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A simple method for the identification of brush-border membrane α-glucosidases is described. The proteins were first solubilized and separated in a gel under native, non-denaturing, conditions. The gel was then incubated in substrate solutions (maltose or sucrose), and the product (glucose) exposed in situ by the oxidation of o-dianisidine, which yields a brown-orange color. Nano-liquid chromatography coupled to mass spectrometry analyses of proteins (nano LC-MS/MS) present in the colored bands excised from the gels, was used to confirm the presence of the enzymes. The stain is inexpensive and the procedure permits testing several substrates in the same gel. Once enzymes are identified, their abundance, relative to that of other proteins in the brush border, can be semi-quantified using nano LC-MS/MS.

Metabolites present in liver provide important clues regarding the physiological state of an organism. The aim of this work was to evaluate a protocol for high-throughput NMR-based analysis of polar and non-polar metabolites from a small quantity of liver tissue. We extracted the tissue with a methanol/chloroform/water mixture and isolated the polar metabolites from the methanol/water layer and the non-polar metabolites from the chloroform layer. Following drying, we re-solubilized the fractions for analysis with a 600 MHz NMR spectrometer equipped with a 1.7 mm cryogenic probe. In order to evaluate the feasibility of this protocol for metabolomics studies, we analyzed the metabolic profile of livers from house sparrow (Passer domesticus) nestlings raised on two different diets: livers from 10 nestlings raised on a high protein diet (HP) for 4 d and livers from 12 nestlings raised on the HP diet for 3 d and then switched to a high carbohydrate diet (HC) for 1 d. The protocol enabled the detection of 52 polar and nine non-polar metabolites in 1H NMR spectra of the extracts. We analyzed the lipophilic metabolites by one-way ANOVA to assess statistically significant concentration differences between the two groups. The results of our studies demonstrate that the protocol described here can be exploited for high-throughput screening of small quantities of liver tissue (approx. 100 mg wet mass) obtainable from small animals.

Borderline personality disorder (BPD) is a severe mental disorder characterized by pervasive patterns of relational instability, chronic feelings of emptiness, sense of abandonment, self-injurious and anticonservative attempts. Pharmacological treatment has been found useful only for the management of severe symptoms and management of comorbidities, while psychotherapy is the main treatment for BPD. Although the disorder has long been considered resistant to any treatment, in recent years research has not only shown that BPD can be treated but also provided several manualized and empirically validated psychotherapeutic treatments. This paper set out to examine the most effective current psychotherapies for the treatment of BPD. All articles published in the last five years on the new psychotherapic treatments for BPD were included. Articles not relevant to this topic, as well as case reports and articles on animal models, were excluded. EBs forms of psychotherapy directed at symptom control and comorbidities occurring in BPD and forms termed generalist, were analyzed. Overall, the study found that there is no single form of psychotherapy that can fully treat BPD. The most effective forms of psychotherapy in controlling impulsive and self-injurious symptoms and in managing comorbidities remain Dialectical Behaviour Therapy and Schema Therapy.

Abstract Background Dengue is a serious public health problem worldwide, including Panama. During the last years, the number of dengue cases has increased. This may be due to the presence of mosquito populations resistant to insecticides. The aim of this study was to characterize the resistance status, its enzymatic mechanisms and Kdr mutations in wild populations of Aedes aegypti and Aedes albopictus. Methods Standard WHO bioassays were performed using insecticide-treated filter papers to determine resistance in populations Ae. aegypti and Ae. albopictus to pyrethroids insecticides, organophosphates, to the carbamate propoxur and to the organochlorine DDT. Biochemical assays were conducted to detect metabolic resistance mechanisms and real-time PCR was performed to determine the frequencies of the Kdr mutations Val1016IIe and F1534C. Results The strains Ae. aegypti El Coco showed confirmed resistance to deltamethrin (78.5% mortality) and lambda-cyhalothrin (81%), Aguadulce to deltamethrin (79.3%), David to deltamethrin (74.8%) and lambda-cyhalothrin (87.5%) and Puerto Armuelles to permethrin (83%). Aedes aegypti El Empalme showed confirmed resistance to pirimiphos-methyl (62.3% mortality), chlorpyrifos-methyl (55.5%) and propoxur (85.3%). All strains of Ae. albopictus showed possible resistance to PYs and five strains to DDT. Only Ae. albopictus Canto del Llano showed confirmed resistance to pirimiphos-methyl (70% mortality) and malathion (62%). Esterase activity was variable across sites with the most frequent expression of α-EST compared to β-EST in Ae. aegypti populations. In Ae. Albopictus, the expressed enzymes were β-EST and MFOs. Through ANOVA, significant differences were established in the levels of enzymatic activity of α- and β-EST, MFOs and GST, with p

Background Schizophrenia is characterized by significant cognitive impairments and affects up to 98% of patients. Neurofeedback (NF) offers a means to modulate neural network function through cognitive processes such as learning and memorization, with documented structural changes in the brain, most notably an increase in grey matter volume in targeted regions. Methods The present 2-week, open-label, preliminary study aims to evaluate the efficacy on cognition of an adjunctive short and intensive (8 daily sessions lasting 30 minutes) alpha/theta NF training in a sample of subjects affected by schizophrenia on stabilized treatment with atypical antipsychotic drugs. The efficacy was measured at baseline and at the end of the study by the Brief Neuropsychological Examination 2 (ENB 2), the Mini Mental State Examination (MMSE), and the Stroop color-word interference test; the clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Results A final sample of nine patients completed the study. Regarding the cognitive performance, at the final assessment (week 2), the NF treatment significantly improved the performance in the “Story Recall Immediate” (p = 0.024), “Story Recall Delayed” (p = 0.007), “Interference Memory 30 s” (p = 0.024), “Clock Test” (p = 0.014) sub-tests, and the ENB2 Total Score (p = 0.007). Concerning the clinical symptoms, no significant changes were observed in the PANSS subscales and the PANSS Total score. Conclusions NF could represent an adjunctive treatment strategy in the therapeutic toolbox for schizophrenia cognitive symptoms.

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.

Non-Invasive Brain Stimulation (NIBS) techniques seem to be effective in treating tobacco use disorder. We aimed to analyze what kinds of protocols are used to treat nicotine addiction in term of cessation and/or reduction and to evaluate the long-term effects of NIBS techniques.We searched PubMed, Scopus, and Web of Science for papers published, with combinations of the following search terms: “Non-invasive brain stimulation OR TMS OR transcranial magnetic stimulation OR tDCS OR transcranial direct current stimulation OR transcranial electrical stimulation OR TES AND Nicotine addiction”.We conducted a preliminary search, which revealed papers on the topic. Articles were included in the review according to the following inclusion criteria: English language, publication in peer reviewed journals, articles about studies performed on non-invasive brain stimulations techniques, and RCT studies. Studies involving clinical populations with organic or psychiatric diseases were excluded. We found 280 articles. Of these, at the first screening and conducted by title and abstract, 63 studies were excluded after duplicates were removed (118). After the second screening conducted by full-text examination, 45 articles were excluded. Ten studies met the inclusion criteria and were included in the review.The clinical benefits of NIBS, including the fast onset and minor side effects, showed that this kind of treatment could be helpful in patients with a long history of smoking in terms of cessation and abstinence rates.

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.

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.

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.

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.

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.

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.

Background: Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital “R. Dulbecco” in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients.

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.

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.

(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: 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.

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

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.

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.

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.

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: 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.

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.

Introduction: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto’s thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. Methods: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. Results: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. Conclusions: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.

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.

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.

BackgroundArtificial neural networks (ANNs) and logistic regression (LR) are the models of chosen in many medical data classification tasks. Several published articles were based on summarizing the differences and similarities of these models from a technical point of view and critically assessing the quality of the models. The aim of this study was to compare ANN and LR the statistical techniques to predict gastrointestinal cancer in an elderly cohort in Southern Italy (ONCONUT study).MethodIn 1992, ONCONUT was started with the aim of evaluating the relationship between diet and cancer development in a Southern Italian elderly population. Patients with gastrointestinal cancer (ICD-10 from 150.0 to 159.9) were included in the study (n = 3,545).ResultsThis cohort was used to train and test the ANN and LR. LR was evaluated separately for macro- and micronutrients, and the accuracy was evaluated based on true positives and true negatives versus the total (97.15%). Then, ANN was trained and the accuracy was evaluated (96.61% for macronutrients and 97.06% for micronutrients). To further investigate the classification capabilities of ANN, k-fold cross-validation and genetic algorithm (GA) were used after balancing the dataset among classes.ConclusionsBoth LR and ANN had high accuracy and similar performance. Both models had the potential to be used as decision clinical support integrated into clinical practice, because in many circumstances, the use of a simple LR model was likely to be adequate for real-world needs, but in others in which there were large amounts of data, the application of advanced analytic tools such as ANNs could be indicated, and the GA optimizer needed to optimize the accuracy of ANN.