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Paola Galozzi, Sara Bindoli, Andrea Doria, Paolo Sfriso Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, ItalyCorrespondence: Paola Galozzi, Rheumatology Unit, Department of Medicine DIMED, University of Padova, via Giustiniani, 2, Padova, 35128, Italy, Tel +39 049 821 8654, Email paola.galozzi@unipd.itAbstract: Adult-onset Still’s disease (AOSD) is a rare multifactorial autoinflammatory disorder of unknown etiology, characterized by an excessive release of cytokines triggered by dysregulated inflammation and articular and systemic manifestations. The clinical spectrum of AOSD ranges from self-limiting forms with mild symptoms to life-threatening cases and presents clinical and biological similarities with the juvenile form (sJIA). Nowadays, the advances in biologic agents no longer limit the treatment to NSAIDs, glucocorticoids, or conventional synthetic DMARDs. The blockade of IL-1 and IL-6 is effective in the treatment of systemic and articular inflammation of AOSD patients; however, novel compounds with different properties and targets are now available and others are being studied. In this review, starting from the pathogenesis of AOSD, we summarized the current and emerging biological therapies, possible effective agents for achieving AOSD control and remission.Keywords: biologics, AOSD, IL-1 inhibitors, IL-6 inhibitors, small molecules, new treatment

This study investigates the biomass production and growth strategies of the relict seagrass Zostera marina, a species sensitive to high temperatures, within the Venice Lagoon (Italy). Monthly data collected from January to December 2019 and November 2020 to October 2021 in a single station in proximity of one lagoon port-entrance, along with seasonal data from 2018 and 2021 for the whole lagoon, were analyzed in conjunction with environmental parameters and macroalgal presence. The objective was to understand the impact of climate changes, particularly rising water temperatures, on the cover, standing crop and net primary production of Z. marina and the effect of the MoSE gate closures designed to protect Venice from high-water events. Despite expectations of a decline due to temperature increase and reduced water exchange, our findings reveal a notable adaptability of Z. marina, with increases in both cover and biomass. This resilience suggests that Z. marina can counteract environmental challenges, making this study relevant for broader ecological and conservation contexts beyond the Venice Lagoon.

Dopamine and histamine receptors D2R and H3R are G protein-coupled receptors (GPCRs) which can establish physical receptor–receptor interactions (RRIs), leading to homo/hetero-complexes in a dynamic equilibrium. Although D2R and H3R expression has been detected within the carotid body (CB), their possible heterodimerization has never been demonstrated. The aim of this work was to verify D2R and H3R colocalization in the CB, thus suggesting a possible interplay that, in turn, may be responsible of specific D2R–H3R antagonistic functional implications. The CBs of both Sprague–Dawley rats (n = 5) and human donors (n = 5) were dissected, and immunolocalization of D2R and H3R was performed; thereafter, in situ proximity ligation assay (PLA) was developed. According to experimental evidence (immunohistochemistry and double immunofluorescence), all the samples displayed positive D2R/H3R elements; hence, PLA assay followed by confocal microscopy analysis was positive for D2R–H3R RRIs. Additionally, D2R–H3R heterodimers were mainly detected in type I cells (βIII-tubulin-positive cells), but type II cells’ involvement cannot be excluded. RRIs may play a role in functional modulation of CB cells; investigating RRIs in the CB may guide toward the comprehension of its plastic changes and fine regulatory role while also unveiling their possible clinical implications.

Introduction: Chemodynamic therapy (CDT) holds great promise in achieving cancer therapy through Fenton and Fenton-like reactions, which generate highly toxic reactive species. However, CDT is limited by the lower amount of catalyst ions that can decompose already existing intracellular H2O2 and produce reactive oxygen species (ROS) to attain a therapeutic outcome. Objectives: To overcome these limitations, a tailored approach, which utilizes dual metals cations (Ag+, Fe2+) based silver pentacyanonitrosylferrate or silver nitroprusside (AgNP) were developed for Fenton like reactions that can specifically kill cancer cells by taking advantage of tumor acidic environment without used of any external stimuli. Methods: A simple solution mixing procedure was used to synthesize AgNP as CDT agent. AgNP were structurally and morphologically characterized, and it was observed that a minimal dose of AgNP is required to destroy cancer cells with limited effects on normal cells. Moreover, comprehensive in vitro studies were conducted to evaluate antitumoral mechanism. Results: AgNP have an effective ability to decompose endogenous H2O2 in cells. The decomposed endogenous H2O2 generates several different types of reactive species (•OH, O2•−) including peroxynitrite (ONOO−) species as apoptotic inducers that kill cancer cells, specifically. Cellular internalization data demonstrated that in short time, AgNP enters in lysosomes, avoid degradation and due to the acidic pH of lysosomes significantly generate high ROS levels. These data are further confirmed by the activation of different oxidative genes. Additionally, we demonstrated the biocompatibility of AgNP on mouse liver and ovarian organoids as an ex vivo model while AgNP showed the therapeutic efficacy on patient derived tumor organoids (PDTO). Conclusion: This work demonstrates the therapeutic application of silver nitroprusside as a multiple ROS generator utilizing Fenton like reaction. Thereby, our study exhibits a potential application of CDT against HGSOC (High Grade Serous Ovarian Cancer), a deadly cancer through altering the redox homeostasis.

The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-to-pregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal anti-inflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns.

ObjectiveInflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF.MethodsThe risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still’s disease patients and Behçet’s disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression.Results580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet’s disease patients and 497 Still’s disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still’s disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet’s disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5, p=0.002).ConclusionsThe risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

The changes in macrophyte biodiversity and cover from the soft bottoms of 87 stations spread in the entire Venice Lagoon in 2011, 2014, 2018 and 2021 have been analyzed. Results showed a strong macrophyte resilience with an increase in the spread of sensitive macroalgae and aquatic angiosperms, especially Z. noltei and R. cirrhosa, which were not affected by the increase of non-indigenous species (NIS) introduction.The simultaneous analysis of macrophyte variables and the main water and sediment parameters carried out in 2021 highlighted the key role of water transparency and salinity to regulate the vegetation, especially the presence/absence of aquatic angiosperms and sensitive macroalgae. Vice versa, high chlorophyll-a, total suspended solids, nitrogen and silicate concentrations in the water column, and high moisture, low grain-size and phosphorus concentrations in surface sediments favored the presence of opportunistic species, especially Ulva rigida, Gracilariopsis longissima, Agardhiella subulata and Solieria filiformis. The distribution of the aquatic angiosperms and the 41 most widespread macroalgae in association with the main environmental parameters allowed us to highlight their different ecological value, their possible presence/absence and abundance; indeed, their spatial and temporal changes can be excellent tools to determine and predict the ecological status of transitional water systems (TWS).These results carried out in a polyhedric basin such as the Venice Lagoon, composed by a complex of very different microhabitats, can be considered representative of most environmental conditions present in the main TWS of the Italian coastline, and spatial and temporal macrophyte changes can be excellent tools to determine and predict their ecological status evolution.

Blau syndrome (BS) is a rare autoinflammatory granulomatosis characterized by granulomatous arthritis, uveitis, and dermatitis. Ocular complications are particularly severe in BS, significantly contributing to morbidity. This study aims to identify potential biomarkers for BS ocular degeneration through proteomic profiling of tear samples from affected patients. Seven subjects from the same family, including four carriers of the BS-associated NOD2 mutation (p.E383K), were recruited alongside healthy controls. Tear samples were collected using Schirmer strips and analyzed via mass spectrometry. A total of 387 proteins were identified, with significant differences in protein expression between BS patients, healthy familial subjects, and healthy controls. Key findings include the overexpression of alpha-2-macroglobulin (A2M) and immunoglobulin heavy constant gamma 4 (IGHG4) in BS patients. Bioinformatic analysis revealed that differentially expressed proteins are involved in acute-phase response, extracellular exosome formation, and protein binding. Notably, neutrophils’ azurophilic granule components, as azurocidin (AZU1), myeloperoxidases (MPO), and defensins (DEFA3), were highly expressed in the most severely affected subject, suggesting a potential role of neutrophils in BS ocular severity. These proteins might be promising biomarkers for ocular involvement in BS, facilitating early detection and tailored treatment strategies.

Seagrasses play a vital role in marine ecosystems worldwide. However, until recently these ecosystems were experiencing declines due to various global and local threats. In response to this issue, initiatives have been launched to combat seagrass loss by addressing local and regional major stressors and actively engaging in restoration efforts by transplantation. Although seagrass restoration has progressed significantly with the development of numerous transplant techniques, these are not always crowned with success. This is often due to the fact that the environmental parameters of water, sediment and biota of the recipient sites are not carefully considered in their suitability for transplantation. In this study, the multi-year experiences and data from numerous environmental surveys in transitional water systems have been condensed to define limit values for the ideal growth conditions and the extreme values in which the survival of four aquatic angiosperm species is possible: Cymodocea nodosa, Zostera marina, Zostera noltei and Ruppia cirrhosa. Approaches to transplants, seasonality and critical issues have been explored. The identified limits and parameters of water, sediment and biota will help to define the suitability of a recipient site for the rooting of seagrasses, increasing the chances of success for transplant operations.

Chronic coronary syndrome (CCS) is one of the leading cardiovascular causes of morbidity, mortality, and use of medical resources. After the introduction by international guidelines of the same level of recommendation to non-invasive imaging techniques in CCS evaluation, a large debate arose about the dilemma of choosing anatomical (with coronary computed tomography angiography (CCTA)) or functional imaging (with stress echocardiography (SE), cardiovascular magnetic resonance (CMR), or nuclear imaging techniques) as a first diagnostic evaluation. The determinant role of the atherosclerotic burden in defining cardiovascular risk and prognosis more than myocardial inducible ischemia has progressively increased the use of a first anatomical evaluation with CCTA in a wide range of pre-test probability in CCS patients. Functional testing holds importance, both because the role of revascularization in symptomatic patients with proven ischemia is well defined and because functional imaging, particularly with stress cardiac magnetic resonance (s-CMR), gives further prognostic information regarding LV function, detection of myocardial viability, and tissue characterization. Emerging techniques such as stress computed tomography perfusion (s-CTP) and fractional flow reserve derived from CT (FFRCT), combining anatomical and functional evaluation, appear capable of addressing the need for a single non-invasive examination, especially in patients with high risk or previous revascularization. Furthermore, CCTA in peri-procedural planning is promising to acquire greater importance in the non-invasive planning and guiding of complex coronary revascularization procedures, both by defining the correct strategy of interventional procedure and by improving patient selection. This review explores the different roles of non-invasive imaging techniques in managing CCS patients, also providing insights into preoperative planning for percutaneous or surgical myocardial revascularization.

IntroductionThe effectiveness of canakinumab may change according to the different times it is used after Still’s disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment.MethodsPatients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still’s disease. Seventy-seven (51 females and 26 males) patients with Still’s disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent.ResultsNo statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment.ConclusionCanakinumab has proved to be effective in patients with Still’s disease, regardless of its line of biologic treatment.

Objective Still’s disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still’s disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still’s disease.Methods Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still’s disease.Results A total of 411 patients suffering from Still’s disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still’s disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p

Background Different patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still’s disease. Thus, we aimed at deriving and validating disease clusters in a multicentre, observational, prospective study to stratify these patients.Methods Patients included in GIRRCS AOSD-study group and AIDA Network Still Disease Registry were assessed if variables for cluster analysis were available (age, systemic score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and ferritin). K-means algorithm with Euclidean metric and Elbow plot were used to derive an adequate number of clusters.Results K-means clustering assessment provided four clusters based on means standardised according to z-scores on 349 patients. All clusters mainly presented fever, skin rash and joint involvement. Cluster 1 was composed by 115 patients distinguished by lower values of age and characterised by skin rash myalgia, sore throat and splenomegaly. Cluster 2 included 128 patients identified by lower levels of ESR, ferritin and systemic score; multiorgan manifestations were less frequently observed. Cluster 3 comprised 31 patients categorised by higher levels of CRP and ferritin, they were characterised by fever and joint involvement. Cluster 4 contained 75 patients derived by higher values of age and systemic score. Myalgia, sore throat, liver involvement and life-threatening complications, leading to a high mortality rate, were observed in these patients.Conclusions Four patient clusters in Still’s disease may be recognised by a multidimensional characterisation (‘Juvenile/Transitional’, ‘Uncomplicated’, ‘Hyperferritinemic’ and ‘Catastrophic’). Of interest, cluster 4 was burdened by an increased rate of life-threatening complications and mortality, suggesting a more severe patient group.

Abstract Undifferentiated connective tissue diseases (UCTDs) are clinical entities characterised by signs and symptoms suggestive of a systemic autoimmune disease, which do not fulfil the diagnostic criteria for a defined connective tissue disease. Lung involvement can complicate the course and management of the disease, often determining a worse outcome. Respiratory dysfunction as the first clinical manifestation has seldom been reported. We describe a case of a female patient who developed significant respiratory dysfunction as the principal clinical sign. Video-assisted thoracoscopy was performed and a histological pattern of nonspecific interstitial pneumonia (NSIP) was found. A pathological diagnosis suggested careful follow-up with extensive immunological screening which then detected Raynaud's phenomenon and positivity of antinuclear antibodies. After a multidisciplinary discussion (pneumologist, radiologist, pathologist and rheumatologist) a final diagnosis of NSIP associated with UCTD was made. The diagnosis of UCTD should be considered when NSIP is diagnosed even in cases with evident first clinical manifestations of severe respiratory dysfunction. A multidisciplinary approach in the field of interstitial lung disease with NSIP, also including rheumatologic expertise, is fundamental to achieve a prompt and correct diagnosis.

The Mar Piccolo of Taranto (southern Italy, Mediterranean Sea), a site of the European LTER network, is a transitional water system, where a century-old intensive mussel farming activity has been carried out, together with an intense import-export business of bivalve mollusks. Previous studies showed that this basin is third for NIS seaweed introduction in the Mediterranean Sea, after the Thau Lagoon and the Venice Lagoon. The present paper deals with the results of 11-year monitoring activity on non-indigenous species (NIS) of seaweeds, which was performed in the Mar Piccolo. In the studied period (2011–2021), two different time frames (i.e., 2011–2015 and 2016–2021) were considered, since they were based on a different number of sampling sites. To investigate spatial and temporal differences in the seaweed assemblage, a multivariate analysis was performed considering the NIS and the most important native species in terms of temporal occurrence. Fourteen NIS were recorded in total in the Mar Piccolo of Taranto during this period, with variable abundances among sites and years: nine species in the first time period, and thirteen species in the second one. Caulerpa cylindracea, recorded with negligible biomass in the first period, was absent in the second-period samplings. Molecular analyses confirmed the taxonomy of three species (i.e., Grateloupia minima, Neopyropia koreana, and Polysiphonia morrowii), previously identified only through morphological features. The most abundant species was Hypnea corona, which almost doubled its biomass in the second time period compared to the first one. Three species (i.e., Caulacanthus okamurae, G. minima, and P. morrowii) increased their biomass by an order of magnitude in the second time period. No significant differences were found over years. Site 1 resulted in significant differences among the sites and different seasonal pattern occurred among the investigated sites. No significant long-term changes occurred in the seaweed assemblages, suggesting the absence of strong disturbances due to the settlement of NIS.

Gout is caused by the deposition of monosodium urate crystals in the joint and represents the most common form of inflammatory arthritis in men. Its prevalence is rising worldwide mainly due to the increase of risk factors associated with the disease, in particular hyperuricemia. Besides gout, hyperuricemia leads to an increased inflammatory state of the body with consequent increased risk of comorbidities such as cardiovascular diseases. Increasing evidence shows that bioactive compounds have a significant role in fighting inflammatory and immune chronic conditions. In gout and hyperuricemia, these molecules can exert their effects at two levels. They can either decrease serum uric acid concentrations or fight inflammation associated with monosodium urate crystals deposits and hyperuricemia. In this view, they might be considered valuable support to the pharmacological therapy and prevention of the disease. This review aims to provide an overview of the beneficial role of bioactive compounds in hyperuricemia, gout development, and inflammatory pathways of the disease.

Programmed cell death 1 ligand 1 (PD-L1) expressed in non-immune cells is involved in immune-mediated tissue damage in the context of inflammatory conditions and tumor immune escape. Emerging evidence suggests soluble (s)PD-L1 as a marker of inflammation. Based on well-established sex-specific differences in immunity, we tested the novel hypotheses that (i) endothelial cell PD-L1 is modulated by inflammatory cytokines and vascular endothelial growth factor (VEGF) in a sex-specific fashion, and (ii) the endothelium is a source of sPD-L1. After exposure of human umbilical vein endothelial cells (HUVECs) to lipopolysaccharide, interleukin (IL)1β or VEGF for 24 h, total PD-L1 levels were upregulated solely in cells from female donors, while being unchanged in those from male donors. Accordingly, exposure to synovial fluids from patients with inflammatory arthritis upregulated PD-L1 levels in HUVECs from female donors only. Membrane PD-L1 expression as measured by flow cytometry was unchanged in response to inflammatory stimuli. However, exposure to 2 ng/mL IL-1β or 50 ng/mL VEGF time-dependently increased sPD-L1 release by HUVECs from female donors. Treatment with the metalloproteinase (MMP) inhibitor GM6001 (10 μM) prevented IL-1β-induced sPD-L1 release and enhanced membrane PD-L1 levels. The anti-VEGF agents bevacizumab and sunitinib reduced both VEGF-induced PD-L1 accumulation and sPD-L1 secretion. Thus, inflammatory agents and VEGF rapidly increased endothelial PD-L1 levels in a sex-specific fashion. Furthermore, the vascular endothelium may be a sPD-L1 source, whose production is MMP-dependent and modulated by anti-VEGF agents. These findings may have implications for sex-specific immunity, vascular inflammation and response to anti-angiogenic therapy.

We studied the ecological and functional aspects (such as role in sediment characteristics and plant–animal interactions) of a Ruppia cirrhosa (Petagna) Grande meadow during its vegetative season in the choked Valle Campo lagoon, a sub-basin of the wider Valli di Comacchio, on the Northern Adriatic coast. Sampling campaigns were carried out with a roughly fortnightly frequency in 2017 at two sites, one with the Ruppia meadow and one with bare sediment. Sediment parameters analyzed were microphytobenthic chlorophyll-a, protein, carbohydrate, and lipid content, and total organic matter. The macrobenthos was identified at the lowest possible taxonomic level. Chlorophyll a, as a surrogate of microphytobenthos, showed differences between the two sites, probably mainly related to light intensity; thus, it is expected that the absence of seagrass canopy results in the higher production of microphytobenthos. At both sites, proteins were the dominant class of labile compounds, suggesting that detrital organic matter present at both study sites is of high nutritional quality. The high protein/carbohydrate ratio also suggests the presence of non-aged organic matter. We recorded a total of 18 macroinvertebrate taxa. The Ruppia meadow showed a positive influence on macrofauna abundance, diversity, species richness, and composition of trophic groups. Only the infaunal taxa Capitella capitata and Chironomus salinarius exhibited higher abundance at the bare site. The ecological quality status measured by the M-AMBI index was unsatisfactory everywhere. However, the presence of the Ruppia meadow resulted in index values being consistently higher. The role of this minor seagrass has been proved to be of great importance, improving the nutritional quality of the organic matter in the sediments and, above all, providing new habitats and new niches for a number of benthic macrofauna species.

The purpose of the study was to evaluate the antibody response after COVID-19 vaccination in patients affected by systemic autoinflammatory diseases (SAID) undertaking IL-1 inhibitors (IL-1i) compared to healthy vaccinated controls (HC). The course of COVID-19 in vaccinated patients on IL-1i was also assessed. The serological response was evaluated in SAID patients using the CLIA MAGLUMI TM 2000 Plus test after the first vaccination cycle and the booster dose. Fifty-four fully vaccinated healthcare workers were enrolled as HCs. GraphPad Prism 8 software was used for statistical analysis. All patients developed an adequate antibody response. No differences were observed between the antibody titers of patients on IL-1i and those not on IL-1i, either after the first vaccination cycle or the booster dose (p = 0.99), and to HC (p = 0.99). With increasing age, a decrease in antibody production was assessed after the second vaccine in SAID (r = 0.67, p = 0.0003). In general, 11.6% of SAID patients had COVID-19 after receiving vaccination. None of them developed severe disease or experienced flares of their autoinflammatory disease. In conclusion, patients receiving IL-1i develop an antibody response comparable to HC. No side effects after vaccination were observed; IL-1i was continued before and after injections to avoid flare-ups.

Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine that is involved in various innate and adaptive immune processes related to infection, inflammation, and autoimmunity. Therefore, it is described as a key mediator of autoinflammatory diseases associated with the development of macrophage activation syndrome (MAS), including systemic juvenile idiopathic arthritis and adult-onset Still’s disease. This review focuses on the role of IL-18 in inflammatory responses, placing emphasis on autoinflammatory diseases associated with chronic excess of serum IL-18, which correlate with clinical and biological signs of the disease. Therefore, it is useful for the diagnosis and monitoring of disease activity. Researchers are currently investigating IL-18’s role as a therapeutic target for the treatment of inflammatory diseases. The inhibition of IL-18 signaling through recombinant human IL-18BP (IL-18 binding protein) seems to be an effective therapeutic strategy, though further studies are necessary to clarify its importance as a therapeutic target.

In the last decade, the Venice Lagoon showed a significant environmental recovery that changed the assemblages of macroalgal and aquatic angiosperm dominant species and significantly increased the primary production. The decreasing of anthropogenic impacts, such as eutrophication and clam harvesting, favored a strong reduction of Ulvaceae, replaced by species with higher ecological value, and the recolonization of aquatic angiosperms. Consequently, hypo-anoxic conditions, once frequently occurring in the lagoon, have been considerably reduced and aquatic angiosperms have recolonized the area, covering 94.8 km2 in comparison to the 55.9 km2 recorded in 2003 (+70%). Cymodocea nodosa, Zostera marina, and Zostera noltei expanded by 37.5%, 44.6%, and 191%, respectively, with a significant increase in biomass and primary production. In late spring 2018, angiosperms showed a standing crop of approximately 372 ktonnes (+77%) and a net primary production of approximately 1189 ktonnes FW (+67%). In the meantime, Ruppia cirrhosa, which since the 1980s had disappeared from the lagoon areas subjected to tidal expansion, but was still present in some fishing valleys, recolonized the bottoms of the northern lagoon with meadows of over 6 km2; this accounted for a standing crop and net primary production of 8.9 and 18.0 ktonnes, respectively. Based on surveys carried out in 2021, ecological conditions are still improving, and this is increasing both the biodiversity and the production of macroalgae and aquatic angiosperms.

ObjectiveThe present manuscript aims to describe an international, electronic-based, user-friendly and interoperable patient registry for monogenic autoinflammatory diseases (mAIDs), developed in the contest of the Autoinflammatory Diseases Alliance (AIDA) Network.MethodsThis is an electronic platform, based on the Research Electronic Data Capture (REDCap) tool, used for real-world data collection of demographics, clinical, laboratory, instrumental and socioeconomic data of mAIDs patients. The instrument has flexibility, may change over time based on new scientific acquisitions, and communicate potentially with other similar registries; security, data quality and data governance are corner stones of the platform.ResultsAIDA project will share knowledge and expertise on mAIDs. Since its start, 118 centers from 24 countries and 4 continents have joined the AIDA project. Fifty-nine centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 337 users (122 Principal Investigators, 210 Site Investigators, 2 Lead Investigators, and 3 data managers). The Registry collects baseline and follow-up data using 3,748 fields organized into 21 instruments, which include demographics, patient history, symptoms, trigger/risk factors, therapies, and healthcare information for mAIDs patients.ConclusionsThe AIDA mAIDs Registry, acts both as a research tool for future collaborative real-life studies on mAIDs and as a service to connect all the figures called to participate. On this basis, the registry is expected to play a pivotal role in generating new scientific evidence on this group of rare diseases, substantially improving the management of patients, and optimizing the impact on the healthcare system. NCT 05200715 available at https://clinicaltrials.gov.

The trophic evolution of the Venice lagoon was analyzed by studying the particulate collected monthly with sedimentation traps in many areas of the Venice lagoon since 1989, and at Goro in 2018–2019. Sedimentation rates were strongly related to the presence of macrophytes, which reduced sediment resuspension, and to anthropogenic pressures, such as clam harvesting and naval-boat traffic, that triggered sediment resuspension and loss. The highest mean annual sedimentation rates (from 2000 to over 4000 g DWT m−2 day−1) have been recorded in many areas of the Venice lagoon between 1998–1999 to 2001–2002, during the intense fishing activities of the clam Ruditapes philippinarum. High values (daily peaks up to 5224 g DWT m−2 day−1) were also recorded in areas affected by marine and/or recreational traffic, due to the high wave motion. In contrast, the presence of high biomasses of macroalgae, or seagrasses, reduced significantly sediment resuspension and settlement, with mean annual sedimentation rates ranging between 40 and 140 g DWT m−2 day−1 and minimum values of 6–10 g DWT m−2 day−1. High sedimentation rates were strongly related to a lower sediment grain-size, with loss of the fine fraction and dispersion of nutrients and pollutants in the whole lagoon.

Genome damage has been related to the induction of autoimmune processes, chronic inflammation, and apoptosis. Recent studies suggest that some rheumatological diseases are associated with overall genomic instability in the T cell compartment. However, no data regarding leucocyte abnormalities in synovial fluid (SF) and their relationship with inflammation are available. The aim of this study was to investigate cellular phenotypes in SF collected from patients with different inflammatory arthropathies, including rhematoid arthritis (RA), psoriatic arthritis (PsA), crystal-induced arthritis (CIA), and non-inflammatory arthropathies, such as osteoarthritis (OA). We found high percentage of micronuclei in SF from CIA compared to the other groups and a high frequency of pyknotic cell in RA and CIA patients. A correlation between pyknosis and immature polymorphonuclear cells with local inflammatory indices was observed. The study of the apoptosis process revealed an increased BAX expression in CIA and RA compared to OA and PsA, while Bcl-2 was higher in CIA. Caspase-3 activity was increased in SF from RA patients and correlates with inflammatory and anti-inflammatory cytokines. In conclusion, our results showed that inflammatory SF is associated with genomic instability and abnormal cell subsets.

Salicornia is a highly taxonomically problematic genus due to the reduced morphological observable characters. Ten Eurasian species are currently recognized: S. alpini, S. europaea, S. fruticosa, S. hispanica, S. lagascae, S. perennans, S. perennis, S. persica, S. procumbens, and S. pruinosa. In addition, eleven subspecies are accepted, mainly based on their distribution areas. Along the Venetian coasts and in Sardinia, in the past, an endemic species called S. veneta was recognized, but this name was later synonymized with S. procumbens subsp. procumbens. The aim of the present research is investigating different Italian Salicornia populations by a molecular point of view, using the nuclear ribosomal external transcribed spacer ETS and the plastid psbA-trnH intergenic spacer. A particular focus is on the comparison between Venetian (including those occurring in locus classicus of S. veneta) and Sardinian S. procumbens and other Italian populations of this species. The molecular analyses based on the plastid marker highlight that the Italian S. procumbens populations form two well distinct groups. In particular, some of the Venetian (Locus classicus of S. veneta) and all the Sardinian specimens are genetically distinct (=plastid haplotype 1) from the other investigated populations (=plastid haplotype 2). This indicates that the psbA-trnH haplotype 1 glassworts represent a distinct entity, which we suppose to coincide with the former S. veneta. Therefore, we suggest to recognize this taxonomic entity at the subspecies rank, as S. procumbens subsp. veneta comb. and stat. nov. However, contrary to the results found with the plastid psbA-trnH intergenic spacer, the ETS locus does not show a separation into two distinct clades for S. procumbens, probably due to a different evolution of the two loci. Nevertheless, in the ETS phylogenetic reconstruction, the Sardinian specimens (=ribotypes 2 and 3) are placed, together with a Moroccan sample, in a subclade separated from all the other S. procumbens. These results suggest that the Sardinian populations can represent a subspecies/incipient speciation process, probably due to geographic isolation. In the light of this, morphometric analyses (k-means, MANOVA, PCA, DA, and Box-Plot) have been carried out on the Sardinian and Venetian populations to verify if this distinction is detectable also by a morphological point of view. The morphometric analyses highlight the existence of two groups, concerning both the nuclear and plastid trees. Six characters were found to be diagnostic.

Schematic representation of multiple ROS-generation-based tumor-therapy approach of AgNP. [Display omitted] • A simple mixing procedure has been utilized to synthesize bimetallic silver nitroprusside (AgNP) as CDT agent together with peroxynitrite generator. • AgNP decomposes more endogenous H 2 O 2 to produce highly toxic radicals. • AgNP are involved in the inhibition of AKT pathway, which is involved in cell survival, angiogenesis, proliferation, and apoptosis. • AgNP showed biocompatible nature towards normal mouse liver and ovarian organoids while are toxic on PDTO through altering the redox homeostasis. Chemodynamic therapy (CDT) holds great promise in achieving cancer therapy through Fenton and Fenton-like reactions, which generate highly toxic reactive species. However, CDT is limited by the lower amount of catalyst ions that can decompose already existing intracellular H 2 O 2 and produce reactive oxygen species (ROS) to attain a therapeutic outcome. To overcome these limitations, a tailored approach, which utilizes dual metals cations (Ag+, Fe2+) based silver pentacyanonitrosylferrate or silver nitroprusside (AgNP) were developed for Fenton like reactions that can specifically kill cancer cells by taking advantage of tumor acidic environment without used of any external stimuli. A simple solution mixing procedure was used to synthesize AgNP as CDT agent. AgNP were structurally and morphologically characterized, and it was observed that a minimal dose of AgNP is required to destroy cancer cells with limited effects on normal cells. Moreover, comprehensive in vitro studies were conducted to evaluate antitumoral mechanism. AgNP have an effective ability to decompose endogenous H 2 O 2 in cells. The decomposed endogenous H 2 O 2 generates several different types of reactive species (•OH, O 2 •−) including peroxynitrite (ONOO−) species as apoptotic inducers that kill cancer cells, specifically. Cellular internalization data demonstrated that in short time, AgNP enters in lysosomes, avoid degradation and due to the acidic pH of lysosomes significantly generate high ROS levels. These data are further confirmed by the activation of different oxidative genes. Additionally, we demonstrated the biocompatibility of AgNP on mouse liver and ovarian organoids as an ex vivo model while AgNP showed the therapeutic efficacy on patient derived tumor organoids (PDTO). This work demonstrates the therapeutic application of silver nitroprusside as a multiple ROS generator utilizing Fenton like reaction. Thereby, our study exhibits a potential application of CDT against HGSOC (High Grade Serous Ovarian Cancer), a deadly cancer through altering the redox homeostasis. [ABSTRACT FROM AUTHOR]