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Joyce S Ramos,1,2 Lance C Dalleck,2,3 Rebecca C Stennett,1 Gregore I Mielke,1 Shelley E Keating,1 Lydia Murray,4 Sumaira Z Hasnain,4,5 Robert G Fassett,1 Michael McGuckin,4,6 Ilaria Croci,1,7 Jeff S Coombes1 1Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Queensland, Australia; 2Caring Futures Institute and SHAPE Research Centre, Exercise Science and Clinical Exercise Physiology, College of Nursing and Health Sciences, Flinders University, Adelaide, South Australia, Australia; 3Recreation, Exercise, and Sport Science Department, Western State Colorado University, Gunnison, Colorado, USA; 4Immunopathology Group, Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia; 5Australian Infectious Disease Research Centre, University of Queensland, Brisbane, Queensland, Australia; 6Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia; 7K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Sor Trondelag, NorwayCorrespondence: Joyce S Ramos Email joyce.ramos@flinders.edu.auIntroduction: IL-22 may have a role in the alleviation of the metabolic syndrome (MetS) via protection of pancreatic beta and endothelial cells from oxidative and lipid-induced damage. We aimed to investigate the effects of moderate-intensity continuous training (MICT) and different volumes of high-intensity interval training (HIIT) on changes in circulating IL-22.Methods: This was a sub-study of the “Exercise in the prevention of Metabolic Syndrome” (EX-MET) a multi-center, randomized trial. This study used data collected at the Brisbane site. Thirty-nine individuals with MetS were randomized to one of three 16-wk interventions: 1) MICT (n=10, 30min at 60– 70% HR peak, 5x/wk); 2) 4HIIT (n=13, 4x4min at 85– 95% HR peak, interspersed with 3min of active recovery at 50– 70% HR peak, 3x/wk); or 3) 1HIIT (n=16, 1x4min at 85– 95% HR peak, 3x/wk). Serum IL-22 concentration was measured following a 12-hr fast via an enzyme linked immunosorbent assay, before and after the intervention. MetS severity, insulin resistance (IR), visceral adipose tissue (VAT), and cardiorespiratory fitness (CRF) were also measured via MetS z-score, HOMA-IR, dual-energy X-ray absorptiometry, and indirect calorimetry (maximal exercise test), respectively.Results: The median (IQR) IL-22% changes from pre- to post-intervention in the MICT, 4HIIT, and 1HIIT groups were − 17% (− 43.0% to 31.3%), +16.5% (− 18.9% to 154.9%), and +15.9% (− 28.7% to 46.1%), respectively. Although there were no significant between-group differences in IL-22 concentration change, there was a medium-to-large group × time interaction effect [F(2,35)=2.08, p=0.14, η2=0.14].Conclusion: Although there was no statistically significant between-group difference in IL-22 change, the study suggests that different exercise intensities may have opposing effects on IL-22 concentration in individuals with MetS.Keywords: high-intensity interval training, IL-22, inflammation, cardiovascular disease, metabolic syndrome, cytokine

Background and aims: Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis). Methods: The neural contractile response to electrical field stimulation of longitudinal muscle strips from the colon of patients undergoing surgery for colonic cancer or diverticulitis was challenged by different receptor agonists and antagonists. Results: Contractions of colonic strips from healthy controls and diverticulitis specimens were abolished by atropine. The 13 adrenergic agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar potency in reducing the electrical twitch response in controls and diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1 receptor, had no intrinsic activity in control preparations but potentiated the neural twitch in diseased tissues by up to 196% in a concentration dependent manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular disease patients. Colonic levels of the endogenous ligand of cannabinoid and vanilloid TRPV1 receptors anandamide were more than twice those of control tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had opposite effects in the two preparations, completely inhibiting the contractions of control strips but potentiating those in diverticular preparations, an effect selectively inhibited by SR140333. Conclusions: Neural control of colon motility is profoundly altered in patients with diverticulitis. Their raised levels of anandamide, apparent desensitisation of the presynaptic neural cannabinoid CB1 receptor, and the SR141716 induced intrinsic response, suggest that endocannabinoids may be involved in the pathophysiology of complications of colonic diverticular disease. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season., Methods: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations., Results: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration., Conclusions: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures., (© 2024. The Author(s).)

Background: Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged <1 year., Methods: From December 2015 to December 2019, participating hospitals recruited all infants with pertussis-like symptoms. Cases were vaccine-eligible infants testing positive for Bordetella pertussis by PCR or culture; controls were those testing negative to all Bordetella spp. For each vaccine dose, we defined an infant as vaccinated if she/he received the corresponding dose >14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it)., Results: Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36-73). Adjusted VE was 48 % (95 %CI: 5-71) for dose one (416 eligible infants) and 76 % (95 %CI: 43-90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose., Conclusions: Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three., Competing Interests: Declaration of competing interest No conflict of interest to declare except for Elmira Flem who has been employed since April 2019 by Merck & Co., Inc., North Wales, PA, USA. The work for the current study was conducted by Dr. Flem under the previous affiliation at the Norwegian Institute of Public Health., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Human respiratory syncytial virus (RSV) is one of the most frequent causes of respiratory infections in children under 5 years of age, but its socioeconomic impact and burden in primary care settings is still little studied., Methods: During the 2022/2023 winter season, 55 pediatricians from five Italian regions participated in our community-based study. They collected a nasal swab for RSV molecular test from 650 patients under the age of 5 with acute respiratory infections (ARIs) and performed a baseline questionnaire. The clinical and socioeconomic burden of RSV disease in primary care was evaluated by two follow-up questionnaires completed by the parents of positive children on Days 14 and 30., Results: RSV laboratory-confirmed cases were 37.8% of the total recruited ARI cases, with RSV subtype B accounting for the majority (65.4%) of RSV-positive swabs. RSV-positive children were younger than RSV-negative ones (median 12.5 vs. 16.5 months). The mean duration of symptoms for all children infected by RSV was 11.47 ± 6.27 days. We did not observe substantial differences in clinical severity between the two RSV subtypes, but RSV-A positive patients required more additional pediatric examinations than RSV-B cases. The socioeconomic impact of RSV infection was considerable, causing 53% of children to be absent from school, 46% of parents to lose working days, and 25% of families to incur extra costs., Conclusions: Our findings describe a baseline of the RSV disease burden in primary care in Italy before the introduction of upcoming immunization strategies., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Introduction: Quality of life in childhood cancer survivors is largely affected by survivorship care and transition from treatment to long-term follow-up (LTFU). Referring to evidence-based recommendations, we wanted to evaluate LTFU care for survivors through a survey among the Italian Association for Pediatric Hematology-Oncology (AIEOP) centers. The project aimed to evaluate the availability of services in Italy, investigate strengths and weaknesses, analyze improvements of awareness in the field, and identify the gaps that need to be addressed by different centers., Methods: Together with the family representatives, on behalf of AIEOP's Late Effects Working Group, we developed a questionnaire on assisting childhood cancer survivors. All AIEOP centers received one questionnaire including information on local health system organizations; LTFU for childhood cancer survivors; services for adult survivors of childhood cancer; information provided to survivors/caregivers and care plan delivery., Results: Forty-eight AIEOP centers were contacted and 42 replied, with a response rate of 87.5%. The majority of respondents confirmed their interest in assisting patients with a survivorship care plan (95.2%), regardless of a clinic or dedicated staff., Discussion: This is the first overview of LTFU in Italy, which provides detailed results at national levels, prompting consideration of improvements in the last decade. Although there is a high level of interest in survivorship care, many centers lack resources to implement such programs. The identification of these challenges is useful for planning future strategies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Aims: High-intensity interval training (HIIT) is a therapeutic option for people with nonalcoholic steatohepatitis (NASH). However, the perspectives and experiences of HIIT for people with NASH are unknown, limiting translation of research. We explored the experiences and perspectives of both professionally supervised and self-directed HIIT in people with NASH and evaluated participant-reported knowledge, barriers, and enablers to commencing and sustaining HIIT., Methods: Twelve participants with NASH underwent 12 weeks of supervised HIIT (3 days/week, 4×4 minutes at 85-95% maximal heart rate, interspersed with 3 minutes active recovery), followed by 12-weeks of self-directed (unsupervised) HIIT. One-on-one, semistructured participant interviews were conducted by exercise staff prior to HIIT and following both supervised and self-directed HIIT to explore prior knowledge, barriers, enablers, and outcomes at each stage. Interviews were audio-recorded, transcribed, coded, and thematically analyzed by two independent researchers., Results: Four dominant themes were identified: (1) no awareness of/experience with HIIT and ambivalence about exercise capabilities; (2) multiple medical and social barriers to commencing and continuing HIIT; (3) exercise specialist support was a highly valued enabler, and (4) HIIT was enjoyed and provided holistic benefits., Conclusions: People with NASH may lack knowledge of and confidence for HIIT, and experience multiple complex barriers to commencing and continuing HIIT. Exercise specialist support is a key enabler to sustained engagement. These factors need to be addressed in future clinical programs to augment the uptake and long-term sustainability of HIIT by people with NASH so they can experience the range of related benefits., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Background: Emerging technologies have demonstrated outstanding potential in improving healthcare, yet their full integration remains a challenge for all medical specialties, including pediatrics. To support the swift implementation of technologies, we identified the current trends through a bibliometric review, and we conducted a survey on Italian pediatricians to gauge educational needs and willingness to integrate technologies into clinical practice., Methods: A working group of pediatricians representing various backgrounds designed and coordinated the study. To identify relevant topics for educational strategy development, we focused on virtual reality, telehealth, natural language processing, smartphone applications, robotics, genomics, and artificial intelligence. A bibliometric analysis limited to 2018-2023 was performed to identify trends and emerging applications within each topic. Based on the results, a questionnaire was developed and made available online to all Italian pediatricians. The results were analyzed through descriptive analysis and a multivariable logistic regression to explore associations between technology adoption and sociodemographic characteristics., Results: A total of 3,253 publications were found, with Telehealth and Telemedicine having the highest number of publications and Natural Language Processing the lowest. The number of respondents to the online questionnaire was 1,540, predominantly medical doctors with over 20 years of experience working as family pediatricians. Telehealth had the highest level of knowledge (95.2%), followed by smartphone applications (89.1%) and genomics (63.2%). The greatest potential for increased use through education programs was projected for natural language processing (+ 43.1%), artificial intelligence (+ 39.6%), and virtual and mixed reality (+ 38.1%). Female respondents and older individuals were less likely to use emerging technologies. Hospital pediatricians and residents were more likely to use AI., Conclusions: We developed a replicable strategy to identify emerging themes in medical technologies relevant to pediatrics and assess the educational needs of pediatricians. A significant gap still exists between current and potential usage of emerging technologies among Italian pediatricians although they showed a positive attitude towards implementing these technologies following specific education programs. The study highlights the need for comprehensive education programs on emerging technologies in pediatrics and recommends addressing gender and age disparities in technology adoption., (© 2023. Società Italiana di Pediatria.)

Introduction: Growing scientific evidence indicates that sphingolipids predict cardiometabolic risk, independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, it remains largely unknown if and how exercise, a simple, low-cost, and patient-empowering modality to optimise cardiometabolic health, influences sphingolipid levels. The SphingoHIIT study aims to assess the response of circulating sphingolipid species to a single session of high-intensity interval training (HIIT). Methods: This single-centre randomised controlled trial (RCT) will last 11 days per participant and aim to include 32 young and healthy individuals aged 20-29 (50% females). Participants will be randomly allocated to the HIIT (n= 16) or control groups (physical rest, n= 16). Participants will self-sample fasted dried blood spots for three consecutive days before the intervention (HIIT versus rest) to determine baseline sphingolipid levels. Dried blood spots will also be collected at five time points (2, 15, 30, 60min, and 24h) following the intervention (HIIT versus rest). To minimise the dietary influence, participants will receive a standardised diet for four days, starting 24 hours before the first dried blood sampling. For females, interventions will be timed to fall within the early follicular phase to minimise the menstrual cycle's influence on sphingolipid levels. Finally, physical activity will be monitored for the whole study duration using a wrist accelerometer. Ethics and dissemination: The Ethics Committee of Northwest and Central Switzerland approved this protocol (ID 2022-00513). Findings will be disseminated in scientific journals and meetings. Trial Registration The trial was registered on www.clinicaltrials.gov (NCT05390866, https://clinicaltrials.gov/ct2/show/NCT05390866) on May 25, 2022., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Carrard J et al.)

Weight restoration is the primary goal of treatment for patients with Anorexia Nervosa (AN). This observational pilot study aims to describe adherence to the Mediterranean Diet (MD) and the consequent process of weight and functional recovery in outpatient adolescents diagnosed with AN. Eight patients with a median age of 15.1 (14.0-17.1) years were seen at baseline and after six months. Anthropometrics, body composition, and resting energy expenditure (REE) were assessed. The KIDMED questionnaire, the 24 h recall, and a quantitative food frequency questionnaire were used to evaluate adherence to the MD. The median KIDMED score increased from 5.5 (T0) to 10 (T1), which was not significant. Intakes of grams of carbohydrates, lipids, mono-unsaturated fatty acids, and fiber increased ( p = 0.012, p = 0.036, p = 0.036, p = 0.025). Weight significantly increased ( p = 0.012) as well as lean body mass ( p = 0.036), with a resulting improvement of the REE ( p = 0.012). No association between anthropometrics and body composition and the KIDMED score was found. The MD could represent an optimal dietary pattern for weight gain and nutritional restoration in patients with AN, and it could lead to an improvement in body composition and resting energy expenditure.

We tested the performance of a machine learning (ML) algorithm based on signs and symptoms for the diagnosis of RSV infection or pertussis in the first year of age to support clinical decisions and provide timely data for public health surveillance. We used data from a retrospective case series of children in the first year of life investigated for acute respiratory infections in the emergency room from 2015 to 2020. We collected data from PCR laboratory tests for confirming pertussis or RSV infection, clinical symptoms, and routine blood testing results, which were used for the algorithm development. We used a LightGBM model to develop 2 sets of models for predicting pertussis and RSV infection: for each type of infection, we developed one model trained with the combination of clinical symptoms and results from routine blood test (white blood cell count, lymphocyte fraction and C-reactive protein), and one with symptoms only. All analyses were performed using Python 3.7.4 with Shapley values (Shap values) visualization package for predictor visualization. The performance of the models was assessed through confusion matrices. The models were developed on a dataset of 599 children. The recall for the pertussis model combining symptoms and routine laboratory tests was 0.72, and 0.74 with clinical symptoms only. For RSV infection, recall was 0.68 with clinical symptoms and laboratory tests and 0.71 with clinical symptoms only. The F1 score for the pertussis model was 0.72 in both models, and, for RSV infection, it was 0.69 and 0.75. ML models can support the diagnosis and surveillance of infectious diseases such as pertussis or RSV infection in children based on common symptoms and laboratory tests. ML-based clinical decision support systems may be developed in the future in large networks to create accurate tools for clinical support and public health surveillance., Competing Interests: AET has been working as an expert consultant on vaccine strategies for Pfizer and Sanofi. FG received support for participating in MSD and Moderna meetings. 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., (© 2023 Mc Cord—De Iaco, Gesualdo, Pandolfi, Croci and Tozzi.)

TikTok, a social media platform for creating and sharing short videos, has seen a surge in popularity during the COVID-19 pandemic. To analyse the Italian vaccine conversation on TikTok, we downloaded a sample of videos with a high play count (Top Videos), identified through an unofficial Application Programming Interface (consistent with TikTok's Terms of Service), and collected public videos from vaccine sceptic users through snowball sampling (Vaccine Sceptics' videos). The videos were analysed using qualitative and quantitative methods, in terms of vaccine stance, tone of voice, topic, conformity with TikTok style, and other characteristics. The final datasets consisted of 754 Top Videos (by 510 single users) plus 180 Vaccine Sceptics' videos (by 29 single users), posted between January 2020 and March 2021. In 40.5% of the Top Videos the stance was promotional, 33.9% were indefinite-ironic, 11.3% were neutral, 9.7% were discouraging, and 3.1% were ambiguous (i.e. expressing an ambivalent stance towards vaccines); 43% of promotional videos were from healthcare professionals. More than 95% of the Vaccine Sceptic videos were discouraging. Multiple correspondence analysis showed that, compared to other stances, promotional videos were more frequently created by healthcare professionals and by females, and their most frequent topic was herd immunity. Discouraging videos were associated with a polemical tone of voice and their topics were conspiracy and freedom of choice. Our analysis shows that Italian vaccine-sceptic users on TikTok are limited in number and vocality, and the large proportion of videos with an indefinite-ironic stance might imply that the incidence of affective polarisation could be lower on TikTok, compared to other social media, in the Italian context. Safety is the most frequent concern of users, and we recorded an interesting presence of healthcare professionals among the creators. TikTok should be considered as a medium for vaccine communication and for vaccine promotion campaigns., (© 2023. The Author(s).)

Background: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH)., Aims: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH., Methods: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m 2 , 64% male), NAFLD Activity Score 5 (range 3-7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85-95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined as ≥ 70% program completion and ≥ 70% global adherence (including session attendance, interval intensity adherence, and duration adherence) were assessed. Changes in cardiorespiratory fitness (V̇O 2 peak), exercise capacity (time-on-test) and peripheral insulin sensitivity (euglycemic hyperinsulinemic clamp) were assessed. Data were analysed using ANCOVA with baseline value as the covariate., Results: There were no HIIT-related adverse events and HIIT was globally feasible [program completion 75%, global adherence 100% (including adherence to session 95.4 ± 7.3%, interval intensity 95.3 ± 6.0% and duration 96.8 ± 2.4%)]. A large between-group effect was observed for exercise capacity [mean difference 134.2 s (95% CI 19.8, 248.6 s), ƞ 2 0.44, p = 0.03], improving in HIIT (106.2 ± 97.5 s) but not CON (- 33.4 ± 43.3 s), and for peripheral insulin sensitivity [mean difference 3.4 mg/KgLegFFM/min (95% CI 0.9,6.8 mg/KgLegFFM/min), ƞ 2 0.32, p = 0.046], improving in HIIT (1.0 ± 0.8 mg/KgLegFFM/min) but not CON (- 3.1 ± 1.2 mg/KgLegFFM/min)., Conclusions: HIIT is safe, feasible and efficacious for improving exercise capacity and peripheral insulin sensitivity in people with NASH., Clinical Trial Registration Number: Australian New Zealand Clinical Trial Registry (anzctr.org.au) identifier ACTRN12616000305426 (09/03/2016)., (© 2022. The Author(s).)

Eating disorders are considered one of the psychiatric disorders with a higher risk of death. Food addiction, related to some food addictive-like behaviours, is often in comorbidity with eating disorders and is associated with worse psychopathology. The present study aims to outline the food addiction profile, investigated using the Yale Food Addiction Scale 2.0 (YFAS 2.0), in 122 adolescents (median age: 15.6 years) suffering from eating disorders and to investigate its association with psychopathology. Patients filled out the Youth Self Report, the Multidimensional Anxiety Scale for Children 2, The Children Depression Inventory 2, and the Eating Disorder Inventory 3 (EDI-3). Pearson's chi-square test and multiple correspondence analysis were used to identify profiles. The mean symptom count was 2.8 ± 2.7. The "withdrawal" symptom was the most frequent (51%) and the most associated with clinical scores. The diagnosis of bulimia nervosa and the EDI-3 bulimia scale resulted to be the only variables to be associated with positive YFAS 2.0 symptoms. Conversely, anorexia nervosa, restrictive and atypical, was not associated with YFAS 2.0 symptoms. In conclusion, outlining the food addiction profile of eating disorders may give information about a patient's phenotype and could help to identify specific treatment models.

Web-based digital interventions may play a central role for health promoting strategies in the first "1000 days", from conception through the first 2 years of life. We developed a web platform providing evidence-based recommendations in the first 1000 days through short videos, and we studied engagement by users from preconception through parenthood in the second year of life. We described the access to videos by topic and used a multilevel model to explore the user characteristics associated with access to the video recommendations. Overall, breastfeeding, physical activity and nutrition were the most popular topics (normalized views: 89.2%, 87.2% and 86.4% respectively), while content on paternal health and smoking and alcohol was less engaging (37.3% and 42.0%). Nutrition content was the most viewed in the preconception period and during the first two trimesters of pregnancy. Nutrition and breastfeeding were also the most popular topics for users with children less than 2 years old. Higher levels of health literacy were associated only with child health content. The study findings indicate that digital strategies should be adapted according to the time period in the first 1000 days. Alternative digital promotion strategies for the less engaging topics should be considered.

Chromosome 9p deletion syndrome is a rare autosomal dominant disorder presenting with a broad spectrum of clinical features, including congenital heart defects (CHDs). To date, studies focused on a deep characterization of cardiac phenotype and function associated with this condition are lacking. We conducted a multicentric prospective observational study on a cohort of 10 patients with a molecular diagnosis of 9p deletion syndrome, providing a complete cardiological assessment through conventional echocardiography and tissue Doppler imaging echo modality. As a result, we were able to demonstrate that patients with 9p deletion syndrome without major CHDs may display subclinical cardiac structural changes and left-ventricle systolic and diastolic dysfunction. Albeit needing validation in a larger cohort, our findings support the idea that a complete cardiac assessment should be performed in patients with 9p deletion syndrome and should be integrated in the context of a long-term follow-up.

Virtual reality (VR) represents a promising digital intervention for managing distress and anxiety in children with tumors undergoing painful medical procedures. In an experimental cross-over study, we administered a VR intervention consisting of relaxing games during central venous catheter (CVC) dressing. The VR sessions were compared with no-VR during CVC medication. We used the distress thermometer and RCMAS-2 scale to assess distress and anxiety levels. We also explored the satisfaction level in patients and families. We enrolled 22 children. The distress levels after medication were lower in the VR group than in those without VR (VR: median 2; IQR 0-2; no-VR: median 4; IQR: 3-5). No variation in anxiety levels was detected by VR intervention. Satisfaction for using VR was very high in children and their families although a total of 12% of children were disappointed by the effect of VR. Most healthcare workers felt that VR would be useful in routine clinical practice. A VR intervention is highly acceptable, may be efficacious in decreasing distress in children with cancer undergoing painful procedures, but it is less likely that it has a measurable impact on anxiety. Evidence from larger studies is needed to assess VR translation into the clinical workflow.

Objectives: The aim of this study was to elucidate predictors of death and reintervention after mitral valve (MV) surgery in children., Methods: A single-centre retrospective study was performed enrolling 142 patients younger than 18 years who underwent primary index surgical mitral repair or replacement at Bambino Gesù Children's Hospital in Rome from July 1982 to April 2020. Patients with complete, transitional or partial atrioventricular septal defect and patients with single ventricle physiology were excluded. Patients were stratified according to the age group: group 1 (<1 year old), group 2 (1-5 years old) and group 3 (>5 years old). The composite primary outcome was freedom from death or transplant. The secondary outcome was freedom from redo MV surgery., Results: Transplant-free survival was 89% at 5 years and 88% at 10 years. Stratified by age, group 1 had poorer outcome in comparison with other groups (log-rank test P = 0.105). Both univariate and multivariate analyses showed that age <1 year was a significant risk factor for death or transplant (P = 0.044). Age <1 year was associated with increased risk of reoperation (aHR = 3.38, P = 0.009), while the presence of genetic syndrome (aHR = 0.22) and preoperative EF% (aHR = 0.97) were protective factors for reoperation., Conclusions: The overall survival and freedom from reoperation in children undergoing MV surgery still need improvements. Younger age was a significant risk factor for death and reintervention both after repair and replacement of the MV. In particular, infants and neonates have a three-fold risk for death compared to children., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Developmental coordination disorder (DCD) is a motor disorder of unknown aetiology that may have long-term consequences on daily activities, and psychological and physical health. Studies investigating risk factors for DCD have so far provided inconsistent results., Objectives: To assess, using a parent-report screening tool, risk of DCD in school-age very preterm children born in Italy, and investigate the associated early biomedical and sociodemographic factors., Methods: A prospective area-based cohort (804 children, response rate 73.4%) was assessed at 8-11 years of age in three Italian regions. Perinatal data were abstracted from medical records. DCD risk was measured using the Italian-validated version of the Developmental Coordination Disorder Questionnaire (DCDQ-IT). For this study, children with cognitive deficit (i.e. intelligence quotient <70), cerebral palsy, severe vision and hearing disabilities, and other impairments affecting movement were excluded. A total of 629 children were analysed. We used inverse probability weighting to account for loss to follow-up, and multilevel, multivariable modified Poisson models to obtain adjusted risk ratio (aRR) and 95% confidence interval (CI). Missing values in the covariates were imputed., Results: 195 children (weighted proportion 31.8%, 95% CI 28.2, 35.6) scored positive on the DCDQ-IT, corresponding to the 15th centile of the reference Movement-ABC test. Factors associated with overall DCD risk were male sex (aRR 1.35, 95% CI 1.05, 1.73), intrauterine growth restriction (aRR 1.45, 95% CI 1.14, 1.85), retinopathy of prematurity (aRR 1.62, 95% CI 1.07, 2.45), and older maternal age at delivery (aRR 1.39, 95% CI 1.09, 1.77). Complete maternal milk feeding at discharge from the neonatal unit and higher parental socio-economic status were associated with decreased risk., Conclusions: Both biomedical and sociodemographic factors increase DCD risk. These findings can contribute to elucidating the origins of this disorder, and assist in the identification of children at risk for early referral and intervention., (© 2022 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

The application of artificial intelligence (AI) systems is emerging in many fields in recent years, due to the increased computing power available at lower cost. Although its applications in various branches of medicine, such as pediatric oncology, are many and promising, its use is still in an embryonic stage. The aim of this paper is to provide an overview of the state of the art regarding the AI application in pediatric oncology, through a systematic review of systematic reviews, and to analyze current trends in Europe, through a bibliometric analysis of publications written by European authors. Among 330 records found, 25 were included in the systematic review. All papers have been published since 2017, demonstrating only recent attention to this field. The total number of studies included in the selected reviews was 674, with a third including an author with a European affiliation. In bibliometric analysis, 304 out of the 978 records found were included. Similarly, the number of publications began to dramatically increase from 2017. Most explored AI applications regard the use of diagnostic images, particularly radiomics, as well as the group of neoplasms most involved are the central nervous system tumors. No evidence was found regarding the use of AI for process mining, clinical pathway modeling, or computer interpreted guidelines to improve the healthcare process. No robust evidence is yet available in any of the domains investigated by systematic reviews. However, the scientific production in Europe is significant and consistent with the topics covered in systematic reviews at the global level. The use of AI in pediatric oncology is developing rapidly with promising results, but numerous gaps and challenges persist to validate its utilization in clinical practice. An important limitation is the need for large datasets for training algorithms, calling for international collaborative studies., 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 Tozzi, Fabozzi, Eckley, Croci, Dell’Anna, Colantonio and Mastronuzzi.)

In the context of the European Joint Action on Vaccination, we analyzed, through quantitative and qualitative methods, a random sample of vaccine-related tweets published in Italy between November 2019 and June 2020, with the aim of understanding how the Twitter conversation on vaccines changed during the first phase of the pandemic, compared to the pre-pandemic months. Tweets were analyzed by a multidisciplinary team in terms of kind of vaccine, vaccine stance, tone of voice, population target, mentioned source of information. Multiple correspondence analysis was used to identify variables associated with vaccine stance. We analyzed 2,473 tweets. 58.2% mentioned the COVID-19 vaccine. Most had a discouraging stance (38.1%), followed by promotional (32.5%), neutral (22%) and ambiguous (2.5%). The discouraging stance was the most represented before the pandemic (69.6%). In February and March 2020, discouraging tweets decreased intensely and promotional and neutral tweets dominated the conversation. Between April and June 2020, promotional tweets remained more represented (36.5%), followed by discouraging (30%) and neutral (24.3%). The tweets' tone of voice was mainly polemical/complaining, both for promotional and for discouraging tweets. The multiple correspondence analysis identified a definite profile for discouraging and neutral tweets, compared to promotional and ambiguous tweets. In conclusion, the emergence of SARS-CoV-2 caused a deep change in the vaccination discourse on Twitter in Italy, with an increase of promotional and ambiguous tweets. Systematic monitoring of Twitter and other social media, ideally combined with traditional surveys, would enable us to better understand Italian vaccine hesitancy and plan tailored, data-based communication strategies., Competing Interests: AT received grants from MSD for invited lectures. 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. The reviewer CN declared a past collaboration with the authors FG, MR, AT, and CR to the handling editor., (Copyright © 2022 Gesualdo, Parisi, Croci, Comunello, Parente, Russo, Campagna, Lanfranchi, Rota, Filia, Tozzi and Rizzo.)

Physical inactivity (PI) is a leading risk factor for global mortality worldwide, a major preventable cause of non-communicable diseases (NCDs) and a socioeconomic burden for healthcare systems. Fortunately, evidence shows that exercise interventions delivered by qualified exercise science graduates is an effective way to reduce PI, prevent and treat NCDs. This study compares the integration of exercise science graduates, defined as university graduates with degrees in sport and exercise science, in the healthcare systems of Australia, a commonly cited model in this regard, and Switzerland, a country considered to have an effective but costly healthcare system. For both countries, three domains were reviewed: healthcare system, exercise science graduates' education, and roles played by exercise science graduates in healthcare system. Australia formally recognizes specifically trained exercise science graduates (referred to as Accredited Exercise Physiologists) as healthcare professionals. The exercise interventions they deliver, which were shown to be cost-effective and lead to positive health outcomes, are covered by Medicare, the Australian universal health insurance. However, Medicare covers only a maximum of 5 yearly sessions of all allied-health services taken together. Conversely, Switzerland, despite offering university master's degrees that focus on physical activity delivery to clinical populations, does not recognize the respective graduates as healthcare providers. As a result, their services are not covered by the Swiss health insurances. The latter do, however, cover a generous number of services (not formally limited) delivered by other allied-health professionals. In conclusion, Australia makes a better use of exercise science graduates than Switzerland does. Switzerland would benefit from establishing a clinical profession for exercise science graduates, defining competencies that they should acquire and setting their scope of practice. The very restricted number of therapy sessions covered by Medicare might limit the positive impact exercise science graduates have on the Australian healthcare system. Overall, mutual learning between countries can promote development and global recognition of clinical positions for exercise science graduates., 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 Carrard, Gut, Croci, McMahon, Gojanovic, Hinrichs and Schmidt-Trucksäss.)

Background: The gut microbiome has been associated with cardiorespiratory fitness., Objectives: To assess the effects of oligofructose (FOS)-enriched inulin supplementation on the gut microbiome and the peak oxygen uptake (V̇O2peak) response to high-intensity interval training (HIIT)., Methods: The study was a randomized controlled trial. Forty sedentary and apparently healthy adults [n = 31 women; aged 31.8 ± 9.8 y, BMI (in kg⋅m-2) 25.9 ± 4.3] were randomly allocated to 1) 6 wk of supervised HIIT (4 × 4-min bouts at 85-95% peak heart rate, interspersed with 3 min of active recovery, 3·wk-1) + 12 g·d-1 of FOS-enriched inulin (HIIT-I) or 2) 6 wk of supervised HIIT (3·wk-1, 4 × 4-min bouts) + 12 g·d-1 of maltodextrin/placebo (HIIT-P). Each participant completed an incremental treadmill test to assess V̇O2peak and ventilatory thresholds (VTs), provided a stool and blood sample, and completed a 24-h diet recall questionnaire and FFQ before and after the intervention. Gut microbiome analyses were performed using metagenomic sequencing. Fecal short-chain fatty acids were measured by mass spectrometry., Results: There were no differences in the mean change in V̇O2peak response between groups (P = 0.58). HIIT-I had a greater improvement in VTs than HIIT-P [VT1 (lactate accumulation): mean difference + 4.3% and VT2 (lactate threshold): +4.2%, P < 0.05]. HIIT-I had a greater increase in the abundance of Bifidobacterium taxa [false discovery rate (FDR) < 0.05] and several metabolic processes related to exercise capacity (FDR < 0.05). Exploratory analysis of merged data found participants with a greater response to HIIT (V̇O2peak ≥3.5 mL⋅kg-1⋅min-1) had a 2.2-fold greater mean abundance of gellan degradation pathways (FDR < 0.05) and a greater, but not significant, abundance of Bifidobacterium uniformis species (P < 0.00023, FDR = 0.08)., Conclusions: FOS-enriched inulin supplementation did not potentiate HIIT-induced improvements in V̇O2peak but led to gut microbiome changes possibly associated with greater ventilatory threshold improvements in healthy inactive adults. Gellan degradation pathways and B. uniformis spp. were associated with greater V̇O2peak responses to HIIT., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts., Methods: We used harmonized aggregated data from 15 population-based cohorts of children born at <32 weeks of gestational age (GA) or <1500 g from 1985 to 2013 in 13 countries with information on maternal education and assessments of general development at 2-3 years and/or intelligence quotients between 4 and 15 years. Term-born controls (≥37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor's/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years., Results: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (<27 vs ≥27 weeks) in children without severe neonatal morbidity and term controls yielded similar results., Conclusions: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Several countries have targeted adolescents for immunization against SARS-CoV-2 to mitigate COVID-19 spread. In Italy, immunization for children ≥ 12 years has been available starting from June 2021. We conducted a cross-sectional study to investigate the knowledge, attitude and intention to vaccinate children < 18 years in Italian families. We used a multinomial logistic regression model to investigate factors associated with intention to vaccinate. We collected a total of 1696 responses. Among the 491 families of children ≥ 12 years, 41.2% would not vaccinate their children and 21.2% were uncertain, while among the 1205 families of children < 12 years, 36.1% would not vaccinate and 33.8% were uncertain. Determinants of intention to vaccinate both age groups were perceived safety and efficacy of vaccines and perceived risk of transmitting infection to adults. For children < 12 years, additional determinants were perceived risk of being infected and being hospitalized because of COVID-19. In view of the expanding strategy to vaccinate adolescents and the availability of immunization for children < 12 years, our results call for a communication strategy targeted at families of children focused on the safety and efficacy of COVID-19 vaccine in children and on the dynamics of infection spread across different age groups. As perceptions in families are volatile and may change rapidly over time, repeated surveys for measuring attitudes to vaccinate would be advisable.

Background: Italy has experienced severe consequences (ie, hospitalizations and deaths) during the COVID-19 pandemic. Online decision support systems (DSS) and self-triage applications have been used in several settings to supplement health authority recommendations to prevent and manage COVID-19. A digital Italian health tech startup, Paginemediche, developed a noncommercial, online DSS with a chat user interface to assist individuals in Italy manage their potential exposure to COVID-19 and interpret their symptoms since early in the pandemic., Objective: This study aimed to compare the trend in online DSS sessions with that of COVID-19 cases reported by the national health surveillance system in Italy, from February 2020 to March 2021., Methods: We compared the number of sessions by users with a COVID-19-positive contact and users with COVID-19-compatible symptoms with the number of cases reported by the national surveillance system. To calculate the distance between the time series, we used the dynamic time warping algorithm. We applied Symbolic Aggregate approXimation (SAX) encoding to the time series in 1-week periods. We calculated the Hamming distance between the SAX strings. We shifted time series of online DSS sessions 1 week ahead. We measured the improvement in Hamming distance to verify the hypothesis that online DSS sessions anticipate the trends in cases reported to the official surveillance system., Results: We analyzed 75,557 sessions in the online DSS; 65,207 were sessions by symptomatic users, while 19,062 were by contacts of individuals with COVID-19. The highest number of online DSS sessions was recorded early in the pandemic. Second and third peaks were observed in October 2020 and March 2021, respectively, preceding the surge in notified COVID-19 cases by approximately 1 week. The distance between sessions by users with COVID-19 contacts and reported cases calculated by dynamic time warping was 61.23; the distance between sessions by symptomatic users was 93.72. The time series of users with a COVID-19 contact was more consistent with the trend in confirmed cases. With the 1-week shift, the Hamming distance between the time series of sessions by users with a COVID-19 contact and reported cases improved from 0.49 to 0.46. We repeated the analysis, restricting the time window to between July 2020 and December 2020. The corresponding Hamming distance was 0.16 before and improved to 0.08 after the time shift., Conclusions: Temporal trends in the number of online COVID-19 DSS sessions may precede the trend in reported COVID-19 cases through traditional surveillance. The trends in sessions by users with a contact with COVID-19 may better predict reported cases of COVID-19 than sessions by symptomatic users. Data from online DSS may represent a useful supplement to traditional surveillance and support the identification of early warning signals in the COVID-19 pandemic., (©Alberto Eugenio Tozzi, Francesco Gesualdo, Emanuele Urbani, Alessandro Sbenaglia, Roberto Ascione, Nicola Procopio, Ileana Croci, Caterina Rizzo. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 13.08.2021.)

Objectives: The aim of this study was to identify the predictors of death and of reintervention after mitral valve replacement (MVR) in children., Methods: A single-centre retrospective study was performed including 115 patients under the age of 18 undergoing MVR between 1982 and 2019. For all patients, the ratio of prosthetic valve size (diameter in mm) to weight (kg) at surgery was calculated and long-term result was assessed. The primary outcome was freedom from mitral valve (MV) re-replacement. The composite secondary outcome was freedom from death or transplant., Results: Fifty-four patients had a previous surgical attempt to MV repair. The median age at surgery was 5.5 years (interquartile range 1.21-9.87). Death/transplant-free survival was 77 ± 4% at 5 years and 72 ± 5% at 10 years. Univariate analysis showed a size/weight ratio higher than 2 and age <2 years as significant risk factors for death or transplant. Freedom from MV re-replacement at 5 and 10 years was 90 ± 3% and 72 ± 6%, respectively. Biological prosthesis implanted at first replacement (P = 0.007) and size/weight ratio higher than 2 (P = 0.048) were predictors of reoperation. Significant upsizing (P < 0.0001) of mitral prosthesis was observed at re-replacement., Conclusions: MVR is a viable strategy in children with unrepairable MV disease. Mortality can be predicted based on size/weight ratio and age <2 years. MV re-replacement can be performed with low morbidity and mortality and a larger-size prosthesis can often be placed at the time of redo., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Low cardiorespiratory fitness (V̇O 2peak ) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O 2peak , there is considerable inter-individual variability in the V̇O 2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O 2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O 2 peak response following exercise training., Methods: Participant change in objectively measured V̇O 2 peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P < 1 × 10 -5 ) with the magnitude of V̇O 2 peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research., Results: No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O 2 peak , individual study, principal components which were significantly associated with the trait). A Quantile-Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O 2 peak response that reached suggestive significance (P < 1 × 10 -5 ). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10 -7 ). A PPS created from the 12 lead SNPs was unable to predict V̇O 2 peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P < 1 × 10 -4 ) and the validation study (P <  × 10 -6 ), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent., Conclusions: Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O 2 peak response variance, and whether genomic predictors for V̇O 2 peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .