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Aim: To review the qualitative literature regarding how people with fibromyalgia experience and are impacted by stigma., Design: A systematic review and metasynthesis of qualitative studies was conducted following the Thomas and Harden method., Methods: The electronic databases PubMed, CINAHL, PsycInfo, Embase and Scopus were queried (September 2023). No publication year limit was set. Twelve studies were included in the final analysis. The findings were reported according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) statement., Findings: Three main themes with 11 sub-themes were identified: manifestations and roots of stigma, avoidance and coping strategies, and consequences of stigma. Stigma arises from disbelief due to the invisibility of symptoms, protracted time to diagnosis and gender stereotyping, especially against women. Various strategies to avoid or cope with prejudice may involve social isolation, hiding the disease, controlling information, getting closer to or further away from other patients, acknowledging and understanding the disease. Stigmatisation can diminish a person's integrity and dignity, undermine trust in health care professionals and worsen suffering., Conclusion: The metasynthesis findings align with previous research highlighting the pervasive stigma associated with chronic pain conditions. Greater awareness of the impact of disease-related stigma on individuals with fibromyalgia is crucial, not only among health care professionals but also within broader societal and institutional contexts., Implications for the Profession And/or Patient Care: Understanding the stigma experienced by individuals with fibromyalgia can guide health care professionals in adopting more empathtic approaches, potentially improving the diagnostic process and the overall management of the condition., Impact: This study highlights the profound impact of stigma on individuals with fibromyalgia, emphasising the need for greater awareness and targeted interventions to address stigma in clinical practice and societal contexts., Patient or Public Contribution: No patient or public contribution., (© 2025 The Author(s). Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background and Purpose: Fremanezumab, a monoclonal antibody targeting the calcitonin gene-related peptide for migraine prevention, is available in monthly (225 mg) and quarterly (675 mg) doses. Previous studies showed efficacy and safety for both regimens, but a real-life comparison is lacking. This study aimed to compare the effectiveness and safety of monthly and quarterly fremanezumab in a real-life setting., Methods: This Italian, prospective, multicenter study enrolled 95 migraine patients. During a 3-month treatment period, patients received either monthly or quarterly fremanezumab (49 monthly, 46 quarterly). A 6-month treatment period involved 79 patients (43 monthly, 36 quarterly). Monthly headache (MHD) and migraine days (MMD), number of days (AMD) and pills (AMP) of acute medication intake, and Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS) test, and Numeric Rating Scale (NRS) scores were recorded at baseline and after 3 and 6 months of treatment. Adverse events (AEs), responder rates, and medication overuse were also investigated., Results: Both monthly and quarterly treatments led to significant reductions in MMD, MHD, AMP, AMD, HIT-6, MIDAS, and NRS scores after 3 and 6 months. The monthly regimen exhibited a slightly greater reduction in MMD and MHD after the first quarter, with no significant difference observed after 6 months. The most common AE was transient injection-site reaction, without between-group differences. Responder rates and resolution of medication overuse did not significantly differ between the groups., Conclusions: Both monthly and quarterly regimens were effective and safe, with a tendency for an advantage of the monthly regimen only in the first quarter of treatment., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Multiple sclerosis (MS) is a neurological disorder characterized by immune dysregulation. It begins with a first clinical manifestation, a clinically isolated syndrome (CIS), which evolves to definite MS in case of further clinical and/or neuroradiological episodes. Here we evaluated the diagnostic value of transcriptional alterations in MS and CIS blood by machine learning (ML). Deep sequencing of more than 200 blood RNA samples comprising CIS, MS and healthy subjects, generated transcriptomes that were analyzed by the binary classification workflow to distinguish MS from healthy subjects and the Time-To-Event pipeline to predict CIS conversion to MS along time. To identify optimal classifiers, we performed algorithm benchmarking by nested cross-validation with the train set in both pipelines and then tested models generated with the train set on an independent dataset for final validation. The binary classification model identified a blood transcriptional signature classifying definite MS from healthy subjects with 97% accuracy, indicating that MS is associated with a clear predictive transcriptional signature in blood cells. When analyzing CIS data with ML survival models, prediction power of CIS conversion to MS was about 72% when using paraclinical data and 74.3% when using blood transcriptomes, indicating that blood-based classifiers obtained at the first clinical event can efficiently predict risk of developing MS. Coupling blood transcriptomics with ML approaches enables retrieval of predictive signatures of CIS conversion and MS state, thus introducing early non-invasive approaches to MS diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: While John Cunningham virus (JCV) is known to cause neuronal damage in progressive multifocal leukoencephalopathy (PML) among natalizumab-treated MS patients, its association with axonal loss in non-PML conditions remains unclear., Methods: In a cohort of 128 natalizumab-treated MS patients, serum neurofilament (sNfL) levels and JCV antibody titres were measured., Results: Among 128 patients (mean age = 38.4 years, 71.9% female), 51 (40%) were JCV positive. NfL levels increased by 15.3% for JCV index <0.7 (95% confidence interval [CI] = 0.963-1.381), by 18.6% for index 0.7-1.5 (95% CI = 1.009-1.394) and by 21.1% for index >1.5 (95% CI = 1.040-1.409) compared to JCV negative patients., Conclusion: These findings indicate a potential link between JCV burden and neuroaxonal degeneration in natalizumab-treated MS patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: G.D.C., M.P., T.C., F.S., B.C., A.H., and R.G. report no disclosures. VM has received honoraria for activities with Biogen, Merck, Bayer, TEVA and Sanofi-Genzyme as a speaker. L.M. has received honoraria for speaking in scientific meetings and for advisory board from Biogen TEVA, Sanofi-Genzyme, and Merck. R.F. has received honoraria for speaker activities from Biogen, Merck, Novartis, Roche and Teva. L.L. has received honoraria for consulting services and/or speaking activity from Biogen, Novartis and Excemed. G.C. has received personal compensation for consulting services and/or speaking activities from Novartis, Teva, Sanofi, Sanofi-Genzyme, Merck, Biogen, Excemed, Serono Symposia International Foundation, Roche, Almirall, Receptos, Celgene and Forward Pharma.

Rapid urbanization has led to negative, and sometimes unintended, consequences on biodiversity and human health. While cities offer numerous advantages in meeting the basic needs of a growing population, they also pose less apparent and longer-term health costs. To address the multifaceted impacts of urbanization, an evidence-based design framework for establishing mitigation and regeneration actions is essential. Via a "One Health" approach, this perspective provides recommendations and strategies for the urban ecosystem rehabilitation of future cities, placing biodiversity and ecosystem services at the core of designing healthy and sustainable urban spaces. The framework we propose is based on a Hub and Spoke model to integrate diverse perspectives from public and private sectors and declined in a six-building-blocks structure. This will ensure that efforts are sustainable, health-centered, socially inclusive, and grounded in high-quality data, reinforcing the essential connection between healthy environments and thriving communities., Competing Interests: M.B., B.P., and N.R. are inventors of exp-EIA© (experiential Environmental Impact Assessment) method (Patent 1: Italian Publication Number 102021000017168 - 30/06/2021; International Publication Number WO 2023/275679 A1 - 5.1.2023). M.B., L.M., B.P., and N.R. are inventors of exp-EIA© (experiential Environmental Impact Assessment) method (Patent 2: Italian Patent Publication filed Number 102024000011161 - 16.5.2024). The other authors declare no competing interests., (© 2024 The Author(s).)

Introduction: Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized controlled trial (RCT). We aimed to assess real-world evidence (RWE), long-term effectiveness, tolerability, and safety of fremanezumab in people with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and various comorbidities., Methods: A 48-week, prospective, multicenter (n = 26), cohort study assessed fremanezumab's effectiveness, safety, and tolerability in consecutive adults with HFEM or CM with > 3 treatment failures. Primary endpoint was variation from baseline in monthly migraine days (MMD) in HFEM and monthly headache days (MHD) in CM at weeks 45-48. Secondary endpoints were changes in monthly analgesic medications, Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), and the Migraine Disability Assessment Scale (MIDAS) scores and ≥ 50%, ≥ 75%, and 100% responder rates., Results: Of 533 participants who had received ≥ 1 fremanezumab dose, 130 were treated for ≥ 48 weeks and considered for effectiveness analysis. No participant missed any treatment dosage every other consecutive month during the 12-month period., Primary Endpoint: fremanezumab significantly (p < 0.001) reduced both MMD (- 6.4) in HFEM and MHD (- 14.5) in CM. Secondary endpoints: a significant reduction (p < 0.001) was observed in monthly analgesic medications (HFEM - 6.0; CM -16.5), NRS (HFEM - 3.4; CM - 3.4), HIT-6 (HFEM - 16.9; CM - 17.9) and MIDAS score (HFEM - 50.4; CM - 76.6). The ≥ 50%, ≥ 75%, and 100% response rates to fremanezumab were 75.5%, 36.7%, and 2% in HFEM and 71.6%, 44.4%, and 3.7% in CM. Corresponding response rates were 60.5%, 37.2%, and 2.3% in individuals with psychiatric comorbidities, 74.2%, 50%, and 4.8% in CM with medication overuse, and 60.9%, 39.1%, and 4.3% in CM with medication overuse and psychiatric comorbidities. Mild and transient treatment-emergent adverse events occurred in 7.8% of the participants. No subject discontinued the treatment for any reason., Conclusion: This RWE study documents that long-term fremanezumab treatment is highly effective and remarkably well tolerated in subjects with HFEM or CM with multiple (> 3) therapeutic failures, even in the presence of concomitant medication overuse, psychiatric comorbidities, or both. The effectiveness-to-tolerability ratio appears to be better in RWE than in RCTs., (© 2024. The Author(s).)

Objectives: While a single 12-month treatment cycle (TrC) with anti-CGRP mAbs is not disease-modifying for most patients, there is limited understanding of the effects of multiple TrCs on migraine course. We evaluated whether a second TrC might modify the migraine course by comparing the occurrence of migraine relapse after discontinuation of the second TrC to that following the cessation of the first TrC., Methods: In a real-life, multicenter, prospective study we considered all consecutive patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and treated with any anti-CGRP mAbs for ≥ 2 consecutive 12-month TrCs who were responders at week 12. The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at the first month of treatment discontinuation after the second TrC (D2) compared to the first TrC (D1). Secondary endpoints included variations in monthly analgesic medications (MAM), Numeric Rating Scale (NRS), and Headache Impact Test (HIT-6) scores, ≥ 50%, ≥ 75%, and 100% response rates, and relapse from episodic migraine to CM and from no-medication overuse (MO) to MO at D2 vs. D1., Results: One-hundred-seventy-eight patients completed two 12-month TrCs with anti-CGRP mAbs. At D2, patients experienced a significant reduction in MMD (- 0.6, p = 0.028), MHD (- 2.6, p < 0.001), monthly analgesic medications (- 2.0, p < 0.001), and HIT-6 score (- 2.2, p < 0.001) compared to D1, indicating improved effectiveness. The ≥ 50% response rate at weeks 45-48 during the first TrC was 95.5%, while at weeks 45-48 of the second TrC was 99.4%. Corresponding rates at D1 was 20.2% whereas at D2 was 51.6% (p < 0.0001). No statistical difference emerged in ≥ 75% and 100% responders. The relapse rate from episodic migraine to CM at D2 was lower than at D1 (12.3% vs 30.4%; p = 0.0002) Fewer patients experienced relapse from no-MO to MO at D2 compared to D1 (29.5% vs 68.7%; p = 0.00001)., Discussion: A second TrC with anti-CGRP mAbs demonstrated clinical improvements compared to the first one, as indicated by a milder migraine relapse at D2 compared to D1. Multiple TrCs with anti-CGRP mAbs could progressively modify migraine evolution by reducing CGRP-dependent neuroinflammatory nociceptive inputs to the brain., (© 2024. The Author(s).)

Objective: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders)., Methods: In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks., Results: A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain-either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)-a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020)., Conclusion: Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2-3 months of treatment., (© 2024. The Author(s).)

When researchers and clinicians try to identify appropriate and effective ways to improve well-being among different populations, music is often included in interventions or research projects. The existing literature has consistently reported interactions between the effects of personality traits and music listening. However, the interrelations between individual traits and well-being after music listening are still partially unclear. This systematic review, registered on PROSPERO, investigates the relationship between everyday music listening, individual characteristics - operationalized as stable and transient personality traits - and well-being. Articles were searched on PubMed, Scopus, and Google Scholar, with a final result of 115 records. After eligibility screening, eight studies were included in the review. The results showed that both stable and transient personality traits influence music's effect on well-being. As a result of the scoping review, a theoretical perspective combining the emotional dimension, the principle of emotional congruence, and the dimension of music immersion and well-being was identified. Based on this knowledge, music listening could be systematically introduced into daily routines to improve everyday well-being and prevent or reduce stressful states.

Objective: The aim of this multicentric cross-sectional study was to collect phenotypes and clinical variability on a large sample of 244 patients enrolled in different university centers in Italy, trying to differentiate subtypes of VM., Background: VM is one of the most frequent episodic vertigo characterized by a great clinical variability for duration of attacks and accompanying symptoms. Diagnosis is based only on clinical history of episodic vertigo in 50% of cases associated with migrainous headache or photo/phonophobia., Methods: We enrolled in different university centers 244 patients affected by definite VM according to the criteria of the Barany Society between January 2022 and December 2022. An audiometric examination and a CNS MRI were performed before inclusion. Patients with low-frequency sensorineural hearing loss were not included, as well as patients with an MRI positive otherwise that for microischemic lesions. Patients were asked to characterize vestibular symptoms choosing among (multiple answers were allowed): internal vertigo, dizziness, visuo-vestibular symptoms/external vertigo; onset of vertigo and duration, neurovegetative, and cochlear accompanying symptoms (hearing loss, tinnitus, and fullness during attacks) were collected as well as migrainous headache and/or photo/phonophobia during vertigo; autoimmune disorders were also analyzed. A bedside examination was performed including study of spontaneous-positional nystagmus with infrared video goggles, post head shaking ny, skull vibration test, and video head impulse test., Results: We included 244 subjects, 181 were females (74.2%). The age of onset of the first vertigo was 36.6 ± 14.5 while of the first headache was 23.2 ± 10.1. A positive correlation has been found between the first headache and the first vertigo. The mean duration of vertigo attacks was 11 ± 16 h. We carried on a cluster analysis to identify subgroups of patients with common clinical features. Four variables allowed to aggregate clusters: age of onset of vertigo, duration of vertigo attacks, presence of migrainous headache during vertigo, and presence of cochlear symptoms during vertigo. We identified 5 clusters: cluster 1/group 1 (23 subjects, 9.4%) characterized by longer duration of vertigo attacks; cluster 2/group 2 (52 subjects, 21.3%) characterized by absence of migrainous headache and cochlear symptoms during vertigo; cluster 3/group 3 (44 subjects, 18%) characterized by presence of cochlear symptoms during vertigo but not headache; cluster 4/group 4 (57 subjects, 23.4%) by the presence of both cochlear symptoms and migrainous headache during vertigo; cluster 5/group 5 (68 subjects, 27.9%) characterized by migrainous headache but no cochlear symptoms during vertigo., Conclusion: VM is with any evidence a heterogeneous disorder and clinical presentations exhibit a great variability. In VM, both symptoms orienting toward a peripheral mechanism (cochlear symptoms) and central ones (long lasting positional non-paroxysmal vertigo) may coexist. Our study is the first published trying to characterize subgroups of VM subjects, thus orienting toward different pathophysiological mechanisms., (© 2023. Fondazione Società Italiana di Neurologia.)

The COVID-19 pandemic has increased the vulnerability of adults to mental health effects, and the study of protective factors has become crucial. Cognitive reserve (CR) is a well-known protective factor against cognitive decline and several health factors; however, its protective effect on mental health during the pandemic has been rarely addressed. Thus, this study explored, through a mixed-method design, the effect of CR on perceived distress and PTSD-like symptoms in middle-aged participants who have survived severe COVID-19 and a matched control group. A total of 432 participants filled out self-report measures of CR, PTSD, depression, and anxiety, and were also asked to provide narration about their COVID-19-related experience. COVID-19 significantly affected the chances of reporting different mental health symptoms; levels of CR played a protective role in reducing their severity. Moreover, adults with higher CR seemed to be more realistic, focusing less on positive emotions, and elaborating more on the sense of anxiety when describing their experience: this might be an indication of a lower use of suppression to regulate emotions. Practical implications of these findings and future directions have been also discussed.

The concept of trust has been extensively studied within the field of medicine. Yet, a list of factors that clearly influence patients' trust is still under debate. Moreover, the methodological approaches found in literature have been reported to be lacking in their assessments and measurements of trust relationships in the medical field although trust between a patient and medical provider has been proven to increase adherence and improve health outcomes. Hence, adding data to this debate and exploring a reliable method to explore the construct of trust is relevant. This study collects new evidence of the most salient indicators of patient trust by using a narrative approach and highlighting the potential of this method in collecting indicators that could be used to build training that aims to increase patients' trust. We used the Linguistic Inquiry and Word Count software for text analysis to examine the spontaneous narrations of episodes of trust and distrust within the doctor-patient relationship with a sample of 82 adult patients. Results demonstrate the role of the emotional aspects of the doctor-patient relationship. Data highlights the importance of doctors' benevolence toward patients, and positive emotions seem to be deeply connected with any experience of trust, which leads patients to feel more secure. Methods are presented to use these insights to construct mechanisms that establish medical trust and allow providers to implement effective interventions.

Background: We aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide receptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect following treatment discontinuation., Methods: This was a randomized, double-blind, placebo-controlled, multicenter trial with a crossover design performed in adult episodic migraine patients with previous treatment failure. Patients were randomized (1:1) to 12 weeks of erenumab 140 mg or placebo, followed by a 12-week crossover. Resting state (RS) functional connectivity (FC) changes of brain networks involved in migraine were investigated using a seed-based correlation approach., Results: Sixty-one patients were randomized to treatment. In each treatment sequence, 27 patients completed the visit at week 12. Forty-four enrolled patients, 22 in each treatment sequence, completed the study procedures with no major protocol violations. We observed a carry-over effect of erenumab during the placebo treatment and therefore data analysis was performed as a parallel comparison of erenumab vs placebo of the first 12 weeks of treatment. From baseline to week 12, compared to placebo, patients receiving erenumab showed RS FC changes within the cerebellar, thalamic and periaqueductal gray matter networks, significantly associated with clinical improvement. Compared to non-responders, patients achieving a 50% reduction in migraine days had distinct patterns of thalamic and visual network RS FC. Brain RS FC changes reversed when erenumab was stopped. A lower baseline RS FC of the pontine network identified patients responding to erenumab., Conclusion: Erenumab modulates RS FC of networks involved in migraine pathophysiology. In line with clinical response, erenumab-induced brain RS FC changes tend to reverse when treatment is stopped., (© 2023. The Author(s).)

Background: Monoaminergic network dysfunction may have a role in multiple sclerosis (MS) fatigue pathogenesis., Objective: To investigate modifications of fatigue severity and resting state (RS) functional connectivity (FC) in monoaminergic networks of 45 fatigued MS patients after different symptomatic treatments., Methods: Patients were randomly, blindly assigned to fampridine (n = 15), amantadine (n = 15) or placebo (n = 15) treatment and underwent clinical and 3T-MRI evaluations at baseline (t0) and week 4 (w4), i.e. after four weeks of treatment. Fifteen healthy controls (HC) were enrolled. Dopamine-, noradrenaline- and serotonin-related RS FC was assessed by PET-guided constrained independent component analysis., Results: At t0, MS patients showed widespread monoamine-related RS FC abnormalities. At w4, fatigue scores decreased in all groups (p = range < 0.001-0.002). Concomitantly, fampridine and amantadine patients showed increased insular RS FC in dopamine-related and noradrenaline-related networks (p < 0.001, uncorrected). Amantadine patients also showed increased RS FC of anterior cingulate cortex in dopamine-related and noradrenaline-related networks (p < 0.001, uncorrected). Placebo patients showed increased precuneus/middle cingulate RS FC in the noradrenaline-related network (p < 0.001, uncorrected). In fampridine and placebo patients, just tendencies towards correlations between RS FC and fatigue modifications were found., Conclusions: In MS patients, specific RS FC modifications in PET-guided monoaminergic networks were observed, concomitantly with fatigue improvements following treatment., Trial Registration Number: EudraCT 2010-023678-38., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Vestibular migraine (VM) is a neurological condition that causes vertigo and headache. It is considered the most common cause of episodic vertigo. However, specific treatments are missing, and medications currently used in VM are borrowed from migraine therapy. A comprehensive practical review of the literature assessing the evidence for abortive and preventive interventions in adults with VM was published in 2022, providing practical recommendations about VM treatment. The aim of our paper is to provide an updated overview of the current state of the art of VM treatment, illustrating new evidence available in this field. Along with traditional pharmacological preventive therapies, medications targeting the CGRP pathways have recently been investigated in terms of treatment effect in VM patients, with encouraging results. Also, there is new evidence of the efficacy of non-pharmacological interventions. However, the overall evidence base for VM treatment remains sparse.

Background: Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments., Results: In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism., Conclusion: GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Urbanization and the expansion of human activities foster radical ecosystem changes with cascading effects also involving host-pathogen interactions. Urban pollinator insects face several stressors related to landscape and local scale features such as green habitat loss, fragmentation and availability reduction of floral resources with unpredictable effects on parasite transmission. Furthermore, beekeeping may contribute to the spread of parasites to wild pollinators by increasing the number of parasite hosts. Here we used DNA-based diagnostics tools to evaluate how the occurrence of parasites, namely microsporidians ( Nosema spp.), trypanosomatids ( Crithidia spp.) and neogregarines ( Apicystis bombi ), is shaped by the above-mentioned stressors in two bumblebee species (i.e. Bombus terrestris and Bombus pascuorum ). Infection rates of the two species were different and generally higher in B. terrestris . Moreover, they showed different responses towards the same ecological variables, possibly due to differences in body size and foraging habits supposed to affect their susceptibility to parasite infection. The probability of infection was found to be reduced in B. pascuorum by green habitat fragmentation, while increased along with floral resource availability. Unexpectedly, B. terrestris had a lower parasite richness nearby apiaries maybe due to the fact that parasites are prone to be transmitted among the most abundant species. Our finding supports the need to design proper conservation measures based on species-specific knowledge, as suggested by the variation in the parasite occurrence of the two species. Moreover, conservation policies aiming at safeguarding pollinators through flower planting should consider the indirect effects of these measures for parasite transmission together with pollinator biodiversity issues., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Several studies reported cognitive reserve (CR) as an important factor in promoting healthy aging within a non-clinical aging population., Aims: The main goal of the present study is to investigate the link between higher levels of CR and more effective emotion regulation. In more detail, we examine the association between a number of CR proxies and the habitual use of two emotion regulation strategies, cognitive reappraisal and emotional suppression., Methods: Three hundred and ten older adults aged between 60 and 75 (mean = 64.45, SD = 4.37; 69.4% female) joined this cross-sectional study by filling out self-report measures of CR and emotion regulation.² RESULTS: Reappraisal and suppression use were correlated. Practicing different leisure activities constantly over many years, being more original and having a higher education promoted more frequent use of cognitive reappraisal. These CR proxies were also significantly related to suppression use, even though the percentage of variance explained was lower., Discussion and Conclusions: Exploring the role played by the cognitive reserve on different emotion regulation techniques can be useful in understanding which variables predict the use of antecedent-focused (reappraisal) or response-focused (suppression) emotion regulation strategies in aging individuals., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Vestibular impairment and vertigo in the pediatric population have an estimated prevalence ranging between 0.4% and 5.6% and are a topic of interest in recent years. The Bárány Society has recently reclassified migraine-related vertigo syndromes as vestibular migraine of childhood (VMC), probable vestibular migraine of childhood (probable VMC), and recurrent vertigo of childhood (RVC)., Methods: Applying the criteria established by the Bárány Society, we retrospectively analyzed data on 95 pediatric patients suffering from episodic vertigo that were recruited from 2018 to 2022. In applying the revised criteria, 28 patients had VMC, 38 had probable VMC, and 29 had RVC., Results: Visuo-vestibular symptoms (external vertigo) or internal vertigo were reported by 20 of 28 VMC patients (71.4%) compared to 8 of 38 probable VMC patients (21%) ( P  < .001). None of the RVC patients reported external vertigo. Duration of vertigo was demonstrably longer in the VMC patients than in the probable VMC ( P  < .001) and RVC ( P  < .001) patients. Cochlear symptoms were reported by 28.6% of VMC patients and by 13.1% of probable VMC patients. No cochlear symptoms were reported by any RVC patients. Familial cases for headache and episodic vertigo showed no significant difference between groups., Discussion: The most frequent finding during bedside examination in all three groups was central positional nystagmus. Differences in the duration of attacks and in accompanying symptoms may underline different pathophysiological mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Teggi, Colombo, Familiari, Cangiano, Bussi and Filippi.)

Menière's disease and vestibular migraine (VM) are two common inner ear disorders whose diagnoses are based on clinical history and audiometric exams. In some cases, patients have been reporting different episodes of vertigo for years but not fulfilling the Bárány Society criteria for either. These are called Recurrent Vestibular Symptoms-Not Otherwise Specified (RVS-NOS). It is still under debate if this is a single disease entity or a part of the spectrum of already established disorders. The purpose of our work was to establish similarities and differences with VM in terms of clinical history, bedside examination, and family history. We enrolled 28 patients with RVS-NOS who were followed for at least 3 years with stable diagnosis; results were compared with those of 34 subjects having a diagnosis of definite VM. The age of onset of vertigo was lower in VM than in RVS-NOS (31.2 vs. 38.4 years). As for the duration of attacks and symptoms, we detected no differences other than subjects with RVS-NOS reporting milder attacks. Cochlear accompanying symptoms were more frequently reported by VM subjects (one subject reporting tinnitus and another one reported tinnitus and fullness). Motion sickness was equally reported by subjects across two samples (around 50% for both). Bipositional long-lasting, non-paroxysmal nystagmus was the most common finding in the two groups, with no significant difference. Finally, the percentage of familial cases of migrainous headache and episodic vertigo did not differ between the two samples. In conclusion, RVS-NOS shares some common aspects with VM, including the temporal profile of attacks, motion sickness (commonly considered a migraine precursor), bedside examination, and family history. Our results are not inconsistent with the possibility that RVS-NOS may be a heterogeneous disorder, even if some of these subjects may share common pathophysiological mechanisms with VM.

Background: To verify the long-term (24-week) efficacy, safety, and tolerability of fremanezumab in real-life patients with high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM: ≥ 15 days/month), and multiple preventive treatment failures., Methods: This is a prospective, cohort, real-life study at 28 headache centers on consecutive patients affected by HFEM or CM with multiple preventive treatment failures who were prescribed subcutaneous fremanezumab (225 mg monthly/675 mg quarterly) for ≥ 24 weeks. Primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM at weeks 21-24 compared to baseline. Secondary endpoints encompassed changes in monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS, HIT-6 and MIDAS scores at the same time interval. Changes in MMDs/MHDs, monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS and HIT-6 scores at week 4 were also monitored., Results: Four hundred ten patients who had received ≥ 1 dose of fremanezumab were considered for safety analysis while 148 patients treated for ≥ 24 weeks were included in the efficacy analysis. At weeks 21-24, fremanezumab significantly (p < 0.001) reduced MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM compared to baseline. The proportions of ≥ 50%, ≥ 75% and 100% responders at weeks 21-24were 75.0%, 30.8%, 9.6% (HFEM), and 72.9, 44.8 and 1% (CM). A significant (p < 0.001) decrease in MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM was already present at week 4. The proportions of ≥ 50%, ≥ 75%, and 100% responders at week 4 were 67.6%, 32.4%, 11.8% (HFEM) and 67.3%, 40%, 1.8% (CM). CM remitted to episodic migraine and medication overuse to no-medication overuse in 83.3 and 75% of patients at week 24, and in 80 and 72.4% at week 4. Adverse events were rare (2.4%), mild and transient. No patient discontinued treatment for any reason., Conclusions: Fremanezumab is characterized by an early and sustained efficacy in HFEM and CM patients with multiple preventive treatment failures in real-life, revealing an optimal safety and tolerability profile., (© 2023. The Author(s).)