Interleukin-9 protects from microglia- and TNF-mediated synaptotoxicity in experimental multiple sclerosis.

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.

Fatal acute graft-versus-host disease in Sézary Syndrome treated with Mogamulizumab and hematopoietic cell transplantation.

Sézary syndrome (SS) is a rare and aggressive T-cell lymphoma with a poor prognosis in advanced stages. Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure, but complications such as graft-versus-host disease (GvHD) remain a clinical challenge. Mogamulizumab, a humanized anti-CC chemokine receptor 4 (CCR4) antibody, is sometimes used as a bridge to transplantation, but its potential interactions with allo-HCT are unclear. This report describes the case of a 37-year-old man with advanced SS who received mogamulizumab therapy followed by allo-HCT from an HLA-identical sibling donor. The patient developed severe gastrointestinal acute GvHD, which was treated with steroids and infliximab. However, the condition rapidly progressed to severe intestinal symptoms and life-threatening haemorrhagic shock, ultimately resulting in the patient's death. This case highlights a potential link between mogamulizumab and severe acute GvHD promoted by drug-induced suppression of regulatory T cells. Further research is required to fully understand the interaction between mogamulizumab and allo-HCT and to determine whether it is an optimal approach as a bridge to transplant therapy. This paradigmatic case suggests the need of personalizing transplant strategies by selecting appropriate conditioning therapy and GvHD prophylaxis to minimize potential toxicity.

Interaction between miR-142-3p and BDNF Val/Met Polymorphism Regulates Multiple Sclerosis Severity.

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 (IL1ß), 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 IL1ß 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 IL1ß 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 IL1ß-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.

Low-contrast visual acuity test is associated with central inflammation and predicts disability development in newly diagnosed multiple sclerosis patients.

Introduction: The 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. Methods: We 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. Results: A 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 < 0.001, n = 62) of follow-up, and negative correlations were found with Multiple Sclerosis Severity Score (MSSS) at first (Spearman's Rho = -0.359, p = 0.004, n = 62) and second year (Spearman's Rho = -0.472, p < 0.001, n = 62). All the data were confirmed by a mixed effect model, considering other clinical variables. A positive correlation was found between the CSF concentrations of IL-10 and LCVA at 2.5% (Spearman's Rho = 0.272, p = 0.020, n = 76), and 1.25% (Spearman's Rho, = 0.276, p = 0.018, n = 76), also evidenced in a linear regression. Discussion: In MS patients at diagnosis, altered LCVA may be associated with CSF inflammation and represent a useful parameter to identify patients with worse disease course.

Neuroanatomical correlates of peripersonal space: bridging the gap between perception, action, emotion and social cognition.

Peripersonal space (PPS) is a construct referring to the portion of space immediately surrounding our bodies, where most of the interactions between the subject and the environment, including other individuals, take place. Decades of animal and human neuroscience research have revealed that the brain holds a separate representation of this region of space: this distinct spatial representation has evolved to ensure proper relevance to stimuli that are close to the body and prompt an appropriate behavioral response. The neural underpinnings of such construct have been thoroughly investigated by different generations of studies involving anatomical and electrophysiological investigations in animal models, and, recently, neuroimaging experiments in human subjects. Here, we provide a comprehensive anatomical overview of the anatomical circuitry underlying PPS representation in the human brain. Gathering evidence from multiple areas of research, we identified cortical and subcortical regions that are involved in specific aspects of PPS encoding.We show how these regions are part of segregated, yet integrated functional networks within the brain, which are in turn involved in higher-order integration of information. This wide-scale circuitry accounts for the relevance of PPS encoding in multiple brain functions, including not only motor planning and visuospatial attention but also emotional and social cognitive aspects. A complete characterization of these circuits may clarify the derangements of PPS representation observed in different neurological and neuropsychiatric diseases.

Costic acid, a sesquiterpene from Nectandra barbellata (Lauraceae), attenuates sponge implant-induced inflammation, angiogenesis and collagen deposition in vivo.

Sesquiterpenes are a class of metabolites derived from plant species with immunomodulatory activity. In this study, we evaluated the effects of treatment with costic acid on inflammation, angiogenesis, and fibrosis induced by subcutaneous sponge implants in mice. One sponge disc per animal was aseptically implanted in the dorsal region of the mice and treated daily with costic acid (at concentrations of 0.1, 1, and 10 µg diluted in 10 µL of 0.5% DMSO) or 0.5% DMSO (control group). After 9 days of treatment, the animals were euthanized, and the implants collected for further analysis. Treatment with costic acid resulted in the reduction of the inflammatory parameters evaluated compared to the control group, with a decrease in the levels of inflammatory cytokines and chemokines (TNF, CXCL-1, and CCL2) and in the activity of MPO and NAG enzymes. Costic acid administration altered the process of mast cell degranulation. We also observed a reduction in angiogenic parameters, such as a decrease in the number of blood vessels, the hemoglobin content, and the levels of VEGF and FGF cytokines. Finally, when assessing implant-induced fibrogenesis, we observed a reduction in the levels of the pro-fibrogenic cytokine TGF-ß1, and lower collagen deposition. The results of this study demonstrate, for the first time, the anti-inflammatory, anti-angiogenic, and anti-fibrotic effects of costic acid in an in vivo model of chronic inflammation and reinforce the therapeutic potential of costic acid.

Off-Label Use of Balloon-Expandable Transcatheter Valves to Treat Pure Aortic Regurgitation.

Transcatheter aortic valve implantation (TAVI) in native pure aortic regurgitation (AR) with off-label use of balloon-expandable valves (BEV) has been reported. However, there are scant data regarding optimal oversizing and its safety, and our study assessed BEV oversizing and outcomes of TAVI. Thirteen consecutive tricuspid aortic valve patients who underwent transfemoral TAVIs for pure AR with Sapien BEV at our center between 2019 and 2023 (69.2% males, mean age 80.8 years, Society of Thoracic Surgeons 4.0%) were divided into small annulus (SA) group (≤618 mm2) where ≥20% oversizing is achievable based on published data on BEV overexpansion, and larger annulus (LA) group (>618 mm2). Overexpansion and actual oversizing were measured on postprocedural computed tomography scan. Technical success was 92.3% with 1 valve embolization in the LA group. The postprocedural computed tomography showed a mean 28.3% oversizing, significantly higher in SA (31.2%) than in LA group (19.4%), p = 0.0092. Oversizing ≥20% was achieved in 100% SA versus 33.3% LA patients (p = 0.046). In conclusion, TAVI in pure AR with oversized Sapien BEV showed good procedural and short-term outcomes when ≥20% oversizing was predictably achievable.

The role of the vascular surgeon in transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become the standard treatment for severe aortic valve stenosis in patients at increased surgical risk. Percutaneous transfemoral (TF) is the access of choice due to its reduced invasiveness and perioperative morbidity/mortality compared with the trans-axillary, aortic, and apical routes. On the other hand, vascular access complications (VACs) of the TF access are associated with prolonged hospitalization, 30-day, and 1-year mortality. In addition, the concomitance of peripheral arterial disease may require associated endovascular management. A multidisciplinary team with Interventional Cardiologists and Vascular Surgeons may minimize the rate of VACs in patients with challenging femoral-iliac access or concomitant disease of other vascular districts, thus optimizing the outcome of TF-TAVI. The aim of this study was to evaluate the role of Vascular Surgeons in TF TAVI procedures. METHODS: We conducted a retrospective single-center review of all TF-TAVI procedures assisted by Vascular Surgeons between January 2016 and December 2020 in a high-volume tertiary hospital. Pre, intra, and postoperative data were analyzed by a dedicated group of Interventional Cardiologists and Vascular Surgeons. VACs were defined according with the Valve Academic Research Consortium (VARC) three guidelines. The outcomes of TF-TAVI procedures with Vascular Surgeons involvement were assessed as study's endpoints. RESULTS: Overall, 937 TAVI procedures were performed with a TF approach ranging between 78% (2016) and 98% (2020). Vascular Surgeons were involved in 67 (7%) procedures with the following indications: concomitant abdominal aortic aneurysm (EVAR + TAVI) - 3 (4%), carotid stenosis (TAVI + CAS) - 2 (3%), hostile femoral/iliac access, or VACs - 62 (93%). Balloon angioplasty of iliac artery pre-TAVI implantation was performed in 51 cases (conventional PTA: 38/51%-75%; conventional PTA + intravascular lithotripsy: 13/51%-25%; stenting: 5/51%-10%). TAVI procedure was successfully completed by percutaneous TF approach in all 62 cases with challenging femoral/iliac access. VACs necessitating interventions were 18/937 (2%) cases, localized to the common femoral or common/external iliac artery in 15/18 (83%) and 3/18 (17%) cases, respectively. They were managed by surgical or endovascular maneuvers in 3/18 (17%) and 15/18 (83%) cases, respectively. Fifteen/18 (83%) VACs were treated during the index procedure. There was no procedure-related mortality or 30-day readmission. CONCLUSION: In our experience, Vascular Surgeon assistance in TAVI procedures was not infrequent and allowed safe and effective device introduction through challenging TF access. Similarly, the concomitant significant disease of other vascular districts could be safely addressed, potentially reducing postoperative related mortality and morbidity. The implementation of multidisciplinary team with interventional cardiologists and vascular surgeons should be encouraged whenever possible.

Mood disturbances in newly diagnosed Parkinson's Disease patients reflect intrathecal inflammation.

In Parkinson's disease (PD), neuroinflammation may be involved in the pathogenesis of mood disorders, contributing to the clinical heterogeneity of the disease. The cerebrospinal fluid (CSF) levels of interleukin (IL)-1ß, IL-2, IL-6, IL-7, IL-8, IL-9, IL-12, IL-17, interferon (IFN)γ, macrophage inflammatory protein 1-alpha (MIP-1a), MIP-1b, granulocyte colony stimulating factor (GCSF), eotaxin, tumor necrosis factor (TNF), and monocyte chemoattractant protein 1 (MCP-1), were assessed in 45 newly diagnosed and untreated PD patients and in 44 control patients. Spearman's correlations were used to explore possible associations between CSF cytokines and clinical variables including mood. Benjamini-Hochberg (B-H) correction for multiple comparisons was applied. Linear regression was used to test significant associations correcting for other clinical variables. In PD patients, higher CSF concentrations of the inflammatory molecules IL-6, IL-9, IFNγ, and GCSF were found (all B-H corrected p < 0.02). Significant associations were found between BDI-II and the levels of IL-6 (Beta = 0.438; 95%CI 1.313-5.889; p = 0.003) and IL-8 (Beta = 0.471; 95%CI 0.185-0.743; p = 0.002). Positive associations were also observed between STAI-Y state and both IL-6 (Beta = 0.452; 95%CI 1.649-7.366; p = 0.003), and IL-12 (Beta = 0.417; 95%CI 2.238-13.379; p = 0.007), and between STAI-Y trait and IL-2 (Beta = 0.354; 95%CI 1.923-14.796; p = 0.012), IL-6 (Beta = 0.362; 95%CI 0.990-6.734; p = 0.01), IL-8 (Beta = 0.341; 95%CI 0.076-0.796; p = 0.019), IL-12 (Beta = 0.328; 95%CI 0.975-12.135; p = 0.023), and IL-17 (Beta = 0.334; 95CI 0.315-4.455; p = 0.025). An inflammatory CSF milieu may be associated with depression and anxiety in the early phases of PD, supporting a role of neuroinflammation in the pathogenesis of mood disturbances.

Development of collagenous scaffolds for wound healing: characterization and in vivo analysis.

The development of wound dressings from biomaterials has been the subject of research due to their unique structural and functional characteristics. Proteins from animal origin, such as collagen and chitosan, act as promising materials for applications in injuries and chronic wounds, functioning as a repairing agent. This study aims to evaluate in vitro effects of scaffolds with different formulations containing bioactive compounds such as collagen, chitosan, N-acetylcysteine (NAC) and ε-poly-lysine (ε-PL). We manufactured a scaffold made of a collagen hydrogel bioconjugated with chitosan by crosslinking and addition of NAC and ε-PL. Cell viability was verified by resazurin and live/dead assays and the ultrastructure of biomaterials was evaluated by SEM. Antimicrobial sensitivity was assessed by antibiogram. The healing potential of the biomaterial was evaluated in vivo, in a model of healing of excisional wounds in mice. On the 7th day after the injury, the wounds and surrounding skin were processed for evaluation of biochemical and histological parameters associated with the inflammatory process. The results showed great cell viability and increase in porosity after crosslinking while antimicrobial action was observed in scaffolds containing NAC and ε-PL. Chitosan scaffolds bioconjugated with NAC/ε-PL showed improvement in tissue healing, with reduced lesion size and reduced inflammation. It is concluded that scaffolds crosslinked with chitosan-NAC-ε-PL have the desirable characteristics for tissue repair at low cost and could be considered promising biomaterials in the practice of regenerative medicine.

Acute taurine reduced alcohol intake and preference in alcohol-experienced, but not in alcohol-näive rats by central mechanisms.

Taurine is a non-essential ß sulfonated amino acid involved in a plethora of biological functions in the mammalian central nervous system. Taurine is easily accessible in energy drinks for human consumption. Previous preclinical and clinical reports suggest that acute systemic administration of taurine could inhibit some of the behavioral and metabolic effects of alcohol use disorder. Overall, both in rodent and human studies, acute taurine administration reduced voluntary alcohol intake. This study aimed to assess the pharmacological effects of taurine (intracerebroventricular; i.c.v.) on ethanol intake/preference of rats either control (i.e., alcohol naïve) or forced ethanol intake (since juvenile age with a chronic intermittent access model). In addition, to explore anxiety-like behavior (through defensive burying behavior test) as pharmacological control of taurine. We found that acute (i.c.v.) taurine reduced alcohol consumption, i.e., taurine significantly decreased both alcohol intake and preference in adult male Wistar rats. Moreover, taurine elicits an anxiolytic-like effect in all administered groups independently of previous alcohol exposure.

Percutaneous balloon-assisted ultrasound-guided direct thrombin embolization of superficial femoral artery pseudoaneurysm: a case series and literature review.

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.

Attention Deficit Hyperactivity Disorder (ADHD) and Polyphenols: A Systematic Review.

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.

A proposed index of myocardial staining for vein of Marshall ethanol infusion: an Italian single-center experience.

BACKGROUND: Mitral isthmus (MI) conduction block is a fundamental step in anatomical approach treatment for persistent atrial fibrillation (PeAF). However, MI block is hardly achievable with endocardial ablation only. Retrograde ethanol infusion (EI) into the vein of Marshall (VOM) facilitates MI block. Fluorographic myocardial staining (MS) during VOM-EI could be helpful in predicting procedural alcoholization outcome even if its role is qualitatively assessed in the routine. The aim was to quantitatively assess MS during VOM-EI and to evaluate its association with MI block achievement. METHODS: Consecutive patients undergoing catheter ablation for PeAF at Fondazione Toscana Gabriele Monasterio (Pisa, Italy) from February 2022 to May 2023 were considered. Patients with identifiable VOM were included. A proposed index of MS (MSI) was retrospectively calculated in each included patient. Correlation of MSI with low-voltage zones (LVZ) extension after VOM-EI and its association with MI block achievement were assessed. RESULTS: In total, 42 patients out of 49 (85.8%) had an identifiable VOM. MI block was successfully achieved in 35 patients out of 42 (83.3%). MSI was significantly associated with the occurrence of MI block (OR 1.24 (1.03-1.48); p = 0.022). A higher MSI resulted in reduced ablation time (p = 0.014) and reduced radiofrequency applications (p = 0.002) to obtain MI block. MSI was also associated with MI block obtained by endocardial ablation only (OR 1.07 (1.02-1.13); p = 0.002). MSI was highly correlated with newly formed LVZ extension (r = 0.776; p = 0.001). CONCLUSIONS: In our study cohort, optimal MSI predicts MI block and facilitates its achievement with endocardial ablation only.

Preventive exercise and physical rehabilitation promote long-term potentiation-like plasticity expression in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Loss of long-term potentiation (LTP) expression has been associated with a worse disease course in relapsing-remitting multiple sclerosis (RR-MS) and represents a pathophysiological hallmark of progressive multiple sclerosis (PMS). Exercise and physical rehabilitation are the most prominent therapeutic approaches to promote synaptic plasticity. We aimed to explore whether physical exercise is able to improve the expression of LTP-like plasticity in patients with multiple sclerosis (MS). METHODS: In 46 newly diagnosed RR-MS patients, we explored the impact of preventive exercise on LTP-like plasticity as assessed by intermittent theta-burst stimulation. Patients were divided into sedentary or active, based on physical activity performed during the 6 months prior to diagnosis. Furthermore, in 18 patients with PMS, we evaluated the impact of an 8-week inpatient neurorehabilitation program on clinical scores and LTP-like plasticity explored using paired associative stimulation (PAS). Synaptic plasticity expression was compared in patients and healthy subjects. RESULTS: Reduced LTP expression was found in RR-MS patients compared with controls. Exercising RR-MS patients showed a greater amount of LTP expression compared with sedentary patients. In PMS patients, LTP expression was reduced compared with controls and increased after 8 weeks of rehabilitation. In this group of patients, LTP magnitude at baseline predicted the improvement in hand dexterity. CONCLUSIONS: Both preventive exercise and physical rehabilitation may enhance the expression of LTP-like synaptic plasticity in MS, with potential beneficial effects on disability accumulation.

Dental anxiety, Quality of Life and body image: gender differences in Italian and Spanish population.

BACKGROUND: Dental anxiety is an excessive and irrational negative emotional state experienced by population; the dental anxiety is common throughout the lifespan and is an obstacle to improving oral health behaviors and outcomes. The aim of this study was to assess gender differences in dental anxiety and to investigate if oral health impacts patients' Quality of Life and the perception of their body image. METHODS: The sample consisted of 366 subjects selected in Italy and Spain (January 2021-September 2021). For this study, data were gathered using Google Forms (Google LLC, Mountain View, CA, USA). Data were collected including the Dental Anxiety Scale (DAS), Oral Health Impact Profile (OHIP-14) questionnaires and Body Uneasiness Test. RESULTS: Women showed higher scores than men for the dental anxiety. The regression analysis showed that gender, age, and Oral Health Impact are predictors of "dental anxiety." A borderline significance emerges for the independent variable body uneasiness. CONCLUSIONS: The dental anxiety is widespread in the population, with a higher prevalence among women and increases with increasing age. It can negatively affect patients' Quality of Life, well-being, and self-esteem. These results underline the importance of addressing both individual and group strategies for preventing or treating dental anxiety.

The Human Affectome.

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective constructs and operationalizations. However, an assumption about the purpose of affective phenomena can guide us to a common set of metaphysical and mechanistic assumptions. In this capstone paper, we home in on a nested teleological principle for human affective phenomena in order to synthesize metaphysical and mechanistic assumptions. Under this framework, human affective phenomena can collectively be considered algorithms that either adjust based on the human comfort zone (affective concerns) or monitor those adaptive processes (affective features). This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope the Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.

Physical exercise and synaptic protection in human and pre-clinical models of multiple sclerosis.

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.

Eco-Anxiety: An Evolutionary Line from Psychology to Psychopathology.

According to the scientific literature, climate change, due to human activities, can damage the environment, with psycho-physical consequences for humans. The scientific literature has highlighted how severe weather events can cause fear, stress, concern for the future, and eco-anxiety. In light of this information, this study aims to explore the concept of eco-anxiety. However, climate change is still perceived as a secondary problem. It would also be worth investigating the real importance that people attach to environmental issues compared to other circumstances, such as wars or pandemics.

Fabry-Perot Cavity Optimization for Absolute Strain Sensing Using Finite Element Analysis.

The finite element method (FEM) was used to investigate the optical-mechanical behavior of a Fabry-Perot Interferometer (FPI) composed of a capillary segment spliced between two sections of standard optical fiber. The developed FEM model was validated by comparing it with theory and with previously published experimental data. The model was then used to show that the absolute strain on the host substrate is usually smaller than the strain measurement obtained with the sensor. Finally, the FEM model was used to propose a cavity geometry that can be produced with repeatability and that yields the correct absolute strain experienced by the host substrate, without requiring previous strain calibration.