An ultra-rare mixed phenotype with combined AP-4 and ERF mutations. The first report in a pediatric patient and a literature review

Abstract: The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly. Despite a history of febrile seizures, subsequent years were devoid of seizures, with normal EEG. Exome sequencing revealed pathogenic variants in both the AP4B1 and ERF genes. Significantly, the patient exhibited features associated with AP4B1 mutations, including distinctive traits such as cranial malformations. The ERF gene variant, linked to craniosynostosis, likely contributes to the observed trigonocephaly. This case represents the initial documentation of a concurrent mutation in the AP4B1 and ERF genes, underscoring the critical role of exome analysis in unraveling complex phenotypes. Understanding these complex genotypes offers valuable insights into broader syndromic conditions, facilitating comprehensive patient management

Management, treatment, and clinical approach of Sydenham's chorea in children: Italian survey on expert-based experience

: Sydenham's chorea (SC), an autoimmune disorder affecting the central nervous system, is a pivotal diagnostic criterion for acute rheumatic fever. Primarily prevalent in childhood, especially in developing countries, SC manifests with involuntary movements and neuropsychiatric symptoms. Predominantly occurring between ages 5 and 15, with a female bias, SC may recur, particularly during pregnancy or estrogen use. The autoimmune response affecting the basal ganglia, notably against dopamine, underlies the pathophysiology. Clinical management necessitates an integrated approach, potentially involving immunomodulatory therapies. To address discrepancies in SC management, a survey was conducted across Italy, targeting specialists in neurology, pediatrics, child neuropsychiatry, and rheumatology. Of the 51 responding physicians, consensus favored hospitalization for suspected SC, with broad support for laboratory tests and brain MRI. Treatment preferences showed agreement on oral prednisone and IVIG, while opinions varied on duration and plasmapheresis. Haloperidol emerged as the preferred symptomatic therapy. Post-SC penicillin prophylaxis and steroid therapy gained strong support, although opinions differed on duration. Follow-up recommendations included neuropsychological and cardiological assessments. Despite offering valuable insights, broader and more studies are needed in order to guide treatment decisions in this well-known yet challenging complication of acute rheumatic fever, which continues to warrant scientific attention and concerted clinical efforts

Antioxidant properties of resveratrol and piceid on lipid peroxidation in micelles and monolamellar liposomes.

The antioxidant activities of trans-resveratrol (trans-3,5,4′-trihydroxystilbene) and trans-piceid (trans-5,4′- dihydroxystilbene-3-O-β-D-glucopyranoside), its more widespread glycosilate derivative, have been compared measuring their inhibitory action on peroxidation of linoleic acid (LA) and the radical scavenging ability towards different free radicals (such as DPPH) and radical initiators. It has been found that the two stilbenes have similar antioxidant capacity, while the comparison with BHT (2,6-di-tert-butyl-4-methylphenol) and α-tocopherol (vitamin E, vit. E), taken as reference, points out a slower but prolonged protective action against lipid peroxidation. Furthermore, piceid appears more efficacious than resveratrol as a consequence of the reaction of the latter with its radical form. The DSC profiles of phosphatidylcholine liposomes of various chain lengths, and EPR measurements of spin labelled liposomes demonstrated that the susceptible hydroxyl group of these compounds are located in the\ud lipid region of the bilayer close to the double bonds of polyunsatured fatty acids, making these stilbenes particularly suitable for the prevention and control of the lipid peroxidation of the membranes

Identification of hemodynamically stable patients with acute pulmonary embolism at high risk for death: external validation of different models

Background: The optimal strategy for identification of hemodynamically stable patients with acute pulmonary embolism (PE) at risk for death and clinical deterioration remains undefined. Objectives: We aimed to assess the performances of currently available models/scores for identifying hemodynamically stable patients with acute, symptomatic PE at risk of death and clinical deterioration. Methods: This was a prospective multicenter cohort study including patients with acute PE (NCT03631810). Primary study outcome was in-hospital death within 30 days or clinical deterioration. Other outcomes were in-hospital death, death, and PE-related death, all at 30 days. We calculated positive and negative predictive values, c-statistics of European Society of Cardiology (ESC)-2014, ESC-2019, Pulmonary Embolism Thrombolysis (PEITHO), Bova, Thrombo-embolism lactate outcome study (TELOS), fatty acid binding protein, syncope and tachicardia (FAST), and National Early Warning Scale 2 (NEWS2) for the study outcomes. Results: In 5036 hemodynamically stable patients with acute PE, positive predictive values for the evaluated models/scores were all below 10%, except for TELOS and NEWS2; negative predictive values were above 98% for all the models/scores, except for FAST and NEWS2. ESC-2014 and TELOS had good performances for in-hospital death or clinical deterioration (c-statistic of 0.700 and 0.722, respectively), in-hospital death (c-statistic of 0.713 and 0.723, respectively), and PE-related death (c-statistic of 0.712 and 0.777, respectively); PEITHO, Bova, and NEWS2 also had good performances for PE-related death (c-statistic of 0.738, 0.741, and 0.742, respectively). Conclusion: In hemodynamically stable patients with acute PE, the accuracy for identification of hemodynamically stable patients at risk for death and clinical deterioration varies across the available models/scores; TELOS seems to have the best performance. These data can inform management studies and clinical practice

The Influence of Ketogenic Diet on Gut Microbiota: Potential Benefits, Risks and Indications

The ketogenic diet (KD) restricts carbohydrate consumption, leading to an increase in ketone bodies, such as acetoacetate, β-hydroxybutyrate, and acetone, which are utilized as energy substrates. This dietary approach impacts several biochemical processes, resulting in improved clinical management of various disorders, particularly in childhood. However, the exact mechanisms underlying the efficacy of KD remain unclear. Interestingly, KD may also impact the gut microbiota, which plays a pivotal role in metabolism, nutrition, and the development of the immune and nervous systems. KD has gained popularity for its potential benefits in weight loss, blood sugar control, and certain neurological conditions. This narrative review sums up KD-related studies published over 30 years. While short-term studies have provided valuable insights into the effects of KD on the gut microbiota, persistent uncertainties surround its long-term efficacy and potential for inducing dysbiosis. The significant influence of KD on epigenetic mechanisms, intracellular pathways, and gut microbial composition underscores its potential as a therapeutic choice. However, a judicious consideration of the potential risks associated with the strict adherence to a low-carbohydrate, high-fat, and high-protein regimen over prolonged periods is imperative. As KDs gain popularity among the adolescent and young adult demographic for weight management, it becomes imperative to undertake additional research to comprehensively assess their impact on nutritional status and gut microbiota, ensuring a holistic and sustainable approach to medical nutrition

Mothers and fathers of children with epilepsy: Gender differences in post-traumatic stress symptoms and correlations with mood spectrum symptoms

Background: Post-traumatic stress disorder (PTSD) and post-traumatic stress spectrum have been recently applied to understand the impact of life-threatening disease or injury in one’s child; nevertheless, scant data are available on a particular chronic illness such as epilepsy whose phenotypic expression is seizures, which are acute, sudden, and unpredictable manifestations. Subjects with bipolar disorders or with mood spectrum symptoms demonstrated to be more vulnerable to develop PTSD in the aftermath of a trauma. Objectives: The main aim of this study was to evaluate post-traumatic symptoms among 134 parents of children with a diagnosis of epilepsy, followed at the outpatient neurologic unit of Department of Pediatrics in Santa Chiara Hospital in Pisa, as well as gender differences. The second aim of this study was to estimate the impact of lifetime mood spectrum on post-traumatic stress symptoms in the same study sample after fulfillment of the Trauma and Loss Spectrum-Self Report (TALS-SR) and the Mood Spectrum-Self Report (MOODS-SR) lifetime version. Results: Results showed 10.4% and 37.3% of PTSD full and partial, respectively. Demographic characteristics and clinical features of the study sample did not show any impact on stress symptomatology. Mothers presented higher rates at all Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 PTSD symptoms’ clusters except avoidance. Nevertheless, noteworthy correlations between post-traumatic symptomatology and mood spectrum symptoms detected with the self-report tools, emerged only in the subgroup of the fathers. Conclusion: These findings corroborate the need to provide assistance to caregivers of pediatric patients and confirm the hypothesis that lifetime mood spectrum may have an impact on reaction to traumas

Exploring Headaches in Pediatric Behçet Disease: Prevalence, Clinical Impact, and Management

Beh & ccedil;et's Disease (BD), also recognized as Beh & ccedil;et Syndrome, manifests uniquely in pediatric populations as Pediatric Beh & ccedil;et's Disease (PBD), characterized by multisystemic inflammatory symptoms including recurrent oral and genital aphthae, and diverse ocular, vascular, and neurological involvements. This review elucidates the prevalence, burden, and management strategies of headaches in children with PBD, focusing on both primary headaches, such as migraine and tension-type headaches, and secondary headaches linked to systemic disease manifestations. It explores the pathophysiological underpinnings specific to PBD-related headaches and discusses the intricate relationship between systemic inflammatory processes and neurological symptoms. By examining the literature from 2004 to 2024, this study highlights the high frequency of headache in PBD patients, underscoring its diagnostic and clinical significance. We aim to provide a detailed understanding of headache management in PBD, emphasizing tailored therapeutic strategies that address the unique challenges faced by this patient population. This review also underscores the importance of comprehensive clinical evaluations to optimize outcomes and mitigate long-term sequelae, proposing that awareness and understanding of headache in PBD can significantly enhance both diagnosis and management

Antithrombotic strategies in the catheterization laboratory for patients with acute coronary syndromes undergoing percutaneous coronary interventions: insights from the EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units Registry

AimsIn the last decades, several new therapies have emerged for the treatment of acute coronary syndromes (ACS). We sought to describe real-world patterns of use of antithrombotic treatments in the catheterization laboratory for ACS patients undergoing percutaneous coronary interventions (PCI).MethodsEmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in ACS patients in Italy.ResultsOver a 3-week period, a total of 2585 consecutive ACS patients have been enrolled in 203 cardiac care units across Italy. Among these patients, 1755 underwent PCI (923 with ST-elevation myocardial infarction and 832 with non-ST-elevation ACS). In the catheterization laboratory, unfractioned heparin was the most used antithrombotic drug in both ST-elevation myocardial infarction (64.7%) and non-ST-elevation ACS (77.5%) undergoing PCI and, as aspirin, bivalirudin and glycoprotein IIb/IIIa inhibitors (GPIs) more frequently employed before or during PCI compared with the postprocedural period. Any crossover of heparin therapy occurred in 36.0% of cases, whereas switching from one P2Y12 inhibitor to another occurred in 3.7% of patients. Multivariable analysis yielded several independent predictors of GPIs and of bivalirudin use in the catheterization laboratory, mainly related to clinical presentation, PCI complexity and presence of complications during the procedure.ConclusionIn our contemporary, nationwide, all-comers cohort of ACS patients undergoing PCI, antithrombotic therapies were commonly initiated before the catheterization laboratory. In the periprocedural period, the most frequently employed drugs were unfractioned heparin, leading to a high rate of crossover, followed by GPIs and bivalirudin, mainly used during complex PCI.Clinical Trial Registration. URLhttp://www.clinicaltrials.gov. Unique identifier: NCT02015624

Erice 2018 Charter on the role of the National Health Service in the prevention of doping

The Erice 2018 Charter was unanimously approved at the conclusion of the 53rd Residential Course of the International School of Epidemiology and Preventive Medicine "Adapted Physical Activity in Sport, Wellness and Fitness; the role of the Departments of Prevention and of the National Health Service in doping prevention and health promotion", held on 15-19 May 2018 in Erice, Italy, at the "Ettore Majorana" Foundation and Centre for Scientific Culture, and promoted by the Study Group on "Movement Sciences for Health" of the Italian Society of Hygiene, Preventive Medicine and Public Health. The event was part of a larger project supported by the Ministry of Health aimed at preventing doping in the general population involved in sport and physical activities. After an intense discussion the participants focused on ten statements involving the following critical issues: responsibility, priority, message, alphabetization, networks and alliances, school promoting health, player and opportunities, competences, know-how, programming and acting. These statements provide hints to approach doping within a public health frame and summarize the role of the Departments of Prevention and NHS in promoting and coordinating preventive actions with other institutions and stakeholders. Doping represents a complex phenomenon related to cultural, social, economic and legal issues. In addition to regulatory or repressive actions, education to health and legality is proposed as the fundamental strategy to contrast doping by promoting healthy lifestyles, based on scientific knowledge and respect for legality

Erice 2018 Charter on the role of the National Health Service in the prevention of doping

The Erice 2018 Charter was unanimously approved at the conclusion of the 53rd Residential Course of the International School of Epidemiology and Preventive Medicine “Adapted Physical Activity in Sport, Wellness and Fitness; the role of the Departments of Prevention and of the National Health Service in doping prevention and health promotion”, held on 15-19 May 2018 in Erice, Italy, at the “Ettore Majorana” Foundation and Centre for Scientific Culture, and promoted by the Study Group on “Movement Sciences for Health” of the Italian Society of Hygiene, Preventive Medicine and Public Health. The event was part of a larger project supported by the Ministry of Health aimed at preventing doping in the general population involved in sport and physical activities. After an intense discussion the participants focused on ten statements involving the following critical issues: responsibility, priority, message, alphabetization, networks and alliances, school promoting health, player and opportunities, competences, know-how, programming and acting. These statements provide hints to approach doping within a public health frame and summarize the role of the Departments of Prevention and NHS in promoting and coordinating preventive actions with other institutions and stakeholders. Doping represents a complex phenomenon related to cultural, social, economic and legal issues. In addition to regulatory or repressive actions, education to health and legality is proposed as the fundamental strategy to contrast doping by promoting healthy lifestyles, based on scientific knowledge and respect for legality