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Brucellosis represents a major public health concern worldwide. Human transmission is mainly due to the consumption of unpasteurized milk and dairy products of infected animals. The gold standard for the diagnosis of Brucella spp in ruminants is the bacterial isolation, but it is time-consuming. Polymerase Chain Reaction (PCR) is a quicker and more sensitive technique than bacterial culture. Droplet digital PCR (ddPCR) is a novel molecular assay showing high sensitivity in samples with low amount of DNA and lower susceptibility to amplification inhibitors. Present study aimed to develop a ddPCR protocol for the detection of Brucella abortus in buffalo tissue samples. The protocol was validated using proficiency test samples for Brucella spp by real time qPCR. Furthermore, 599 tissue samples were examined. Among reference materials, qPCR and ddPCR demonstrated same performance and were able to detect up to 225 CFU/mL. Among field samples, ddPCR showed higher sensitivity (100%), specificity and accuracy of 93.4% and 94.15%, respectively. ddPCR could be considered a promising technique to detect B. abortus in veterinary specimens, frequently characterized by low amount of bacteria, high diversity in matrices and species and poor storage conditions.

Math affect (i.e., attitudes/beliefs about math) and feedback are predictors of mathematical performance. How these factors jointly influence cognition during mathematical problem-solving is less understood. A computer mouse-tracking task was used to assess math affect and computation ability of 78 undergraduate volunteers, before and after feedback (none; positive; negative). Positive affect toward math significantly predicted better accuracy on mathematical computations, but performance improved noticeably after positive feedback. This led to the question of whether or not feedback and affective components of math impact decision-making. Post-baseline, participants' ability to calculate the mathematical problems sped up significantly — evidence of a practice effect. Individuals with more negative attitudes toward math exhibited more indecision in their responses when they received feedback, whereas participants with more positive attitudes toward computation reduced their indecision after feedback. This suggests that feedback interacts with math affect in important ways, impacting in-the-moment cognitive processing during mathematical calculation.

Abstract Background Chronic Kidney Disease (CKD) is characterized by a methionine-related metabolic disorder involving reduced plasma levels of hydrogen sulfide (H2S) and increased lanthionine. The gut microbiota influences methionine metabolism, potentially impacting sulfur metabolite dysfunctions in CKD. We evaluated whether gut microbiota dysbiosis contributes to H2S and lanthionine metabolic alterations in CKD. Methods The gut microbiota of 88 CKD patients (non-dialysis, hemodialysis, and transplant patients) and 26 healthy controls were profiled using 16 S-amplicon sequencing. H2S and lanthionine concentrations were measured in serum and fecal samples using the methylene blue method and LC-MS/MS, respectively. Results The CKD population exhibited a tenfold increase in serum lanthionine associated with kidney dysfunction. Despite lanthionine retention, hemodialysis and transplant patients had significantly lower serum H2S than healthy controls. Fecal H2S levels were not altered or related to bloodstream H2S concentrations. Conversely, fecal lanthionine was significantly increased in CKD compared to healthy controls and associated with kidney dysfunction. Microbiota composition varied among CKD groups and healthy controls, with the greatest dissimilarity observed between hemodialysis and transplant patients. Changes relative to the healthy group included uneven Ruminococcus gnavus distribution (higher in transplant patients and lower in non-dialysis CKD patients), reduced abundance of the short-chain fatty acid-producing bacteria Alistipes indistinctus and Coprococcus eutactus among transplant patients, and depleted Streptococcus salivarius in non-dialysis CKD patients. A higher abundance of Methanobrevibacter smithii, Christensenella minuta, and Negativibacillus massiliensis differentiated hemodialysis patients from controls. No correlation was found between differentially abundant species and the metabolic profile that could account for the H2S and lanthionine alterations observed. Conclusions The metabolic deregulation of H2S and lanthionine observed in the study was not associated with alterations in the gut microbiota composition in CKD patients. Further research on microbial sulfur pathways may provide a better understanding of the role of gut microbiota in maintaining H2S and lanthionine homeostasis.

Abstract Introduction Multiple sclerosis (MS) is a chronic neurodegenerative disease that leads to impaired cognitive function and accumulation of disability, with significant socioeconomic burden. Serious unmet need in the context of managing MS has given rise to ongoing research efforts, leading to the launch of new drugs planned for the near future, and subsequent concerns about the sustainability of healthcare systems. This study assessed the changes in the Italian MS market and their impact on the expenditures of the Italian National Healthcare Service between 2023 and 2028. Methods A horizon-scanning model was developed to estimate annual expenditure from 2023 to 2028. Annual expenditure for MS was calculated by combining the number of patients treated with each product (clinical inputs) and the yearly costs of therapy (economic inputs). Baseline inputs (2020–2022) were collected from IQVIA® real-world data, while input estimation for the 5-year forecast was integrated with analog analyses and the insights of clinicians and former payers. Results The number of equivalent patients treated in 2028 in Italy was estimated at around 67,000, with an increase of 10% versus 2022. In terms of treatment pattern evolution, first-line treatments are expected to reduce their shares from 47% in 2022 to 27% in 2028, and Bruton tyrosine kinase inhibitors are expected to reach 23% of patient shares. Overall, expenditure for MS is estimated to decrease from €721 million in 2022 to €551 million in 2028, mainly due to losses of exclusivity and renegotiation of drug prices. Conclusion Despite the increase in the number of patients treated for MS and the launch of new molecules that will reach high market penetration, the model confirmed sustainability for the Italian National Healthcare Service.

Herein, we present the design and fabrication of a portable biochemical sensor based on the Screen Printed Electrode (SPE) concept and applied for detecting interleukin-6 (IL-6), a key player in the complex process of inflammation, in real human saliva. The sensing mechanism relies on the antigen-antibody binding between the IL-6 molecule and its antibody immobilized over a surface of a Thermally Exfoliated Graphene Oxide (TEGO) layer. TEGO, deposited by Aerosol Jet Printing (AJP), provides advantages in terms of a time/cost consumingfast, easy and efficient biofunctionalization. The biosensor shows a dynamic range comprising IL-6 concentrations falling within the normal IL-6 levels in saliva. An extensive analysis of device performance, focused on the assessment of the sensor Limit of Detection (LoD) by two modes (i.e. from the lin-log calibration curve and from blank measurements), provides a best value of about 1 × 10−2 pg/ml of IL-6 in saliva. Our work aims at providing a contribution toward applications in real environment, going beyond a proof of concept or prototyping at lab scale. Hence, the characterization of the sensor was finalized to find a reliable device-to-device reproducibility and calibration through the introduction of a measurement protocol based on comparative measurements between saliva samples without (blank) and with IL-6 spiked in it, in place of the standard addition method used in daily laboratory practice. Device-to-device reproducibility has been accordingly tested by acquiring multiple experimental points along the calibration curve using different individual devices for each point.

Abstract Herein, additive manufacturing, which is extremely promising in different sectors, has been adopted in the electrical energy storage field to fabricate efficient materials for supercapacitor applications. In particular, Al2O3-, steel-, and Cu-based microparticles have been used for the realization of 3D self-assembling materials covered with reduced graphene oxide to be processed through additive manufacturing. Functionalization of the particles with amino groups and a subsequent "self-assembly" step with graphene oxide, which was contextually partially reduced to rGO, was carried out. To further improve the electrical conductivity and AM processability, the composites were coated with a polyaniline-dodecylbenzene sulfonic acid complex and further blended with PLA. Afterward, they were extruded in the form of filaments, printed through the fused deposition modeling technique, and assembled into symmetrical solid-state devices. Electrochemical tests showed a maximum mass capacitance of 163 F/g, a maximum energy density of 15 Wh/Kg at 10 A/g, as well as good durability (85% capacitance retention within 5000 cycles) proving the effectiveness of the preparation and the efficiency of the as-manufactured composites.

Abstract Environmental pollutants from different chemical families may reach the gut microbiome, where they can be metabolized and transformed. However, how our gut symbionts respond to the exposure to environmental pollution is still underexplored. In this observational, cohort study, we aim to investigate the influence of environmental pollution on the gut microbiome composition and potential activity by shotgun metagenomics. We select as a case study a population living in a highly polluted area in Campania region (Southern Italy), proposed as an ideal field for exposomic studies and we compare the fecal microbiome of 359 subjects living in areas with high, medium and low environmental pollution. We highlight changes in gut microbiome composition and functionality that were driven by pollution exposure. Subjects from highly polluted areas show higher blood concentrations of dioxin and heavy metals, as well as an increase in microbial genes related to degradation and/or resistance to these molecules. Here we demonstrate the dramatic effect that environmental xenobiotics have on gut microbial communities, shaping their composition and boosting the selection of strains with degrading capacity. The gut microbiome can be considered as a pivotal player in the environment-health interaction that may contribute to detoxifying toxic compounds and should be taken into account when developing risk assessment models. The study was registered at ClinicalTrials.gov with the identifier NCT05976126.

Abstract Background Brain injury in hereditary hemoglobinopathies is commonly attributed to anemia-related relative hypoperfusion in terms of impaired oxygen blood supply. Supratentorial and infratentorial vascular watershed regions seem to be especially vulnerable, but data are very scarce. Aims We investigated a large beta-thalassemia sample with arterial spin labeling in order to characterize regional perfusion changes and their correlation with phenotype and anemia severity. Methods We performed a multicenter single-scanner cross-sectional 3T-MRI study analyzing non-invasively the brain perfusion in 54 transfusion-dependent thalassemia (TDT), 23 non-transfusion-dependent thalassemia (NTDT) patients and 56 Healthy Controls (HC). Age, hemoglobin levels, and cognitive functioning were recorded. Results Both TDT and NTDT patients showed globally increased brain perfusion values compared to healthy controls, while no difference was found between patient subgroups. Using age and sex as covariates and scaling the perfusion maps for the global cerebral blood flow, beta-thalassemia patients showed relative hyperperfusion in supratentorial/infratentorial watershed regions. Perfusion changes correlated with hemoglobin levels (p = 0.013) and were not observed in the less severely anemic patients (hemoglobin level > 9.5 g/dL). In the hyperperfused regions, white matter density was significantly decreased (p = 0.0003) in both patient subgroups vs. HC. In NTDT, white matter density changes correlated inversely with full-scale Intelligence Quotient (p = 0.007) while in TDT no correlation was found. Conclusion Relative hyperperfusion of watershed territories represents a hemodynamic hallmark of beta-thalassemia anemia challenging previous hypotheses of brain injury in hereditary anemias. A careful management of anemia severity might be crucial for preventing structural white matter changes and subsequent long-term cognitive impairment.

IntroductionBacterial infection of the central nervous system (CNS) poses a clinical challenge and is a leading cause of neurological disorders in cattle. Human studies have demonstrated an increase in cerebrospinal fluid (CSF) L-lactate levels in bacterial meningitis. The aims of this study were to establish a Reference Interval (RI) for L-lactate in bovine CSF and assess its potential as a biomarker for detecting infectious-inflammatory disorders.MethodsCSF L-lactate was measured in the field using a commercially available lactate monitor. The RI for CSF L-lactate was calculated on healthy animals; univariate and receiver operating characteristic (ROC) analyses were performed to disclose an association between CSF L-lactate levels and interpretation of CSF in sick animals.ResultsTwenty-seven healthy cattle and 86 sick cattle with either CNS infectious-inflammatory disorders (47/86) or CNS disorders of other etiology (39/86) were included in this prospective study. The RI for CSF L-lactate was 1.1–2.4 mmol/L. The concentration was higher in the cattle with neutrophilic pleocytosis and the area under the ROC curve was 0.92 compared to other animals. Based on a cut-off of 3.15 mmol/L, CSF L-lactate had diagnostic sensitivity and specificity for neutrophilic pleocytosis of 93 and 80%, respectively.DiscussionThis is the first study to determine a RI for CSF L-lactate in cattle. Elevated CSF L-lactate levels indicated neutrophilic pleocytosis, which is often manifested in acute bacterial infection. The present findings may aid in diagnosis and correct use of antimicrobial drugs.

Abstract Magneto‐plasmonic particles, comprising gold and iron oxide, exhibit substantial potential for biosensing applications due to their distinct properties. Gold nanoparticles (AuNPs) provide plasmonic features, while iron oxide composites, responsive to an external magnetic field, significantly reduce detection time compared to passive diffusion. This study explores core@satellite magneto‐plasmonic particles (CSMPs), featuring magnetic nanoparticle clusters and numerous satellite‐like AuNPs, to amplify the optical response on a nanostructured gold surface. Using a sandwich scheme, target analytes are detected as hybrid nanoparticles bind to the pre‐immobilized target on the AuNPs surface, inducing changes in the immunosensor's extinction spectrum. Application of an external magnetic field notably enhances biosensor response and sensitivity, reducing assay time from hours to minutes. Leveraging the properties of CSMPs, the immunosensor detects specific immune protein at low concentrations within minutes. CSMPs hold considerable promise for precise and sensitive analyte detection, offering potential applications in rapid testing and mass screening.

BackgroundTelerehabilitation (TR) offers a valuable opportunity to improve access to care and has shown results comparable to onsite rehabilitation (SR) across different conditions. The present study aimed to explore the efficacy of TR and SR in improving clinically meaningful outcomes in people with multiple sclerosis (pwMS).Materials and methodsSubjects enrolled in the study were assigned to one of two treatment arms: a 6-week TR intervention or a 6-week onsite rehabilitation (SR) intervention. Pre-and post-intervention evaluation included assessment of global wellbeing using the Multiple Sclerosis Quality of Life-54 scale (QoL), fatigue using the Fatigue Severity Status scale (FSS), cognitive status using the Symbol Digit Modalities Test (SDMT), and balance dysfunction using the Berg Balance Scale (BBS). Group-level and single-subject improvements were considered as outcome measures, with QoL as the primary endpoint. To determine significant group changes over time for the entire pwMS cohort, a paired t-test was applied to the overall QoL score, focusing on both physical and mental composites. An independent sample t-test was used to assess differences in baseline and follow-up performance, as well as changes over time between the intervention groups (TR and SR). This same analysis was repeated for the other clinical domains (FSS, BBS, and SDMT). The minimal clinically important difference (MCID) according to treatment group (TR vs. SR) was explored using logistic regression. Additionally, a multiple linear regression model was applied to evaluate the impact of baseline clinical-demographic features on the observed post-intervention modifications.ResultsA total of 51 subjects completed the study (37 women, mean age 46.3 ± 9.8, median Expanded Disability Status Scale 3.5, min. 2, max. 6.5). The entire sample benefited from the rehabilitation treatment, with significant improvements observed at both the group and individual levels across all measured domains for both intervention groups (TR vs. SR). Quality of life improved significantly (p = 0.005), as did fatigue and balance (both p < 0.001), and cognition (p = 0.003).ConclusionsBoth SR and TR approaches effectively improved the perception of fatigue, cognitive performance, balance, and quality of life in a population of MS patients with moderate disability.

Background and purposeClinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation.MethodLogistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number.ResultsFrom March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p

Pathogen infections constitute a serious problem in the field of lung diseases, especially in severe conditions such as chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). Exacerbations of COPD and ARDS can be significantly influenced by bacterial infections from Pseudomonas aeruginosa and Staphylococcus aureus, which can hasten the decline of lung function. Moreover, the abuse of high-dose antibiotics used to treat obstinate infections is contributing to the growing issue of multidrug resistance (MDR) by microorganisms. Currently, new therapeutic strategies capable of surprising and fighting pathogens with new modalities are missing. In this framework, bio-composite nanogels (NGs) based on natural polymers with intrinsic antimicrobial properties such as chitosan (CS) and hyaluronic acid (HA) have been developed for the treatment of lung infections. The DLS and TEM results showed that NGs have a spherical shape with a size smaller than 100 nm, making it possible for them to potentially reach the lung site and evade the clearance of alveolar macrophages. FTIR spectra demonstrated that only electrostatic interactions, not chemical reactions, occur between NG precursors. Rheological analysis highlighted NGs’ injectability and mucoadhesive capacity. Moreover, an MTT assay on human lung fibroblast cells for biocompatibility evaluation showed good viability up to 48 h. Finally, an antimicrobial test on P. aeruginosa and S. aureus showed an increase in antimicrobial activity as the NG concentration increases, with a reduction in bacterial growth of around 60% at 375 μg/mL.

Patient-reported outcomes (PROs) are essential for understanding the effects of MS and its treatments on patients’ lives; they play an important role in multiple sclerosis (MS) research and practice. We present the protocol for an observational study to prospectively assess the effect of cladribine tablets on PROs and their correlation to disability and physical activity in adults with highly active relapsing MS switching from a first disease modifying drug (DMD) to cladribine tablets in routine clinical practice at study sites in Italy. The primary objective will be to evaluate changes from baseline in the impact of highly active MS on self-assessed physical functioning 52 weeks after the switch to cladribine tablets using the Multiple Sclerosis Impact Scale-29 (MSIS-29). Secondary objectives will include self-assessed psychological impact of highly active MS in daily life and general health after the switch to cladribine tablets as well as changes in cognitive function, anxiety, and depression symptoms. Additional PRO measures will include the Hospital Anxiety and Depression Scale (HADS), the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI:MS), and the Patient-Reported Outcomes Measurement Information System (PROMIS). Wearable devices will acquire activity data (step counts, walking speed, time asleep, and energy expenditure). Additional clinical, radiological, and laboratory data will be collected when available during routine management. The findings will complement data from controlled trials by providing insight from daily clinical practice into the effect of cladribine tablets on the patient’s experience and self-assessed impact of treatment on daily life.

This study examined repeating and growing pattern knowledge and their associations with procedural and conceptual arithmetic knowledge in a sample of U.S. children (N = 185; M[subscript age] = 79.5 months; 55% female; 88% White) and adults (N = 93; M[subscript age] = 19.5 years; 62% female; 66% White) from 2019 to 2020. Three key findings emerged: (1) repeating pattern tasks were easier than growing pattern tasks, (2) repeating pattern knowledge robustly predicted "procedural" calculation skills over and above growing pattern knowledge and covariates, and (3) growing pattern knowledge modestly predicted "procedural" and "conceptual" math outcomes over and above repeating pattern knowledge and covariates. We expand existing theoretical models to incorporate these specific links and discuss implications for supporting math knowledge.

Research in psychology and education indicates that corrective feedback can be a powerful learning tool. We provide a developmental perspective to focus specifically on how corrective feedback influences learning in childhood ([approximately]ages 3-11). Based on a systematic search, we review 44 empirical papers published between 1990 and 2022 examining the effects of corrective feedback on children's performance in the domains of literacy (n = 18), mathematics (n = 14), and problem solving (n = 12). Across these domains, we synthesize research on how children respond to lessons and practice with, versus without, corrective feedback to provide theoretical and practical insights into (1) the effectiveness of corrective feedback in early childhood, (2) the features of effective feedback messages at different ages, and (3) the role of individual learner differences. We make several novel recommendations with some focused on future research questions and others focused on ways teachers can provide effective feedback to children.

The production of spherical powders has recently registered a boost due to the need to fabricate new printing materials for Additive Manufacturing applications, from polymers and resins to metals and ceramics. Among these materials, stainless steels powders play a leading role, since they are widely used in industry and everyday life; indeed, micron-sized spherical stainless steel powders have specific characteristics and are considered as one of the best candidates for Additive Manufacturing systems and for application in a wide range of sectors. In this paper, stainless steel 316 L powders were used to explore and identify the best process parameters of a thermal plasma process able to produce spherical powders for Additive Manufacturing applications. X-ray Diffraction, Scanning Electron Microscopy, Particle Size Distribution and Flowability analysis were performed to characterize reagents and products. Powders with a high circularity (>0.8) and improved flowability (

Antimicrobial resistance is a growing concern for the scientific community and the public, so many countries have stepped up monitoring to tackle it and promote correct antimicrobial use. The welfare assessment protocol for dairy cows used by the Italian National Reference Centre for Animal Welfare (CReNBA) recommends lowering the use of antibiotics, so this study assessed the effects of the introduction of the welfare score on antimicrobial use and animal welfare between 2015 and 2018. For this study, 23 dairy farms in northern Italy (Piedmont) were enrolled. Data on animal categories (calf, heifer and cow) and antimicrobial use were extrapolated from mandatory farm registers. The antimicrobial animal-defined daily dose (ADDD) and the ADDD per year (ADDD/year) were calculated. Each farm was evaluated with the CReNBA welfare assessment protocol for dairy cows. An increase was recorded for 2018 regarding the number of reared animals (especially adult cows) and in the welfare (2015: 71.44% ± 7.84% vs. 2018: 76.18% ± 6.40%; p

Background and purposeSome studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID-19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID-19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID-19 severity amongst PwMS.MethodsData were retrieved from an Italian web-based platform (MuSC-19) which includes PwMS with COVID-19. PM2.5 2016-2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID-19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID-19 severity.ResultsIn all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID-19 course (odds ratio 1.90; p = 0.009).ConclusionsEven if several other factors explain the unfavourable course of COVID-19 in PwMS, the role of air pollutants must be considered and further investigated.