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Background: Lung cancer carries a high burden of systemic symptoms, including in survivors, leading to a reduced quality of life (QoL). We assessed whether a 12-week multicomponent supervised exercise programme, including muscular strength and aerobic training, was beneficial in patients who had undergone surgery for early non-small cell lung cancer (NSCLC) in terms of physical performance, QoL, and metabolic and nutritional analytical parameters. Methods: Physical performance was measured by gait speed, handgrip strength, 30 s sit-to-stand (30s-STS) test repetitions, distance covered in the 6 min walk test (6MWT), and the Short Physical Performance Battery (SPPB) score. QoL was assessed with the EORTC-QLQ-C30 questionnaire. Blood glucose, cholesterol, triglycerides, total proteins, albumin, pre-albumin, creatinine, c-reactive protein, insulin-growth factor 1 (IGF-1), and the haemoglobin and hematocrit percentages were measured before and after the intervention in order to observe any beneficial effects related to metabolic markers. Results: After the intervention, the mean scores for the 6MWT (p < 0.001), STS (p < 0.001), 6MWT (p < 0.01), and SPPB (p < 0.01) had significantly improved. However, handgrip strength and nutritional analytical were unchanged. The EORTC-QLQ-C30 functions and symptoms significantly improved after the intervention (p < 0.05 and p < 0.01, respectively). A significant decrease in cholesterol, triglycerides, and IGF-1 and a significant increase in pre-albumin in blood was also observed post-intervention (p < 0.05). Conclusions: This supervised, community-based 12-week multicomponent was feasible (adherence rate 70.35%) and provided benefits not only to physical performance but also to the quality of life of patients with NSCLC.

Abstract Objectives to evaluate over a 48-month follow-up period the: 1) long-term effectiveness and safety; 2) drug retention rate (DRR); 3) impact of comorbidities and bDMARDs line on MDA and DAPSA remission/low disease activity (LDA) of secukinumab in a multicenter Italian cohort of PsA patients. Methods Consecutive PsA patients receiving secukinumab were followed prospectively in Italian centers between 2016 and 2023. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were recorded. Treatment response was evaluated at 6 and 12 months after initiation, and every year up to 48 months (T48). DRR was assessed according to clinical and demographic features, comorbidities and bDMARDs line. Adverse events (AE) were recorded. Results Six hundred eighty-five patients [42.5% male] were enrolled; 32.9% naïve received secukinumab; 74.2% had ≥ 1 comorbidity. Overall, secukinumab yielded improved outcomes at T48: naïve maintained lower disease activity vs. non-naïve [DAPSA 4.0 (1.4–8.1) vs. 6.0 (2.2–10.4);p = 0.04]; 76.9% naïve and 66.2% non-naïve achieved MDA; MDA no comorbidities vs. 1–3 comorbidities 78.8% vs. 73.3% (p 3 comorbidities 78.8% vs. 48.7% (p 3 comorbidities. Treatment was discontinued in 233 patients due to loss of effectiveness, and in 41 due to AE. The overall DRR at T48 was 66%, with differences according to bDMARDs line (p

Adherence to hand hygiene procedures is crucial for all populations, and the World Health Organization (WHO) has implemented specific guidelines for infection control. Frequent and correct hand hygiene can prevent infections, but non-compliance with hand hygiene is pervasive. Nursing students address this issue from the beginning of their training. In nursing training, self-efficacy is crucial in enhancing students’ competence, motivation, and clinical performance. We performed a cross-sectional multicenter study in five European countries, with a cross-sectional design with an online application of an instrument measuring hand hygiene knowledge based on WHO guidelines and general self-efficacy and specific self-efficacy for infection control. A total of 638 first-year nursing students participated in this study. The mean percentage of correct answers was 67.9%, with a considerable difference depending on the items. The worst results were obtained for questions related to sources of infection and types of hand hygiene methods in different situations. Finnish students displayed significantly (p < 0.001) higher scores in HH knowledge, whereas Estonian students had significantly (p < 0.001) higher levels of self-efficacy. There were significant correlations between the hand hygiene knowledge score and the self-efficacy score (p < 0.001). A multivariate analysis by linear regression analysis showed significant associations between the hand hygiene knowledge survey score and the students’ age (p < 0.001, OR = 0.18, 95% CI 0.04–0.10), as well as their country of origin (p = 0.01, OR = 0.09, 95% CI 0.03–0.34). HH knowledge is quite low among nursing students, and is correlated with self-efficacy, although the strongest predictors are age and country of origin. Different nursing curricula must favor HH knowledge, with varying degrees of emphasis depending on the country.

Background: Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. Many patients with ASD often show behavioral problems at mealtimes, including food selectivity and atypical feeding behaviors. The Mediterranean diet (MD) has a beneficial effect on mental health for the general population across different ages. There is evidence that good adherence to the MD is effective in reducing peripheral inflammatory markers, such as the cytokine interleukin-6 (IL-6). The present study was designed to evaluate adherence to the MD in children with ASD using age- and sex-matched, typically developing individuals (TDs) as a control group and to determine whether differences in adherence to the MD are associated with salivary IL-6 and IL-6 receptor concentration. Methods: Twenty children and adolescents with ASD (mean age 9.95 ± 0.65 years) and twenty TDs (mean age: 9.85 ± 0.59 years) participated in this study (N = 16 males and N = 4 females in each group). Participants with ASD were enrolled in a psychiatric consultation in Valencia (Spain), and TDs were recruited from two public schools in Valencia. The parents of both ASD and TD groups answered the items in a validated Mediterranean Diet Quality Index for children and adolescents (KIDMED) questionnaire on their children’s adherence to the MD. Results: The mean adherence to MD score was significantly lower in the ASD group (9.10 ± 0.42) (range 6–12) than in the TD group (10.35 ± 0.31) (range 8–12) (p = 0.02, Mann–Whitney U test). There was no statistically significant association between adherence to the MD and age or sex in both groups, but there was a significant correlation between the total KIDMED score and body mass index (BMI) in the ASD group. Regarding the concentration of Il-6 and the Il-6 receptor in saliva samples, there were no significant differences between the two groups; however, linear regression analysis by group revealed significant associations between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the ASD group (p = 0.003, OR = 0.68, 95% CI 0.007 to −0.02; p = 0.009, OR = −0.64, 95% CI −0.01 to −0.00). In contrast, no significant associations were observed between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the TD group. Conclusions: Children and adolescents with ASD showed significantly lower adherence to the MD, which can contribute to nutritional deficits described in ASD, and the role of BMI composition (fat versus lean mass) needs to be further investigated in this group. The concentration of IL-6 and its receptor in saliva is associated with adherence to the MD, suggesting a possible link between IL-6 and diet in ASD. Further studies to clarify the associations between IL-6, psychiatric alterations, and diet in ASD are needed.

Brain water homeostasis not only provides a physical protection, but also determines the diffusion of chemical molecules key for information processing and metabolic stability. As a major type of glia in brain parenchyma, astrocytes are the dominant cell type expressing aquaporin water channel. How astrocyte aquaporin contributes to brain water homeostasis in basal physiology remains to be understood. We report that astrocyte aquaporin 4 (AQP4) mediates a tonic water efflux in basal conditions. Acute inhibition of astrocyte AQP4 leads to intracellular water accumulation as optically resolved by fluorescence-translated imaging in acute brain slices, and in vivo by fiber photometry in mobile mice. We then show that aquaporin-mediated constant water efflux maintains astrocyte volume and osmotic equilibrium, astrocyte and neuron Ca2+ signaling, and extracellular space remodeling during optogenetically induced cortical spreading depression. Using diffusion-weighted magnetic resonance imaging (DW-MRI), we observed that in vivo inhibition of AQP4 water efflux heterogeneously disturbs brain water homeostasis in a region-dependent manner. Our data suggest that astrocyte aquaporin, though bidirectional in nature, mediates a tonic water outflow to sustain cellular and environmental equilibrium in brain parenchyma.

ObjectivesThis study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA).MethodsConsecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded.ResultsWe enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex.ConclusionsSecukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR.

In video analysis, collection and labeling of data can be time and resource-consuming. To solve the scarcity of data problems, synthetic data augmentation is a promising solution. In this paper, we present an approach to generate synthetic videos for action recognition using Unity, the popular game engine. The synthetic videos are generated with high variability in lighting, subjects’ models, backgrounds, animations, and camera positions. We use the generated data to augment a small dataset of subjects who are executing physical exercises for action recognition. We tested the augmented data on two state-of-the-art models for action classification and demonstrated the significant benefits of synthetic data augmentation for improving the performance of these models on small datasets in the context of video action recognition.

Family caregivers of people with neuropsychiatric conditions are at risk of caregiver burden and declining health. The aims of this study were to identify the impact of caring on long-term family caregivers and their unmet needs and to explore their self-care strategies for achieving a successful caregiving experience. A mixed-method study was conducted using semi-structured interviews and a questionnaire in which standardized, self-reported measures of burden, health behaviors, sleep, and mental well-being were administered. Participants were family caregivers of people with neuropsychiatric disorders. Convenience sampling of 28 caregivers: 13 of people with mental health disorders (schizophrenia and bipolar disorder) and 15 with Alzheimer’s disease. Based on the analysis of the semi-structured interviews, data saturation was reached. Analysis of self-reported measures indicated that 32.1% of long-term caregivers had high caregiver burden, 64.3% had reduced quality of life, 39.3% had low sleep quality, 21.4% had low adherence to the Mediterranean diet, 50.0% had a physical activity below the recommendation, 42.9% had high anxiety symptoms, 35.7% had high depressive symptoms, and 71.4% had reduced self-care agency. Content analysis and statistical analysis were conducted. Two themes were identified: (1) the impact of long-term caregiving and unmet needs and (2) successful self-care strategies. Caregivers of people with Alzheimer’s disease spent less time doing physical activity, had higher caregiver burden, and poorer health-related quality of life. The negative impact of caregiving could be prevented/managed by assessing the individual’s circumstances for the development of cross-sectional self-care strategies involving physical, emotional, and social spheres.

Background and Objectives: Adjuvant treatment with aromatase inhibitors (AIs) in breast cancer (BC) survivors can cause adverse effects such as metabolic syndrome (MS) (insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension) associated with morbidity and premature mortality. We evaluate the effect of a multimodal program based on physical exercise and health education on MS and health-related quality of life (QoL) in postmenopausal women with BC under AIs. Methods: A total of 56 postmenopausal women, diagnosed with BC, aged 60 years or older (mean age 67.2 years) and on hormonal treatment with AIs, were included in the multimodal physical exercise and health education program, and evaluated before and after their participation. The assessment of the five criteria of the MS included the following: waist circumference, high blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Two main instruments were used to evaluate the impact of the intervention on QoL: the EORTC QLQ C30 (questionnaire for cancers in general) and the EORTC QLQ BR23 (specifically for breast cancer patients). The EuroQol 5D (EQ-5D) was also used to compare these results. Results: The percentage of women meeting the MS criteria was 37.7% at baseline and fell to 15.1% at 3 months after the intervention (p = 0.02). The intervention significantly reduced hypertension (p < 0.001), central obesity (p < 0.001), and the concentration of triglycerides (p = 0.016). No significant changes were observed in fasting glucose and HDL concentration. A statistically significant improvement was found in QoL (on both the QLQ30 and BR23 scales). A multivariate regression model analysis identified marital status (being married) (95% CI: 1.728–131.615, p = 0.014), and percentage of attendance at health education sessions (95% CI: 1.010–1.211, p = 0.029) as positive predictive variables of improvement in MS. Conclusions: The implementation of multimodal, community-based programs of physical exercise and health education improve the prevalence of MS and specific criteria of MS and QoL in postmenopausal women with breast cancer receiving AI treatment.

ObjectiveInflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF.MethodsThe risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still’s disease patients and Behçet’s disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression.Results580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet’s disease patients and 497 Still’s disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still’s disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet’s disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5, p=0.002).ConclusionsThe risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Abstract The approval of anticancer therapeutic strategies is still slowed down by the lack of models able to faithfully reproduce in vivo cancer physiology. On one hand, the conventional in vitro models fail to recapitulate the organ and tissue structures, the fluid flows, and the mechanical stimuli characterizing the human body compartments. On the other hand, in vivo animal models cannot reproduce the typical human tumor microenvironment, essential to study cancer behavior and progression. This study reviews the cancer-on-chips as one of the most promising tools to model and investigate the tumor microenvironment and metastasis. We also described how cancer-on-chip devices have been developed and implemented to study the most common primary cancers and their metastatic sites. Pros and cons of this technology are then discussed highlighting the future challenges to close the gap between the pre-clinical and clinical studies and accelerate the approval of new anticancer therapies in humans.

ObjectivesAn increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old.MethodsRA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected.ResultsA total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p

Poor sleep quality, a global public health concern, poses a significant burden on individuals, particularly health care university students facing intense academic stress. A three-center cross-sectional study was conducted at the Higher Institute of Nursing and Health Sciences in Tetouan (Morocco), Faculty of Medicine in Tangier (Morocco) and Faculty of Nursing in Valencia (Spain). We collected various data using a sociodemographic questionnaire, the Pittsburgh sleep quality questionnaire, the international physical activity questionnaire (IPAQ) and the smartphone addiction questionnaire short-version (SAS-SV). A total of 1210 students were included in our study (mean age 20.4 years, 67.2% female, nursing students (66.2%) and medical students (33.8%), 76.1% students from Morocco and 33.9% from Spain). Analysis revealed a higher prevalence of poor sleep quality among Moroccans students compared to Spanish ones (p < 0.001), that nursing students showed less favorable sleep quality than medical students (p < 0.011) and that living with a chronic disease was linked to less favorable sleep quality (p < 0.001). Lastly, intense or weak physical activity and smartphone addiction were correlated with poor sleep quality (p < 0.001). In the multivariate analysis, an association persisted between poor sleep quality and factors such as the country of study (Odds ratio (OR): 6.25 [95% Confidence Interval (CI): 4.34–9.09]), involvement in nursing studies (OR: 3.50 [95% CI: 2.36–5.27]), and the presence of chronic diseases (OR: 2.70 [95% CI: 1.72–4.16]), (p < 0.01 each). Our findings highlight the multifaceted factors affecting sleep quality in young university students. The implications underscore the imperative of interventions tailored to this demographic group.

BackgroundPsoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease involving several articular and extra-articular structures. Despite the important progresses recently made in all of the aspects of this disease, its management is still burdened by unresolved issues. The aim of this exercise was to provide a set of statements that may be helpful for the management of PsA.MethodsA group of 38 Italian rheumatologists with recognized expertise in PsA selected and addressed the following four topics: “early PsA,” “axial-PsA,” “extra-articular manifestations and comorbidities,” “therapeutic goals.” Relevant articles from the literature (2016–2022) were selected by the experts based on a PubMed search. A number of statements for each topic were elaborated.ResultsNinety-four articles were selected and evaluated, 68 out of the 1,114 yielded by the literature search and 26 added by the Authors. Each of the four topic was subdivided in themes as follows: transition from psoriasis to PsA, imaging vs. CASPAR criteria in early diagnosis, early treatment for “early PsA”; axial-PsA vs. axialspondyloarthritis, diagnosis, clinical evaluation, treatment, standard radiography vs. magnetic resonance imaging for “axial PsA”; influence of inflammatory bowel disease on the therapeutic choice, cardiovascular comorbidity, bone damage, risk of infection for “comorbidities and extra-articular manifestations”; target and tools, treat-to-target strategy, role of imaging for “therapeutic goals.” The final document consisted of 49 statements.DiscussionThe final product of this exercise is a set of statements concerning the main issues of PsA management offering an expert opinion for some unmet needs of this complex disease.

Objectives To explore the effects of anti-ribosomal P protein (anti-P) and anti-N-methyl-D-aspartic acid receptor subunit 2 (anti-NR2) autoantibodies on depression and cognitive dysfunction and their relationships with functional brain connectivity in SLE.Methods This cross-sectional study included adult patients who fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology 2019 SLE criteria. Anti-P and anti-NR2 were quantified using ELISA. A 1-hour battery of neuropsychological testing interpreted by a neuropsychologist explored depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D), cognitive domains and quality of life (SF-12). Resting-state functional connectivity (rs-fc) MRI analysis was performed within 1 month, and region-of-interest to region-of-interest (ROI-to-ROI) analyses with the graph theory were performed.Results Thirty-three patients with SLE (9% male) were enrolled, mean age (SD) of 43.5 (14) years and median disease duration of 10.4 years (2.9–25.4). Anti-P was positive in 6 (18.2%) and anti-NR2 in 14 (42.4%) patients. Depressive symptoms were found in 14 (42.4%) patients using the CES-D (range 0–51). After correction for age, disease duration, disease activity and white matter lesion load, the CES-D score was independently associated with anti-P serum level (β=0.32; p=0.049) and prednisone daily dose (β=0.38; p=0.023). Nineteen patients (57.6%) showed at least a cognitive test alteration, but no significant association with autoantibodies was found. The rs-fc MRI analysis revealed an independent association between the anti-P serum levels and many altered brain ROI properties but no anti-NR2 and prednisone effects on the cerebral network.Conclusions Anti-P was associated with brain network perturbation, which may be responsible for depressive symptoms in patients with SLE.

BackgroundIn psoriatic arthritis (PsA), the primary goal of treatment is clinical remission. This study aimed to characterize the molecular profile underlying the induced clinical remission in patients with PsA, comparing the remission state and the healthy condition.MethodsWhole blood transcriptomic analysis was performed on groups of 14 PsA patients in TNFi-induced clinical remission (DAPSA ≤ 4), 14 PsA patients with active disease (DAPSA > 14), and 14 healthy controls (HCs). Then, all differentially expressed genes (DEGs) derived from remission vs. HC comparison were analyzed for functional and biological characteristics by bioinformatics software. The gene expression of 12 genes was then validated by RT-qPCR in an extended cohort of 39 patients in clinical remission, 40 with active disease, and 40 HCs.ResultsThe transcriptomic analysis of PsA remission vs. HCs highlighted the presence of 125 DEGs, and out of these genes, 24 were coding genes and showed a great involvement in immune system processes and a functional network with significant interactions. The RT-qPCR validation confirming the down- and upregulation of FOS (FC −2.0; p 0.005) and CCDC50 (FC +1.5; p 0.005) genes, respectively, in line with their role in orchestrating inflammation and bone metabolism processes, may be related to PsA pathophysiology.ConclusionThe transcriptomic profile of clinical remission in PsA is similar to a healthy condition, but not identical, differing for the expression of FOS and CCDC50 genes, which appears to play a key role in its achievement.

First-line treatment in postmenopausal women with estrogen- and/or progesterone-positive breast cancer consists of aromatase inhibitors (AROi). The ability of AROi to promote or worsen cognitive function, depressive symptoms, sleep quality and performance in basic activities of daily life as primary and concomitant outcomes in long longitudinal studies in post-menopausal women has been seldom investigated. This study is a cohort trial which aimed to determine if there were differences in cognitive function assessment, depressive symptoms, and sleep quality after 1 year under AROi treatment and to determine the interrelations between these symptoms. Methods: A prospective 1-year longitudinal study was performed in a representative sample of tertiary hospital. Women with localized breast cancer newly treated with AROi therapy were evaluated for cognitive functions, depressive symptoms, sleep problems and ability to perform basic activities of the daily life at baseline and after 6 months and 12 months under adjuvant AROi treatment. Results: Analysis of cognitive functions by the Mini-Mental State Examination (MMSE) scores did not show significantly worsening under AROi treatment after 6 months and 12 months of treatment compared to the baseline. Analysis of depressive symptoms with the Geriatric Depression Scale and sleep quality with the Athens Insomnia Scale (AIS) scores showed significant (p

Abstract Background This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet’s syndrome (BS) over 2 years of follow-up. Methods Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains. Results During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p

Abstract Background Perineuronal nets (PNNs) are specialized extracellular matrix structures mainly found around fast-spiking parvalbumin (FS-PV) interneurons. In the adult, their degradation alters FS-PV-driven functions, such as brain plasticity and memory, and altered PNN structures have been found in neurodevelopmental and central nervous system disorders such as Alzheimer’s disease, leading to interest in identifying targets able to modify or participate in PNN metabolism. The serine protease tissue-type plasminogen activator (tPA) plays multifaceted roles in brain pathophysiology. However, its cellular expression profile in the brain remains unclear and a possible role in matrix plasticity through PNN remodeling has never been investigated. Result By combining a GFP reporter approach, immunohistology, electrophysiology, and single-cell RT-PCR, we discovered that cortical FS-PV interneurons are a source of tPA in vivo. We found that mice specifically lacking tPA in FS-PV interneurons display denser PNNs in the somatosensory cortex, suggesting a role for tPA from FS-PV interneurons in PNN remodeling. In vitro analyses in primary cultures of mouse interneurons also showed that tPA converts plasminogen into active plasmin, which in turn, directly degrades aggrecan, a major structural chondroitin sulfate proteoglycan (CSPG) in PNNs. Conclusions We demonstrate that tPA released from FS-PV interneurons in the central nervous system reduces PNN density through CSPG degradation. The discovery of this tPA-dependent PNN remodeling opens interesting insights into the control of brain plasticity.

Over the last decades, lactate has emerged as important energy substrate for the brain fueling of neurons. A growing body of evidence now indicates that it is also a signaling molecule modulating neuronal excitability and activity as well as brain functions. In this review, we will briefly summarize how different cell types produce and release lactate. We will further describe different signaling mechanisms allowing lactate to fine-tune neuronal excitability and activity, and will finally discuss how these mechanisms could cooperate to modulate neuroenergetics and higher order brain functions both in physiological and pathological conditions.

This study investigates the association between the Functional Health Pattern Assessment Screening Tool (FHPAST) and frailty in hospitalized geriatric patients. One hundred and forty patients (mean age 78.2 years, age range 65–90) were screened for frailty using the Frail Scale during hospitalization in the geriatric unit. Among them, 57 patients were identified as prefrail (40.7%), and 83 were identified as frail (59.3%). A comparative analysis between groups in terms of the FHPAST components covering health risk, general well-being, and health promotion was performed. Correlations between FHAPST components, socio-demographic data, frailty criteria, as well as logistic regression to identify variables that better predict frailty were also sought. Frailty was mainly associated with difficulty urinating, limitations in performing activities of daily living and walking, physical discomfort, less positive feelings in controlling one’s own life, lower compliance with recommendations from the healthcare provider, and engagement in seeking healthcare services. Patients with difficulty urinating and walking had a probability of 4.38 times (OR = 4.38, CI 95% [1.20–15.94]), p = 0.025) and 65.7 times (OR = 65.7, CI 95% [19.37–223.17], p < 0.001) higher of being frail rather than prefrail. The relationship between frailty and prefrailty in hospitalized geriatric patients and components of nursing Functional Health Patterns (FHP) has yet to be explored. This study provides evidence of the most prevalent needs of frail geriatric patients in hospital settings.

Introduction: Recent evidence reported mental health issues in university students such as anxiety and depressive symptoms and poor sleep quality. Decreased plasma brain-derived neurotrophic factor (BDNF) levels have been proposed as a biomarker of depressive symptoms, whereas cortisol levels are an index of energy mobilization and stress and have been linked to sleep quality. Given that salivary biomarkers represent an interesting new field of research, the aim of this cross-sectional study was to evaluate salivary BDNF and cortisol levels in university students to assess whether they have associations with psychological disturbances such as anxiety and depressive symptoms, sleep quality, and stress level. Methods: Salivary BDNF and cortisol levels were measured by specific immunoassays in 70 students whose mental health was also evaluated on the same day through the evaluation of anxiety and depression symptoms (Goldberg scale), sleep quality (Pittsburg Sleep Quality Index and Athens Insomnia Scale), and stress (self-perceived stress scale) and healthy lifestyle habits (alcohol consumption, smoking, regular exercise, and body mass index) were also measured. Multivariate regression analyses were performed in order to identify the strengths of associations between psychological alterations and the concentrations of BDNF, cortisol, and other variables. Results: Salivary BDNF levels were significantly higher in students with more depressive symptoms, whereas no significant differences were found for cortisol levels. When performing the binary logistic regression model, BDNF levels are included as a predictor variable for a high-depressive-symptoms burden (p < 0.05). Students with worse sleep quality on the Pittsburg Scale had higher cortisol levels (p < 0.05). The subdomains of sleep latency and sleep medication were those significantly associated with salivary cortisol levels in logistic regression analyses (OR = 15.150, p = 0.028). Sleep medication only appeared to be related to cortisol levels (OR = 185.142, p = 0.019). Perceived stress levels and anxiety symptoms were not associated with BDNF or cortisol levels. Conclusions: BDNF could play a key role in the pathophysiology of mood-related disorders, and elevation of its peripheral levels could contribute to protecting neurons from the development of mental illness. Higher salivary cortisol levels measured in the morning are accompanied by poorer sleep quality. More research is needed, focusing on salivary biomarkers of disorders related to depressive symptoms and poor sleep quality as a potential tool for the diagnosis and prevention of mental illness.

IntroductionThe pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is widely unknown, and the role of autoantibodies is still undetermined.MethodsTo identify brain-reactive autoantibodies possibly related to NPSLE, immunofluorescence (IF) and transmission electron microscopy (TEM) on rat and human brains were performed. ELISA was used to reveal the presence of known circulating autoantibodies, while western blot (WB) was applied to characterize potential unknown autoantigen(s).ResultsWe enrolled 209 subjects, including patients affected by SLE (n=69), NPSLE (n=36), Multiple Sclerosis (MS, n=22), and 82 age- and gender-matched healthy donors (HD). Autoantibody reactivity by IF was observed in almost the entire rat brain (cortex, hippocampus, and cerebellum) using sera from NPSLE and SLE patients and was virtually negative in MS and HD. NPSLE showed higher prevalence (OR 2.4; p = 0.047), intensity, and titer of brain-reactive autoantibodies than SLE patients. Most of the patient sera with brain-reactive autoantibodies (75%) also stained human brains. Double staining experiments on rat brains mixing patients’ sera with antibodies directed against neuronal (NeuN) or glial markers showed autoantibody reactivity restricted to NeuN-containing neurons. Using TEM, the targets of brain-reactive autoantibodies were located in the nuclei and, to a lesser extent, in the cytoplasm and mitochondria. Given the high degree of colocalization between NeuN and brain-reactive autoantibodies, we assumed NeuN was a possible autoantigen. However, WB analysis with HEK293T cell lysates expressing or not expressing the gene encoding for NeuN protein (RIBFOX3) showed that patients’ sera carrying brain-reactive autoantibodies did not recognize the NeuN corresponding band size. Among the panel of NPSLE-associated autoantibodies (e.g., anti-NR2, anti-P-ribosomal protein, antiphospholipid) investigated by ELISA assay, only the anti-β2-glycoprotein-I (aβ2GPI) IgG was exclusively found in those sera containing brain-reactive autoantibodies.ConclusionIn conclusion, SLE and NPSLE patients possess brain-reactive autoantibodies but with higher frequency and titers found in NPSLE patients. Although many target antigens of brain-reactive autoantibodies are still undetermined, they likely include β2GPI.

Florenzo Iannone,1 Fabrizio Conti,2 Alberto Cauli,3 Alberto Farina,4 Roberto Caporali5 1Rheumatology Unit, Department of Emergency and Organ Transplantation, Università Degli Studi Di Bari Aldo Moro, Bari, Italy; 2Rheumatology Unit, Department of Clinical, Internal, Anesthetic and Cardiovascular Sciences, Sapienza Università di Roma, Rome, Italy; 3Rheumatology Unit, Department of Medical Sciences and Public Health, AOU and University of Cagliari, Monserrato, Italy; 4Medical Affairs Department, Celltrion Healthcare Italy srl, Milan, Italy; 5Department of Clinical Sciences and Community Health, Research Centre for Adult and Pediatric Rheumatic Diseases, University of Milan, Milan, ItalyCorrespondence: Florenzo Iannone, Rheumatology Unit, Department of Emergency and Organ Transplantation, Università Degli Studi Di Bari Aldo Moro, 11, Piazza Giulio Cesare, Bari (BA), 70124, Italy, Tel +39 080 5592775, Fax +39 080 5478802, Email florenzo.iannone@uniba.itAbstract: The first subcutaneous (SC) formulation of infliximab CT-P13 has been authorized for the treatment of rheumatoid arthritis (RA) in Europe in 2019. Later, in 2020, approved indications were extended also to ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn’s disease (CD) and ulcerative colitis (UC). The present review provides summary of the key features of SC infliximab, with particular focus on pharmacokinetic profile, clinical development program in comparison with the intravenous (IV) formulation, and the latest evidence in the literature. We conclude that SC infliximab represents a new and promising approach in the treatment of patients with RA, offering an optimized clinical profile and a more practical option in comparison to the IV formulation. Nevertheless, SC formulation can improve the use of national health systems resources (e.g., through the time of healthcare workers not having to supervise infusions) and facilitate social distancing measures during the COVID-19 pandemic, as the patient can self-inject the medicine at home without going to the hospital. The limitations of the SC infliximab are mainly due to the limited experience of use in clinical practice and the absence of long-term drug retention data.Keywords: rheumatoid arthritis, TNF inhibitors, infliximab, subcutaneous, intravenous, SC, IV, RA

Family caregivers of people with neuropsychiatric conditions are at risk of caregiver burden and declining health. The aims of this study were to identify the impact of caring on long-term family caregivers and their unmet needs and to explore their self-care strategies for achieving a successful caregiving experience. A mixed-method study was conducted using semi-structured interviews and a questionnaire in which standardized, self-reported measures of burden, health behaviors, sleep, and mental well-being were administered. Participants were family caregivers of people with neuropsychiatric disorders. Convenience sampling of 28 caregivers: 13 of people with mental health disorders (schizophrenia and bipolar disorder) and 15 with Alzheimer's disease. Based on the analysis of the semi-structured interviews, data saturation was reached. Analysis of self-reported measures indicated that 32.1% of long-term caregivers had high caregiver burden, 64.3% had reduced quality of life, 39.3% had low sleep quality, 21.4% had low adherence to the Mediterranean diet, 50.0% had a physical activity below the recommendation, 42.9% had high anxiety symptoms, 35.7% had high depressive symptoms, and 71.4% had reduced self-care agency. Content analysis and statistical analysis were conducted. Two themes were identified: (1) the impact of long-term caregiving and unmet needs and (2) successful self-care strategies. Caregivers of people with Alzheimer's disease spent less time doing physical activity, had higher caregiver burden, and poorer health-related quality of life. The negative impact of caregiving could be prevented/managed by assessing the individual's circumstances for the development of cross-sectional self-care strategies involving physical, emotional, and social spheres. [ABSTRACT FROM AUTHOR]

Background and Objectives: Adjuvant treatment with aromatase inhibitors (AIs) in breast cancer (BC) survivors can cause adverse effects such as metabolic syndrome (MS) (insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension) associated with morbidity and premature mortality. We evaluate the effect of a multimodal program based on physical exercise and health education on MS and health-related quality of life (QoL) in postmenopausal women with BC under AIs. Methods: A total of 56 postmenopausal women, diagnosed with BC, aged 60 years or older (mean age 67.2 years) and on hormonal treatment with AIs, were included in the multimodal physical exercise and health education program, and evaluated before and after their participation. The assessment of the five criteria of the MS included the following: waist circumference, high blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Two main instruments were used to evaluate the impact of the intervention on QoL: the EORTC QLQ C30 (questionnaire for cancers in general) and the EORTC QLQ BR23 (specifically for breast cancer patients). The EuroQol 5D (EQ-5D) was also used to compare these results. Results: The percentage of women meeting the MS criteria was 37.7% at baseline and fell to 15.1% at 3 months after the intervention (p = 0.02). The intervention significantly reduced hypertension (p < 0.001), central obesity (p < 0.001), and the concentration of triglycerides (p = 0.016). No significant changes were observed in fasting glucose and HDL concentration. A statistically significant improvement was found in QoL (on both the QLQ30 and BR23 scales). A multivariate regression model analysis identified marital status (being married) (95% CI: 1.728–131.615, p = 0.014), and percentage of attendance at health education sessions (95% CI: 1.010–1.211, p = 0.029) as positive predictive variables of improvement in MS. Conclusions: The implementation of multimodal, community-based programs of physical exercise and health education improve the prevalence of MS and specific criteria of MS and QoL in postmenopausal women with breast cancer receiving AI treatment. [ABSTRACT FROM AUTHOR]

Background: Lung cancer carries a high burden of systemic symptoms, including in survivors, leading to a reduced quality of life (QoL). We assessed whether a 12-week multicomponent supervised exercise programme, including muscular strength and aerobic training, was beneficial in patients who had undergone surgery for early non-small cell lung cancer (NSCLC) in terms of physical performance, QoL, and metabolic and nutritional analytical parameters. Methods: Physical performance was measured by gait speed, handgrip strength, 30 s sit-to-stand (30s-STS) test repetitions, distance covered in the 6 min walk test (6MWT), and the Short Physical Performance Battery (SPPB) score. QoL was assessed with the EORTC-QLQ-C30 questionnaire. Blood glucose, cholesterol, triglycerides, total proteins, albumin, pre-albumin, creatinine, c-reactive protein, insulin-growth factor 1 (IGF-1), and the haemoglobin and hematocrit percentages were measured before and after the intervention in order to observe any beneficial effects related to metabolic markers. Results: After the intervention, the mean scores for the 6MWT (p < 0.001), STS (p < 0.001), 6MWT (p < 0.01), and SPPB (p < 0.01) had significantly improved. However, handgrip strength and nutritional analytical were unchanged. The EORTC-QLQ-C30 functions and symptoms significantly improved after the intervention (p < 0.05 and p < 0.01, respectively). A significant decrease in cholesterol, triglycerides, and IGF-1 and a significant increase in pre-albumin in blood was also observed post-intervention (p < 0.05). Conclusions: This supervised, community-based 12-week multicomponent was feasible (adherence rate 70.35%) and provided benefits not only to physical performance but also to the quality of life of patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background and Objectives: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children and adolescents, and is associated with stress and other psychological alterations. This study aims to assess psychological and sleep disorders and health-related quality of life in young people with T1DM and to determine the relationship between these parameters and levels of salivary cortisol, a hormone widely associated with stress and several psychological symptoms. Materials and Methods: In our cross-sectional study performed in 60 Moroccan children and adolescents with T1DM, detailed psychological evaluations were performed to assess symptoms of anxiety, attention-deficit hyperactivity disorder (ADHD), sleep quality and diabetes-specific quality of life (using the RCMAS-2, ADHD rating scale, Pittsburgh scale and the DQoL scale, respectively), and cortisol concentration was measured from saliva samples taken mid-morning. Results: A total of 60 children and adolescents with T1DM were recruited. The mean age was 11.05 ± 0.35 (6–17). The mean salivary cortisol level in ng/mL was 4.7 ± 0.49 (0.7–20.2) and was significantly associated with an anxiety RCMAS2 score for the Worry subdomain and DQoL subdomain “Anxiety”. Linear regression analysis showed that salivary cortisol was significantly higher in girls compared to boys (p = 0.004) (beta coefficient: 3.384 CI95%: 1.137–5.630) and with Hb1AC level as a continuous variable (p = 0.0001) (beta coefficient: 1.135 CI95%: 0.509–1.760). The other variables included in the model were not significant (p > 0.05). There was an association between salivary cortisol concentration with anxiety RCMAS2 score for Worry subdomain and QoL sub-domain “Anxiety”. Still, a significant (p = 0.018) association emerged for anxiety RCMAS2 score Worry subdomain and QoL anxiety subdomain (p = 0.044). Conclusions: Children and adolescents with T1DM experienced significantly elevated symptoms of anxiety and sleep disturbances, particularly in girls, and frequent symptoms of ADHD, particularly in boys. Salivary cortisol concentration collected in the morning is associated with anxiety burden but not with other psychological alterations. Further studies are needed to clarify the associations between salivary cortisol concentration and anxiety in type 1 diabetes in order to propose the hormone as a biomarker for interventions aimed to reduce anxiety levels in these patients.

Background: Androgen deprivation therapy (ADT) is a mainstay of prostate cancer in both adjuvant and palliative settings. Since androgens are crucial for functional status and psychological functions, we evaluated whether blood testosterone, androstenedione, or DHEA concentrations were associated with functional status and psychological alterations in patients with localised (PCa) or metastatic prostate cancer (mPCa) receiving ADT with analogues of luteinising hormone-releasing hormone (LHRH). Methods: The five Fried criteria were considered to identify frailty syndrome. In addition, complementary evaluations were carried out to measure other variables of interest. Sleep quality was assessed using the Athens Insomnia Scale, cognitive functions were assessed using the Mini-Mental State Examination, and symptoms of depression were measured using the Yesavage Geriatric Depression Scale. Logistic regression analysis was performed to determine if the androgens level could be related to frailty syndrome, sleep impairment, depressive symptoms, and cognitive functions. Results: The results of the multivariate analyses show that high concentrations of androstenedione were significantly associated with frailty syndrome in both groups (p = 0.018; odds ratio = 4.66, 95% confidence interval [1.30–16.6]). There were significant relationships between frailty syndrome and the systemic concentration of androstenedione (p = 0.01), but not the concentration of testosterone (p = 0.60) or DHEA (p = 0.42). In addition, the results of the non-parametric tests show significant results between a decreased gait speed in the two groups (metastatic and localised) and the concentration of androstenedione (p = 0.015). High androstenedione levels were associated with a slow walking speed in the mCaP group (p = 0.016), while high testosterone levels were associated with a better walking speed in the localised CaP group (p = 0.03). For the concentration of androstenedione in plasma, the area under the curve was 0.72, with a 95% CI of 0.55–0.88 with acceptable values, and with a cut-off point of 4.51 pg/mL, a sensitivity of 82.9%, and specificity of 53.8%. No relationships between the concentration of androgens in plasma and sleep quality, cognitive functions, or symptoms of depression suggest that the changes were specific to frailty syndrome. Conclusions: Further research into the role of androstenedione should be evaluated in follow-up studies in order to recommend its use as a suitable biomarker of frailty syndrome in prostate cancer patients.

Poor sleep quality is a major public health concern for all ages. In particular, university students often face stress levels and changes in social life habits that negatively influence their quality of sleep. This could be associated with psychological well-being in terms of anxiety and depressive symptoms, stress levels, and a poor self-perceived health status. The increases in the pro-inflammatory cytokine interleukin 6 (IL-6), IL-1 beta (IL-1β), and tumor necrosis factor alpha (TNFα), in blood have been linked to poor sleep quality in many diseases, but data on salivary cytokine levels in students are missing or are seldom analyzed. In this study we determined the quality of sleep in a sample of university students and the role of psychological assessment and factors affecting sleep (alcohol intake, tobacco, consumption of stimulant drinks, exercise, and body mass index). We also aimed to shed new light on the associations between sleep quality and salivary inflammatory cytokines (IL-1β, IL-6, and TNFα). Sleep quality was measured with the Athens Insomnia Scale (AIS) and Pittsburgh Sleep Quality Index (PSQI). Perceived stress was assessed using Cohen’s Perceived Stress Scale (PSS), and the Goldberg Anxiety and Depression Scale (GADS) was used to assess the level of anxiety or depression. Perceived health status was measured with a visual analogue. Saliva samples was taken in the morning and the inflammatory cytokines was measured via enzyme-linked immunoassay. There was a direct and significant association between the salivary IL-1β concentration and AIS score (r = 0.248; p = 0.038, Pearson correlation) and Pittsburgh scale score (r = 0.274; p = 0.022, Pearson correlation). The relationship between IL-1β and AIS controlling for sex, age, and chronic disease, is still significant (r = 0.260; p = 0.033). The relationship between IL-1β and PSQI controlling for the influence of these variables is also significant (r = 0.279; p = 0.022). Salivary IL-1β concentrations were not significantly associated with any of the scores of the other psychological assessments (PSS, anxiety, depression symptoms, or self-perceived health). Salivary TNFα was significantly and inversely associated with self-perceived health (r = −0.259; p = 0.033, Pearson correlation), but the salivary IL-6 concentration was not associated with any of the sleep quality scale or psychological assessment scores. Our results provide a novel relationship between pro-inflammatory cytokine IL-1β in saliva and poor sleep quality. However, the role of inflammation in poor sleep quality requires further study to identify strategies that could lower inflammation and thus, likely improve sleep quality.

Sarcopenia and frailty are important conditions that become increasingly prevalent with age. There is partial overlap between the two conditions, especially in terms of the physical aspects of the frailty phenotype: low grip strength, gait speed, and muscle mass. This study examined whether administration of the essential branched-chain amino acid leucine, besides improving sarcopenia, may reduce frailty assessed by frailty index (FI) in older institutionalized people living in nursing homes. We conducted a secondary analysis of a placebo-controlled, randomized, double-blind design study (ClinicalTrials.gov NCT03831399). The study included fifty males and females aged 65 and over who were living in nursing homes and did not have dementia. The participants were randomized to a parallel group intervention of 13 weeks’ duration, with a daily intake of leucine (6 g/day) or placebo (lactose, 6 g/day). The outcome of this study was to evaluate whether there was a change in the level of a 95 item FI compared to the baseline and to compare the effect of the leucine group versus the placebo group. A significant inverse correlation was found between FI and performance of the activities of daily life, cognitive function, gait and balance, muscle function parameters, and nutritional status (p < 0.001 in all cases). There were no statistically significant differences in FI levels at baseline (placebo group FI 0.27 ± 0.08 and leucine group FI 0.27 ± 0.10) and at the 13 week follow-up (placebo group FI 0.28 ± 0.10 and leucine group FI 0.28 ± 0.09). There were also no significant differences between the leucine and placebo groups in the mean FI difference between baseline and follow-up (p = 0.316, Cohen’s d: 0.04). This pilot study showed that a nutritional supplementation with leucine did not significantly modify the frailty index in older nursing home residents.

Frailty syndrome is associated with poor outcomes, morbidity and premature mortality. We performed a cross-sectional study to evaluate the presence of frailty syndrome based on Fried’s frailty phenotype in post-menopausal women with breast cancer. We further analyzed the association between frailty syndrome with geriatric assessments and the association with the concentration of gonadotropins LH and FSH, estrogens, androgens and the aromatase activity index in the blood. We enrolled 47 post-menopausal women with localized breast cancer (mean age 66.8 ± 1.3 years (range 52–83)) prior to the starting of adjuvant endocrine therapy. Patients were identified as “non-frail” (robust) or “prefrail/frail” if they fulfilled at least one frailty criteria. In order to determine associations among variables and to control for other variables potentially affecting frailty syndrome (age, comorbidity index and previous chemotherapy treatment), we performed a logistic regression analysis. The receiver operating characteristic curve was performed to assess the sensitivity and specificity of the hormonal concentration to discriminate prefrail/frail versus non-frail individuals. Significant positive associations were observed between the severity of frailty syndrome and estrone, FSH and LH concentrations and the aromatase activity index in the blood (p < 0.05). Further research into the role of hormonal biomarkers should be evaluated in follow-up studies in order to recommend their use as suitable biomarkers of frailty syndrome in breast cancer patients.

Cav3.2 T-type calcium channel is a major molecular actor of neuropathic pain in peripheral sensory neurons, but its involvement at the supraspinal level is almost unknown. In the anterior pretectum (APT), a hub of connectivity of the somatosensory system involved in pain perception, we show that Cav3.2 channels are expressed in a subpopulation of GABAergic neurons coexpressing parvalbumin (PV). In these PV-expressing neurons, Cav3.2 channels contribute to a high-frequency-bursting activity, which is increased in the spared nerve injury model of neuropathy. Specific deletion of Cav3.2 channels in APT neurons reduced both the initiation and maintenance of mechanical and cold allodynia. These data are a direct demonstration that centrally expressed Cav3.2 channels also play a fundamental role in pain pathophysiology.