distribution was statistically different (p = 0.0003) by dividing the 2 diseases: for Ush2 patients it was 45.7% (high/high), 39.1% (low/high) and 15.2% (low/low); for arRP patients it was 8.7% (high/high), 56.5% (low/high), and 34.8% (low/low). The severity class of the variants significantly affected visual acuity and EZ width parameters (p = 0.004 and p = 0.002, respectively). Conclusion: Retinal disease, as evaluated by means of SD-OCT, shows more advanced degeneration signs in the syndromic than the nonsyndromic form of retinal dystrophy related to USH2A gene. Variant types and allelic profiles are determining factors for the onset of syndromic features. However, since the 3 allelic profiles can be found in both Usher and RP patients, other factors must necessarily play a determining role.

Propolis is a complex natural product that possesses antioxidant, anti-inflammatory, immunomodulatory, antibacterial, and antiviral properties mainly attributed to the high content in flavonoids, phenolic acids, and their derivatives. The chemical composition of propolis is multifarious, as it depends on the botanical sources from which honeybees collect resins and exudates. Nevertheless, despite this variability propolis may have a general pharmacological value, and this review systematically compiles, for the first time, the existing preclinical and clinical evidence of propolis activities as an antiviral and immunomodulatory agent, focusing on the possible application in respiratory diseases. In vitro and in vivo assays have demonstrated propolis broad-spectrum effects on viral infectivity and replication, as well as the modulatory actions on cytokine production and immune cell activation as part of both innate and adaptive immune responses. Clinical trials confirmed propolis undeniable potential as an effective therapeutic agent; however, the lack of rigorous randomized clinical trials in the context of respiratory diseases is tangible. Since propolis is available as a dietary supplement, possible use for the prevention of respiratory diseases and their deleterious inflammatory drawbacks on the respiratory tract in humans is considered and discussed. This review opens up new perspectives on the clinical investigation of neglected propolis biological properties which, now more than ever, are particularly relevant with respect to the recent outbreaks of pandemic respiratory infections.

The removal of NOx from low-temperature diesel engine emissions still represents a big challenge in view of the upcoming more stringent worldwide regulations. In our previous studies, we proved the ability of novel AdSCR (Adsorption + Selective Catalytic Reduction) systems, based on the combination of a chemical trapping compound and a conventional SCR catalyst, to trap cold start NOx emissions and to desorb and simultaneously reduce them with ammonia at higher temperature. In the present work, we extend the investigation of Cu-CHA + BaO/Al2O3 systems under more realistic conditions, focusing on the impact of H2O and CO2. The experimental results reveal a reduction of the AdSCR system performances with respect to dry and CO2-free conditions. Despite this, the system is still able to store and reduce NOx. The NOx storage capacity on barium oxide is more affected by the presence of CO2 than by H2O. However, H2O hinders the NO oxidative activation in the zeolite cages, which is a fundamental step in order to be able to trap NOx on the storage material at low temperature. We further demonstrate that the detrimental effect of H2O can be mitigated by small amounts of NO2 in the gaseous feed or by including a 13X zeolite guard bed prior to the AdSCR bed.

The exact role of malignant ascites in the development of intraperitoneal metastases remains unclear, and the mechanisms by which extracellular vesicles (EVs) promote tumor progression in the pre‐metastatic niche have not been fully discovered. In this study, we characterized ascites from high‐grade epithelial ovarian cancer patients. Small‐EVs (30–150 nm) were isolated from two sources—the bulk ascites and the ascitic fluid‐derived tumor cell cultures—and assessed with a combination of imaging, proteomic profiling, and protein expression analyses. In addition, Gene Ontology and pathway analysis were performed using different databases and bioinformatic tools. The results proved that the small‐EVs derived from the two sources exhibited significantly different stiffness and size distributions. The bulk ascitic fluid‐derived small‐EVs were predominantly involved in the complement and coagulation cascade. Small‐EVs derived from ascites cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators, and we observed an increase in transforming growth factor‐β‐I (TGFβI), plasminogen activator inhibitor 1 (PAI‐1), and fibronectin expression after neoadjuvant chemotherapy. When measured in the two sources, we demonstrated that fibronectin exhibited opposite expression patterns in small‐EVs in response to chemotherapy. These findings highlight the importance of an ascites cell isolation workflow in investigating the treatment‐induced cancer adaption processes., The mechanisms by which extracellular vesicles (EVs) promote ovarian cancer progression in the pre‐metastatic niche have not been fully discovered. This study showed that sampling ascites before and after chemotherapy allows characterizing small‐EVs released by tumor cells, reflecting their biological status. Small‐EVs derived from ascitic fluid‐derived tumor cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators.

Thrombotic complications are common in patients with severe COVID-19 pneumonia with important consequences on the diagnostic and therapeutic management. We report a consecutive series of five patients on long-term oral anticoagulation therapy who presented to our hospital for severe COVID-19 pneumonia associated with segmental acute pulmonary embolism despite adherence to therapy and with an adequate anticoagulant range at the time of the event. Four patients were receiving a direct oral anticoagulant (two with edoxaban, one with rivaroxaban and one with apixaban) and one patient a vitamin K antagonist. No significant thrombotic risk factors, active cancer, or detectable venous thromboembolism were present. In all cases, elevated d-dimer and fibrinogen levels with a parallel rise in markers of inflammation were documented. The combination of these findings seems to support the hypothesis that considers the local vascular damage determined by severe viral infection as the main trigger of thrombi detected in the lungs, rather than emboli from peripheral veins.

The existence of epitaxy in polybutene-1 form II-on-form I cross-nucleation was investigated by nanofocused synchrotron X-ray diffraction. To this aim, form I hedrites, which show a lamellar stacking with a uniform crystal lattice orientation, were adopted as the substrate. The form II crystals develop a spherulitic transcrystalline layer on the lateral surface of the form I substrate, due to cross-nucleation. Through mapping both the intensity and azimuthal orientation of characteristic planes of the two polymorphs, a clearly defined nucleation area between form II (daughter) and form I (parent) could be identified. Comparing the two-dimensional diffraction patterns in that area, a preferred mutual orientation of the two structure is revealed. In particular, the (200)II plane of form II and the (110)I plane of form I are reciprocally oriented at a fixed angle of ∼8.5°. This orientation results in almost parallel (110) planes between the two structures. It is calculated that the mismatch between interchain distances within the common (110) planes is about 4%, while that along the chain axes is less than 10%, both well below the accepted mismatch criterion for epitaxial crystallization. These results provide solid evidence for the existence of an epitaxial relationship in the cross-nucleation between polybutene-1 form II and form I. We note that the (110) contact plane between the two structures in cross-nucleation is the same as the one involved in the well-studied solid-state phase transformation from form II to form I. Moreover, the X-ray nanofocus approach and the proposed data analysis could be effectively applied to other cross-nucleating systems to shed light on the role of epitaxy in this peculiar phenomenon of nucleation between polymorphs.

The growing numbers related to plastic pollution are impressive, with ca. 70 % of produced plastic (>350 tonnes/year) being indiscriminately wasted in the environment. The most dangerous forms of plastic pollution for biota and human health are micro- and nano-plastics (MNPs), which are ubiquitous and more bioavailable. Their elimination is extremely difficult, but the first challenge is their detection since existing protocols are unsatisfactory for microplastics and mostly absent for nanoplastics. After a discussion of the state of the art for MNPs detection, we specifically revise the techniques based on photoluminescence that represent very promising solutions for this problem. In this context, Nile Red staining is the most used strategy and we show here its pros and limitations, but we also discuss other more recent approaches, such as the use of fluorogenic probes based on perylene-bisimide and on fluorogenic hyaluronan nanogels, with the added values of biocompatibility and water solubility.

Native lignin, a major structural polymer in lignocellulosic biomass, offers unique advantages as a feedstock for high-performance bio-based polymeric materials. In this work, depolymerized native ...

Venetoclax, a potent B-cell lymphoma-2 (BCL-2) inhibitor, has demonstrated clinical efficacy in chronic lymphocytic leukemia (CLL). VENICE II is an open-label, single-arm, phase 3b study (NCT02980731) evaluating the impact of venetoclax monotherapy (400 mg once daily) for ≤2 years on health-related quality of life (HRQoL) of patients with relapsed/refractory CLL. The primary endpoint was mean change in the global health status (GHS)/quality of life (QoL) subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) from baseline to Week 48. Overall, 210 patients received ≥1 dose of venetoclax; median treatment duration was 67.4 weeks. The primary endpoint was met with mean improvement of +9.3 points (n = 156, 95% confidence interval 6.1-12.5; p=.004) in GHS/QoL. At Week 48, clinically meaningful improvements were observed for role functioning, fatigue, and insomnia domains of EORTC QLQ-C30, suggesting venetoclax monotherapy has a positive impact on HRQoL. No new safety signals were reported.

The introduction of optical coherence tomography angiography (OCTA) has granted a significant improvement in the assessment of patients with diabetes. In this review, we will provide a description of the prominent OCTA findings in diabetes. In detail, this imaging technology proved that both the retinal and choroidal circulation is affected in diabetic subjects. The recent employment of widefield technology and a three-dimensional (3D) visualization in OCTA imaging are also discussed.

Background: Vascular remodeling processes induced by acute and chronic injuries are characterized by inflammation and oxidative stress. In arteriosclerosis, atherosclerosis, and restenosis, the progression of neointimal hyperplasia is a key event of vascular damage. Objective: Our study was aimed to investigate the inflammation and oxidative stress development during vascular impairment and the potential efficacy of treatment of new micro composite N-palmitoylethanolamine/Rutin at a ratio of 1:1 (PEA/RUT). The anti-inflammatory effects of Palmitoylethanolamide (PEA) are well known. Rutin has important pharmacological actions, including antioxidant and vasoprotective. Methods: As a model of vascular injury, we used the complete ligature of the left carotid artery for fourteen days and administered PEA/RUT at the dose of 10 mg/Kg. Results: This study demonstrated that after fourteen days of carotid ligation, there is a substantial structural change in the vessel morphology, with inflammatory cell infiltration and reactive oxygen species production. PEA/RUT administration reduced change in vascular morphology, cytokines like monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules expression like intercellular adhesion molecules-1 (ICAM-1), proinflammatory cytokines production (IL-1 β, IL-6 and TNF- α), oxidative and nitrosative stress (nitrotyrosine and PARP expression and NRF2 pathway). Conclusions: Our data clearly demonstrate the beneficial effect of PEA/RUT administration in reducing inflammation, oxidative stress, and vascular damage.

A non-waterproofed surface flow constructed wetland (SFCW), treating agricultural drainage water in Northern Italy, was investigated to gain information on the potential ability for effective pesticide abatement. A mixture of insecticide imidacloprid, fungicide dimethomorph, and herbicide glyphosate was applied, by simulating a single rain event, into 470-m-long water course of the SFCW meanders. The pesticides were monitored in the wetland water and soil for about 2 months after treatment. Even though the distribution of pesticides in the wetland was not uniform, for each of them, a mean dissipation of 50% of the applied amount was already observed at ≤7 days. The dissipation trend in the water phase of the wetland fitted (r2 ≥ 0.8166) the first-order model with calculated DT50 of 20.6, 12.0, 5.8, and 36.7 days for imidacloprid, dimethomorph, glyphosate, and the glyphosate metabolite AMPA, respectively. The pesticide behavior was interpreted based on the chemical and physical characteristics of both the substances and the water-soil system. Despite the fast abatement of glyphosate, traces were detected in the water until the end of the trial. The formation of soluble 1:1 complex between glyphosate and calcium, the most representative cation in the wetland water, was highlighted by infrared analyses. Such a soluble complex was supposed to keep traces of the herbicide in solution.

The photosynthesis of vitamin D3 in mammalian skin results from UV-B irradiation of provitamin D3 (7-dehydrocholesterol, DHC) at ca. 290 nm. Upon return to the ground state, the hexatriene product, previtamin D3, undergoes a conformational equilibration between helical gZg and more planar tZg and tZt forms. The helical gZg forms provide a pathway for the formation of vitamin D3 via a [1,7]-sigmatropic hydrogen shift. Steady state photolysis and UV transient absorption spectroscopy are combined to explore the conformational relaxation of previtamin D3 formed from DHC in isotropic solution and confined to lipid bilayers chosen to model the biological cell membrane. The results are compared with measurements for two analogues: previtamin D2 formed from ergosterol (provitamin D2) and previtamin D3 acetate formed from DHC acetate. The resulting spectral dynamics are interpreted in the context of simulations of optical excitation energy and oscillator strength as a function of conformation. In solution, the relaxation dynamics and steady state product distributions of the three compounds are nearly identical, favoring tZg forms. When confined to lipid bilayers, the heterogeneity and packing forces alter the conformational distributions and enhance the population of a gZg conformer capable of vitamin D formation.

The fan shell Pinna nobilis is the largest bivalve endemic to the Mediterranean and is actually a strongly endangered species. Due to the biological, ecological, and historical relevance of this species, the research of a non-lethal method to relate the element content in organism’s tissues and environment can provide information potentially useful to evaluate environmental pollution and organism physiological status. In this study, a screening on element concentration in the animal growing environment (seawater and sediments) and in four soft tissues (hepatopancreas, gills, mantle, and muscle), and two acellular tissues (calcite shell layer, and byssus) was performed. The comparison among these results was used to assess whether the no-lethal acellular tissue element concentration can be used to reveal the element presence in the environment and soft tissues. Elements, such as B, Ag, As, Mn, Mo, Pb, or Se, showed a possible relationship between their presence in the byssus and soft tissues. In the byssus Cr, Sb, Sn, and V have shown to be mostly related to the environment, more than the soft tissues, and might be used to draw a historical record of the exposure of the organism. The element concentration in the calcite shell layer did not relate with environmental element concentrations. Essential elements, like Cu, Fe, Ni, and Zn, were present in calcite shell layer and byssus and are likely related to their biological activity in the organism. The research also gave an overview on the presence of pollution and on the preferential intake route of the element. In summary, this study, performed on a limited number of specimens of this protected species, indicated that element concentration in the byssus can be applied as non-lethal method to monitor this endangered species and its interaction with the elements in the growing environment.

The disorganized and inefficient tumor vasculature is a major obstacle to the delivery and efficacy of antineoplastic treatments. Antiangiogenic agents can normalize the tumor vessels, improving vessel function and boosting the distribution and activity of chemotherapy. The type III repeats (T3R) domain of thrombospondin-1 contains different potential antiangiogenic sequences. We therefore hypothesized that it might affect the tumor vasculature. Ectopic expression of the T3R domain by the tumor cells or by the host, or administration of recombinant T3R, delayed the in vivo growth of experimental tumors. Tumors presented marked reorganization of the vasculature, with abundant but smaller vessels, associated with substantially less necrosis. Mechanistically, the use of truncated forms of the domain, containing different active sequences, pointed to the FGF2/FGFR/ERK axis as a target for T3R activity. Along with reduced necrosis, the expression of T3R promoted tumor distribution of chemotherapy (paclitaxel), with a higher drug concentration and more homogeneous distribution, as assessed by HPLC and MALDI imaging mass spectrometry. T3R-expressing tumors were more responsive to paclitaxel and cisplatin. This study shows that together with its known role as a canonical inhibitor of angiogenesis, thrombospondin-1 can also remodel tumor blood vessels, affecting the morphological and functional properties of the tumor vasculature. The ability of T3R to reduce tumor growth and improve the response to chemotherapy opens new perspectives for therapeutic strategies based on T3R to be used in combination therapies.

Background Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P Interpretation According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.

Bis[(2-diphenylphosphino)phenyl] ether (DPEphos) was used as chelating ligand to prepare the corresponding borohydride complex [Cu(κ2–BH4)(DPEphos)], whose structure was ascertained spectroscopically and by means of X-ray diffraction. The spectroscopic assignments related to the coordinated borohydride were confirmed by preparing the isotopologue [Cu(κ2–BD4)(DPEphos)]. Reaction of [Cu(κ2–BH4)(DPEphos)] with triflic acid afforded the dimer [Cu2(μ–BH4)(DPEphos)2][OTf] (OTf = triflate). The borohydride complexes exhibited appreciable blue emission upon excitation with UV light at room temperature. [Cu(κ2–BH4)(DPEphos)] revealed to be a suitable precursor for the preparation of luminescent heteroleptic copper(I) complexes having general formula [Cu(N^N)(DPEphos)]+ (N^N = 1,10-phenantroline, 2,9-dimethyl-1,10-phenantroline, 2,2’-bypiridine, 4,4’-dimethyl-2,2’bipyridine).

This study evaluated the influence of Libidibia ferrea (Lf) extract used as dentin pretreatment on the resin-dentin bond strength stability and dentin endogenous enzymatic activity. The phytochemical profile (PP) of the Lf extract was evaluated by liquid chromatography; particle size, polydispersity index (PdI), and zeta potential (ZP) were evaluated by dynamic light scattering. The tested groups were ER-Scotchbond Universal (SBU) in the etch-and-rinse (ER) mode; ERLf-SBU in the ER mode + Lf after etching; SE- SBU in the self-etch (SE) mode; and LfSE-Lf before SBU in the SE mode. Sticks were obtained for microtensile bond strength tests and failure mode (24 hr and 12 months). The hybrid layer was evaluated using scanning electron microscopy. The endogenous enzymatic activity of the underlying dentin was analyzed by in situ zymography with the same treatments. The PP showed the presence of quercetin (2.6% w/w). Lf particles were considered large after the analysis of the PdI. The ZP remained stable over time. The ER and ERLf groups had lower bond strength after 12 months, but SE and LfSE remained stable. The predominant failure mode was adhesive for both times. ER and ERLf had longer resin tags and a thicker hybrid layer. The ER and LfSE groups showed higher enzymatic activity than the ERLf and SE groups after 12 months. The Lf extract may contribute to inhibit the dentin endogenous enzymatic activity when associated with an adhesive system in the ER mode.

The superoxide disproportionation reaction is a key step in the chemistry of aprotic metal oxygen batteries that controls the peroxide formation upon discharge and opens the way for singlet oxygen release. Here we clarify the energy landscape of the disproportionation of superoxide in aprotic media catalyzed by group 1A cations. Our analysis is based on ab initio multireference computational methods and unveils the competition between the expected reactive path leading to peroxide and an unexpected reaction channel that involves the reduction of the alkaline ion. Both channels lead to the release of triplet and singlet O2. The existence of this reduction channel not only facilitates singlet oxygen release but leads to a reactive neutral solvated species that can onset parasitic chemistries due to their well-known reducing properties. Overall, we show that the application of moderate overpotentials makes both these channels accessible in aprotic batteries.

We report the realization of an acoustic capacitive microphone formed by graphene/poly(methyl methacrylate) (PMMA). It is the first time that the ultra-large graphene/PMMA membrane suspended fully over the cavity has been fabricated by releasing the silicon dioxide sacrificial layer underneath the membrane. The novelty in the fabrication method is that the silicon dioxide layer has been etched by hydrogen fluoride vapor from the back of the partly etched silicon substrate. Using the new process, the ultra-large graphene/PMMA membrane, with a diameter to thickness ratio of 7800, has been suspended over the cavity with a 2 μm air gap. The spacing of 2 μm is the minimum gap over the graphene-based acoustic capacitive microphones which have been reported so far. The static deformation of the suspended graphene/PMMA membrane after silicon dioxide has been etched is estimated to be 270 nm. The aspect ratio of the membrane's diameter over its static deformation is around 13,000, which shows that the graphene/PMMA membrane with a diameter of a few millimeters can be transferred and suspended over the substrate with relatively small deformation by releasing the sacrificial silicon dioxide layer. The dynamic behavior of the device under electrostatic actuation has been characterized. The acoustic response of the graphene/PMMA capacitive microphone has been measured, and the sensitivity has been observed to be -47.5 dB V (4.22 mV/Pa) ± 10%. The strain in the graphene/PMMA membrane is estimated to be 0.034%.

[EN] High-pressure synchrotron X-ray diffraction studies of cobalt iodate, Co(IO3)(2), reveal a counterintuitive pressure-induced expansion along certain crystallographic directions. High-pressure Raman and infrared spectroscopy, combined with density-functional theory calculations, reveal that with increasing pressure, it becomes energetically favorable for certain I-O bonds to increase in length over the full range of pressure studied up to 28 GPa. This phenomenon is driven by the high-pressure behavior of iodate ion lone electron pairs. Two pressure-induced isosymmetric monoclinic-monoclinic phase transitions are observed at around 3.0 and 9.0 GPa, which are characterized by increasing oxygen coordination of the iodine atoms and the probable formation of pressure-induced metavalent bonds. Pressure-volume equations of state are presented, as well as a detailed discussion of the pressure dependences of the observed Raman- and infrared-active modes, which clarifies previous inconsistencies in the literature., This work was supported by the Generalitat Valenciana under Project PROMETEO 2018/123-EFIMAT and by the Spanish Ministerio de Ciencia, Universidades, e Investigacion under Projects PID2019-106383GB-41/42/43, as well as through MALTA Consolider Team research network (RED2018102612-T). A.M. and P.R.-H. acknowledge computing time provided by Red Espan~ola de Supercomputacion (RES) and the MALTA Consolider Team cluster. D.E. acknowledges the resources and technical assistance provided by the Informatics Service of Universitat de Valencia through the Tirant III cluster. A.L. and D.E. would like to thank the Generalitat Valenciana for the Ph.D. Fellowship no. GRISOLIAP/2019/025. R.T. acknowledges funding from the Spanish Ministerio de Economia y Competitividad (MINECO) via the Juan de la Cierva Formacion fellowship (FJC2018-036185-I). C.P. is thankful for the financial support of the Spanish Mineco Project no. FIS2017-83295-P. E.B would like to thank the University of Valencia for his "Attraccio de Talent" postdoctoral contract (UV-INV_POSTDOC19-1026935). The authors thank Sandrine Beauquis from Symme, Universite Savoie Mont Blanc (France), for her technical assistance concerning the SEM and ADX analyses. PXRD experiments were performed at the MSPD beamline of ALBA Synchrotron (experiment no. 2019083663). IR experiments were performed at the MIRAS beamline of ALBA Synchrotron (experiment no. 2020024118).

The aim of this study was to investigate the action spectrum of two urea derivatives, the 1,3-di(benzo[d]oxazol-5-yl)urea (5-BDPU) and the 1,3-di(benzo[d]oxazol-6-yl)urea (6-BDPU). In order to evaluate a possible adjuvant activity on cytokinins the compounds alone or in the simultaneous presence of different cytokinins were assayed either on in vitro typical cytokinin-related bioassays, or on in planta interaction with cytokinin signal transduction pathway. The compounds ability to activate the cytokinin receptor CRE1/AHK4 was studied either by a heterologous bacterial assay or by a competitive binding assay and docking simulations were performed with the crystal structure of the same receptor. Then, owing to their chemical structure which resembles that of urea-type cytokinins, the ability of 5- and 6-BDPU to inhibit the activity of cytokinin oxidase/dehydrogenase of Zea mays (ZmCKX1) was investigated and docking simulations were performed as well. Accordingly to the experimental results, we speculate that BDPUs could show a dual activity: the blocking of the conformational re-adaption of CRE1/AHK4 receptor maintaining the cytokinin inside its binding pocket, thus possibly enhancing its kinase action; the inhibition of cytokinin oxidase/dehydrogenase activity thus possibly preventing its cleavage of natural cytokinins with isoprenoid side chain. Graphic abstract

Several compositional parameters (fatty acids, tocopherols, polar phenols and volatiles) in virgin olive oils from varieties located at the center of Tunisia, namely Baldi, Chemchali, Neb Jmel, Tounsi and Besbessi from Gafsa and Chemchali and Sehli cultivated in Sidi Bouzid, were studied. To the best of our knowledge, this is the first study focusing on the chemical composition of virgin olive oils (VOO) from Sidi Bouzid. Significant differences were found between varieties from Sidi Bouzid and Gafsa in monounsaturated saturated fatty acid levels, some volatile compounds and γ-tocopherol amounts. Notably, Tounsi and Baldi VOOs showed the highest six carbon atoms alcohol contents, whereas Neb Jmel VOO revealed the highest aldehyde six carbon atoms content. Fatty acid composition, as well as tocopherol content, showed differences among different VOO. Principal component analysis and hierarchical component analysis on polar phenols, fatty acids, tocopherols and volatiles data evidenced a good discrimination among oils from the different investigated varieties.

The growing demand for energy and materials in modern society pushes scientific research to finding new alternative sources to traditional fossil feedstocks. The exploitation of biomass promises to be among the viable alternatives with a lower environmental impact. Making biomass exploitation technologies applicable at an industrial level represents one of the main goals for our society. In this work, the most recent scientific studies concerning the enhancement of lignocellulosic biomasses through the use of deep eutectic solvent (DES) systems have been examined and reported. DESs have an excellent potential for the fractionation of lignocellulosic biomass: the high H-bond capacity and polarity allow the lignin to be deconvolved, making it easier to break down the lignocellulosic complex, producing a free crystallite of cellulose capable of being exploited and valorised. DESs offer valid alternatives of using the potential of lignin (producing aromatics), hemicellulose (achieving furfural) and cellulose (delivering freely degradable substrates through enzymatic transformation into glucose). In this review, the mechanism of DES in the fractionation of lignocellulosic biomass and the main possible uses for the valorisation of lignin, hemicellulose and cellulose were reported, with a critical discussion of the perspectives and limits for industrial application.

Peatlands account for a large fraction of global methane ( $$\mathrm {CH_4}$$ ) emissions. These environments exchange $$\mathrm {CH_4}$$ with the atmosphere via three main mechanisms: diffusion through the peat and water, plant-mediated diffusion, and sporadic release of $$\mathrm {CH_4}$$ bubbles. While rapid advances have been made in measuring $$\mathrm {CH_4}$$ fluxes above peatlands on sub-daily time scales, partitioning $$\mathrm {CH_4}$$ fluxes into ebullition and background diffusion remains a formidable challenge. Such partitioning is becoming necessary for future projection of methane concentration as atmospheric, hydrologic, and edaphic drivers of these two types of methane releases may differ significantly. Using surface renewal theory, a framework for partitioning measured methane fluxes based on the mass transfer mechanism is introduced with the overall objective of characterizing the intermittency of $$\mathrm {CH_4}$$ source and its strength at the ground. This approach is tested using a large dataset of measured turbulent air velocity and multiple scalar concentrations (including heat, water vapour, and carbon dioxide) for flow above a boreal peatland in Finland. The transport efficiencies of different gas transfer mechanisms are then evaluated for scalars characterized by background diffusion (e.g., water vapour) or by intermittent sources (e.g., methane). Whether environmental variables such as water-table levels and atmospheric conditions have a signature on the occurrence of $$\mathrm {CH_4}$$ hotspots is then investigated. Building upon the classical surface renewal theory, this work introduces a novel approach for inferring the intermittent nature of scalar sources at the ground and for exploring how non-homogeneity affects the efficiency of gas turbulent transport in the atmospheric surface layer.

DNA/RNA synthesis precursors are especially vulnerable to damage induced by reactive oxygen species occurring following oxidative stress. Guanosine triphosphates are the prevalent oxidized nucleosites, which can be misincorporated during replication, leading to mutations and cell death. Here, we present a novel method based on micro-Raman spectroscopy, combined with ab initio calculations, for the identification, detection, and quantification of low concentrations of oxidized nucleotides. We also show that the Raman signature in the terahertz spectral range (< 100 cm$^{-1}$) contains information on the intermolecular assembly of guanine in tetrads, which allows to further boost the oxidative damage detection limit. Eventually, we provide evidence that similar analyses can be carried out on samples in very small volumes at very low concentrations by exploiting the high sensitivity of Surface Enhanced Raman Scattering combined with properly designed superhydrophobic substrates. These results pave the way for employing such advanced spectroscopic methods for quantitatively sensing the oxidative damage of nucleotides in the cell., 11 pages, 7 figures

The development of highly selective, stable, and sensitive materials for the various gas emissions is a challenging task concerning the numerous applications: environmental control, security systems, energy, and, more recently, biological monitoring. One of the major challenges to reach this activity's requirements is developing nanostructured functional and smart materials that can selectively detect and monitor the gases at high temperatures. The semiconductor materials based on metallic oxides have gained increasing attention within this scenario, especially titanium dioxide (TiO2), due to their excellent properties. The literature presents multiple sensors based on TiO2 nanoparticles to detect various gases: CO, ethanol, benzene, toluene, NO2, O2, CO, SO2, NOx, NH3, Cl2, H2S, alkanes, among others. This review initially explores some aspects of TiO2 and its properties regarding the sensor sensitivity's influence. Then, the insertion of noble metals (Ag, Pt, Au, and Ru) and carbon structures (graphene, carbon nanotube, and other carbon forms) was also explored in the search to improve the TiO2 capacity as a gas sensor. This review focuses on the most significant achievements related to TiO2 and TiO2 combined with carbon structures or noble metals for gas sensor applications. Several studies were presented, highlighting the synthesis methods employed, the sensor response/recovery times, and some detection mechanisms after the carbon and noble metal insertion. Finally, the influence of a triple combination between TiO2-carbon-metal was also explored.

Microvascular damage is the main cause of delayed graft function (DGF) after kidney transplant. Assessing its extent may be helpful in predicting DGF to achieve better postoperative management, especially in terms of an immunosuppressive regimen. Our aim was to explore the capability of intraoperative indocyanine green (ICG) angiography to examine the microvasculature of the kidney.We conducted a prospective cohort study on 37 kidney transplant recipients in a high-volume kidney transplant center. During surgery, after graft implant, an ICG angiography was performed through a high-definition Storz camera system (Karl Storz GmbH, Tuttlingen, Germany) with successive quantitative assessment of fluorescence using Icy bioimage analysis.All transplanted kidneys that showed immediate recovery of their function had a fluorescent intensity ≥49.953 with a mean of 96.930 ± 21. The fluorescence intensity for kidneys that showed a delayed recovery of their function never exceeded 55.648, and the mean was 37.718 ± 13. The difference between the 2 groups was statistically significant with a P value.001. The only kidney that never recovered showed a fluorescence intensity consistently25.220, the lowest detected.This study demonstrates that intraoperative ICG angiography may be used to assess the microvasculature of the graft. A statistically significant difference in terms of fluorescent intensity can be highlighted between kidneys that immediately recover their function and those with delayed recovery. Further larger studies are needed to confirm the capability of the technique to predict DGF to optimize the transplanted patients' management.

Objective:To identify histopathological and immunophenotypical features with potential predictive or prognostic value in patients undergoing pulmonary metastasectomy from renal cell carcinoma (RCC).Methods:We retrospectively collected all consecutive patients undergoing pulmonary metastasectomy from RCC after prior nephrectomy. Paired samples of primary tumors and corresponding pulmonary metastases were analyzed, revising histopathological features and testing C-MET, mTOR, and PD-L1 by immunohistochemistry.Results:A total of 25 patients were included. Median overall survival (mOS) from metastasectomy was 5.5 years (95% CI = 1.9–9.1). The laterality of metastases had a significant predictive value, with median relapse-free survival (mRFS) from metastasectomy not reached (NR) at mean follow-up (FU) of 60.8 months for left lung involvement, mRFS of 52.9 months (95% CI = 0–145.5) for the right lung and 6.4 months (95% CI = 1.7–11) for bilateral metastases ( p = 0.028). Primary RCC with positive expression of mTOR had higher mOS after metastasectomy than negative cases ( p < 0.001), NR at mean FU of 4.3 years versus mOS of 2 years (95% CI = 0.7–3.3), respectively. PD-L1 positivity on intra-tumor (TILs) and peri-tumor (RILs) infiltrating lymphocytes of metastases was related to higher OS, NR versus 2 years (95% CI = 1.2–2.7, p = 0.003), and NR versus 1.4 years (95% CI = 0.2–2.6, p = 0.012), respectively. The shorter was the surgical interval, the more probably the metastases had high c-MET expression (>70%) ( p = 0.007) and PD-L1 expression >10% on TILs ( p = 0.024).Conclusions:mTOR positivity on primary RCC could be a favorable prognostic factor to select patients for pulmonary metastasectomy. The positive impact of PD-L1 expression on immune cells is opposite to the well-known negative prognostic value of PD-L1 on tumor cells in RCC.

Continuous adsorption of nitrate in a fixed-bed column can be an effective method for its removal from water. In this study, an amine-rich polymer composite adsorbent was prepared by crosslinking chitosan (CS) and polyethyleneimine (PEI) with glutaraldehyde (GLA). The CS-PEI-GLA was packed into columns and the effect of flow rate, influent concentration, bed height, and other ionic species on the column performance was investigated. The highest adsorption capacity was achieved at the lowest flow rate and highest influent concentration and bed height. Maximum adsorption capacity of 137.62 mg NO3−-N/g was determined from the Thomas model. The column had acceptable nitrate removal in the presence of 1000 ppm chloride but poor performance in the presence of 1000 ppm sulfate due to the competitive effect of sulfate for binding sites. The best recovery agent was 0.5 M NaCl as it could regenerate the column to

Background: Indocyanine green (ICG) fluorescence imaging has been extensively used in a variety of applications in visceral surgery. In minimally invasive liver resections, the detection of small s...

The case of a toddler with long-channel cloaca, mild chronic kidney disease (CKD) due to renal dysplasia, and early onset of ulcerative colitis (UC) is herein reported. The patient underwent definitive repair of cloaca, that included vaginal elongation with colon, at 5 months of age and was admitted for episodes of vaginal bleeding at 22 months of age. A vaginoscopy revealed a severe inflammation of the colonic neovagina. As rectal bleeding was also noticed, she underwent a colonscopy that showed the same macroscopic inflammatory picture. Neovaginal and colonic biopsies confirmed UC. The mother turned out to be affected by UC since adolescence. The patient is now on oral therapy with mesalazine and topical steroid and mesalazine in the neovagina. The association between cloaca and inflammatory bowel disease (IBD) is anecdotal, but the family history of IBD should be considered when planning the surgical reconstruction of patients with cloaca. In this patient, the occurrence of UC may require a new neovagina in the future and the concomitance of CKD may complicate the overall management due to the potential nephrotoxicity of drugs used for UC therapy.

BACKGROUND: Treatment outcomes in multidrug‐resistant TB (MDR‐TB) patients are suboptimal in several low‐incidence countries.METHODS: The primary outcome measure was the proportion of successfully treated patients in Italy during an 18‐year period. Secondary outcomes were treatment outcomes in certain drug‐containing regimens and the possibility for the WHO shorter MDR‐TB regimen.RESULTS: In the 191 patients included (median age at admission: 33 years; 67.5% male, following drug‐resistance patterns were found: MDR‐TB in 68.6%, pre‐extensively drug‐resistant TB (pre‐XDR‐TB) in 30.4% and XDR‐TB in 1.1% patients. The most frequently prescribed drugs were fluoroquinolones in 84.6% cases, amikacin in 48.7%, linezolid in 34.6% and meropenem/clavulanic acid in 29.5%. The median duration of treatment was 18 months. Treatment success was achieved in 71.2% patients, of whom, 44% were cured and 27.2% completed treatment. Treatment success rates did not statistically differ between the MDR‐ (68.8%) and pre‐XDR‐TB (77.6%) groups (P = 0.26). Treatment success rates had large variability between North and South of Italy (81.3% vs. 53.3%). Only 22.5% of the cases would have been eligible for shorter MDR‐TB regimensCONCLUSION: Our study highlights variability in treatment outcomes in MDR‐ and pre‐XDR‐TB patients. Study findings confirmed the potential utility of linezolid and, for patients with limited oral options, meropenem/clavulanic acid and amikacin.

Biofilms, flavins and pyocyanin have been identified as metabolites for species-specific electrogenicity. In this work, open circuit voltages (OCV) >500 mV earlier produced by electrogens in glucose-based media was used in confirming electrogens. Biofilms of test electrogens were grown on anodes of microbial fuel cells (MFCs) fed with glucose-based media. Electrogens used were anodophilic Enterobacter aerogenes 102, flavinogenic Bacillus sp. 101, Pichia kudriavzevii 103 and four pyocyanogenic Pseudomonads. Treatments with inhibitors (norspermidine, dichloro-diaminobenzene, and Raloxifene) negatively affected their electrogenicity. To enhance electrogenicity, increased anodic-biofilm was achieved by anode pretreatments with ultraviolet radiation and hydrogen peroxide, while pyocyanin-induced electrogenicity was enhanced by treatment with sophorolipds. Improved flavin yield and electrogenicity production was achieved by treatment with dimethyl-diaminobenzene. Bioelectricity production using metabolically-enhanced electrogens was carried out in a modified MFC and optimum yields were achieved using a consortium of all electrogens exposed to metabolic enhancements. Measurements of electrochemical potential showed improved electrogenicity in metabolically-enhanced consortium compared to the unenhanced consortium. Using eight MFCs in series, OCV value of 5000 mV was achieved, while parallel connections yielded increased current up to 6000 mA/m2. Electron microscopy showed well-developed biofilms formed by metabolically-enhanced consortium. EPS from consortium biofilm were also characterized using fourier transform-infrared (FT-IR) spectroscopy.