Search Results (1,518)

Dopamine (DA) is a critical catecholaminergic neurotransmitter that facilitates signal transduction across synaptic junctions and modulates essential neurophysiological processes, including motor coordination, motivational drive, and reward-motivated behaviors. The fabrication of cost-effective, miniaturized, and high-fidelity analytical platforms is imperative for real-time DA monitoring. Due to its inherent electrochemical activity, carbon-based amperometric sensors constitute the primary modality for DA quantification. In this study, graphite, multi-walled carbon nanotubes (MWCNTs), and graphene were immobilized within an ethyl 2-cyanoacrylate (ECA) polymer matrix. ECA was selected for its rapid polymerization kinetics and established biocompatibility in electrochemical frameworks. All fabricated composites demonstrated robust electrocatalytic activity toward DA; however, MWCNT- and graphene-based sensors exhibited superior analytical performance, characterized by highly competitive limits of detection (LOD) and quantification (LOQ). Specifically, MWCNT-modified electrodes achieved an interesting LOD of 0.030 ± 0.001 µM and an LOQ of 0.101 ± 0.008 µM. Discrepancies in baseline current amplitudes suggest that the spatial orientation of carbonaceous nanomaterials within the cyanoacrylate matrix significantly influences the electrochemical surface area and resulting baseline characteristics. The impact of interfering species commonly found in biological environments on the sensors’ response was systematically evaluated. The best-performing sensor, the graphene-based one, was used to measure the DA intracellular content of PC12 cells. Full article

Bartonella henselae is a flea-borne zoonotic bacterium for which domestic cats constitute the principal reservoir. However, contemporary molecular epidemiological data from Portugal remain scarce. This retrospective laboratory study analysed EDTA-stabilised blood samples from apparently healthy cats submitted for routine screening by 74 veterinary centres across mainland Portugal and autonomous regions over an 11-year period (2015–2025). DNA extracts were tested using a species-specific TaqMan qPCR assay for B. henselae with an internal extraction control, and a subset of samples was subsequently confirmed by nested PCR followed by Sanger sequencing (ribC). Among 270 cats, 47 tested positive, yielding a qPCR prevalence of 17.4% (95% confidence interval [CI] 13.1–22.5). Submissions were predominantly from Northern Portugal, and infection status was not statistically associated with the Nomenclature of Territorial Units for Statistics (NUTS) level 2 region (p = 0.478). Infection was more frequent in younger cats (median age 2 years, interquartile range [IQR] 1–5; p = 0.037), while sex (p = 0.103) and breed (p = 0.730) were not significantly associated with infection status. These findings support endemic circulation of B. henselae in Portuguese cats at levels comparable to other temperate European regions. The detection of subclinical infection in apparently healthy cats is relevant to transfusion medicine and supports the inclusion of B. henselae qPCR screening in donor selection protocols. Full article

Background: Comprehensive genomic profiling (CGP) is a tool used in precision oncology to identify genomic alterations and match them with targeted therapies across several tumor types. However, real-world data on its clinical utility and impact remains limited. The FRONTAL study (Foundation Medicine Real wOrld evideNce in porTugAL) is a multicenter academic initiative that established a national registry of Portuguese patients with solid tumors who underwent CGP with FoundationOne CDx, Liquid CDx or FoundationOne Heme assays. Methods: Eligible patients had advanced solid tumors not suitable for curative treatment at the time of recruitment. Prior CGP testing was permitted if taken within 12 months before study initiation. Genomic profiling data were extracted from FoundationOne Medicine reports, and clinical information was extracted from medical records. Actionable alterations were defined as those associated with approved treatments or with clinical evidence of benefit in other cancers, per NCCN guidelines. Variant interpretation was also reviewed according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) guidelines. The primary outcome was disease control at 16 weeks, defined by the absence of progression. Results: The study included 205 patients between 2020 and 2025 across 10 sites, with colorectal (40, 19.5%), sarcomas (28, 13.7%), and other gastrointestinal tumors (22, 10.7%) being the most common pathologies. Actionable alterations were identified in 104 cases (50.7%). Genomic findings guided therapy decisions in 50 patients (24.4%), of whom 30 achieved disease control at 16 weeks (14.6%). Conclusions: The FRONTAL study highlighted the clinical relevance of CGP in advanced solid tumors. Over half of the patients had actionable alterations, a quarter had therapy changes based on CGP results, and improved disease outcome was observed in approximately 15% of the cohort. Full article

Coronary artery disease (CAD) remains the leading cause of cardiovascular mortality worldwide. Accurate and non-invasive quantification of coronary hemodynamics, namely in the right coronary artery (RCA), is essential for clinical decision-making but remains challenging due to the complex interaction among vessel geometry, pulsatile flow, and blood rheology. This study presents and validates a transparent computational framework for non-invasive fractional flow reserve (FFR) estimation using patient-specific RCA geometries reconstructed from coronary computed tomography angiography (CCTA) using SimVascular 27-03-2023. The proposed workflow integrates realistic boundary conditions through a Womersley velocity profile and a three-element Windkessel outlet model, coupled with a viscoelastic blood rheology formulation (sPTT) implemented via user-defined functions (UDFs). This work integrates all clinically relevant conditions of invasive FFR assessment into a single patient-specific computational framework, while delivering results within a time frame compatible with clinical practice, representing a meaningful methodological advance. The methodology was applied to seven patient-specific cases, and the resulting non-invasive FFR values were compared with both invasive wire-based measurements and commercial HeartFlow^® outputs (Mountain View, CA, USA). Under hyperemic conditions, the computed FFR values showed strong agreement with invasive references, with a mean relative error of 8.4% ± 6.3%, showing diagnostic consistency similar to that of HeartFlow^® (8.3% ± 8.1%) for the selected dataset. These findings demonstrate the ability of the proposed CFD-based pipeline to accurately replicate physiological coronary behavior under hyperemia. This novel workflow provides a fully on-site, open-source, reproducible, and cost-effective framework. Ultimately, this study advances the clinical applicability of non-invasive CFD tools for the functional assessment of CAD, particularly in the RCA. Full article

Pathological reduction in enzymatic activity of the tissue-non-specific alkaline phosphatase (TNSALP) is the molecular hallmark of hypophosphatasia (HPP), a group of rare inborn systemic diseases, mainly characterized by pathological affections of calcified tissue mineralization and the musculoskeletal system. The disease, in all clinical forms, is biochemically characterized by variable degrees of chronically reduced activity of circulating total alkaline phosphatase (ALP). Repeated detection of low values of ALP activity is mandatory to diagnose the presence of HPP, but, alone, it is not sufficient for the diagnosis of the disease. Detection of increased circulating levels of one of the main natural substrates of TNSALP, the pyridoxal 5′-phosphate (PLP), is needed to biochemically confirm the diagnosis of HPP. Urinary and/or blood levels of phosphoethanolamine (PEA) and inorganic pyrophosphate (PPi), two other natural substrates of TNSALP, can be elevated in a percentage of HPP patients. The contemporary biochemical evaluation of ALP activity and its target substrates is of great help in the diagnosis of HPP, and also for the monitoring of a patient’s response to enzymatic replacement therapy or other pharmacological treatments. Here, we describe and discuss possibilities and challenges of biochemical screenings for HPP, based also on the experience gained in our analysis laboratory. Full article

This paper presents the design and implementation of the Power Stage GAIA (PSG), a high-current digital bias board developed by the Italian National Institute for Astrophysics (INAF) to extend the capabilities of the GAIA bias system. The PSG was developed within the Advanced European THz Receiver Array (AETHRA) project to support next-generation cryogenic receivers for millimeter-wave astronomy. Specifically, the AETHRA Work Package 1 (WP1) W-band downconverter integrates Monolithic Microwave Integrated Circuits (MMICs) requiring currents significantly exceeding the 50 mA limit of standard bias boards. To address these requirements, the PSG introduces a modular extension providing ten independent channels, each capable of delivering up to 500 mA with a programmable output range of 0–5 V. A key feature of the design is the adoption of a fully linear architecture based on LT1970 power amplifiers and INA225 precision sensors managed via an I²C digital interface. This approach ensures the high current capability required by modern power amplifiers while strictly avoiding the spectral noise and Radio Frequency Interference (RFI) typical of switching power supplies. Experimental validation confirms the system’s robustness and precision: the board demonstrated linear operation up to 460 mA and exceptional long-term stability, with a measured RMS voltage deviation below 50 µV. These results establish the PSG as a scalable, low-noise solution suitable for biasing high-power MMICs in future cryogenic receiver arrays. Full article

Background/Objectives: Patients with complex chronic disorders constitute a growing share of the general population and are frequently hospitalised for acute care in Internal Medicine Departments. Little is known about long-term rates and predictors of post-discharge mortality, possibly contributing to suboptimal and discontinuous care, including delayed referral to palliative programmes. Methods: To assess the long-term post-discharge mortality of patients admitted to Internal Medicine Departments and its predictors, we analysed a cohort of old, multi-morbid subjects, corresponding to the whole population of patients admitted to an Internal Medicine Department over 12 months (February 2016–March 2017). Public health registries were interrogated to assess the five-year mortality (up to 2022) of patients discharged alive. Results: Post-discharge mortality was 57% at follow-up end, with an early peak rate of 32% at year 1, a 10–14% intermediate rate at years 2–4, and a 7% late rate, approaching expected figures in the general population. Cancer, neurological and liver disorders, and respiratory failure were significantly associated with early and intermediate mortality, while renal disorders, dependence for daily activities, and immunodepression were selectively relevant for death in the first year. Cardiovascular and upper gastrointestinal disorders were associated with late mortality. Surrogate measures of frailty, intensity of care, and patient complexity were also able to predict early-, intermediate-, and late-mortality risk. Conclusions: A relevant fraction of patients hospitalised in Internal Medicine Departments might require palliative care. Dissecting the differential contribution of clinical and healthcare-associated variables for short, medium-, and long-term mortality might facilitate patient management and identify subjects in need of early or simultaneous palliative care. Full article

Neurodevelopmental disorders (NDDs) are a heterogeneous group of conditions characterised by impairments in cognition, motor function, behaviour, and social interaction. Their genetic basis is highly diverse, and next-generation sequencing has become central to improving diagnostic yield. We retrospectively analysed 94 paediatric patients (0–18 years) with NDDs referred to the Paediatric and Rare Diseases Clinic, Microcitemico Hospital “A. Cao,” between January 2019 and July 2024. Each patient underwent detailed clinical evaluation and whole-exome sequencing (WES). Variants were prioritised according to ACMG guidelines. Gene burden analysis of rare predicted loss-of-function variants was performed using the Cohort Allelic Sums Test to detect enrichment in NDD cases relative to controls. WES identified 12 pathogenic variants, 16 likely pathogenic variants, and 10 variants of uncertain significance. Autosomal dominant disorders were the most frequent (n = 35 patients), while autosomal recessive and X-linked dominant conditions were identified in a single case each. The findings of this study further highlight the importance of WES in identifying novel genetic variants and in providing explanations for previously unexplained NDD cases. Moreover, the Cohort Allelic Sums Test (CAST) demonstrated that rare variants are enriched in genes implicated in neuronal development in affected individuals. Full article

Background: Behçet-like syndrome (BLS) refers to the presence of Behçet’s disease (BD) features occurring in association with distinct clinical–pathological conditions such as inborn errors of immunity, myeloproliferative disorders, infections, or drug exposure. BLS may differ clinically from BD and is increasingly recognized as a separate entity. Distinguishing BLS from primary BD is essential for appropriate management, and studying BLS may provide insights into BD pathogenesis. Objectives: To summarize clinical features, treatments, and genetic abnormalities reported in BLS, we reviewed all published cases up to January 2024. Methods: A systematic search of PubMed, Scopus, and Embase was performed using the terms “Behçet-like syndrome”, “Behçet-like disease”, and “Pseudo-Behçet disease”. We included English-language reports of patients > 12 years old with a defined underlying etiology and Behçet-like manifestations, defined by ≥2 ICBD criteria and/or gastrointestinal involvement, mucosal ulcers, thrombosis, or non-recurrent disease. Epidemiological, clinical, laboratory, histological, and treatment data were extracted and analyzed descriptively. Results: Of 679 publications, 53 met inclusion criteria, comprising 100 patients with BLS. The median age was 44 years (IQR 22–52), with a female predominance (1:2). Fifty-three percent were from non-European countries. A genetic disorder was identified in 70% of cases, while HLA-B51 was present in 10%. Frequent manifestations included skin lesions (68%), fever (56%), intestinal involvement (43%), and joint symptoms (43%). Treatments included glucocorticoids (65%), conventional DMARDs (32%), and biologics (22%), mainly anti-TNF agents. Antiviral/antibiotic therapy was used in 9% and chemotherapy in 15%. Two patients with trisomy-8 MDS underwent allogeneic stem cell transplantation. Conclusions: Diverse conditions—including monogenic diseases, immune defects, myeloproliferative disorders, infections, and drug-related reactions—can produce Behçet-like features. Our findings highlight differences in clinical expression and treatment response across BLS etiologies. Recognizing BLS is essential for appropriate management and may contribute to a deeper understanding of BD pathogenesis and future targeted therapies. Full article

Port wine production involves the addition of grape spirit to halt fermentation and retain natural sweetness. This spirit, produced by distilling wine and its by-products, must comply with legal standards, including a mandatory sensory assessment. Because grape spirit influences Port wine’s volatile composition, this study investigated the odour-active compounds present in several grape spirits intended for fortification. Volatile compounds were extracted by liquid–liquid extraction, concentrated, and analysed using gas chromatography–olfactometry (GC-O) and gas chromatography–mass spectrometry (GC-MS). In GC-O, based on frequency detection, a panel of assessors sniffed the extracts to determine the presence of aroma compounds. The results revealed a wide range of odour-active compounds in grape spirits, belonging to several chemical families such as esters, alcohols, terpenic compounds and acids. These compounds exhibited both pleasant aromas, such as fruity, floral and caramel notes as well as undesirable ones like cheese and foot odour. Most of these compounds originate from the fermentation process and are also found in other unaged distilled beverages, including young Cognac, Calvados and fruit spirits. This research highlights the aromatic complexity of grape spirits and, for the first time, determined the aroma thresholds for 25 of 36 the compounds studied at an ethanol content of 20%. Full article

Background: Hospitalisation for paediatric oncohaematological diseases entails significant physical and psychological stress, often compromising children’s emotional regulation and daily functioning. In this context, complementary interventions can provide additional support to the clinical work conducted with children and adolescents undergoing treatment, fostering emotional awareness and well-being. This study evaluates the feasibility and perceived benefits of an animal-assisted psychoeducational intervention to enhance emotional coping during hospitalisation. Methods: A single-centre observational study was conducted at Regina Margherita Children’s Hospital in Italy in collaboration with the ZOOM Foundation (Turin, Italy), between September 2023 and May 2025. Sixty patients aged 6–15 years participated in an intervention combining observation of an in-ward aquarium, virtual animal encounters, and completion of a psychoeducational booklet promoting emotional reflection through symbolic identification with animal behaviours. Results: The intervention showed high feasibility and acceptability: 90% of participants (54/60) reported positive emotions and enjoyment, 80% (48/60) found the booklet engaging, and all participants (100%) perceived care and attention from facilitators. The activities fostered engagement, curiosity, and well-being, though their impact on deeper emotional processing appeared limited. Conclusions: Animal-assisted psychoeducational interventions are feasible and well-received in paediatric oncohaematology, offering complementary support to clinical care by promoting emotional resilience and enriching the hospital experience. Full article

Dental caries is a multifactorial chronic infectious disease that impacts healthcare costs globally, caused by alterations of the plaque microbiome and proliferation of cariogenic Streptococcus mutans. Treatments targeting S. mutans, such as alternative strategies using probiotics, might be effective in preventing the development of dental caries. In this study, the probiotic formulation of Lactobacillus reuteri SGL01, vitamin C, and acerola was tested against S. mutans DSM20523. Antimicrobial activity was assessed by deferred antagonism and spot-on-lawn assays for L. reuteri SGL01. MIC and MBC of L. reuteri SGL01 cell-free supernatant (CFS), vitamin C, and acerola were determined with the microdilution method. Time–kill assays determined the bactericidal kinetics for each compound. The checkerboard method was used to evaluate the potential synergistic activity of CFS–vitamin C or CFS–acerola at scalar dilutions from 1 to 8X MIC. Lastly, antibiofilm activity was tested for each compound. Antimicrobial activity of L. reuteri SGL01 was first assessed by classic methods. MIC and MBC values differed for one dilution for all compounds, with values of 25% and 50% for CFS, 9.3 mg/mL and 18.7 mg/mL for vitamin C, and 18.7 mg/mL and 37.5 mg/mL for acerola, respectively. Moreover, time–kill assays confirmed the bactericidal activity at different timepoints: 4 h for CFS, 6 h for vitamin C, and 24 h for acerola. The fractional inhibitory concentration index (FICI) showed indifference for all combinations, and for associations tested at 2, 4, and 8XMIC. S. mutans biofilm production was impaired for all components, with stronger activity by vitamin C and acerola at lower concentrations. The probiotic formulation containing L. reuteri SGl01, vitamin C, and acerola extract exerts a bactericidal effect, especially strong for the CFS, as well as antibiofilm activity. Thus, the combination of these three components could be advantageous for their complementary effects, with use as a novel treatment against the development of dental caries by S. mutans. Full article

Stromboli’s volcanic activity fluctuates in intensity and style, and periods of heightened activity can trigger hazardous events such as crater collapses and lava overflows. This study investigates the volcano’s explosive behavior surrounding the 19 May 2021 crater-rim failure, which primarily affected the N2 crater and partially involved N1, by integrating high-frequency thermal imaging and high-resolution unmanned aerial system (UAS) surveys to quantify eruption parameters and vent morphology. Typically, eruptive periods preceding vent instability are characterized by evident changes in geophysical parameters and by intensified explosive activity. This is quantitatively monitored mainly through explosion frequency, while other eruption parameters are assessed qualitatively and sporadically. Our results show that, in addition to explosion rate, the spattering rate, the predominance of bomb- and gas-rich explosions, and the number of active vents increased prior to the collapse, reflecting near-surface magma pressurization. UAS surveys revealed that the pre-collapse configuration of the northern craters contributed to structural vulnerability, while post-collapse vent realignment reflected magma’s adaptation to evolving stress conditions. The May 2021 events were likely influenced by morphological changes induced by the 2019 paroxysms, which increased collapse frequency and amplified the 2021 failure. These findings highlight the importance of integrating quantitative time series of multiple eruption parameters and high-frequency morphological surveys into monitoring frameworks to improve early detection of system disequilibrium and enhance hazard assessment at Stromboli and similar volcanic systems. Full article

Background/Objectives: Patients in need of specialized palliative care are clinically highly complex, with pain being the most prevalent problem. Furthermore, in these patients, a self-report for characterization of pain could be difficult to obtain. This cross-sectional, exploratory study investigates the use of clinical parameters and peripheral blood biomarkers for potentially identifying and characterizing pain (assessed using Pain Assessment in Advanced Dementia (PAINAD) and Numeric Scale (NS)) in patients under palliative care, including a population with dementia where pain is often underdiagnosed. Methods: Fifty-three patients with non-oncological diseases were analyzed in a cross-sectional study using medical and nursing records. Among previous biomarkers related to monocytes and platelets assessed by flow cytometry, we selected the most significative ones for pain characterization in a logistic regression analysis (multivariate analysis), alongside patient-specific characteristics such as renal function, nutritional status, and age. Results: Our exploratory findings suggest strong relationships between chronic pain and advanced age, reduced glomerular filtration rate (GFR), and malnutrition within this cohort. Furthermore, the percentage of lymphocytes, total and classical monocytes, the relative expression in monocytes of CD206, CD163, the CD163/CD206 ratio, and the relative expression in platelets of CD59 emerged as potential predictors of pain. Statistical analyses highlighted the challenges of multicollinearity among variables such as age, GFR, and nutritional status. A classification model further suggested that all patients over 65 years in our specific sample reported pain. Conclusions: This pilot study provides preliminary support for prior evidence linking chronic pain to aging, nutritional deficits, and renal impairment, and highlights potential novel peripheral blood biomarkers for pain assessment. This work emphasizes the promise of clinical and molecular biomarkers to improve pain detection and management, contributing to personalized and effective palliative care strategies. Full article

BTK (Bruton’s tyrosine kinase) has become a key therapeutic target across several hematologic diseases, beginning with its original use in CLL/SLL. As a central mediator of B-cell receptor signaling and microenvironment interactions, BTK supports survival, proliferation, and trafficking in multiple mature B-cell malignancies (mantle cell lymphoma, marginal zone lymphoma, Waldenström macroglobulinemia, and other indolent/aggressive lymphomas) and in selected immune-mediated conditions such as chronic graft-versus-host disease. Covalent BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib) irreversibly bind the C481 residue and have produced high response rates and durable disease control, often replacing chemoimmunotherapy in the relapsed setting and, for some entities, even in the first line. Differences in kinase selectivity lead to different safety profiles: second-generation covalent agents generally maintain efficacy while reducing significant off-target toxicities, especially atrial fibrillation and hypertension. Resistance to covalent BTK inhibitors most commonly develops through BTK C481 substitutions and activating PLCG2 mutations, with other kinase-domain variants increasingly recognized. Non-covalent BTK inhibitors (e.g., pirtobrutinib) bind BTK independently of C481, can overcome classic C481-mediated resistance, and extend BTK pathway targeting into later lines of therapy. Overall, BTK inhibition has evolved into a versatile platform enabling long-term, often chemo-free management strategies. Full article