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The phenotypic diagnosis of von Willebrand disease (VWD) is a multistep process with classification dependent on the quantification of von Willebrand factor (VWF) multimeric structure. VWF multimer analysis is a technically challenging, lengthy and non‐standardised assay, usually performed in specialist laboratories. Recently, a new semi‐automated multimer assay, the Hydragel 5 von Willebrand multimers (H5VWM) has become available. This study, performed in two European centres, compared existing in‐house multimer assays to the H5VWM in individuals with and without VWD. Overall agreement of 91.1% was observed in 74 individuals with normal VWF levels, 57 patients grouped as type 1 VWD, 33 type 2A, 16 type 2B, 28 type 2M, 11 type 2N. Patients tested following Desmopressin or VWF concentrate, with thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome were also evaluated. Many of the discrepancies between methods were in patients with genetic mutations linked to more than one type of VWD including p.R1374C/H and p.R1315C. Quantifiable multimer results were available within one working day. Densitometry improved the interpretation of the multimers with slight structural variations that were not apparent by visual inspection of the in‐house method. 5VWM was a rapid, sensitive, standardised assay which used existing technology and could be included as an initial screen of VWF multimers in a VWD diagnostic algorithm in conjunction with traditional multimer analysis.

Background Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function. Methods We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS ( n  = 6), CER20 (single dose of CER-001 20 mg/kg; n  = 6), and CER20 × 2 (two doses of CER-001 20 mg/kg; n  = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n  = 5), Group B (CER-001 5 mg/kg BID, n  = 5), Group C (CER-001 10 mg/kg BID, n  = 5), and Group D (CER-001 20 mg/kg BID, n  = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers. Results CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay. Conclusions CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage. Trial registration The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020–004202-60, Protocol CER-001- SEP_AKI_01) and was added to the EU Clinical Trials Register on January 13, 2021.

Background. The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees. Methods. Samples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant. Results. In patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant. Conclusions. Repeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.

Background: Mechanization in olive harvesting has improved productivity but introduced new ergonomic challenges, particularly related to vibration exposure and sustained overhead work. This study investigates the acute and short-term physiological effects of using an electric olive harvester through objective instrumental assessment. Methods: Ten healthy male volunteers performed a standardized 15-min simulated harvesting task using an electric olive harvester. Muscle tone, stiffness, and elasticity of bilateral deltoid, biceps, and triceps were assessed by myotonometry at baseline (T0), immediately post-task (T1), and after 2 h recovery (T2). Infrared thermography evaluated cervical, dorsal, and lumbar skin temperature at the same timepoints. Results: Significant, side-dependent alterations in myotonometric parameters were observed, with marked increases in tone and stiffness of dominant upper-limb muscles and asymmetric adaptations between limbs (p < 0.001, large effect sizes). Infrared thermography revealed significant post-task reductions in skin temperature across spinal regions, with a partial return toward baseline within the 2 h observation window (p < 0.01). These findings describe short-term, task-related thermoregulatory responses following sustained work. Conclusions: Even short-term use of electric olive harvesters induces measurable biomechanical and thermophysiological stress. The integrated use of myotonometry and infrared thermography provides a sensitive, field-adaptable framework for early ergonomic risk detection and prevention of work-related musculoskeletal disorders in agriculture.

Since 2001, human Metapneumovirus has been a significant cause of human respiratory disease worldwide, and no vaccine or preventive treatment is currently available. The ELISA-based live virus microneutralization assay is a method to detect neutralizing antibodies against a target pathogen. The aim of this study was to demonstrate the suitability of this approach to quantifying neutralizing antibodies against A1 and B1 virus subtypes in human serum samples. To standardize and validate this microneutralization assay, we carried out analytical procedures according to the International Council of Harmonization guidelines; these procedures are described in detail. In addition, we compared the validated method with the indirect ELISA, and confirmed that the ELISA-based microneutralization assay provides reliable, accurate and reproducible results. The use of this high-throughput method for large-scale serological studies could effectively support the evaluation of the immunogenicity of new vaccines, thereby improving therapeutical strategies against human Metapneumovirus.

Bullous dermatoses encompass a group of disorders marked by blister formation on the skin and/or mucosa with diverse etiologies. This case report aims to describe a rare occupationally induced bullous dermatosis in a worker exposed to polyvinyl chloride (PVC) welding fumes, and to highlight the need for improved protective measures in industrial environments. A 48-year-old male employed in a PVC manufacturing plant developed recurrent bullous skin lesions on the hands, face, and neck after operating a PVC film-welding machine without personal protective equipment. Clinical evaluation was supported by histopathology, direct and indirect immunofluorescence, serologic testing (ELISA for anti-desmoglein-1, anti-desmoglein-3, BP230, and BP180), and a porphyrin screen. Patch tests and autoimmunity screening were also performed. Direct immunofluorescence revealed linear C3 and IgG deposits along the basement membrane zone, consistent with a bullous pemphigoid-like pattern, while other autoimmunity markers were negative. Complete remission of lesions occurred after cessation of exposure and job reassignment, without the need for ongoing pharmacologic treatment. A clear \"stop-restart\" relationship between exposure and symptoms supported a causal association. This report describes the first documented case of bullous dermatosis triggered by occupational exposure to PVC welding fumes. The findings emphasize the relevance of occupational assessment in unusual dermatologic presentations and support the implementation of adequate protective measures and exposure monitoring in high-risk settings.

Background Vector-borne diseases (VBDs) represent an emerging global threat to public health due to the geographical expansion of arthropod vectors. The study aims to assess the seroprevalence of selected vector-borne pathogens (VBPs) in different groups of outdoor workers and the occupational risk factors for exposure to arthropod bites. Methods A cross-sectional study was conducted on 170 workers recruited in two different regions of southern Italy, including farmers, forestry workers, veterinarians, geologists/agronomists and administrative employees, and tested for IgG antibodies against Bartonella henselae , Borrelia spp. Coxiella burnetii and Rickettsia conorii , using a chemiluminescent immunoassay (CLIA). The relationship among job characteristics, tick exposure and the prevalence of seropositive subjects for each pathogen was investigated by applying categorical principal component analysis (CATPCA). Results A high seroprevalence for C. burnetii (30.0%) and R. conorii (15.3%) was reported, mainly in farmers (67.7% and 54.8%, respectively) and forestry workers (29.0% and 16.1%, respectively), while a low prevalence was observed for B. henselae and Borrelia spp. (8.8% and 4.1%, respectively). The regression equation by CATPCA was significant for C. burnetii and R. conorii ( P  < 0.001), showing a positive association with job, tick bite exposure, working area and contact with animals. Conclusions These findings highlight the need of activating an appropriate occupational health response for minimizing the risk of arthropod vector exposure in workplaces, considering specific preventive measures in particular in high-risk job categories. Graphical Abstract

Background Hereditary transthyretin amyloidosis (ATTRv) is a rare disorder caused by pathogenic TTR gene variants. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are potential biomarkers for astrocyte activation and neuroaxonal damage, respectively. This study investigates serum GFAP (sGFAP) and NfL (sNfL) levels in ATTRv patients, pre-symptomatic subjects, and healthy controls (HCs) to evaluate their utility as biomarkers of disease progression and CNS involvement. Methods Our multicenter cross-sectional study included 111 ATTRv patients (56 symptomatic, 55 pre-symptomatic subjects) and 183 HCs. Serum levels of sGFAP and sNfL were measured using ultrasensitive immunoassays. The statistical comparisons were performed using ANCOVA models (age and sex adjusted), with correlations examined between serum biomarkers and disease severity (Neuropathy Impairment Score, NIS). Results sGFAP levels were elevated in symptomatic (median: 238.35 pg/ml) and pre-symptomatic subjects (median: 105.50 pg/ml) vs. HCs (median: 75.5 pg/ml, p  < 0.001). sNfL was elevated only in symptomatic patients (median: 43.68 pg/ml) compared to pre-symptomatic subjects (median: 9.36 pg/ml) and HCs (median: 7.54 pg/ml, p  < 0.001). Both biomarkers correlated significantly with NIS, reflecting disease severity. Female HCs had higher sGFAP levels than males (median 88.6 pg/ml vs. 59.8 pg/ml; p 0.011). Conclusion sGFAP and sNfL mark distinct ATTRv stages, with sGFAP indicating early preclinical changes and sNfL correlating with neurological progression. Sex differences in sGFAP levels among HCs suggest that sex should be considered as a covariate in biomarker analyses.

Human T-lymphotropic virus 1 and 2 (HTLV-1/2) belong to the delta group of retroviruses which may cause a life-long infection in humans, HTLV-1 leading to adult T-cell leukemia/lymphoma and other diseases. Different transmission modes have been described, such as breastfeeding, and, as for other blood-borne pathogens, unsafe sexual activity, intravenous drug usage, and blood transfusion and transplantation. The present systematic review was conducted to identify all peer-reviewed studies concerning the work-related infection by HTLV-1/2. A literature search was conducted from January to May 2021, according to the PRISMA methodology, selecting 29 studies: seven related to health care workers (HCWs), five to non-HCWs, and 17 to sex workers (SWs). The findings showed no clear evidence as to the possibility of HTLV-1/2 occupational transmission in HCWs, according to the limited number and quality of the papers. Moreover, non-HCWs showed a higher prevalence in jobs consistent with a lower socioeconomic status or that could represent a familial cluster, and an increased risk of zoonotic transmission from STLV-1-infected non-human primates has been observed in African hunters. Finally, a general increase of HTLV-1 infection was observed in SWs, whereas only one paper described an increased prevalence for HTLV-2, supporting the urgent need for prevention and control measures, including screening, diagnosis, and treatment of HTLV-1/2, to be offered routinely as part of a comprehensive approach to decrease the impact of sexually transmitted diseases in SWs.

Differences in the demographic and clinical characteristics of patients infected with the Alpha and Delta SARS-CoV-2 variants of concern in a large region of Southern Italy were assessed. Two cohorts of positive patients were compared. The Alpha group consisted of 11,135 subjects diagnosed between 21 March and 21 April 2021, and the Delta group consisted of 499 positive subjects diagnosed between 21 July and 21 August 2021. A descriptive and statistical analysis of the demographic and clinical characteristics of the two groups was performed. The proportion of patients with mild and moderate infections was significantly higher in the Delta than in the Alpha group (p < 0.001). In fully vaccinated patients, the proportion of symptomatic individuals was significantly higher in the Delta than in the Alpha group. The Delta group showed odds ratios of 3.08 (95% CI, 2.55–3.72) for symptomatic infection and 2.66 (95% CI, 1.76–3.94) for hospitalization. Improving COVID-19 vaccination rates is a priority, since infection with the SARS-CoV-2 Delta variant has a significant impact on patient outcomes. Additional targeted prevention strategies such as social distancing, the use of masks in indoor settings irrespective of vaccination status, and the use of a sanitary passport could be crucial to contain further spread of SARS-CoV-2 infection.