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Maddalena Illario,1– 3 Vincenzo De Luca,1 Gabrielle Onorato,2 Giovanni Tramontano,2,3 Ana Maria Carriazo,2,4 Regina Elisabeth Roller-Wirnsberger,5 Joao Apostolo,6 Patrik Eklund,7 Nandu Goswami,8 Guido Iaccarino,9 Maria Triassi,1 John Farrell,2 Jean Bousquet2,10 1Dipartimento di Sanità Pubblica, Università degli Studi di Napoli Federico II, Naples, Italy; 2Executive Board, EIP on AHA Reference Sites Collaborative Network, Brussels, Belgium; 3Research & Development Unit, Azienda Ospedaliera Universitaria Federico II, Naples, Italy; 4Deputy Regional Ministry, Regional Ministry of Health and Families of Andalusia, Seville, Spain; 5Department of Internal Medicine, Medical University of Graz, Graz, Austria; 6Health and Care Sciences Research Unit, Escola Superior de Enfermagem de Coimbra, Coimbra, Portugal; 7Department of Computing Science, Umeå University, Umeå, Sweden; 8Division of Physiology, Medical University of Graz, Graz, Austria; 9Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli Federico II, Naples, Italy; 10MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, FranceCorrespondence: Maddalena Illario, Dipartimento di Sanità Pubblica, Università degli Studi di Napoli Federico II, Via Sergio Pansini n.5, Naples, 80131, Italy, Tel +39 0817464211, Fax +39 0817464212, Email illario@unina.it Nandu Goswami, Division of Physiology, Medical University of Graz, Neue Stiftingtalstraße 6, Graz, 8010, Austria, Tel +43 31638573852, Fax +43 31638579005, Email nandu.goswami@medunigraz.atAbstract: The article describes some of the achievements of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), after eight years in operation. These results were achieved thanks to the collaborative work of the action groups (AGs) and reference sites (RSs). RS regional ecosystems include key organisations committed to investing in innovation to foster active and healthy ageing. The AGs are groups of professionals committed to sharing their knowledge and skills in active and healthy ageing. This article reports on the approach used by the EIP on AHA to bring together experts and regions in identifying and addressing these challenges. Synergies between AGs offered substantial support to RSs, allowing regional health and care priorities and challenges to be identified and pursued through AG commitments. Building upon the experiences of the EIP on AHA, the Reference Sites Collaborative Network has set up a number of thematic action groups that bring together multidisciplinary experts from across Europe to address the main health and social care challenges at regional, national and European level.Keywords: active and healthy ageing, digital health, health policy, health innovation

Salvatore D’Angelo,1 Giuseppina Tramontano,1 Michele Gilio,1 Pietro Leccese,1 Ignazio Olivieri1,2 1Rheumatology Institute of Lucania (IRel) - Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza and Matera, 2Basilicata Ricerca Biomedica (BRB) Foundation, Potenza, Italy Abstract: Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient’s preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed. Keywords: psoriatic arthritis, treatment, biological drugs, TNF inhibitors, ustekinumab, secukinumab

Applying transcranial alternating current stimulation (tACS) at 40 Hz to the frontal and parietal regions, either unilaterally (left or right) or bilaterally, can improve cognitive dysfunctions. This study aimed to explore the influence of tACS at gamma frequency over right fronto-parietal (FP) region on attention. The analysis is based on retrospective data from a clinical intervention. We administered test of variables of attention (TOVA; visual mode) to 44 participants with various neuropsychiatric diagnoses before and after 12 sessions of tACS treatment. Alternating currents at 2.0 mA were delivered to the electrode positions F4 and P4, following the 10-20 EEG convention, for 20 mins in each session. We observed significant improvement across 3 indices of the TOVA, including reduction of variability in reaction time ( p = 0.0002), increase in d-Prime (separability of targets and non-targets; p = 0.0157), and decrease in commission error rate ( p = 0.0116). The mean RT and omission error rate largely remained unchanged. Artificial injection of tACS at 40 Hz over right FP network may improve attention function, especially in the domains of consistency in performance, target/non-target discrimination, and inhibitory control.

Introduction: One of the most common applications of transcranial electrical stimulation (tES) at low current intensity is to induce a relaxed state or reduce anxiety. With technical advancement, different waveforms, montages, and parameters can be incorporated into the treatment regimen. We developed a novel protocol to treat individuals with anxiety disorders by transcranial alternating current stimulation (tACS)., Methods: A total of 27 individuals with anxiety disorders underwent tACS treatment for 12 sessions, with each session lasting 25 min. tACS at 5 Hz was applied to F4 (1.0 mA), P4 (1.0 mA), and T8 (2.0 mA) EEG lead positions (tripod), with sinewave oscillation between T8 and F4/P4. We evaluated the primary and secondary outcomes using the Beck Anxiety Inventory (BAI) and neuropsychological assessments., Results: Of the 27 patients, 19 (70.4 %) experienced a reduction in symptom severity >50 %, with an average reduction of BAI 58.5 %. All reported side effects were mild, with itching or tingling being the most common complaint. No significant differences were noted in attention, linguistic working memory, visuospatial working memory, or long-term memory in neuropsychological assessments., Conclusion: The results suggest the potential of this novel tripod tACS design as a rapid anxiety alleviator and the importance of a clinical trial to verify its efficacy., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest. This work has not been published previously and is not under consideration for publication elsewhere. The publication is approved by all authors, and if accepted, it will not be published elsewhere in the same form, in English, or any other language, including electronically without the written consent of the copyright holder., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Transcranial alternating current stimulation (tACS) at 5-Hz to the right hemisphere can effectively alleviate anxiety symptoms. This study aimed to explore the neural mechanisms that drive the therapeutic benefits., Methods: We collected electroencephalography (EEG) data from 24 participants with anxiety disorders before and after a tACS treatment session. tACS was applied over the right hemisphere, with 1.0 mA at F4, 1.0 mA at P4, and 2.0 mA at T8 (10-10 EEG convention). With eLORETA, we transformed the scalp signals into the current source density in the cortex. We then assessed the differences between post- and pre-treatment brain maps across multiple spectra (delta to low gamma) with non-parametric statistics., Results: We observed a trend of heightened power in alpha and reduced power in mid-to-high beta and low gamma, in accord with the EEG markers of anxiolytic effects reported in previous studies. Additionally, we observed a consistent trend of de-synchronization at the stimulating sites across spectra., Conclusion: tACS 5-Hz over the right hemisphere demonstrated EEG markers of anxiety reduction. The after-effects of tACS on the brain are intricate and cannot be explained solely by the widely circulated entrainment theory. Rather, our results support the involvement of plasticity mechanisms in the offline effects of tACS., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Despite its complexity, deciphering nodal interaction is imperative to understanding a neural network. Network interaction is an even more complicated topic that must be addressed. This study aimed to examine the relationship between the brain waves of two canonical brain structures, i.e., the frontoparietal and limbic compartments, during a resting state., Methods: Electroencephalography (EEG) of 51 subjects in eye-closed condition was analyzed, and the eLORETA method was applied to convert the signals from the scalp to the brain. By way of community detection, representative neural nodes and the associated mean activities were retrieved. Total and lagged coherences were computed to indicate functional connectivity between those neural nodes. Two global network properties were elucidated based on the connectivity measures, i.e., global efficiency and mean functional connectivity strength. The temporal correlation of the global network indices between the two studied networks was explored., Results: It was found that there was a significant trend of positive correlation across the four metrics (lagged vs. total coherence x global efficiency vs. average connectivity). In other words, when the neural interaction in the FP network was stronger, so did that in the limbic network, and vice versa. Notably, the above interaction was not spectrally specific and only existed at a finer temporal scale (under hundreds of milliseconds level)., Conclusion: The concordant change in network properties indicates an intricate balance between FP and LM compartments. Possible mechanisms and implications for the findings are discussed., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Self-management of Type 2 diabetes mellitus (T2D) is challenging. Regular self-monitoring of blood glucose and healthy lifestyles are required to improve glycometabolic control, thus delaying diabetes complications, and reducing hospitalizations. Digital technologies can empower patients in their disease management promoting self-management and motivation to change behaviors. We report the results of an exploratory trial aimed at evaluating the metabolic outcomes of using digital solutions for T2D self-management developed in the ProEmpower project, a European Commission funded Pre-Commercial Procurement., Methods: Two digital solutions, DM4All and DiaWatch, which were codesigned with providers, patients, and caregivers, enabled the collection of clinical parameters by the patient using a smartphone integrated with the medical devices (glucometer, sphygmomanometer, scale, smart watch for heart rate monitoring and step counter). Data were automatically sent to the shared care plan allowing professionals to monitor adherence to treatment, set goals, and communicate more effectively with patients. At baseline and after an average follow-up of 8 months, glycosylated hemoglobin (HbA1c), body weight, blood pressure, and blood lipids were measured in 100 T2D patients using the ProEmpower solutions across different diabetes centers in Campania Region, age 45-79  years, both genders, and compared with a Control cohort of T2D patients ( n  = 100) with similar clinical characteristics and followed for a comparable period of observation in the same centers., Results: At baseline, the ProEmpower participants and the Control subjects were on average overweight, with a similar BMI in the two cohorts, and mean HbA1c was at acceptable levels (around 7.0%). After the 8 month exploratory trial, body weight, HbA1c, systolic and diastolic blood pressure, and plasma and LDL-cholesterol significantly decreased in the ProEmpower participants compared to baseline ( p  < 0.05 for all). The changes in systolic and diastolic blood pressure, and plasma and LDL-cholesterol were significantly different from those observed in the Control cohort ( p  < 0.05 for all)., Conclusion: This pilot study showed positive effects on metabolic outcomes relevant to cardiovascular risk in T2D of adopting digital telemedicine self-monitoring solutions based on automation of measurements and coaching on healthy lifestyles promotion., Competing Interests: CC is employed by Tech4Care Srl. AB is employed by Gnomon Informatics SA. The remaining 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., (Copyright © 2023 De Luca, Bozzetto, Giglio, Tramontano, De Simone, Luciano, Lucibelli, Maffettone, Riccio, Romano, Rossi, Chiatti, Berler, Iaccarino, Illario and Annuzzi.)

Objectives: To determine the cut-off values of Patient Acceptable Symptom State (PASS) for the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Scale (FASmod), and the Polysymptomatic Distress scale (PSD) and to determine the predictors of PASS in patients with fibromyalgia (FM)., Methods: FM patients belonging to the Italian Fibromyalgia Registry (IFR) completed the FIQR, the FASmod and the PSD. The PASS was assessed using a dichotomous answer. The cut-off values were obtained through the receiver operating characteristic curve (ROC) analyses. A multivariate logistic regression analysis was performed to determine predictors of achieving the PASS., Results: 5545 women (93.7%) and 369 males (6.3%) were included in the study. The 27.8% of patients reported an acceptable symptom state. Patients in PASS differed in all patient-reported outcome measures (p <0.001). The FIQR PASS threshold was ≤58 (area under the ROC curve [AUC] = 0.819). The FASmod PASS threshold was ≤23 (AUC = 0.805) and the PSD PASS threshold was ≤16 (AUC = 0.773). In the pairwise AUC comparison, the discriminatory power of the FIQR PASS outperforms both FASmod PASS (p = 0.0124) and PSD PASS (p <0.0001). Multivariate logistic analysis showed that FIQR items related to memory and pain were the only predictors of PASS., Conclusions: The FIQR, FASmod, and PSD PASS cut-off points for FM patients have never been determined before. This study provides additional information to facilitate interpretation of the severity assessment scales in daily practice and clinical research related to FM patients.

Objective: Alzheimer's disease (AD) has prolonged asymptomatic or mild symptomatic periods. Given that there is an increase in treatment options and that early intervention could modify the disease course, it is desirable to devise biological indices that may differentiate AD and nonAD at mild cognitive impairment (MCI) stage., Methods: Based on two well-acknowledged observations of background slowing (attenuation in alpha power and enhancement in theta and delta powers) and early involvement of posterior cingulate cortex (PCC, a neural hub of default-mode network), this study devised novel neural markers, namely, spectral ratios of alpha1 to delta and alpha1 to theta in the PCC., Results: We analysed 46 MCI patients, with 22 ADMCI and 24 nonADMCI who were matched in age, education, and global cognitive capability. Concordant with the prediction, the regional spectral ratios were lower in the ADMCI group, suggesting its clinical application potential., Conclusion: Previous research has verified that neural markers derived from clinical electroencephalography may be informative in differentiating AD from other neurological conditions. We believe that the spectral ratios in the neural hubs that show early pathological changes can enrich the instrumental assessment of brain dysfunctions at the MCI (or pre-clinical) stage.

Background: Irritable bowel syndrome (IBS) is a common multifactorial condition that affects the large intestine and is characterized by chronic and relapsing abdominal pain and altered bowel habit. IBS is due to a combination of genetic, environmental and dietary factors. It's usually a lifelong problem very frustrating to live with and can have a big impact on quality of life, as single-agent therapy ra., Objective: To analyze the approaches and solutions that address the social and health unmet needs of patients with IBS., Design: A quantitative-qualitative approach was adopted in the current study to identify and specify key digital solution and high impact user scenarios applied to IBS patients, through an adaptation of the "Blueprint on Digital Transformation in Health and Care in an Ageing Society" persona methodology., Settings: Digital health solutions bring the potential of supporting health interventions through mobile apps, wearable devices, telemedicine., Patients: A Survey was administered to a group of patients in an anonymous form, and no need for Medical Ethical Committee approval was identified., Interventions: The theoretical elaboration IBS personas was developed through an interdisciplinary Focus Group, which also mapped the pathway for the patient's management., Main Outcome: Three main needs were identified to be met to improve IBS patient's lifestyle: access to psychological support, mHealth solutions supporting diet and adapted physical activity, and home-based digital health support. mHealth intervention has been identified for diet adherence, physical exercise and psychological well-being. The process has been mapped and adapted to integrate the new solutions into the care pathway., Limitation: Further research is needed to evaluate how mHealth services enable IBS patients to manage their conditions and improve their quality of life., Conclusion: The person-centered approach was implemented through a multidisciplinary Focus group that enabled the identification of the need for a mHealth intervention., 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., (Copyright © 2022 Gentile, De Luca, Patalano, Laudisio, Tramontano, Lindner-Rabl, Mercurio, Salvatore, Farrell, Roller-Wirnsberger, Kubitschke, Triassi, Colao, Illario and Vigour Consortium.)

Background: The association between domestic cat hepadnavirus (DCH) infection and feline chronic hepatitis and hepatocellular carcinoma has been suggested. However, studies focused on the association between DCH infection and clinicopathological changes consistent with liver disease in cats are not available., Methods: This retrospective investigation included sera obtained from 96 cats that had the serum activity of at least alanine aminotransferase or alkaline phosphatase measured during initial diagnostic work-up. Based on these haematobiochemical results, cats were categorised according to their likelihood of having liver disease (absent, low, intermediate or high). DCH DNA was detected using real-time PCR, nested PCR and sequencing., Results: Overall, potential liver damage was observed in 44 cats, including cats with low (n = 14), intermediate (n = 10) and high (n = 20) likelihood of liver disease. Four cats (4.2%) were DCH-positive, with three positive cats belonging to the liver disease group (two with low and one with intermediate likelihood of liver disease)., Conclusions: Although the pathogenic potential of DCH in cats still has to be clarified, these results suggest that DCH testing should not be based only on the presence of biochemical changes potentially consistent with liver disease., (© 2022 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Irritable bowel syndrome (IBS) is a common multifactorial condition that affects the large intestine and is characterized by chronic and relapsing abdominal pain and altered bowel habit. IBS is due to a combination of genetic, environmental and dietary factors. It's usually a lifelong problem very frustrating to live with and can have a big impact on quality of life, as single-agent therapy rarely relieves bothersome symptoms for all patients. The objective of this study was to analyze the approaches and solutions that address the social and health unmet needs of patients with IBS. A qualitative approach was adopted in the current study to identify and specify key digital solution and high impact user scenarios applied to IBS patients, through an adaptation of the "Blueprint on Digital Transformation in Health and Care in an Ageing Society" persona methodology. A Survey was administered to a group of patients in anonymous form. The theoretical elaboration IBS personas was developed through an interdisciplinary Focus Group, which also mapped the pathway for the patient's management. Three main needs were identified to be met to improve IBS patient's lifestyle: access to psychological support, mHealth solutions supporting diet and adapted physical activity, and homebased digital health support. mHealth intervention has been identified for diet adherence, physical exercise and psychological well-being. The process has been mapped and adapted to integrate the new solutions into the care pathway. Further research is needed to evaluate how mHealth services enable IBS patients to manage their conditions and improve their quality of life. KEY WORDS: Digital Health, Irritable bowel syndrome, mHealth, Nutrition, Physical activity, Psychological support.