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Abstract Idiopathic Nephrotic Syndrome (INS) is a common childhood glomerular disease requiring intense immunosuppressive drug treatments. Prediction of treatment response and the occurrence of relapses remains challenging. Biofluid-derived extracellular vesicles (EVs) may serve as novel liquid biopsies for INS classification and monitoring. Our cohort was composed of 105 INS children at different clinical time points (onset, relapse, and persistent proteinuria, remission, respectively), and 19 healthy controls. The expression of 37 surface EV surface markers was evaluated by flow cytometry in serum (n = 83) and urine (n = 74) from INS children (mean age = 10.1, 58% males) at different time points. Urine EVs (n = 7) and serum EVs (n = 11) from age-matched healthy children (mean age = 7.8, 94% males) were also analyzed. Tetraspanin expression in urine EVs was enhanced during active disease phase in respect to the remission group and positively correlates with proteinuria levels. Unsupervised clustering analysis identified an INS signature of 8 markers related to immunity and angiogenesis/adhesion processes. The CD41b, CD29, and CD105 showed the best diagnostic scores separating the INS active phase from the healthy condition. Interestingly, combining urinary and serum EV markers from the same patient improved the precision of clinical staging separation. Three urinary biomarkers (CD19, CD44, and CD8) were able to classify INS based on steroid sensitivity. Biofluid EVs offer a non-invasive tool for INS clinical subclassification and “personalized” interventions.

Abstract This study combines volcanic gas compositions, SO2 flux and satellite thermal data collected at Nevado del Ruiz between 2018 and 2021. We find the Nevado del Ruiz plume to have exhibited relatively steady, high CO2 compositions (avg. CO2/ST ratios of 5.4 ± 1.9) throughout. Our degassing models support that the CO2/ST ratio variability derives from volatile exsolution from andesitic magma stored in the 1–4 km depth range. Separate ascent of CO2-rich gas bubbles through shallow (

BackgroundWe performed a transcriptomic analysis of adrenal signaling pathways in various forms of endogenous Cushing’s syndrome (CS) to define areas of dysregulated and druggable targets.MethodologyNext-generation sequencing was performed on adrenal samples of patients with primary bilateral macronodular adrenal hyperplasia (PBMAH, n=10) and control adrenal samples (n=8). The validation groups included cortisol-producing adenoma (CPA, n=9) and samples from patients undergoing bilateral adrenalectomy for Cushing’s disease (BADX-CD, n=8). In vivo findings were further characterized using three adrenocortical cell-lines (NCI-H295R, CU-ACC2, MUC1).ResultsPathway mapping based on significant expression patterns identified PPARG (peroxisome proliferator-activated receptor gamma) pathway as the top hit. Quantitative PCR (QPCR) confirmed that PPARG (l2fc

The worldwide decline of macroalgal forests is raising major concerns for the potentially negative consequences on biodiversity and ecosystem functions, pushing for the definition of specific conservation and restoration measures. Protecting and restoring these habitats requires detailed information on their distribution, ecological status, and drivers of decline. Here, we provide the most updated available information on the distribution of Mediterranean Cystoseira s.l. forests by conducting a comprehensive bibliographic survey of literature published from 2009 to 2021, complemented by unpublished data. We also provide insights into the ecological status of these forests and the stressors affecting them across the Mediterranean basin. Our results show that most Mediterranean coasts remain un(der)studied and that the available information is concentrated in spatially limited coastal areas, restricted to very few species. When the ecological status is reported, data is highly heterogeneous, making any comparisons problematic, what claims for the description and use of easy and standardized monitoring methods for comparative purposes. Drivers of decline of Cystoseira s.l. forest have been even less investigated and, therefore, still poorly characterized. Our results highlight that our current knowledge is still insufficient to implement effective conservation and restoration strategies at the basin scale but also regionally. We call for the urgent need for mapping and standardized monitoring of Cystoseira s.l. forests to obtain baseline information for future management strategies involving their conservation, the mitigation of the stressors threatening them and the restoration of the degraded forests.

BACKGROUND: Venous thromboembolism is a dreaded complication of hospitalised patients, with associated morbidity, mortality and increased healthcare costs. Previous studies have shown that pharmacological thromboprophylaxis, though effective, is inadequately administered in a large proportion of medical inpatients. STUDY AIMS: Our primary aim was to evaluate the contemporary adequacy of thromboprophylaxis in medical inpatients admitted to two Swiss hospitals (a university hospital and a regional hospital). The secondary aim was to estimate the 90-day incidence of relevant thrombotic and bleeding events. METHODS: In this prospective cohort, patients were recruited at the University Hospital of Geneva and the Regional Hospital of Lugano between September 2020 and February 2021 and followed for 90 days for venous thromboembolism and bleeding events. The adequacy of thromboprophylaxis (pharmacological and/or mechanical) at 24h after hospital admission was evaluated according to the simplified Geneva risk score for hospital-associated venous thromboembolism. RESULTS: Among 200 participants (100 at each site, mean age of 65 years), 57.5% were deemed at high risk of venous thromboembolism at admission. Thromboprophylaxis was adequate in 59.5% (95% CI 52.3–66.4%). Among high-risk and low-risk inpatients, thromboprophylaxis was adequate in 71.3% and 43.5%, respectively, with differences between sites. At 90 days, risks of adjudicated venous thromboembolism, major bleeding and mortality were 1.5%, 1.5% and 6.0%, respectively. CONCLUSION: Despite the extensive literature on thromboprophylaxis, the adequacy of thromboprophylaxis has not improved and remains insufficient among medical inpatients. Implementation and evaluation of clinical decision support systems are critically needed in this field. clinicaltrials.gov number: NCT05306821

Invasive species are a leading cause of biodiversity loss and species extinctions across ecosystems on a global scale. The historical and ongoing focus on single-species management of invasive species and species at risk contributes to inefficiencies in management strategies that present an obstacle to achieving desired outcomes. A holistic approach that consolidates and maps linkages between the broader collective of invasive species and species at risk in an area provides a more appropriate entry point for issue-based, rather than species-based, management planning. We present a case study of this approach from British Columbia, Canada, which synthesized the identity, mechanisms of impact, mechanisms of spread, and magnitude of impacts across 782 unique pairs of invasive species and federally listed species at risk, based on a literature review of species at risk documentation. The resulting dataset was used to summarize the nature of interactions across species pairs and taxonomic groups to help guide the development of invasive species response strategies that make the best use of limited management resources. As species invasions and extinctions become increasingly interconnected, holistic approaches rooted in cumulative effects assessment and ecosystem-based management can provide a stronger foundation for reducing or mitigating this growing threat.

Substantial volume and compositional changes in gas emissions from fumaroles on Vulcano island in late 2021 may reflect the degassing of fresh mafic magma, according to in situ and remote sensing measurements of gas emissions coupled with numerical modelling

Data from 6000 geothermal areas worldwide are analyzed with a machine learning approach. The analysis suggests and confirms a dominant role of the terrestrial heat flow, topography, volcanism and extensional tectonics.

Albeit inhalation therapy is the cornerstone in chronic obstructive pulmonary disease (COPD) treatment, inhaler technique is rarely evaluated, and training materials are often insufficient. In this single-center study, we aimed to evaluate the effectiveness of a teaching session complemented by a flyer on inhaler technique in COPD patients and to evaluate the perceived quality of the flyer. A total of 30 participants with stable COPD who had never used a soft mist inhaler before (Respimat®, Boehringer Ingelheim) received a brief teaching session on proper inhaler technique complemented by a flyer (visit 1). The teaching intervention was completed by a pulmonologist. Epidemiological and clinical characteristics of COPD were collected by a questionnaire, and the ability to properly handle the inhaler was assessed. After 14 days, inhaler handling was re-evaluated, and patients were asked to rate the flyer (visit 2). After the initial training, proper inhaler handling was achieved in 80.0% of patients. Inhaler proficiency was maintained after 14 days (83.0% of the patients used the Respimat® correctly, p-value > 0.99). The flyer was considered at least good by 27 patients (90.0%). This study indicated that the administration of an educational intervention resulted in persistent good competence in inhaler technique at a 14-day follow-up.

Background: Most patients with testicular germ cell tumors (GCTs) are treated with cisplatin (CP)-based chemotherapy. However, some of them may develop CP resistance and therefore represent a clinical challenge. Cyclin-dependent kinase 5 (CDK5) is involved in chemotherapy resistance in different types of cancer. Here, we investigated the possible role of CDK5 and other CDKs targeted by dinaciclib in nonseminoma cell models (both CP-sensitive and CP-resistant), evaluating the potential of the CDK inhibitor dinaciclib as a single/combined agent for the treatment of advanced/metastatic testicular cancer (TC). Methods: The effects of dinaciclib and CP on sensitive and resistant NT2/D1 and NCCIT cell viability and proliferation were evaluated using MTT assays and direct count methods. Flow cytometry cell-cycle analysis was performed. The protein expression was assessed via Western blotting. The in vivo experiments were conducted in zebrafish embryos xenografted with TC cells. Results: Among all the CDKs analyzed, CDK5 protein expression was significantly higher in CP-resistant models. Dinaciclib reduced the cell viability and proliferation in each cell model, inducing changes in cell-cycle distribution. In drug combination experiments, dinaciclib enhances the CP effect both in vitro and in the zebrafish model. Conclusions: Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP.

Epstein–Barr (EBV) is a human γ-herpesvirus that undergoes both a productive (lytic) cycle and a non-productive (latent) phase. The virus establishes enduring latent infection in B lymphocytes and productive infection in the oral mucosal epithelium. Like other herpesviruses, EBV expresses its genes in a coordinated pattern during acute infection. Unlike others, it replicates its DNA during latency to maintain the viral genome in an expanding pool of B lymphocytes, which are stimulated to divide upon infection. The reactivation from the latent state is associated with a productive gene expression pattern mediated by virus-encoded transcriptional activators BZLF-1 and BRLF-1. EBV is a highly transforming virus that contributes to the development of human lymphomas. Though viral vectors and mRNA platforms have been used to develop an EBV prophylactic vaccine, currently, there are no vaccines or antiviral drugs for the prophylaxis or treatment of EBV infection and EBV-associated cancers. Natural products and bioactive compounds are widely studied for their antiviral potential and capability to modulate intracellular signaling pathways. This review was intended to collect information on plant-derived products showing their antiviral activity against EBV and evaluate their feasibility as an alternative or adjuvant therapy against EBV infections and correlated oncogenesis in humans.

Abstract Background and objectives Children with multi-drug resistant idiopathic nephrotic syndrome (MDR-INS) usually progress to end-stage kidney disease with a consistent risk of disease recurrence after transplantation. New therapeutic options are needed for these patients. Mesenchymal stromal cells (MSCs) are multipotential non-hematopoietic cells with several immunomodulatory properties and growing clinical applications. Cord blood-derived MSC have peculiar anti-inflammatory and immunosuppressive properties. We aimed at assessing safety and efficacy of cord-blood-derived MSCs (CB-MSCs) in children with MDR-INS. Design, setting, participants Prospective, open-label, single arm phase I–II pilot study. Pediatric patients with MDR-INS, resistant to at least two lines of therapy, were enrolled. Allogenic CB-MSCs were administered intravenously on days 0, 14, and 21 at a dose of 1.5 × 106 cells/kg. Patients were followed for at least 12 months. The primary outcomes were safety and toxicity. The secondary outcome was remission at 12 months evaluated by urinary protein/urinary creatinine ratio (uPr/uCr). Circulating regulatory T cells (Tregs) were monitored. Results Eleven pediatric patients with MDR-INS (10 females, median age 13 years) resistant to a median of 3 previous lines of therapy were enrolled. All patients completed the CB-MSC infusion schedule. No patient experienced any infusion-related adverse event or toxicity. Nine patients were assessable for efficacy. At the 12 months follow-up after the treatment, the median uPr/uCr did not change significantly from baseline (8.13 vs. 9.07; p = 0.98), while 3 patients were in partial or complete remission. A lower baseline uPr/uCr was a predictor of remission (2.55 vs. 8.74; p = 0.0238). Tregs count was not associated with CB-MSCs therapy. Conclusions CB-MSCs are safe and may have a role in the immunosuppressive therapy of pediatric patients with MDR-INS. This preliminary experience paves the way toward further phase II studies addressing MSC efficacy in immune-mediated kidney diseases.

Abstract All over the world, SARS-CoV-2 pneumonia is causing a significant short and medium-term morbidity and mortality, with reported persisting symptoms, radiological and lung alterations up to 6 months after symptoms onset. Nevertheless, the 1-year impact on affected patients is still poorly known. In this prospective observational study, 39 patients with SARS-CoV-2 pneumonia were recruited from a single COVID-19 hospital in Southern Switzerland. They underwent a 3-month and 1-year follow-ups. At 1 year, 38 patients underwent functional follow-up through lung function tests and six minutes walking test and submitted SF-12 and SGRQ questionnaires about health-related quality of life. At 1 year most of the patients showed a persistence of the radiological and functional abnormalities and a reduction of the health-related quality of life. Thirty patients (96.8%) still presented some residual abnormalities on CT scans (31 patients at 3 months), though with a general reduction of the lesional load in all lung lobes. Twenty patients (52.6%) had persisting lung function tests impairment, with an overall improvement of DLCO. As concerning the functional status, lowest SpO2 during 6MWT increased significantly. Finally, 19 patients (50%) reported a pathological St. George’s Respiratory Questionnaire, and respectively 12 (31.6%) and 11 (28.9%) patients a pathological Short Form Survey-12 in physical and mental components. At 1-year follow-up SARS-CoV-2 pneumonia survivors still present a substantial impairment in radiological and functional findings and in health-related quality of life, despite showing a progressive recovery.

The Symani surgical system undergoes scrutiny in this study as part of a series of preclinical investigations. Previous studies compared the precision of robotic-assisted anastomoses with manual techniques. This study aimed to evaluate the critical, histological, and gross parameters at the site of anastomosis and at distant sites in a rat model to provide insights into the safety and efficacy of robotic-assisted microsurgery to enhance its potential for clinical adoption. Experienced microsurgeons performed arterial and venous anastomoses in 16 Wistar rats, randomized into four treatment groups: robotic artery, robotic vein, manual artery, and manual vein. Various parameters were evaluated at two time points (T0 and T30) on the day of the procedure and at Day 28 (T28d). In the second phase of the study, the animals underwent necropsy, histopathologic analysis, micro-CT scans, and angiography imaging of the anastomosis sites, major organs, and distant target organs by a blinded assessor. Patency rates were 100% at T0 and T30 for all anastomoses and stayed at 100% on T28d for the robotic subgroups; however, it decreased to 87.5% for manual arterial anastomoses owing to a case of obstructive thrombus. No evidence of clot migration was observed. Blood flow parameters and procedure times did not differ significantly. The blinded semiquantitative histological analysis revealed no significant disparities between the robotic and manual anastomoses across various pathological indicators. No gross abnormalities were detected in musculoskeletal examinations. This preclinical study demonstrated the safety of the Symani surgical system. Results suggest equivalence between robotic and manual techniques regarding thrombus formation at the anastomotic site and distal organs. [ABSTRACT FROM AUTHOR]

Background: Reverse transcription polymerase chain reaction (RT-PCR) is the current standard of reference in the diagnosis of SARS-CoV-2 infection. In outpatient clinical practice, nasopharyngeal swab RT-PCR testing is still the most common procedure. The purpose of this systematic review and meta-analysis was to evaluate the sensitivity of RT-PCR nasopharyngeal assays. Methods: We searched three databases, including PubMed/MEDLINE, EMBASE, and Cochrane Library, using a comprehensive strategy. Studies investigating the sensitivity of SARS-CoV-2 RT-PCR nasopharyngeal assays in adults were included. Two reviewers extracted data and assessed trial quality independently. Pooled sensitivity and its confidence interval were computed using the meta package in R. Results: Thirteen studies were found eligible for the inclusion in the systematic review. Out of these, 25 different sub-studies were identified and included in the meta-analysis, which reported the sensitivities of 25 different nasopharyngeal RT-PCR assays. Finally, the overall pooled sensitivity resulted 89% (95% CI, 85.4 to 91.8%). Conclusion: Our study suggests that RT-PCR assays on nasopharyngeal specimens have a substantial sensitivity for diagnosing SARS-CoV-2 infection.

ObjectivesMonitoring of SARS-CoV-2 spread and vaccination strategies have relied on antibody (Ab) status as a correlate of protection. We used QuantiFERON™ (QFN) and Activation-Induced Marker (AIM) assays to measure memory T-cell reactivity in unvaccinated individuals with prior documented symptomatic infection (late convalescents) and fully vaccinated asymptomatic donors (vaccinees).MethodsTwenty-two convalescents and 13 vaccinees were enrolled. Serum anti-SARS-CoV-2 S1 and N Abs were measured using chemiluminescent immunoassays. QFN was performed following instructions and interferon-gamma (IFN-γ) measured by ELISA. AIM was performed on aliquots of antigen-stimulated samples from QFN tubes. SARS-CoV-2-specific memory CD4+CD25+CD134+, CD4+CD69+CD137+ and CD8+CD69+CD137+ T-cell frequencies were measured by flow cytometry.ResultsIn convalescents, substantial agreement was observed between QFN and AIM assays. IFN-γ concentrations and AIM+ (CD69+CD137+) CD4+ T-cell frequencies correlated with each other, with Ab levels and AIM+ CD8+ T-cell frequencies, whereas AIM+ (CD25+CD134+) CD4+ T-cell frequencies correlated with age. AIM+ CD4+ T-cell frequencies increased with time since infection, whereas AIM+ CD8+ T-cell expansion was greater after recent reinfection. QFN-reactivity and anti-S1 titers were lower, whereas anti-N titers were higher, and no statistical difference in AIM-reactivity and Ab positivity emerged compared to vaccinees.ConclusionsAlbeit on a limited sample size, we confirm that coordinated, cellular and humoral responses are detectable in convalescents up to 2 years after prior infection. Combining QFN with AIM may enhance detection of naturally acquired memory responses and help stratify virus-exposed individuals in T helper 1-type (TH1)-reactive (QFNpos AIMpos Abshigh), non-TH1-reactive (QFNneg AIMpos Abshigh/low), and pauci-reactive (QFNneg AIMneg Abslow).

Improving volcanic gas monitoring techniques is central to better understanding open-vent, persistently degassing volcanoes. SO2 cameras are increasingly used in volcanic gas studies, but observations are commonly limited to one single camera alone viewing the volcanic plume from a specific viewing direction. Here, we report on high frequency (0.5 Hz) systematic measurements of the SO2 flux at Stromboli, covering a 1-year long observation period (June 2017-June 2018), obtained from two permanent SO2 cameras using the same automated algorithm, but imaging the plume from two different viewing directions. Our aim is to experimentally validate the robustness of automatic SO2 camera for volcano monitoring and to demonstrate the advantage of using two co-exposed SO2 camera stations to better capturing degassing dynamics at open-vent volcanoes. The SO2 flux time-series derived from the two SO2 camera stations exhibit good match, demonstrating the robustness of the automatic SO2 camera method. Our high-temporal resolution SO2 records resolve individual Strombolian explosions as transient, repetitive gas bursts produced by the sudden release of over pressurized gas pockets and scoriae. Calculations show that explosive degassing activity accounts for ∼10% of the total SO2 emission budget (dominated by passive degassing) during mild regular open-vent activity. We show that the temporal variations of the explosive SO2 flux go in tandem with changes in total SO2 flux and VLP seismicity, implicating some commonality in the source processes controlling passive degassing and explosive activity. We exploited the spatial resolution of SO2 camera to discriminate degassing at two distinct regions of the crater area, and to minimize biases due by the station position respect to the target plume. We find that the SO2 fluxes from southwest-central (SWCC) and northeast (NEC) crater areas oscillate coherently but those from the NEC are more sensitive to the changes in the volcanic intensity. We interpret this as due to preferential gas/magma channeling into the structurally weaker north-eastern portion of the crater terrace in response to increasing supply rate of buoyant, bubble-rich magma in the shallow plumbing system.

The search for alternative clinical treatments to fight resistance and find alternative antiviral treatments for the herpes simplex virus (HSV) is of great interest. Plants are rich sources of novel antiviral, pharmacologically active agents that provide several advantages, including reduced side effects, less resistance, low toxicity, and different mechanisms of action. In the present work, the antiviral activity of Californian natural raw (NRRE) and roasted unsalted (RURE) pistachio polyphenols-rich extracts was evaluated against HSV-1 using VERO cells. Two different extraction methods, with or without n-hexane, were used. Results showed that n-hexane-extracted NRRE and RURE exerted an antiviral effect against HSV-1, blocking virus binding on the cell surface, affecting viral DNA synthesis as well as accumulation of ICP0, UL42, and Us11 viral proteins. Additionally, the identification and quantification of phenolic compounds by RP-HPLC-DAD confirmed that extraction with n-hexane exclusively accumulated tocopherols, carotenoids, and xanthophylls. Amongst these, zeaxanthin exhibited strong antiviral activity against HSV-1 (CC50: 16.1 µM, EC50 4.08 µM, SI 3.96), affecting both the viral attachment and penetration and viral DNA synthesis. Zeaxanthin is a dietary carotenoid that accumulates in the retina as a macular pigment. The use of pistachio extracts and derivates should be encouraged for the topical treatment of ocular herpetic infections.

Abstract Background All over the world, SARS-CoV-2 pneumonia is causing a significant short-term morbidity and mortality, but the medium-term impact on lung function and quality of life of affected patients are still unknown. Methods In this prospective observational study, 39 patients with SARS-CoV-2 pneumonia were recruited from a single COVID-19 hospital in Southern Switzerland. At three months patients underwent radiological and functional follow-up through CT scan, lung function tests, and 6 min walking test. Furthermore, quality of life was assessed through self-reported questionnaires. Results Among 39 patients with SARS-CoV-2 pneumonia, 32 (82% of all participants) presented abnormalities in CT scan and 25 (64.1%) had lung function tests impairment at three months. Moreover, 31 patients (79.5%) reported a perception of poor health due to respiratory symptoms and all 39 patients showed an overall decreased quality of life. Conclusions Medium-term follow up at three months of patients diagnosed with SARS-CoV-2 pneumonia shows the persistence of abnormalities in CT scans, a significant functional impairment assessed by lung function tests and a decreased quality of life in affected patients. Further studies evaluating the long-term impact are warranted to guarantee an appropriate follow-up to patients recovering from SARS-CoV-2 pneumonia.

Fumarolic gas survey of dormant volcanoes in hydrothermal activity is crucial to detect compositional and mass flux changes in gas emissions that are potential precursors of violent phreatic or even magmatic eruptions. Here we report on new data for the chemical compositions (CO2, H2S, SO2) and fluxes of fumarolic gas emissions (97–104°C) from La Soufrière volcano in Guadeloupe (Lesser Antilles) obtained from both mobile MultiGas measurements and permanent MultiGas survey. This paper covers the period 2016–2020, encompassing a period of enhanced hydrothermal unrest including an abrupt seismic energy release (M 4.1) on April 27, 2018. Our dataset reveals fumarolic CO2/H2S and SO2/H2S gas trends correlated to the evolution of surface activity and to other geochemical and geophysical parameters. We demonstrate that, even under tropical conditions (high humidity and rainfall), MultiGas surveys of low-T fumarolic emissions permit to distinguish deeply sourced signals of volcanic unrest from secondary changes in degassing due to shallow forcing processes such as water-gas-rock interactions in the hydrothermal system and meteorological effects.

We study the dependence of fragmentation in massive gas-rich galaxy disks at$z > 1$ on feedback model and hydrodynamical method, employing the GASOLINE2SPH code and the lagrangian mesh-less code GIZMO in finite mass mode. Wecompare non-cosmological galaxy disk runs with standard blastwave supernovae(SN)feedback, which introduces delayed cooling in order to drive winds, andruns with the new superbubble SN feedback, which produces winds naturally bymodelling the detailed physics of SN-driven bubbles and leads to efficientself-regulation of star formation. We find that, with blastwave feedback,massive star forming clumps form in comparable number and with very similarmasses in GASOLINE2 and GIZMO. The typical masses are in the range $10^7-10^8M_{\odot}$, lower than in most previous works, while giant clumps with massesabove $10^9 M_{\odot}$ are exceedingly rare. With superbubble feedback,instead, massive bound star forming clumps do not form because galaxies neverundergo a phase of violent disk instability. Only sporadic, unbound starforming overdensities lasting only a few tens of Myr can arise that aretriggered by perturbations of massive satellite companions. We conclude thatthere is a severe tension between explaining massive star forming clumpsobserved at $z > 1$ primarily as the result of disk fragmentation driven bygravitational instability and the prevailing view of feedback-regulated galaxyformation. The link between disk stability and star formation efficiency shouldthus be regarded as a key testing ground for galaxy formation theory.

Combining multiple ultraviolet cameras with synchronous aerial measurements, the authors here present vent-specific gas compositions and fluxes for Stromboli volcano. The results show that gas compositions vary between different vents, mirroring differences in eruptive behavior.

Acting on the cytokine cascade is key to preventing disease progression and death in hospitalised patients with COVID-19. Among anti-cytokine therapies, interleukin (IL)-6 inhibitors have been the most used and studied since the beginning of the pandemic. Going through previous observational studies, subsequent randomised controlled trials, and meta-analyses, we focused on the baseline characteristics of the patients recruited, identifying the most favourable features in the light of positive or negative study outcomes; taking into account the biological significance and predictivity of IL-6 and other biomarkers according to specific thresholds, we ultimately attempted to delineate precise windows for therapeutic intervention. By stimulating scavenger macrophages and T-cell responsivity, IL-6 seems protective against viral replication during asymptomatic infection; still protective on early tissue damage by modulating the release of granzymes and lymphokines in mild-moderate disease; importantly pathogenic in severe disease by inducing the proinflammatory activation of immune and endothelial cells (through trans-signalling and trans-presentation); and again protective in critical disease by exerting homeostatic roles for tissue repair (through cis-signalling), while IL-1 still drives hyperinflammation. IL-6 inhibitors, particularly anti-IL-6R monoclonal antibodies (e.g., tocilizumab, sarilumab), are effective in severe disease, characterised by baseline IL-6 concentrations ranging from 35 to 90 ng/mL (reached in the circulation within 6 days of hospital admission), a ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2) between 100 and 200 mmHg, requirement of high-flow oxygen or non-invasive ventilation, C-reactive protein levels between 120 and 160 mg/L, ferritin levels between 800 and 1600 ng/mL, D-dimer levels between 750 and 3000 ng/mL, and lactate dehydrogenase levels between 350 and 500 U/L. Granulocyte-macrophage colony-stimulating factor inhibitors might have similar windows of opportunity but different age preferences compared to IL-6 inhibitors (over or under 70 years old, respectively). Janus kinase inhibitors (e.g., baricitinib) may also be effective in moderate disease, whereas IL-1 inhibitors (e.g., anakinra) may also be effective in critical disease. Correct use of biologics based on therapeutic windows is essential for successful outcomes and could inform future new trials with more appropriate recruiting criteria.

The present study aims to assess the antioxidant and antiviral effectiveness of leaf extracts obtained from Olea europaea L. var. sativa and Olea europaea L. var. sylvestris. The total antioxidant activity was determined via both an ammonium phosphomolybdate assay and a nitric oxide radical inhibition assay. Both extracts showed reducing abilities in an in vitro system and in human HeLa cells. Indeed, after oxidative stress induction, we found that exposition to olive leaf extracts protects human HeLa cells from lipid peroxidation and increases the concentration of enzyme antioxidants such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase. Additionally, OESA treatment affects viral DNA accumulation more than OESY, probably due to the exclusive oleuropein content. In fact, subtoxic concentrations of oleuropein inhibit HSV-1 replication, stimulating the phosphorylation of PKR, c-FOS, and c-JUN proteins. These results provide new knowledge about the potential health benefits and mechanisms of action of oleuropein and oleuropein-rich extracts.