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A novel method for improving plant disease classification, a challenging and time-consuming process, is proposed. First, using as baseline EfficientNet, a recent and advanced family of architectures having an excellent accuracy/complexity trade-off, we have introduced, devised, and applied refined techniques based on transfer learning, regularization, stratification, weighted metrics, and advanced optimizers in order to achieve improved performance. Then, we go further by introducing adaptive minimal ensembling, which is a unique input to the knowledge base of the proposed solution. This represents a leap forward since it allows improving the accuracy with limited complexity using only two EfficientNet-b0 weak models, performing ensembling on feature vectors by a trainable layer instead of classic aggregation on outputs. To the best of our knowledge, such an approach to ensembling has never been used before in literature. Our method was tested on PlantVillage, a public reference dataset used for benchmarking models' performances for crop disease diagnostic, considering both its original and augmented versions. We noticeably improved the state of the art by achieving 100% accuracy in both the original and augmented datasets. Results were obtained using PyTorch to train, test, and validate the models; reproducibility is granted by providing exhaustive details, including hyperparameters used in the experimentation. A Web interface is also made publicly available to test the proposed methods.

BACKGROUND:Peritumoral inflammation-a response mainly involving polimorphonuclear neutrophils-has traditionally been thought protumoral in its effects. In recent years, however, a number of studies have indicated that it may play an important antitumoral role. This discrepancy has been difficult to explain. METHODS AND FINDINGS:This work describes a tool for simulating tumor growth that obeys the universal model of tumor growth dynamics, and shows through its use that low intensity peritumoral inflammation exerts a protumoral effect, while high intensity inflammation exerts a potent antitumoral effect. Indeed, the simulation results obtained indicate that a sufficiently strong antitumoral effect can reverse tumor growth, as has been suggested several times in the clinical literature. CONCLUSIONS:The present result indicate that an 'immunological threshold' must exist, marking the boundary between states in which peritumoral inflammation is either harmful or beneficial. These findings lend support to the idea that stimulating intense peritumoral inflammation could be used as a treatment against solid tumors.

There is evidence that polymorphonuclear neutrophils (PMNs) can exert severe antineoplastic effects. Cross-talk between tumour cells and endothelial cells (ECs) is necessary for the accumulation of PMN around a tumour. This work reports the ability of two PMN-sensitive, human, permanent cell lines—colorectal adenocarcinoma (HT-29) and pharyngeal squamous-cell carcinoma (FaDu) cells—to act as inflammatory foci. PMNs were cytotoxic to both lines, the adhesion of the PMNs to the tumour cells being important in this effect. The tumour cells released appreciable amounts of IL-8 and GROα, and induced the transmigration of PMN through human microvascular-EC monolayers. Conditioning media associated with both lines induced the adhesion of PMN and the surface expression of ICAM-1 in microvascular-EC. In addition, FaDu-conditioning-medium strongly induced the production of proinflammatory cytokines by microvascular-EC. These results support the idea that tumour cells might normally induce a potent acute inflammatory response, leading to their own destruction.

Abstract Experimental studies identified a role of neuroinflammation in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the role of inflammatory molecules as diagnostic and prognostic biomarkers in patients with ALS is unclear. In this cross-sectional study, the cerebrospinal fluid (CSF) levels of a set of inflammatory cytokines and chemokines were analyzed in 56 newly diagnosed ALS patients and in 47 age- and sex-matched control patients without inflammatory or degenerative neurological disorders. The molecules analyzed included: interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-17, granulocyte colony stimulating factor (GCSF), macrophage inflammatory protein (MIP)-1a, MIP-1b, tumor necrosis factors (TNF), eotaxin. Principal component analysis (PCA) was used to explore possible associations between CSF molecules and ALS diagnosis. In addition, we analyzed the association between CSF cytokine profiles and clinical characteristics, including the disease progression rate score, and peripheral inflammation assessed using the Neutrophil-to-lymphocyte ratio (NLR). PCA identified six principal components (PCs) explaining 70.67% of the total variance in the CSF cytokine set. The principal component (PC1) explained 26.8% of variance and showed a positive load with CSF levels of IL-9, IL-4, GCSF, IL-7, IL-17, IL-13, IL-6, IL-1β, TNF, and IL-2. Logistic regression showed a significant association between PC1 and ALS diagnosis. In addition, in ALS patients, the same component was significantly associated with higher disease progression rate score and positively correlated with NLR. CSF inflammatory activation in present in ALS at the time of diagnosis and may characterize patients at higher risk for disease progression.

Abstract A large number of non‐native trees (NNTs) have been introduced globally and widely planted, contributing significantly to the world's economy. Although some of these species present a limited risk of spreading beyond their planting sites, a growing number of NNTs are spreading and becoming invasive leading to diverse negative impacts on biodiversity, ecosystem functions and human well‐being. To help minimize the negative impacts and maximize the economic benefits of NNTs, Brundu et al. developed eight guidelines for the sustainable use of NNTs globally—the Global Guidelines for the Use of NNTs (GG‐NNTs). Here, we used an online survey to assess perceptions of key stakeholders towards NNTs, and explore their knowledge of and compliance with the GG‐NNTs. Our results show that stakeholders are generally aware that NNTs can provide benefits and cause negative impacts, often simultaneously and they consider that their organization complies with existing regulations and voluntary agreements concerning NNTs. However, they are not aware of or do not apply most of the eight recommendations included in the GG‐NNTs. We conclude that effectively managing invasions linked to NNTs requires both more communication efforts using an array of channels for improving stakeholder awareness and implementation of simple measures to reduce NNT impacts (e.g. via GG‐NNTs), and a deeper understanding of the barriers and reluctance of stakeholders to manage NNT invasions. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Multiple sclerosis (MS) is a progressive neurodegenerative disease of the central nervous system characterized by inflammation-driven synaptic abnormalities. Interleukin-9 (IL-9) is emerging as a pleiotropic cytokine involved in MS pathophysiology. Methods Through biochemical, immunohistochemical, and electrophysiological experiments, we investigated the effects of both peripheral and central administration of IL-9 on C57/BL6 female mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. Results We demonstrated that both systemic and local administration of IL-9 significantly improved clinical disability, reduced neuroinflammation, and mitigated synaptic damage in EAE. The results unveil an unrecognized central effect of IL-9 against microglia- and TNF-mediated neuronal excitotoxicity. Two main mechanisms emerged: first, IL-9 modulated microglial inflammatory activity by enhancing the expression of the triggering receptor expressed on myeloid cells-2 (TREM2) and reducing TNF release. Second, IL-9 suppressed neuronal TNF signaling, thereby blocking its synaptotoxic effects. Conclusions The data presented in this work highlight IL-9 as a critical neuroprotective molecule capable of interfering with inflammatory synaptopathy in EAE. These findings open new avenues for treatments targeting the neurodegenerative damage associated with MS, as well as other inflammatory and neurodegenerative disorders of the central nervous system.

Green practices of companies related to Green supply chain management should also demonstrate their positive impact on companies’ performance. This paper’s goal is to investigate the impact of greening the supply chain on the competitiveness and economic performance of companies in the context of forest-based industry. The study empirically examines the relations between the greening of the phases of the supply chain, related environmental performance and companies’ competitiveness and economic performance. A questionnaire-based survey was performed and data collected among the 333 companies engaged in the forest-based sector in Slovakia to apply a structural equation model. The findings show that companies’ greening supply chain activities, emphasized by requirements for the environmental properties of purchased products and services, contribute to the improvement in environmental performance, which ultimately leads to improving their competitiveness and economic performance.

Proinflammatory cytokines are implicated in promoting neurodegeneration in multiple sclerosis (MS) by affecting excitatory and inhibitory transmission at central synapses. Conversely, the synaptic effects of anti-inflammatory molecules remain underexplored, despite their potential neuroprotective properties and their presence in the cerebrospinal fluid (CSF) of patients. In a study involving 184 newly diagnosed relapsing–remitting (RR)-MS patients, we investigated whether CSF levels of the anti-inflammatory interleukin (IL)-10 were linked to disease severity and neurodegeneration measures. Additionally, we examined IL-10 impact on synaptic transmission in striatal medium spiny neurons and its role in counteracting inflammatory synaptopathy induced by IL-1β in female C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE). Our findings revealed a significant positive correlation between IL-10 CSF levels and changes in EDSS (Expanded Disability Status Scale) scores one year after MS diagnosis. Moreover, IL-10 levels in the CSF were positively correlated with volumes of specific subcortical brain structures, such as the nucleus caudate. In both MS patients’ CSF and EAE mice striatum, IL-10 and IL-1β expressions were upregulated, suggesting possible antagonistic effects of these cytokines. Notably, IL-10 exhibited the ability to decrease glutamate transmission, increase GABA transmission in the striatum, and reverse IL-1β-induced abnormal synaptic transmission in EAE. In conclusion, our data suggest that IL-10 exerts direct neuroprotective effects in MS patients by modulating both excitatory and inhibitory transmission and attenuating IL-1β-induced inflammatory synaptopathy. These findings underscore the potential therapeutic significance of IL-10 in mitigating neurodegeneration in MS.

Background. Cross-sectional and longitudinal psychiatric comorbidity rates could represent a syndromic process rather than the co-occurrence of different disorders. ‘Cothymia’, the concomitant presence of depression and anxiety symptoms, and the ‘neuroticism’ dimension have been proposed as candidate vulnerability factors for psychiatric disorders trajectories. Based on this background, the present research was aimed at assessing the role of cothymia and neuroticism as syndromic processes in lifetime psychiatric disorders, and examining homotypic or heterotypic trends in the diagnostic continuum of comorbid mental disorders. Materials and methods. Data collection was carried out retrospectively through the consultation of medical records at the Psychiatry Unit of the University Hospital of Messina. Cothymia was determined by the lifetime presence of depression and other anxiety disorders, and neuroticism was determined by the presence of borderline personality disorders and other personality disorders. Results. Cothymia and neuroticism were found in 580 patients with higher rates of hospitalization, drug prescription, polypharmacotherapy, and longer duration of illness. Furthermore, diagnostic trajectories in patients with cothymia and neuroticism followed both homotypic and heterotypic progressions. Limitations: This study presented several limitations. The small sample size from a restricted recruitment area, and the retrospective design may have influenced a realistic and accurate estimation of the lifetime prevalence of the disorders. Conclusions. Despite the limitations, the findings of this study confirm the presence of consistent and meaningful homotypic and heterotypic trajectories in psychiatric patients, suggesting that the evolution of lifetime diagnoses should become a focus in theoretical and practical approaches to psychiatric disorders.

Background. The objective of this study is to establish the link between affective temperament traits and maladaptive personality traits, to verify whether the potential presence of elements related to emotional, affective and dysfunctional relational functioning can affect the couple satisfaction, modifying the well-being or discomfort condition. Materials and Methods. A data collection questionnaire was developed to investigate the factors associated with dysfunctional emotional, affective, and relational modes of functioning. The sample consisted of 473 subjects. Data were collected including the TEMPS-A questionnaire, The Dirty Dozen Italian Assessment and the Relationship Assessment Scale (RAS). Results. The findings of this study showed that the subscales of affective temperament were predictors of dark triad traits. The expressive, irritable and hyperthymic temperamental traits were found to be predictors of trait psychopathy; hyperthymic temperament is also a predictor of narcissistic traits and cyclothymic temperament is a predictor of lower couple satisfaction; men show higher scores than women in Dark triad. Conclusions. This study confirmed that temperamental traits can predict maladaptive personality traits belonging to the dark triad and confirms the importance of evaluating maladaptive personality traits to prevent forms of psychological violence in couple.

Abstract Background Superficial femoral artery (SFA) pseudoaneurysms, a rare but potentially life-threatening complication, that can arise after vascular interventions or trauma. This case series explores the efficacy and safety of a minimally invasive treatment modality, percutaneous ultrasound-guided thrombin injection (PUGTI) combined with balloon occlusion, in three patients with SFA pseudoaneurysms. Case presentation Three patients (age: 71–82 years; 3 female) with SFA pseudoaneurysms underwent PUGTI with balloon occlusion. The procedure involved direct thrombin injection under ultrasound guidance while occluding the parent artery using a balloon catheter. Follow-up was conducted at 1 week and 1 month post-procedure to assess technical success, complications, and recurrence. Conclusion PUGTI combined with balloon occlusion appears to be a safe and effective treatment for SFA pseudoaneurysms, particularly for larger pseudoaneurysms. The procedure is associated with a high technical success rate. Balloon occlusion may offer a safer alternative to direct thrombin injection without occlusion, as it potentially minimizes the risk of complications such as distal thromboembolism.

BackgroundSecondary progressive multiple sclerosis (SPMS) is defined by the irreversible accumulation of disability following a relapsing-remitting MS (RRMS) course. Despite treatments advances, a reliable tool able to capture the transition from RRMS to SPMS is lacking. A T cell chimeric MS model demonstrated that T cells derived from relapsing patients exacerbate excitatory transmission of central neurons, a synaptotoxic event absent during remitting stages. We hypothesized the re-emergence of T cell synaptotoxicity during SPMS and investigated the synaptoprotective effects of siponimod, a sphingosine 1-phosphate receptor (S1PR) modulator, known to reduce grey matter damage in SPMS patients.MethodsData from healthy controls (HC), SPMS patients, and siponimod-treated SPMS patients were collected. Chimeric experiments were performed incubating human T cells on murine cortico-striatal slices, and recording spontaneous glutamatergic activity from striatal neurons. Homologous chimeric experiments were executed incubating EAE mice T cells with siponimod and specific S1PR agonists or antagonists to identify the receptor involved in siponimod-mediated synaptic recovery.ResultsSPMS patient-derived T cells significantly increased the striatal excitatory synaptic transmission (n=40 synapses) compared to HC T cells (n=55 synapses), mimicking the glutamatergic alterations observed in active RRMS-T cells. Siponimod treatment rescued SPMS T cells synaptotoxicity (n=51 synapses). Homologous chimeric experiments highlighted S1P5R involvement in the siponimod’s protective effects.ConclusionTransition from RRMS to SPMS involves the reappearance of T cell-mediated synaptotoxicity. Siponimod counteracts T cell-induced excitotoxicity, emphasizing the significance of inflammatory synaptopathy in progressive MS and its potential as a promising pharmacological target.

Capitalizing on the widespread adoption of smartphones among farmers and the application of artificial intelligence in computer vision, a variety of mobile applications have recently emerged in the agricultural domain. This paper introduces GranoScan, a freely available mobile app accessible on major online platforms, specifically designed for the real-time detection and identification of over 80 threats affecting wheat in the Mediterranean region. Developed through a co-design methodology involving direct collaboration with Italian farmers, this participatory approach resulted in an app featuring: (i) a graphical interface optimized for diverse in-field lighting conditions, (ii) a user-friendly interface allowing swift selection from a predefined menu, (iii) operability even in low or no connectivity, (iv) a straightforward operational guide, and (v) the ability to specify an area of interest in the photo for targeted threat identification. Underpinning GranoScan is a deep learning architecture named efficient minimal adaptive ensembling that was used to obtain accurate and robust artificial intelligence models. The method is based on an ensembling strategy that uses as core models two instances of the EfficientNet-b0 architecture, selected through the weighted F1-score. In this phase a very good precision is reached with peaks of 100% for pests, as well as in leaf damage and root disease tasks, and in some classes of spike and stem disease tasks. For weeds in the post-germination phase, the precision values range between 80% and 100%, while 100% is reached in all the classes for pre-flowering weeds, except one. Regarding recognition accuracy towards end-users in-field photos, GranoScan achieved good performances, with a mean accuracy of 77% and 95% for leaf diseases and for spike, stem and root diseases, respectively. Pests gained an accuracy of up to 94%, while for weeds the app shows a great ability (100% accuracy) in recognizing whether the target weed is a dicot or monocot and 60% accuracy for distinguishing species in both the post-germination and pre-flowering stage. Our precision and accuracy results conform to or outperform those of other studies deploying artificial intelligence models on mobile devices, confirming that GranoScan is a valuable tool also in challenging outdoor conditions.

Aim Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non-specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL-1, could provide additional benefit to prevent further recurrences. The aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone.Methods International, all-comers, multicentre, retrospective observational cohort study analysing all consecutive patients treated with anakinra for corticosteroid-dependent and colchicine-resistant recurrent pericarditis. The efficacy endpoint was recurrence rate and the time to the first recurrence.Results A total of 256 patients (mean age 45.0±15.4 years, 65.6% females, 80.9% with idiopathic/viral aetiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow-up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively, 18.8% vs 31.3%; p=0.036) and a longer event-free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021).Conclusions The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence-free survival.

In multiple sclerosis, only immunomodulatory and immunosuppressive drugs are recognized as disease-modifying therapies. However, in recent years, several data from pre-clinical and clinical studies suggested a possible role of physical exercise as disease-modifying therapy in multiple sclerosis. Current evidence is sparse and often conflicting, and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated. Data, mainly derived from pre-clinical studies, suggest that exercise could enhance long-term potentiation and thus neuroplasticity, could reduce neuroinflammation and synaptopathy, and dampen astrogliosis and microgliosis. In humans, most trials focused on direct clinical and MRI outcomes, as investigating synaptic, neuroinflammatory, and pathological changes is not straightforward compared to animal models. The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.

The painting studied, featuring the Virgin contemplating the sleeping Child, is a well-known composition in the religious context, especially popular since the 16th century. The technique, oil on copper plate, and materials were examined applying a multimethodological non-invasive approach. The main goal was to quantitatively characterize the layer composition and thickness. To obtain them, X-ray fluorescence spectroscopy coupled with Monte Carlo simulation was used for the first time, to the best of our knowledge, for this kind of object. This technique was also integrated with more conventional photographic and spectroscopic techniques such as multiband imaging (MBI), Raman spectroscopy, external reflection Fourier transform infrared spectroscopy (ER FT-IR), and optical microscopy. The obtained data showed the use of a background based on lead white, a wide palette, which includes azurite, vermilion, lead white, and some ochers, and documented the conservation status. Although the investigations contended with the object’s complexity, the results demonstrate the efficacy of the XRF–Monte Carlo simulation approach in characterizing the materials constituting the artwork in a totally non-invasive way.

Insulin resistance (IR), marked by reduced cellular responsiveness to insulin, and obesity, defined by the excessive accumulation of adipose tissue, are two intertwined conditions that significantly contribute to the global burden of cardiometabolic diseases. Adipose tissue, beyond merely storing triglycerides, acts as an active producer of biomolecules. In obesity, as adipose tissue undergoes hypertrophy, it becomes dysfunctional, altering the release of adipocyte-derived factors, known as adipokines. This dysfunction promotes low-grade chronic inflammation, exacerbates IR, and creates a hyperglycemic, proatherogenic, and prothrombotic environment. However, the fundamental cause of these phenomena remains unclear. This narrative review points to hypoxia as a critical trigger for the molecular changes associated with fat accumulation, particularly within visceral adipose tissue (VAT). The activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor that regulates homeostatic responses to low oxygen levels, initiates a series of molecular events in VAT, leading to the aberrant release of adipokines, many of which are still unexplored, and potentially affecting peripheral insulin sensitivity. Recent discoveries have highlighted the role of hypoxia and miRNA-128 in regulating the insulin receptor in visceral adipocytes, contributing to their dysfunctional behavior, including impaired glucose uptake. Understanding the complex interplay between adipose tissue hypoxia, dysfunction, inflammation, and IR in obesity is essential for developing innovative, targeted therapeutic strategies.

(1) Multiple sclerosis (MS) is identified by a complex interaction between central inflammation and neurodegeneration. Genetic individual variability could play a significative role in clinical presentation. The interleukin-5 (IL-5) rs2069812 single-nucleotide polymorphism (SNP) seems to define the clinical course of Th2 autoimmune diseases, while its role in MS has never been investigated. (2) In a group of 230 patients diagnosed with relapsing–remitting MS (RR-MS) or progressive MS (P-MS) and controls (IC), rs2069812 polymorphism, cerebrospinal fluid (CSF) levels of inflammatory mediators, and clinical and demographic characteristics were determined. In RR-MS patients, No Evidence of Disease Activity (NEDA-3) at three years of follow-up was detected. (3) We identified higher levels of proinflammatory cytokines, particularly IL-2 (median [IQR], RR-MS = 0.2 [0–0.7]; P-MS = 0.1 [0–1.6]; IC = 0.1 [0.0–0.1]; p < 0.005), IL-6 (RR-MS = 0.9 [0.3–2.3]; P-MS = 0.8 [0.1–2.7]; IC = 0.1 [0.0–0.5]; p < 0.005), IL-12 (RR-MS = 0.5 [0–1.1]; P-MS = 0.5 [0–1.1]; IC = 0.0 [0.0–0.3]; p < 0.005), and GM-CSF (RR-MS = 15.6 [4.8–26.4]; P-MS = 14 [3.3–29.7]; IC = 8.9 [4.7–11.7]; p < 0.005) in MS patients compared with IC. Conversely, anti-inflammatory cytokines, specifically IL-5 (RR-MS = 0.65 [0–2.4]; P-MS = 0.1 [0–0.8]; IC = 1.7 [0.6–2.8]; p < 0.005) and IL-1ra (RR-MS = 14.7 [4.9–26.4]; P-MS = 13.1 [4.7–22.2]; IC = 27.8 [17.7–37.6]; p < 0.005) were higher in controls. According to rs2069812, in MS patients, the T-allele was associated with higher concentrations of proinflammatory mediators (IL-2, CT/TT = 0.2 [0.0–2.0]; CC = 0.1 [0.0–0.4], p = 0.015; IL-6, CT/TT = 1.2 [0.4–3.2] vs. CC = 0.7 [0.1–1.7], p = 0.007; IL-15, CT/TT = 0.1 [0.0–9.5] vs. CC = 0.0 [0.0–0.1], p = 0.019; and GM-CSF, CT/TT = 0.1 [0.0–0.6] vs. CC = 0.05 [0.0–0.1], p < 0.001), and CC was associated with anti-inflammatory mediators (IL-5, CT/TT = 0.03 [0.0–1.9] vs. CC = 1.28 [0.0–2.7], p = 0.001; IL-1ra, CT/TT = 12.1 [4.1–25.9] vs. CC = 18.1 [12.1–26.9], p = 0.006). We found the same differences in RR-MS patients (IL-2, T-allele median [IQR] = 0.3 [0.0–2.0] vs. C-allele, median [IQR] = 0.04 [0.0–0.3]; p = 0.005; IL-6, T-allele, median [IQR] = 1.3 [0.4–3.3] vs. C-allele, median [IQR] = 0.6 [0.03–1.5]; p = 0.001; IL-15, T-allele, median [IQR] = 0.1 [0.0–9.5] vs. C-allele, median [IQR] = 0.0 [0.0–0.1]; p = 0.008; GM-CSF, T-allele, median [IQR] = 0.1 [0.0–97.9] vs. C-allele, median [IQR] = 0.0 [0.0–0.001]; p < 0.001; IL-5, T-allele, median [IQR] = 0.02 [0.0–2.2] vs. C-allele, median [IQR] = 1.5 [0.0–2.9]; p = 0.016; and IL-1ra, T-allele, median [IQR] = 12.1 [4.3–26.4] vs. C-allele, median [IQR] = 18.5 [12.7–28.3]; p = 0.006) but not in P-MS, except for IL-5 (T-allele, median [IQR] = 0.1 [0–0.23] vs. C-allele, median [IQR] = 0.6 [0.0–2.5]; p = 0.022). Finally, we identified an association between CC in RR-MS patients and NEDA-3 after three years of follow-up (p = 0.007). (4) We describe, for the first time, the role of an SNP of the IL-5 gene in regulating central neuroinflammation and influencing clinical course in MS patients.

Background Rilonacept, a once‐weekly interleukin‐1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin‐1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long‐term extension further explored recurrent pericarditis natural history and treatment duration decision‐making during 24 additional months of open‐label rilonacept treatment. Methods and Results Seventy‐four patients commenced the long‐term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off‐treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18‐month decision milestone was 0.04 events/patient‐year versus 4.4 events/patient‐year prestudy while on oral therapies. At the 18‐month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18‐month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P

IntroductionThe visual system is a prominent site of damage in MS since the earliest phases of the disease. Altered low-contrast visual acuity (LCVA) test has been associated with visual impairment and retinal degeneration, predicting medium- and long-term disability. However, it is unclear whether LCVA may also represent a reliable measure of neuroinflammation and a predictor of disease evolution in the very early stages of MS.MethodsWe explored in a group of 76 consecutive newly diagnosed relapsing–remitting MS (RR-MS) patients without visual impairment or altered visual evoked potentials, the association between LCVA scores at 2.5% and 1.25% and clinical characteristics, including prospective disability evaluated after 1- and 2 years of follow-up. Associations between LCVA and the CSF levels of IL-10 at diagnosis were also analyzed.ResultsA negative correlation was found between LCVA at 2.5% and Expanded Disability Status Scale (EDSS) evaluated at first (Spearman’s Rho = −0.349, p = 0.005, n = 62) and second year (Spearman’s Rho = −0.418, p

Psychological violence is characterized by systematic denigration and humiliation of the partner (victim). It is an insidious and manipulative behavior put in place to ensure that the victim begins to doubt themselves, and their own judgments, to the point of feeling confused and wrong. This behavior pattern is called Gaslighting and the personality traits are characterized by lack of empathy, psychopathy, narcissism and Machiavellianism. These three conditions are part of the so-called dark triad and distinguished by the lack of empathy. The aim of this study is to explore psychological aspects and consequences of Gaslighting phenomena. This systematic review was conducted according to Systematic Reviews guidelines (PubMed and Google Scholar databases), using 2 key terms related to this topic “Psychological Violence” AND “Gaslighting”. Data for this systematic review were collected in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The reviewed studies focused on violence on affective manipulation, abuse trauma that compromises a subject's identity, psyche, self-esteem and sense of self, in women's mental health conditions. Most of the research analyzed is focused on the gender violence and manipulative behavior in couples.

Abstract The observation of action seems to involve the generation of the internal representation of that same action in the observer, a process named motor resonance (MR). The objective of this study was to verify whether an experimental paradigm of action observation in a laboratory context could elicit cortical motor activation in 21 early Parkinson’s disease (PD) patients compared to 22 controls. Participants were instructed to simply observe (observation-only session) or to respond (Time-to-contact detection session) at the instant the agent performed a grasping action toward a graspable or ungraspable object. We used functional near-infrared spectroscopy with 20 channels on the motor and premotor brain areas and event-related desynchronization of alpha-mu rhythm. In both groups, response times were more accurate in graspable than ungraspable object trials, suggesting that motor resonance is present in PD patients. In the Time-to-contact detection session, the oxyhemoglobin levels and alpha-mu desynchronization prevailed in the graspable object trials rather than in the ungraspable ones. This study demonstrates the preservation of MR mechanisms in early PD patients. The action observation finalized to a consequent movement can activate cortical networks in patients with early PD, suggesting early rehabilitation interventions taking into account specific observation paradigms preceding motor production.

Pericardial effusions, especially large ones, have traditionally been regarded with concern by clinicians due to the sometimes unpredictable development of life-threatening cardiac tamponade. In the European Society of Cardiology Guidelines on pericardial diseases, the simplified algorithm for pericardial effusion triage and management recommends pericardial drainage in cases of cardiac tamponade and/or suspicion of bacterial or neoplastic etiology. In the presence of acute pericarditis, empiric anti-inflammatory treatment should be given, while when a specific indication known to be associated with pericardial effusion is found, then treatment of the underlying cause is indicated. Notably, the most challenging subgroup of patients includes those with large, asymptomatic, C-reactive-protein-negative, idiopathic effusions. In the latter subjects, pericardial drainage is proposed in cases of chronic effusions (lasting more than three months). However, this recommendation is based on scant data stemming from small-sized non-randomized studies. Nevertheless, recent evidence in a larger cohort of patients pointed out that a watchful waiting strategy is a safe option in terms of complication-free survival. This review summarizes the contemporary evidence on this challenging topic and provides recommendations for tailoring individual patient treatments.

This study, conducted by searching keywords such as “maternal lupus”, “neonatal lupus”, and “congenital heart block” in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

MiR-142-3p has recently emerged as key factor in tailoring personalized treatments for multiple sclerosis (MS), a chronic autoimmune demyelinating disease of the central nervous system (CNS) with heterogeneous pathophysiology and an unpredictable course. With its involvement in a detrimental regulatory axis with interleukin-1beta (IL1β), miR-142-3p orchestrates excitotoxic synaptic alterations that significantly impact both MS progression and therapeutic outcomes. In this study, we investigated for the first time the influence of individual genetic variability on the miR-142-3p excitotoxic effect in MS. We specifically focused on the single-nucleotide polymorphism Val66Met (rs6265) of the brain-derived neurotrophic factor (BDNF) gene, known for its crucial role in CNS functioning. We assessed the levels of miR-142-3p and IL1β in cerebrospinal fluid (CSF) obtained from a cohort of 114 patients with MS upon diagnosis. By stratifying patients according to their genetic background, statistical correlations with clinical parameters were performed. Notably, in Met-carrier patients, we observed a decoupling of miR-142-3p levels from IL1β levels in the CSF, as well as from of disease severity (Expanded Disability Status Score, EDSS; Multiple Sclerosis Severity Score, MSSS; Age-Related Multiple Sclerosis Severity Score, ARMSS) and progression (Progression Index, PI). Our discovery of the interference between BDNF Val66Met polymorphism and the synaptotoxic IL1β-miR-142-3p axis, therefore hampering miR-142-3p action on MS course, provides valuable insights for further development of personalized medicine in the field.

Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions.

Background: Obesity constitutes a chronic, low-grade inflammatory status that predisposes people to the development of insulin resistance and cardiometabolic complications. Hypoxia, a main pathological feature of visceral fat in obese individuals, has been shown to affect the secretome of murine 3T3-L1 adipose cells, causing the upregulation of prothymosin-alpha (ProT-α), which is a protein with immunomodulatory functions that was originally found in the thymus. The aim of this case–control observational study was to measure the circulating levels of ProT-α in obese and lean individuals and determine whether such levels are correlated with inflammatory and metabolic parameters. Methods: Sixty-one obese patients (BMI ≥ 30 Kg/m2) and fifty-one age-matched, lean controls (BMI 18.5–24.9 Kg/m2) were recruited in the Endocrinology Unit (“Mater-Domini”) of the University Hospital of Catanzaro, Italy. The exclusion criteria included affliction with acute and systemic inflammatory states (i.e., leukocytosis), recent infectious diseases or vaccinations, obesity complications (i.e., type 2 diabetes mellitus and cardiovascular diseases), hepatic or renal failure, pregnancy and lactation, cancer, use of drugs or alcohol, and smoking. Apart from routine biochemical determinations, serum samples were screened for the presence of ProT-α using an ELISA method and for the presence of a panel of inflammatory cytokines and growth factors via a multiparametric chemiluminescence micro-array. Results: Between the age-matched groups, no statistically significant differences were shown in relation to fasting glucose, HbA1c, liver function tests, lipid profiles, circulating interleukins (IL)-1α, -1β, -2, -4, -8, and -10, MCP-1, TNF-α, VEGF and EGF. Instead, significantly higher median levels were observed in obese patients vs. lean controls with respect to fasting insulin levels (p < 0.001), a classic insulin resistance marker, and IL-6 (p = 0.004). In addition, ProT-α levels were significantly and considerably higher in obese patients compared to lean controls (median ProT-α, 600.0 vs. 411.5 pg/mL, p = 0.004) and showed a moderate to strong positive relationship with fasting insulin levels and selected cytokines (i.e., TNF-α and IL-8). Conclusions: An increase in circulating levels of ProT-α is linked with obesity and can be detected before any clinical cardiometabolic complications develop. ProT-α may represent a novel and sensitive biomarker for inflammation and insulin resistance in obese individuals.

In the field of neuroscience, brain–computer interfaces (BCIs) are used to connect the human brain with external devices, providing insights into the neural mechanisms underlying cognitive processes, including aesthetic perception. Non-invasive BCIs, such as EEG and fNIRS, are critical for studying central nervous system activity and understanding how individuals with cognitive deficits process and respond to aesthetic stimuli. This study assessed twenty participants who were divided into control and impaired aging (AI) groups based on MMSE scores. EEG and fNIRS were used to measure their neurophysiological responses to aesthetic stimuli that varied in pleasantness and dynamism. Significant differences were identified between the groups in P300 amplitude and late positive potential (LPP), with controls showing greater reactivity. AI subjects showed an increase in oxyhemoglobin in response to pleasurable stimuli, suggesting hemodynamic compensation. This study highlights the effectiveness of multimodal BCIs in identifying the neural basis of aesthetic appreciation and impaired aging. Despite its limitations, such as sample size and the subjective nature of aesthetic appreciation, this research lays the groundwork for cognitive rehabilitation tailored to aesthetic perception, improving the comprehension of cognitive disorders through integrated BCI methodologies.

Thromboembolic conditions are the most common cause of death in developed countries. Anticoagulant therapy is the treatment of choice, and heparinoids and warfarin are the most adopted drugs. Sulphated polysaccharides extracted from marine organisms have been demonstrated to be effective alternatives, blocking thrombus formation by inhibiting some factors involved in the coagulation cascade. In this study, four acidic glycan fractions from the marine sponge Sarcotragus spinosulus were purified by anion-exchange chromatography, and their anticoagulant properties were investigated through APTT and PT assays and compared with both standard glycosaminoglycans and holothurian sulphated polysaccharides. Moreover, their topographic localization was assessed through histological analysis, and their cytocompatibility was tested on a human fibroblast cell line. A positive correlation between the amount of acid glycans and the inhibitory effect towards both the intrinsic and extrinsic coagulation pathways was observed. The most effective anticoagulant activity was shown by a highly charged fraction, which accounted for almost half (about 40%) of the total hexuronate-containing polysaccharides. Its preliminary structural characterization, performed through infrared spectroscopy and nuclear magnetic resonance, suggested that it may consist of a fucosylated chondroitin sulphate, whose unique structure may be responsible for the anticoagulant activity reported herein for the first time.

Radioactive wastes often contain amorphous and crystalline phases, and vapor hydration can affect their durability. In this study, Cs-clinoptilolite was heated (at 1100 °C and for 2–36 h) to prepare the samples that were composed mainly of an amorphous phase (AmP) and CsAlSi5O12 (≥94%) with minor CsAlSi2O6. Six samples with an AmP/CsAlSi5O12 ratio from 26.5 to 0.1 were kept at 21 °C and 55% relative humidity, and their hydration was measured via thermogravimetry (TG) over a period of almost six years. The hydration that resulted was directly related to the AmP quantity. The increase in water content followed a logarithmic trend over time. It reached 1.95% in the AmP-richest material, while it attained only 0.07% in the most crystalline sample. The hydrolysis of the AmP led to an increase over time in the tightly bound water. Samples with an AmP of ≤19% demonstrated slightly higher durability due to the lower Cs content in the AmP.

Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy and its incidence is rising in Western countries. Although surgical resection is considered the only curative treatment, up to 70% of patients are diagnosed at an advanced stage, which precludes surgical intervention. Those who are inoperable become candidates for systemic treatment. Currently, the combination of gemcitabine and cisplatin is the first-line chemotherapy, with a median overall survival (OS) of about one year. Recently, there has been a notable increase in evidence regarding chemotherapy for biliary tract cancer; however, the effectiveness of the new chemotherapy drugs still needs to be evaluated. Today, intra-arterial therapies (IAT), especially trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE), are widely used. Both TACE and TARE have demonstrated good efficacy in controlling localized disease and in improving survival. However, current literature does not conclusively show whether TACE is superior to TARE or vice versa. As recent meta-analyses have indicated, both TACE and TARE offer suboptimal objective response rates but yield similar positive outcomes. It’s important to note that these findings are based on single-center studies, which often include a small number of patients and lack a comparative design. Therefore, when comparing such studies, there’s an inevitable selection bias among the treatment groups (TACE or TARE) and significant heterogeneity. This review outlines the current evidence on the use of interventional IAT in managing ICC.

IntroductionSubtle cognitive dysfunction and mental fatigue are frequent after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, characterizing the so-called long COVID-19 syndrome. This study aimed to correlate cognitive, neurophysiological, and olfactory function in a group of subjects who experienced acute SARS-CoV-2 infection with persistent hyposmia at least 12 weeks before the observation.MethodsFor each participant (32 post-COVID-19 patients and 16 controls), electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) data were acquired using an integrated EEG–fNIRS system during the execution of a P300 odd-ball task and a Stroop test. The Sniffin' Sticks test was conducted to assess subjects' olfactory performance. The Montreal Cognitive Assessment (MoCA) and the Frontal Assessment Battery (FAB) were also administered.ResultsThe post-COVID-19 group consisted of 32 individuals (20 women and 12 men) with an average education level of 12.9 ± 3.12 years, while the control group consisted of 16 individuals (10 women and 6 men) with an average education level of 14.9 ± 3.2 years. There were no significant differences in gender (X2 = 0, p = 1) or age between the two groups (age 44.81 ± 13.9 vs. 36.62 ± 11.4, p = 0.058). We identified a lower concentration of oxyhemoglobin (p < 0.05) at the prefrontal cortical level in post-COVID-19 subjects during the execution of the Stroop task, as well as a reduction in the amplitude of the P3a response. Moreover, we found that post-COVID-19 subjects performed worst at the MoCA screening test (p = 0.001), Sniffin's Sticks test (p < 0.001), and Stroop task response latency test (p < 0.001).ConclusionsThis study showed that post-COVID-19 patients with persistent hyposmia present mild deficits in prefrontal function, even 4 months after the end of the infection. These deficits, although subtle, could have long-term implications for quality of life and cognitive wellbeing. It is essential to continue monitoring and evaluating these patients to better understand the extent and duration of cognitive impairments associated with long COVID-19.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by a burden of comorbid conditions, including depression, that has been related with an increased risk of exacerbations, low adherence to pharmacological treatments and behavioral interventions, and overall mortality rates. The aim of the present review was to explore the comorbidity between depression and COPD by examining epidemiological and etiopathogenetic perspectives, along with shared risk factors including the potential role of hypoxia, systemic inflammation, and drugs for COPD treatment. Methods: the aim of this work was to review studies published in the last eleven years, using Medline/PubMed, Scopus, and Google Scholar as search engines and the following terms “Mood Disorders", "Hypoxia "Pulmonary Disease, Chronic Obstructive", “Chronic obstructive pulmonary disease”, linked by the Boolean operator “AND”. Articles were included in the review if written in English and containing quantitative and qualitative information on Depression, Chronic Obstructive Pulmonary Disease, and Hypoxia. Exclusion criteria were studies in languages other than English, irrelevant articles to the examined topic reviews, case reports, case series, and articles on animal models. Results: The present review has confirmed the increased risk of depression onset in COPD patients, suggesting a strong multifactorial and bidirectional correlation between the two conditions. Hypoxia has been emphasized as a key mechanism in both diseases, whereas evidence on shared inflammatory and molecular pathways is still limited. Conclusions: The multifactorial nature of the bidirectional correlation between COPD and depression is far from being entirely understood. Comorbid depression negatively affects COPD course and severity, along with patients’ functioning, psychological well-being and quality of life. Well-designed pre-clinical and clinical studies on the genetic, molecular, and neurobiological pathways which underlie the comorbidity between COPD and depression are needed for addressing the clinical implications and treatment options. needs more research efforts to be clarified. Further studies are mandatory to improve our knowledge on the co-presence of these two widespread diseases.

Automatic vision-based inspection systems have played a key role in product quality assessment for decades through the segmentation, detection, and classification of defects. Historically, machine learning frameworks, based on hand-crafted feature extraction, selection, and validation, counted on a combined approach of parameterized image processing algorithms and explicated human knowledge. The outstanding performance of deep learning (DL) for vision systems, in automatically discovering a feature representation suitable for the corresponding task, has exponentially increased the number of scientific articles and commercial products aiming at industrial quality assessment. In such a context, this article reviews more than 220 relevant articles from the related literature published until February 2023, covering the recent consolidation and advances in the field of fully-automatic DL-based surface defects inspection systems, deployed in various industrial applications. The analyzed papers have been classified according to a bi-dimensional taxonomy, that considers both the specific defect recognition task and the employed learning paradigm. The dependency on large and high-quality labeled datasets and the different neural architectures employed to achieve an overall perception of both well-visible and subtle defects, through the supervision of fine or/and coarse data annotations have been assessed. The results of our analysis highlight a growing research interest in defect representation power enrichment, especially by transferring pre-trained layers to an optimized network and by explaining the network decisions to suggest trustworthy retention or rejection of the products being evaluated.

Abstract Background To evaluate feasibility, safety and effectiveness of transarterial embolization of acute non-neurologic hemorrhage with Ethylene Vynil Alcohol Copolymer (EVOH). Methods Between January 2018 and June 2021, 211 patients (male 123, mean age 69.7 y + 17.9) who underwent transarterial embolization with Onyx™ for acute non-neurologic arterial bleeding were retrospectively reviewed. Most frequent etiology of bleeding was post-operative (89/211, 42.2%), trauma (62/211, 29.4%) and tumor (18/211, 8.5%). Technical success was defined as the angiographic evidence of target vessel complete occlusion. Clinical success was defined as resolution of bleeding. Any rebleeding within the primitive site, requiring a new intervention during the first 30-days following embolization, was considered a clinical failure. Occurrence of procedure-related complication and mortality within 30 days of the embolization were examined. Results A total of 229 embolization procedures was performed in 211 pts.; technical success rate was 99.5% (210/211 pts). Clinical success rate was 94.3% (199/211 pts). In 11 patients (5.2%) a reintervention was needed because of a rebleeding occurring within the primitive site, whereas in five patients (2.4%) rebleeding occurred within a site different from the primitive. Factors more often associated with clinical failure were coagulopathy/ongoing anticoagulant therapy (5/11, 45.4%), and post-operative etiology (3/11, 27.3%). EVOH was used as the sole embolic agent in 214/229 procedures (93.4%), in association with coils in 11 cases (4.8%), and with microparticles in 4 cases (1.7%). In the present series, major complications occurred in 6 cases (2.8%): respectively, four cases (1.9%) of colonic ischemia and two groin hematomas (0.9%) with active extravasation were observed. 26 (12.3%) patients died during the follow-up. Conclusion Embolization of acute arterial bleeding with EVOH as a first-line embolic agent is feasible, safe and effective.

Background: The American Joint Commission on Cancer on Tumor Node Metastasis (AJCC/TNM) staging system provides adequate information on the risk of differentiated thyroid cancer (DTC)-specific mortality in totally thyroidectomized patients, but its role in predicting persistence and relapse of disease is uncertain. The relatively new 2015 American Thyroid Association (ATA) guidelines recommend stratifying patients at the time of DTC diagnosis with its own risk classification system, in order to identify those at high risk of residual or recurrent morbidity who may benefit from post-operative radioiodine (RAI) administration and/or need additional work-up. Methods: To verify the prevalence proportion of persistence or relapse of disease, a consecutive cohort of 152 patients with a diagnosis of DTC, subjected to total thyroidectomy (+/− post-operative RAI administration as per guidelines indication) and to neck ultrasonography (US), as well as biochemical surveillance for a minimum of 2 years at the Endocrinology Unit of Mater-Domini Hospital (Catanzaro, Italy), was enrolled. The prognostic role of the AJCC/TNM stage and ATA risk classification system was analyzed by logistic regression. Results: At a mean of 9 years after surgical treatment, DTC was found to persist or relapse in 19 (12.5%) participants. The initial risk for these outcomes, based on the ATA classification, was mostly low (53.9%) or intermediate (39.5%). AJCC/TNM stages were predominantly stage I or stage II. Despite a small representation in this cohort, high-risk patients according to the ATA classification had 8-fold higher odds of persistence or relapse of disease than those of low-risk participants, while controlling for potential risk modifiers, including age at DTC diagnosis, male gender, and post-operative RAI administration (p = 0.008). In contrast, the AJCC/TNM stage was not associated with the disease status at the last follow-up visit (p = 0.068 for the 7th Edition; p = 0.165 for the 8th Edition). Furthermore, low-risk participants subjected to post-operative RAI administration had the same probability of persistence or relapse of DTC when compared to those who had undergone total thyroidectomy only. Conclusions: There is a need for the endocrine community to revise the current work-up of DTC. The initial ATA risk classification is a reliable tool for predicting the persistence or relapse of disease in long-term surveillance.

IntroductionThis paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD).MethodsThe project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry.ResultsRespondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0–30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1–50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p

Tumor necrosis factor (TNF) is a key player in multiple sclerosis pathology. TNF signaling is dually regulated by antagonist groups of actors: TNFR1, mediating proinflammatory effects and synaptopathy, CD40L-CD40 dyad, crucial for blood-brain barrier breakdown and facilitation of recruitment of inflammatory cells in the central nervous system, and TNFR2, promoting neuroprotective and reparative functions. A promising therapeutic approach in multiple sclerosis is represented by selective TNFR1 antagonists and TNFR2 agonists, possibly in combination. TNFR2 agonists could exert both central effects such as remyelination, reduction of glutamatergic excitotoxicity, and peripheral immunomodulation by enhancing T cells (Treg) activity. On the other side, the potential therapeutic role of platelet and CD40L-CD40 dyad inhibition could be beneficial to preserve blood-brain barrier integrity and thereby dampen neuroinflammation.

Polyphenols are natural compounds also contained in daily consumed foods that show their efficacy in different clinical fields. Both pre-clinical and clinical studies demonstrated that polyphenols may manage neuroinflammation and oxidative stress processes tightly connected to neurodegenerative diseases and mental disorders. Thus, a neuroinflammatory state may influence the neurotransmitters pathways, such as the noradrenergic, glutamatergic, serotoninergic, and, in particular, dopaminergic ones, whose impairment is strongly associated with attention deficit hyperactivity disorder (ADHD). Therefore, the aim of the present systematic review is to provide an overview of the clinical outcomes’ changes following ADHD treatment with polyphenols alone and in combination with the traditional drugs. This review was conducted according to PRISMA guidelines and recorded on PROSPERO with the number CRD42023438491; PubMed, Scopus, and Web of Science were used as search-engines to lead our research until June 2023. The inclusion criteria were articles written in English, including clinical, placebo-controlled, and case-control trials. We excluded reviews, metanalyses, background articles, and papers published in other languages. To avoid any bias, Rayyan software (COPYRIGHT © 2022 RAYYAN) was used to organize the work and manage the literature review. After screening, 10 studies were included, with a total of 556 patients that met the established inclusion criteria. The data obtained from these studies showed that polyphenols rebalanced oxidative stress pathways through different mechanisms, are effective for the treatment of ADHD both alone and in combination with traditional drugs, and are able to reduce symptoms as well as the side effects related to the use of conventional therapies. Finally, a positive effect of using polyphenols for ADHD prevention could be hypothesized.