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Background: Antibodies against aquaporin-4 (AQP4), a water channel particularly expressed on perivascular astrocytic podocytes, are proposed as a marker for the diagnosis of neuromyelitis optica (NMO). However, a consensus on seroprevalence and optimal detection method has not yet been reached. Objectives: To investigate the performance of different assays to detect anti-AQP4 antibodies. Methods:We set up five different assays. Two of them were capable to detect perivascular IgG reactivity on brain tissue by immunofluorescence (NMO-IgG). Other three assays have been set to detect anti-AQP4 antibodies: immunofluorescence and flow cytometry on AQP4-expressing cells, and a radioimmunoprecipitation assay. We assessed sensitivity and specificity of these assays by interrogating sera of 33 NMO patients, 13 patients at high risk to develop NMO (hrNMO), 6 patients affected by acute partial transverse myelitis (APTM), 20 patients with multiple sclerosis (MS), and 67 age- and sex-matched healthy controls. Results: We found that the presence of serum NMO-IgG and anti-AQP4 reactivity is almost exclusively restricted to patients with NMO and hrNMO. Seroprevalence and sensitivity ranged from 30 to 47%, depending on the assay. Specificity ranged from 95 to 100%. Comparing results obtained in the five assays, we noticed lack of concordance in some samples. Conclusions: Detection of NMO-IgG or anti-AQP4 antibodies may represent a valuable tool to assist neurologists in the differential diagnosis between patients with NMO, hrNMO, APTM, or MS. The current lack of a gold standard to detect anti-AQP4 antibodies implies the necessity to standardize the detection of these antibodies. [ABSTRACT FROM AUTHOR]

The goal of this study was to investigate habitat effects on the population structure and condition of the sea urchins Paracentrotus lividus and Arbacia lixula. Population structure (density, biomass, size frequency distribution) of both species has been investigated in two areas along the Ligurian coast, characterised by a different level of human disturbance, representing two alternative states of the infralittoral rocky bottom habitat, the photophilic algae assemblage and the barren ground. Samplings have been carried out in two sites within each area in two times, during Spring 2006. According to this experimental design, 10 individuals per species have been collected to evaluate trophic and reproductive conditions and analyse their gut contents, and, in order to relate feeding conditions to food availability, benthic assemblages have been characterised. P. lividus and A. lixula densities are different, as much as their diets change according to the benthic assemblage the urchins live in, but their trophic and reproductive conditions are not affected by food availability. Our results suggest that top-down processes rule the population structure while bottom-up ones cause changes in the diet, but do not alter the general conditions of the urchins. [ABSTRACT FROM AUTHOR]

Echinoderm early developmental stages represent a good tool for toxicity testing in different fields, ranging from environment to food contamination, and in full respect of the 3Rs objectives (Reduction, Refinement, Replacement of animal experiments), that will lead to the reduction of vertebrate use for toxicity testing. Further, sea urchins are key species in a wide range of marine habitats, as they are able to structure algal community. Experiments and observations aiming at the characterization of anthropogenic or climate changes effect on their settlement, population structure, feeding behaviour and reproductive condition, may be useful to describe future scenarios regarding the whole marine community. The present paper represents a short review of the possible applications of eco-toxicity bioassays using Paracentrotus lividus gametes and embryos. Further, examples of ecological researches, involving sea urchins, aiming at the definition of future scenarios will be presented. [ABSTRACT FROM AUTHOR]

Background: Needle-free connectors (NFCs) are recommended as closure systems for peripheral and central vascular catheters to reduce needlestick injuries and infections, while potentially reducing blood reflux. However, their performance in short-term dialysis catheters has never been evaluated. The aim of this study was to evaluate the backflow associated with two NFCs (Neutron™ and Tego™) compared to the standard closure., Methods: In this bench study, the physiological blood pressure of the superior vena cava was simulated. Expert operators performed three sealing sequences for each combination of connector and lumens of the catheter, with and without closing the clamp. After that, the backflow was measured in millimeters using a high-precision digital caliper., Results: No combination of caps, lumens, or clamping sequences eliminated the backflow. No differences were observed between standard caps and NFCs in both lumens, apart from the Tego™/ No clamp combination in the proximal lumen that showed higher backflow (standard cap 15 [11; 17] mm vs Tego™ 23 [19; 25] mm, p  < 0.001). Clamping reduced backflow in both the proximal (13 [11; 17] mm vs 20 [13; 25] mm) and distal lumens (12 [11; 16] mm vs 14 [12; 17] mm). No differences were found between standard caps and NFCs in the distal lumen, regardless of clamping. Proximal lumen consistently exhibited larger backflow (14 [12; 22] mm) compared to distal lumens (13 [11; 17] mm, p  = 0.005)., Conclusion: NFCs do not seem to introduce any advantage on backflow reduction as compared to a standard cap combined with lumen and clamping. Our data suggest that clamping should become standard practice when NFCs are used in the management of short-term dialysis catheters., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Emergency departments (EDs) are at high risk for medical errors. Checklist implementation programs have been associated with improved patient outcomes in other high-risk clinical settings and when used to address specific aspects of ED care. The aim of this study was to develop an ED Safety Checklist with broad applicability across different international ED settings. A three-round modified Delphi consensus process was conducted with a multidisciplinary and multinational panel of experts in emergency medicine and patient safety. Initial checklist items were identified through a systematic review of the literature. Each item was evaluated for inclusion in the final checklist during two rounds of web-based surveys and an online consensus meeting. Agreement for inclusion was defined a priori with a threshold of 80% combined agreement. Eighty panel members from 34 countries across all seven world regions participated in the study, with comparable representation from low- and middle-income and high-income countries. The final checklist contains 86 items divided into: (1) a general ED Safety Checklist focused on diagnostic evaluation, patient reassessment, and disposition and (2) five domain-specific ED Safety Checklists focused on handoff, invasive procedures, triage, treatment prescription, and treatment administration. The checklist includes key clinical tasks to prevent medical errors, as well as items to improve communication among ED team members and with patients and their families. This novel ED Safety Checklist defines the essential elements of high-quality ED care and has the potential to ensure their consistent implementation worldwide., (© 2024. The Author(s).)

Introduction: Catheter-related bloodstream infections are among the most critical issues associated with central venous catheters used for dialysis treatment. To reduce the incidence of this life-threatening complication, various strategies have been developed. Among these, Hub Devices have been introduced in clinical practice to prevent microbial growth at the hub of the catheter., Methods: A review was conducted to assess the effectiveness of Hub Devices in reducing bloodstream infections in central venous catheters for dialysis, compared to solid caps. The review analyzed existing literature from three bibliographic databases (PubMed, Embase, and CINAHL) to provide evidence-based recommendations for clinical practice., Results: After a thorough review of the available data, it was found that out of the 873 records screened, only six trials met the inclusion criteria. Albeit the number of patients observed in these trials was more than 25,000, due to the differences in the mechanism of action of different Hub Devices and the lack of a standardized criterion to identify and measure the outcomes, it is difficult to draw a firm conclusion. It is worth noting, however, that in five out of six trials examined, the Hub Devices exhibited a protective effect when compared to solid caps., Conclusions: The use of Hub Devices appears to be associated with a reduction in catheter-related bloodstream infections in the central venous catheter dialysis population. However, the Hub Devices show interesting results that should be investigated with further well-designed prospective studies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Patients with acute stroke often require venous access to facilitate diagnostic investigations or intravenous therapy. The primary aim of this study was to describe the rate and type of complications associated with the placement of a short peripheral catheter (SPC) in patients with acute ischemic or hemorrhagic stroke. A prospective, observational, single-cohort study was conducted at Niguarda Hospital, Italy, with enrolment in the Emergency Department. Adult patients with an ischemic or hemorrhagic stroke requiring an SPC were enrolled. Complications, such as infiltration, occlusion, phlebitis and dislodgment, were recorded daily. Descriptive statistics were used, and the incidence rate ratio (IRR) was estimated to assess the difference in complications, considering catheter calibre, dominant side, exit site, limb, and limb mobility, ictus type (ischemic/haemorrhagic), impairment deficit (language, motor, visual) and EA-DIVA score. A total of 269 participants and 755 SPC were analysed. Removal of SPC due to at least one local complication occurred in 451 (60%). Dislodgment was the major cause of SPC removal (31%), followed by infiltration (18%), occlusion (6%), and phlebitis (5%). The SPC calibre (22G), exit-site other than antecubital and forearm, visual deficit and EA-DIVA ≥ 8 were associated with a higher rate of SPC complications: IRR, 1.71 [1.31; 2.31]; 1.27 [1.01; 1.60], 1.38 [1.06; 1.80], 1.30 [1.04; 1.64], respectively. No other differences in complication rates were observed according to the insertion site, i.e. dominant side, left side, plegic/hyposthenic limb, or exit site. This study provides novel insights into the frequency and types of complications associated with SPC in patients with acute stroke. Compared to the literature, a higher dislodgment rate was observed, being the first cause of SPC removal, whereas no differences in the number of infiltrations, occlusions, and phlebitis were recorded., (© 2024. The Author(s).)

Multidrug-resistant organisms (MDROs) are prevalent in patients admitted to the Emergency Department (ED) and increase the risk of inappropriate empirical antibiotic therapy. Risk stratification for MDRO infection is essential to early identify patients requiring empirical broad-spectrum antibiotic therapy, but it remains challenging for emergency physicians. This study aimed to evaluate prevalence, risk factors, and outcomes of patients admitted to the ED with a bloodstream infection (BSI) caused by MDROs. A retrospective observational study enrolling all consecutive adult patients admitted with a BSI to the ED of Niguarda Hospital, Italy, from January 2019 to December 2021 was performed. 757 patients were enrolled, 14.1% with septic shock. 156 (20%) patients had a BSI caused by MDRO: extended-spectrum beta-lactamase (ESBL) producing Enterobacterales were the most prevalent followed by methicillin-resistant Staphylococcus aureus (MRSA). Risk factors for BSI due to MDRO and specifically for ESBL were chronic renal failure (OR 2.2; 95%CI 1.4-3.6), nursing home residency (OR 4.4; 95%CI 1.9-10.2) and antibiotic therapy in the last 90-days (OR 2.6; 95%CI 1.7-4), whereas for MRSA were dialysis (OR 12.3; 95%CI 1.8-83), antibiotic therapy and/or hospital admission in the past 90-days (OR 3.6; 95%CI 1.2-10.6) and ureteral stent or nephrostomy (OR 7.8; 95%CI 1.5-40.9). Patients with BSI due to MDRO had a higher rate of inappropriate empirical antibiotic therapy (50%) and longer length of stay, but no higher in-hospital mortality. Among patients admitted to the ED with a BSI, MDROs are frequent and often associated with inappropriate empirical antibiotic therapy. Specific updated risk factors for MDRO may help clinicians to better identify patients requiring a broader antibiotic therapy in the ED, while awaiting microbiological results., (© 2024. The Author(s).)

Introduction: Intraprocedural tip control techniques are critical during central venous catheter placement. According to international guidelines (INS 2021), intracavitary electrocardiography is the first method of choice to verify it; when this technique is not feasible, it is considered acceptable to use a contrast-enhanced ultrasound-based tip location method, commonly known as "bubble-test" as an effective alternative., Objective: To assess whether the length of the vascular catheter can alter the time between the injection of the contrast media and its appearance at the catheter tip and the injection duration. Differences between operators stratified according to experience were evaluated as secondary endpoints., Methods: A bench study was conducted using an extracorporeal circuit. For each catheter length (60, 40, and 20 cm), three injections were obtained by each of the five operators with different levels of experience for a total of 45 measurements. Differences among operators were evaluated using ANOVA, and the impact of catheter length and operator expertise on times was assessed using repeated measurement models., Results: Hub-to-tip times of 247.33 ms (SD 168.82), 166 ms (SD 95.46), 138 ms (SD 54.48), and injection duration of 1620 ms (SD 748.58), 1614 ms (SD 570.95), 1566 ms (SD 302.83) were observed for 60, 40, 20 cm catheter length, respectively. A significant time variability between operators was observed. Moreover, moving from 60 to 20 cm, hub-to-tip time was significantly longer for 60 cm devices ( p  = 0.0124), while little differences were observed for injection duration., Conclusions: Catheter length can change both the time between the injection of the contrast media and its appearance at the catheter tip and the injection duration. Hub-to-tip times obtained with 20 and 40 cm and overall injection duration did not differ significantly; skilled personnel could substantially reduce both values analyzed in this study., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

Helmet continuous positive airway pressure is a simple, noninvasive respiratory support strategy to treat several forms of acute respiratory failure, such as cardiogenic pulmonary edema and pneumonia. Recently, it has been largely used worldwide during the COVID-19 pandemic. Given the increased use of helmet continuous positive airway pressure in the emergency department, we aimed to provide an updated practical guide for nurses and clinicians based on the latest available evidence. We focus our attention on how to set the respiratory circuit. Moreover, we discuss the interactions between flow generators, filters, and positive end-expiratory pressure valves and the consequences regarding the delivered gas flow, fraction of inspired oxygen, positive end-expiratory pressure, and noise level., (Copyright © 2023 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

The placement of a short peripheral intravenous catheter (sPIVC) is the most common invasive clinical procedure for patients requiring fluid infusion and multiple blood draws. Phlebitis and infiltration represent the most common catheter-related complications. Occlusions, dislocations, and infections are less frequent. Insufficient knowledge and skills may increase the risk of these complications. This review aims to evaluate the effectiveness of training programmes to reduce sPIVC failure amongst hospitalised patients. We will search PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Vascular Specialized Register through the Cochrane Register of Studies, and Google Scholar. We defined the search query using the PICO framework (Participants: health professionals; Intervention: training programme; Comparison: No training programme; Outcomes: all-cause catheter failure). We will include experimental studies evaluating an educational programme to reduce early sPIVC failure amongst hospitalised patients. Two reviewers will independently screen studies for inclusion, extract data, and perform the risk of bias assessment using the Cochrane Effective Practice and Organisation of Care Risk of Bias tool for randomised controlled trials. This review will highlight important perspectives for future studies on the effectiveness of educational programmes focused on reducing the rate of sPIVC complications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objective: To assess the different effect of filters' application during helmet-CPAP delivered with three different flow generators on the delivered fresh gas flow, FiO 2 , and the noise level inside and outside the helmet., Methods: In a bench study, three flow generators (air-oxygen blender, turbine ventilator and Venturi system) were used to generate two different gas flows (60 L/min and 80 L/min), with a fixed FiO 2 at 0.6, to perform a helmet-CPAP on a manikin. Three different fixed PEEP valves (7.5, 10, and 12.5 cmH 2 O) were applied at the expiratory port. Gas flow, FiO 2 and noise were recorded for each Flow-generator/Flow/PEEP combination, first without filter interposition and then after positioning a heat and moister exchanger filter (HMEF) at the helmet inlet port., Results: The application of the HMEF lead to a significant difference in the flow variation among the three flow generators (p < 0.001). Compared to baseline, the highest flow reduction was observed with the VENTURI (-13.4 ± 1.2 %, p < 0.001), a slight increase with the BLENDER (1.2 ± 0.5 %, p < 0.001), whereas no difference was recorded with the TURBINE (0.1 ± 0.6 %, p = 0.12). After HMEF was interposed, a significant FiO 2 variation was observed only with VENTURI (11.3 ± 1.8 %, p < 0.001). As for the noise, the TURBINE was the least noisy system, both with and without the filter interposition., Conclusions: Flow generators used to deliver helmet-CPAP have different characteristics and responses to HMEF interposition. Users should be aware of the effects on FiO 2 and flow of the different devices in order to make a precise setup of the circuit., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Acute aortic dissection (AAD) is a rare condition but represents a time-sensitive disease for which a wrong and untimely identification in the triage phase could compromise the subsequent diagnostic, therapeutic path and patient's prognosis. The emergency nurse plays a crucial role in identifying and managing patients with possible AAD. The aim of this paper is to describe the emergency department nursing approach to critical patients with suspected hyperacute/acute AAD., Purpose: It is crucial to examine the emergency departments nursing approach to patients with suspected AAD. It is fundamental to have a rapid and standardized approach related to life-saving procedures, practices, and management of critical patients during the triage phase, with the assessment of the most common presentation of clinical signs and symptoms and patient management during each step in the emergency department., Conclusion: Early identification and diagnosis in ED allow prompt treatment that improves prognosis. The emergency nurse plays a crucial role in correctly identifying and managing patients with acute aortic dissection. High clinical suspicion from the triage stages, early diagnosis, monitoring, and initial clinical stabilization in the emergency department plays a key role while awaiting definitive treatment., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: When helmet CPAP is performed using a Venturi system, filters are frequently interposed in the respiratory circuit to reduce noise within the helmet. The effect of the interposition of these filters on delivered fresh gas flow and the resulting F IO 2 is currently unknown., Methods: In a bench study, 2 different Venturi systems (WhisperFlow and Harol) were used to generate 3 different gas flow/F IO 2 combinations (80 L/min-F IO 2 0.6, 100 L/min-F IO 2 0.5, 120 L/min-F IO 2 0.4). Different combinations of filters were applied at the flow generator input line and/or at the helmet inlet port. Two types of filters were used for this purpose: a heat and moisture exchanger filter and an electrostatic filter. The setup without filters was used as baseline. Gas flow and F IO 2 were measured for each setup., Results: Compared to baseline, the interposition of filters reduced the gas flow between 1-13% ( P < .001). The application of a filter at the Venturi system or at the helmet generated a comparable flow reduction (-3 ± 2% vs -4 ± 2%, P = .12), whereas a greater flow reduction (-7 ± 4%) was observed when filters were applied at both sites ( P < .001). An increase in F IO 2 up to 5% was observed with filters applied. A strong inverse linear relationship ( P < .001) was observed between the resulting gas flow and F IO 2 ., Conclusions: The use of filters during helmet CPAP reduced the flow delivered to the helmet and, consequently, modified F IO 2 . If filters are applied, an adequate gas flow should be administered to guarantee a constant CPAP during the entire respiratory cycle and avoid rebreathing. Moreover, it might be important to measure the effective F IO 2 delivered to the patient to guarantee a precise assessment of oxygenation., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2022 by Daedalus Enterprises.)

Purpose: The aim of this study was to evaluate the rate of successful peripheral cannulation between short-axis and long-axis ultrasound guided techniques., Methods: A single-center, two-arm randomized controlled, intention-to-treat, open-label study was conducted at the Emergency Department, between August and November 2020. Patients requiring a peripheral intravenous catheter insertion and identified as having a difficult intravascular access, were enrolled and followed for up to 96 h.The primary endpoint was the correct placement of the peripheral intravenous catheter. The secondary endpoints were number of venipunctures, intra-procedural pain, local complications, and positive blood return during the follow up., Results: A total of 283 patients were enrolled: 141 subjects were randomized to the short-axis and 142 to the long-axis group. Success rate was 96.45% (135/141; 95% CI, 91.92%-98.84%) in the short-axis group compared with 92.25% (132/142; 95% CI, 86.56%-96.07%) in the long-axis group ( p  = 0.126). No significant differences were found in terms of intraprocedural pain and local complications. Higher rate of positive blood return at 72 h [3/17 long-axis, 14/17 short-axis ( p  = 0.005)] and 96 h [1/10 long-axis, 9/10 short-axis 96 h, ( p  = 0.022)] was found for the short-axis group., Conclusions: No differences were found between short-axis and long-axis techniques in terms of success rate, intraprocedural pain, and local complications. Despite this, a slightly higher success rate, a lower number of venipunctures, and a higher rate of positive blood return at 72 and 96 h together with an easier ultrasound technique could suggest a short-axis approach.

The aim of this article is to describe the importance of a multidisciplinary team dedicated to noninvasive ventilation training of the emergency department's staff. In our experience, the presence of a medical and nursing "noninvasive ventilation group" made it possible to quickly teach expertise on the management of noninvasive ventilation of COVID-19 patients among emergency department doctors and nurses. This allowed improving a standardized approach regarding the identification and ventilatory assistance of patients with SARS-CoV-2 pneumonia needing ventilatory support, the correct use of the devices, and quick identification and reduction of the complications associated with noninvasive ventilation. In this article, we would like to encourage the formation of similar working groups in all situations where this is not yet present., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: During COVID-19 outbreak, with the increasing number of patients presenting with acute respiratory failure, a large use of non invasive positive pressure ventilation was done in the emergency departments and medical wards despite the lack of recommendations., Objectives: This study describes the clinical characteristics of patients presenting to the hospital with acute respiratory failure due to COVID-19 related pneumonia undergoing treatment with helmet continuous positive airway pressure (CPAP) with a strict nursing evaluation and monitoring., Methods: A case series study enrolling adult patients admitted to an emergency department of an Italian hospital with acute respiratory failure due to COVID-19 pneumonia from March 18th to April 18th, 2020, was conducted. Only patients who strictly followed a local CPAP protocol were enrolled., Results: A total of 52 patients were included in this study. Thirty-eight patients (73%) were judged eligible for endotracheal intubation (ETI). Eighteen (34.6%) were intubated. Sixteen (30.8%) patients died: seven (38.9%) and nine (26.5%) in the eligible-for-ETI and non eligible-for-ETI group, respectively. The median hospital length of stay was different in the ETI and non-ETI group: 26 days (interquartile range [IQR]: 16-37) vs 15 days [IQR 9-17] (p = 0.005). The median invasive mechanical ventilation time was 11 days [IQR 7-21] with an ICU length of stay of 14.5 days [IQR 10-28]. During the CPAP trial, among patients eligible for ETI variations over time for positive end-expiratory pressure (p = 0.003) and respiratory rate (p = 0.059) were found between intubated and non-intubated patients., Conclusions: A short closed monitored CPAP trial could be considered for acute respiratory failure due to COVID-19 pneumonia before considering ETI. A progressive positive end-expiratory pressure titration should target reduction in a patient's respiratory rate. More studies are needed to evaluate the efficacy and predictors of failure of CPAP and non-invasive positive pressure ventilation in patients with acute respiratory failure due to COVID-19 pneumonia., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Consistently with their diagnostic and prognostic value, autoantibodies specific for systemic sclerosis (SSc) embedded in immune complexes (ICs) elicited a pro-inflammatory and pro-fibrotic cascade in healthy skin fibroblasts, engaging Toll-like receptors (TLRs) via their nucleic acid components. The objective of this study was to investigate the pathogenicity of SSc-ICs in endothelial cells., Methods: ICs were purified from the sera of SSc patients bearing different autoantibody specificities (antibodies against DNA topoisomerase I, centromeric proteins, RNA polymerase, and Th/To), patients with systemic lupus erythematosus (SLE) and primary anti-phospholipid syndrome (PAPS), or healthy controls (NHS) using polyethylene glycol precipitation. Human umbilical vein endothelial cells (HUVECs) were incubated with ICs, positive and negative controls. mRNA levels of endothelin-1 (et-1), collagenIα1 (colIα1), interferon (IFN)-α, and IFN-β were investigated by real-time PCR; et-1 and il-6 mRNA levels were assessed after pre-treatment with bafilomycin. ICAM-1 expression was evaluated by cell ELISA; secretion of IL-6, IL-8, and transforming growth factor (TGF)-β1 in culture supernatants was measured by ELISA. The expression of Fcγ receptors (CD64, CD32, and CD16) was assessed in endothelial cells at FACS analysis. Intracellular signaling pathways culminating with NFκB, p38MAPK, SAPK-JNK, and Akt were assessed by Western blotting. Healthy skin fibroblasts were stimulated with supernatants from HUVECs incubated with ICs, and TGF-β1 secretion and mRNA levels of colIα1 and matrix metalloproteinase (mmp)-1, protein expression of α smooth muscle actin (α-SMA), and IL-6 were evaluated by Western blotting; et-1 mRNA levels were assessed in fibroblasts pre-treated with IL-6 and TGF-β inhibitors and stimulated with ATA-ICs., Results: All SSc stimulated IL-6 secretion; ACA-ICs and anti-Th/To-ICs increased ICAM-1 expression; all SSc-ICs but anti-Th/To-ICs augmented IL-8 levels; all SSc-ICs but ACA-ICs and ARA-ICs upregulated et-1, and all SSc-ICs but ARA-ICs affected TGF-β1 secretion. colIα1, IFN-α, and IFN-β mRNA levels were not affected by any SSc-IC. FcγRII (CD32) and FcγRIII (CD16) were not detectable on HUVECs, while FcγRI (CD64) was minimally expressed. A differential modulation of tlr expression was observed: tlr2, tlr3, and tlr4 were upregulated by ATA-ICs and ACA-ICs, while anti-Th/To-ICs resulted in tlr9 upregulation. Pre-treatment with bafilomycin did not affect the upregulation of et-1 and il-6 induced by ATA-ICs, ACA-ICs, and anti-Th/To-ICs; a 23% reduction in both genes was reported for ARA-ICs. All SSc-ICs activated p38MAPK and Akt, and all SSc-ICs but ARA-ICs yielded the activation of NFκB; ATA-ICs and ACA-ICs increased the activation rate of both subunits of SAPK-JNK. When healthy skin fibroblasts were stimulated with supernatants from HUVECs incubated with SSc-ICs, TGF-β1 secretion, colIα1, α-SMA, and IL-6 expression levels were significantly modulated. Pre-treatment with IL-6 and TGF-β inhibitors prevented et-1 upregulation induced by ATA-ICs by 85% and 77%, respectively., Conclusions: These data provide the first demonstration of the pathogenicity of ICs from scleroderma patients with different autoantibodies on the endothelium. Endothelial activation induced by SSc-ICs ultimately led to a pro-fibrotic phenotype in healthy skin fibroblasts.

Patients with systemic lupus erythematosus (SLE) have a significant increase in cardiovascular (CV) risk although they display a preserved number of circulating angiogenic CD3 + CD31 + CXCR4 + T cells (T ang ), a subpopulation of T cells which promotes repair of damaged endothelium. This happens due to the concomitant expansion of a T ang subset with immunosenescent features, such as the loss of CD28. Therefore, the aim of this study was to elucidate the interplay between T ang subpopulations and endothelial cells in a group of young SLE patients without previous cardiovascular events. Twenty SLE female patients and 10 healthy controls (HCs) were recruited. Flow cytometric analysis of endothelial progenitor cells (EPCs) and T ang subsets were performed and serum levels of interleukin (IL)-6, -8, matrix metalloproteinase (MMP)-9 and interferon (IFN)- γ were measured. Human umbilical vein endothelial cells (HUVECs) proliferation and pro-inflammatory phenotype in response to subjects' serum stimulation were also evaluated. Results showed that the percentage of T ang and EPC subsets was reduced in SLE patients compared with HCs, with a marked increase of senescent CD28 null cells among T ang subset. SLE disease activity index-2000 (SLEDAI-2K) was inversed related to T ang cells percentage. Furthermore, IL-8 serum levels were directly correlated with the percentage of T ang and inversely related to the CD28 null T ang subsets. We indirectly evaluated the role of the T ang subset on the endothelium upon stimulation with serum from subjects with a low percentage of T ang CD3 + cells in HUVECs. HUVECs displayed pro-inflammatory phenotype with up-regulation of mRNA for IL-6, intercellular adhesion molecule (ICAM)-1 and endothelial leukocyte adhesion molecule (ELAM)-1. Cell proliferation rate was directly related to IL-8 serum levels and EPC percentage. In highly selected young SLE patients without previous CV events, we found that the deterioration of T ang compartment is an early event in disease course, preceding the development of an overt cardiovascular disease and potentially mediated by SLE-specific mechanisms. The overcome of the CD28 null subset exerts detrimental role over the T ang phenotype, where T ang could exert an anti-inflammatory effect on endothelial cells and might orchestrate via IL-8 the function of EPCs, ultimately modulating endothelial proliferation rate., (Copyright © 2020 Bortoluzzi, Chighizola, Fredi, Raschi, Bodio, Privitera, Gonelli, Silvagni, Govoni, Cavazzana, Airò, Meroni, Tincani, Franceschini, Piantoni and Casciano.)

With the rapid pandemic spread of the novel coronavirus (SARS-CoV2), Emergency Departments of affected countries are facing an increasing number of patients presenting with hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). Providing mechanical support and endotracheal intubation can be challenging due to a number of patients larger than usual, often exceeding available resources. Considering the lack of recommendations available, we developed a flowchart to standardize the first approach to patients presenting to the Emergency Department with hypoxemic respiratory failure due to COVID-19.

Background: In systemic sclerosis (SSc), autoantibodies provide the most accurate tool to predict the disease subset and pattern of organ involvement. Scleroderma autoantibodies target nucleic acids or DNA/RNA-binding proteins, thus SSc immune complexes (ICs) can embed nucleic acids. Our working hypothesis envisaged that ICs containing scleroderma-specific autoantibodies might elicit proinflammatory and profibrotic effects in skin fibroblasts., Methods: Fibroblasts were isolated from skin biopsies obtained from healthy subjects and patients with diffuse cutaneous SSc (dcSSc). ICs were purified by polyethylene-glycol precipitation from sera of SSc patients bearing different autoantibodies. ICs from patients with systemic lupus erythematosus (SLE) and primary anti-phospholipid syndrome (PAPS) and from normal healthy subjects (NHS) were used as controls. After incubation with ICs, fibroblasts were evaluated for ICAM-1 expression, interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase (MMP)-2, tumor growth factor (TGF)-β1 and Pro-CollagenIα1 secretion, collagen (col)Iα1, mmp-1, toll-like receptor (tlr)2, tlr3, tlr4, tlr7, tlr8, tlr9, interferon (ifn)-α, ifn-β and endothelin-1 mRNA, and NFκB, p38MAPK and SAPK-JNK activation rate. Experiments were also performed after pretreatment with DNase I/RNase and NFκB/p38MAPK inhibitors., Results: The antigenic reactivity for each SSc-IC mirrored the corresponding serum autoantibody specificity, while no positivity was observed in NHS-ICs or sera. SSc-ICs but not NHS-ICs increased ICAM-1 expression, stimulated IL-6, IL-8, MMP-2, MCP-1, TGF-β1 and Pro-CollagenIα1 secretion, upregulated et-1, ifn-α, ifn-β, tlr2, tlr3 and tlr4, and activated NFκB, p38MAPK and SAPK-JNK. tlr9 was significantly upregulated by ARA-ICs, mmp-1 was significantly induced by ACA-ICs whereas colIα1 was not modulated by any SSc-ICs. SLE-ICs and PAPS-ICs significantly upregulated MMP-2 and activated NFκB, p38MAPK and SAPK-JNK. SLE-ICs and PAPS-ICs did not affect colIα1, mmp-1 and Pro-CollagenIα1. DNase I and RNase treatment significantly reduced the upregulation of study mediators induced by SSc-ICs. Pretreatment with NFκB/p38MAPK inhibitors suggested that response to anti-Th/To-ICs was preferentially mediated by p38MAPK whereas ATA-ICs, ACA-ICs and ARA-ICs engaged both mediators. In dcSSc fibroblasts, stimulation with SSc-ICs and NHS-ICs upregulated IL-6 and IL-8., Conclusions: These data provide the first demonstration of the proinflammatory and profibrotic effects of SSc-ICs on fibroblasts, suggesting the potential pathogenicity of SSc autoantibodies. These effects might be mediated by Toll-like receptors via the interaction with nucleic acid fragments embedded in SSc-ICs.

Continuous anthropogenic CO2 emissions to the atmosphere and uptake by the oceans will cause a reduction of seawater pH and saturation state (Ω) of CaCO3 minerals from which marine calcifiers build their shells and skeletons. Sea urchins use the most soluble form of calcium carbonate, high-magnesium calcite, to build their skeleton, spines and grazing apparatus. In order to highlight the effects of increased pCO2 on the test thickness and carbonate elemental composition of juvenile sea urchins and potential differences in their responses linked to the diet, we performed a laboratory experiment on juvenile Paracentrotus lividus, grazing on calcifying (Corallina elongata) and non-calcifying (Cystoseira amentacea, Dictyota dichotoma) macroalgae, under different pH (corresponding to pCO2 values of 390, 550, 750 and 1000 μatm). Results highlighted the importance of the diet in determining sea urchin size irrespectively of the pCO2 level, and the relevance of macroalgal diet in modulating urchin Mg/Ca ratio. The present study provides relevant clues both in terms of the mechanism of mineral incorporation and in terms of bottom-up processes (algal diet) affecting top-down ones (fish predation) in rocky subtidal communities., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The ubiquitously expressed iron storage protein ferritin plays a central role in maintaining cellular iron homeostasis. Cytosolic ferritins are composed of heavy (H) and light (L) subunits that co-assemble into a hollow spherical shell with an internal cavity where iron is stored. The ferroxidase activity of the ferritin H chain is critical to store iron in its Fe3+ oxidation state, while the L chain shows iron nucleation properties. We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). We show that L chain ferritin is undetectable in primary fibroblasts from the patient, and thus ferritin consists only of H chains. Increased iron incorporation into the FtH homopolymer leads to reduced cellular iron availability, diminished levels of cytosolic catalase, SOD1 protein levels, enhanced ROS production and higher levels of oxidized proteins. Importantly, key phenotypic features observed in fibroblasts are also mirrored in reprogrammed neurons from the patient's fibroblasts. Our results demonstrate for the first time the pathophysiological consequences of L-ferritin deficiency in a human and help to define the concept for a new disease entity hallmarked by idiopathic generalized seizure and atypical RLS.

Despite the large body of work published in the last two decades on the reproduction of the sea urchin Paracentrotus lividus, the reproductive aspects linked to hydrodynamic conditions and their influence on gonad production remain poorly understood. The present paper aims to evaluate the effect of hydrodynamism on the reproductive cycle of P. lividus. Variability in the gonadosomatic index (GSI) of P. lividus was estimated seasonally from 2007 to 2008 at two shallow sub-littoral flat basaltic areas at Ustica Island (Western Mediterranean). GSI was higher in the sites characterized by low hydrodynamism than in those with high hydrodynamism. Results also suggest a possible role for hydrodynamism in triggering processes of resource limitation (food shortage), probably by interfering with P. lividus feeding activity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We tried to identify the target/s of autoantibodies to basal ganglia neurons found in a patient with hyperkinetic movement disorders (HMD) characterized by rapid, rhythmic involuntary movements or spasms in both face and neck. Patient and control sera were used in Western blot to probe mouse brain homogenates. Two-dimensional gel electrophoresis (2-DE) SDS-PAGE protein spots recognized by the patient's antibodies were excised and sequenced by mass spectrometry analysis, and the glycolytic enzyme aldolase A was identified as the antigen recognized by the patient's autoantibodies. To assess relevance and specificity of these antibodies to the identified targets as biomarkers of autoimmunity in movement disorders, autoantibody responses to the identified target were then measured by ELISA in various diseases of the central nervous system. Anti-aldolase A autoantibodies were associated mainly with HMD (7/17, 41%) and Parkinson's disease (4/30, 13%) patients, and undetectable in subjects with other inflammatory and non-inflammatory central nervous system diseases. We, thus, identified aldolase A as an autoantigen in a sub-group of patients with HMD, a clinically ill-defined syndrome. Anti-aldolase A antibodies may represent a useful biomarker of autoimmunity in HMD patients.

Pantothenate kinase-associated neurodegeneration (PKAN) is a neurodegenerative disease belonging to the group of neurodegeneration with brain iron accumulation disorders. It is characterized by progressive impairments in movement, speech and cognition. The disease is inherited in a recessive manner due to mutations in the Pantothenate Kinase-2 (PANK2) gene that encodes a mitochondrial protein involved in Coenzyme A synthesis. To investigate the link between a PANK2 gene defect and iron accumulation, we analyzed primary skin fibroblasts from three PKAN patients and three unaffected subjects. The oxidative status of the cells and their ability to respond to iron were analyzed in both basal and iron supplementation conditions. In basal conditions, PKAN fibroblasts show an increase in carbonylated proteins and altered expression of antioxidant enzymes with respect to the controls. After iron supplementation, the PKAN fibroblasts had a defective response to the additional iron. Under these conditions, ferritins were up-regulated and Transferrin Receptor 1 (TfR1) was down-regulated to a minor extent in patients compared with the controls. Analysis of iron regulatory proteins (IRPs) reveals that, with respect to the controls, PKAN fibroblasts have a reduced amount of membrane-associated mRNA-bound IRP1, which responds imperfectly to iron. This accounts for the defective expression of ferritin and TfR1 in patients' cells. The inaccurate quantity of these proteins produced a higher bioactive labile iron pool and consequently increased iron-dependent reactive oxygen species formation. Our results suggest that Pank2 deficiency promotes an increased oxidative status that is further enhanced by the addition of iron, potentially causing damage in cells.

Harmful benthic microalgae blooms are an emerging phenomenon causing health and economic concern, especially in tourist areas. This is the case of the Mediterranean Sea, where Ostreopsis ovata blooms occur in summer, with increasing regularity. Ostreopsis species produce palytoxin (PTX) and analogues, and a number of deaths directly associated with the ingestion of PTX contaminated seafood have been reported. PTX is considered one of the most toxic molecules occurring in nature and can provoke severe and sometimes lethal intoxications in humans. So far in temperate areas, O. ovata blooms were reported to cause intoxications of humans by inhalation and irritations by contact. In addition, invertebrate mass mortalities have been reported, possibly linked to O. ovata blooms, although other causes cannot be ruled out, such as oxygen depletion or high seawater temperature. In order to improve our knowledge about the direct toxicity of this species on invertebrate and vertebrate marine organisms, we performed an ecotoxicological screening to investigate the toxic effects of different concentrations of O. ovata (cultured in the laboratory and sampled in the field during blooms) on crustaceans and fish as model organisms. Artemia salina, Tigriopus fulvus, and Amphibalanus amphitrite larvae and juveniles of the sea bass Dicentrarchus labrax were used as model species. Toxic effects associated with cultured O. ovata cells were investigated using a crossed design: testing two different temperatures (20 and 25 °C), four different cell concentrations, and four treatments (untreated O. ovata culture, filtered and resuspended algal cells, growth medium devoid of algal cells, and sonicated algal cells). The results indicate that the toxicity of cultured O. ovata is related to the presence of living O. ovata cells, and that this effect is amplified by temperature. Furthermore, both tests with laboratory cultured algae and field sampled cells pointed out that A. salina is the most sensitive species even at concentrations below the Environmental Alarm Threshold set by the Italian Ministry of Health. Some possible explanations of such sensitivity are discussed, taking into account evidence of O. ovata cells ingestion and the activity of its toxins on the Na⁺/K⁺-ATPase., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Since a long time, Italy has maintained a dual system to administer childhood immunisations, that is a certain number of mandatory vaccinations and a number of recommended vaccinations. The study aimed to explore the issues surrounding parental acceptance or non-acceptance of the recommended vaccinations for children., Methods: Parents of children aged 3-5 years of day-care centres in Sicily were asked to fill out an anonymous questionnaire. Determinants of the attitude towards recommended vaccinations and social influence on the decision-making process were assessed using logistic regression analysis., Results: Of the 1,500 selected parents, 81.0% participated in the study. Prior to the survey, the majority of children (97.6%) received recommended vaccines. Most parents (74.4%) received information about vaccinations from Family Paediatricians, showed a good knowledge about the side effects of the vaccines (73.1%), did not worry about their potential dangerousness (53.0%) and would have accepted their children to be vaccinated even if it was not required for day care (84.1%). The majority (79.9%) were not disposed to follow the advises of the anti-vaccination movements. Parents' background characteristics, sources of information and social influence were not significantly associated with parental acceptance of recommended vaccines for childhood., Conclusions: This study suggests that health information by Family Paediatricians is significantly associated with parental acceptance of recommended vaccinations., (© 2011 Coniglio et al; licensee BioMed Central Ltd.)

The effect of exposures to the insecticide chlorpyrifos on the larval stages of Paracentrotus lividus (Echinodermata, Euechinoidea) up to metamorphosis was investigated with the aim to identify novel risk biomarkers and a new promising model for toxicity tests. The planktonic sea urchin larvae have the ability to undergo a variable exploratory period, up to the choice of a suitable substrate for adult benthonic life. The juvenile bud (called rudiment) is built inside the larval body that, on environmental cues represented by a variety of signal molecules, is reabsorbed by apoptosis and releases the juvenile on the substrate. In this dialogue between larvae and environment, contaminants interfere with the signals reception, and may alter in dose-dependent way the correct regulation of environment-larva-rudiment interaction. Such interaction is shown by larval plasticity, i.e. the ability of the larva to change body proportions according to the environmental conditions. When exposed to low doses of chlorpyriphos (10(-7) to 10(-10) M) since 2-days after fertilization, the larvae showed altered size and shape, but all reached the metamorphosis at the same time as controls, and in the same percentage. Exposures to high concentrations such as 10(-4) to 10(-6) M since 2-days after fertilization did not allow larval growth and differentiation. Exposures at later stages caused reabsorption of larval structures within a few hours and precocious release of the immature rudiments, followed by death of the juveniles. Although the mechanism of chlorpyriphos toxicity in sea urchin larvae is still rather unclear, the measurable stress biomarkers can constitute the basis for new toxicity tests.