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Background: Transitioning into adulthood can be challenging for individuals with Autism Spectrum Disorder (ASD). Work is one of the most enduring and impactful aspects of adult life, as it plays a key role in helping people find meaning. However, research on the effectiveness of pre-employment programs in improving the health and well-being of autistic adolescents and young adults remains limited. This exploratory study aims to assess the impact of a nationwide internship program, "BottegaMente", on the adaptive functioning, emotion regulation, and quality of life of autistic teens, adults, and their families., Method: The program involved 82 participants, aged 13-36, and required active family involvement to ensure it addressed the needs of autistic individuals from the planning stages through implementation. Quantitative data were collected before (T0) and after the internship (T1)., Results: Our study demonstrated that the internship effectively enhanced adaptive skills, particularly in areas like home life and work skills for autistic adolescents and adults, as reflected by standardized outcomes at T1 compared to T0., Conclusion: This research is one of the pioneering efforts to evaluate the effectiveness of pre-employment internship programs for autistic adolescents and adults. Although preliminary, these findings could help to shape future studies on employment, an essential factor for overall quality of life and well-being., Competing Interests: Declaration of Competing Interest The authors declare that no competing financial interests and no conflicts of interest exist. The project was designed by ACSI and funded by the MINISTRY OF LABOUR AND SOCIAL POLICIES. Notice no. 1/2017 for the financing of initiatives and projects of significant national interest pursuant to art. 72 of Decreto Legislativo 3 July 2017, n. 117., (Copyright © 2024. Published by Elsevier Ltd.)

Prospective memory (PM) is the ability to remember and realize one's intentions in the future; therefore, it is crucial for the daily functioning of children and adolescents and their ability to become independent from caregivers. PM errors can have repercussions during childhood, such as influencing school performance and social relationships. The aim of this systematic review was to synthesize studies analysing PM in children and adolescents (age range: 0-16 years) following PRISMA guidelines. The goal was to outline the most commonly used tasks, offering information on the development of PM, and-through a detailed analysis of the assessment of specific cognitive processes carried out in the primary studies included-providing information on the main cognitive processes involved in PM within this age group. Forty-nine studies were selected that examined PM in children and adolescents with typical development. The studies used many different tasks that can be traced back to eleven different main paradigms to evaluate PM, each structured into a PM and an ongoing task. Older children performed better on PM targets than younger children, suggesting a developmental trajectory of PM that follows a J-shaped function. Children as young as 2 years old exhibited the first signs of PM, while adolescents performed similarly to adults on PM tasks. Several factors are involved in PM development: retrospective memory, executive functions (planning, working memory, inhibitory control, monitoring), attention, metamemory, and motivation. This review May be considered a starting point to summarize the most used tools to evaluate PM in children and adolescents, and to shed light on the primary cognitive functions involved in PM, potentially offering indications to researchers in selecting optimal tasks for measuring PM across different age groups. Additionally, it underscores the importance of developing standardized measures for potential clinical applications., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Guzzardi, Menghini, Costanzo, Vicari and Foti.)

Sleep disturbances (SD) are commonly reported concerns among parents and caregivers of children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). While it is widely acknowledged that SD can worsen various aspects of children and adolescents' well-being (e.g., academic performance and emotional/behavioral state), a comprehensive clinical characterization of ADHD and SD is currently lacking. To address this gap, 136 children and adolescents diagnosed with ADHD (aged 6 to 14 years) were retrospectively selected by reviewing electronic health records of hundreds of patients with neuropsychiatric disorders referred to the children's hospital. Participants were divided into two groups based on the presence of SD, assessed via a parent-report questionnaire (94 ADHD without SD and 42 ADHD with SD). Standardized measures of adaptive behavior, academic performance, ADHD-related and emotional/behavioral symptoms were collected. Results documented that the group of ADHD with SD obtained worse scores in specific aspects of adaptive behavior (conceptual and practical domains), academic performance (text comprehension, writing), ADHD symptoms (inattention) and emotional/behavioral difficulties (especially, mood/emotional regulation and stress) compared to those with ADHD without SD. In addition, our results established a relationship between sleep problems and diverse clinical aspects of children and adolescents with ADHD, while controlling for age, cognitive level, gender, ADHD symptoms severity, and Body Mass Index. From a clinical perspective, our study suggests that the presence of SD in patients with ADHD may serve as an indicator for strengths and weaknesses in this population, even demonstrating an independent relationship with specific clinical dimensions. Implications to improve clinical diagnostic and therapeutic interventions are discussed., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Severe depression is a prevalent psychiatric illness in children and adolescents associated with high levels of morbidity, disability, and a high risk of suicidal behavior. Cognitive factors associated with depression severity in juveniles have been poorly reported., Methods: We investigated the relationship between depression severity and intelligence quotient (IQ)with its subscales in 65 juveniles (aged 10-17 years) with a current major depressive episode evaluated at the Mood Disorder Program of Bambino Gesù Children's Hospital in Rome. Pearson's correlation analyses were followed by a Benjamini-Hochberg correction and linear multivariable regression model., Results: Depression severity measured with the total score of the Children's Depression Rating Scale-Revised (CDRS-R) was positively associated with the Verbal Comprehension Index (VCI; Pearson's r = 0.309 [0.042-0.534]; p = 0.024). The CDRS-R subscales positively associated with VCI by Pearson's correlation were depressed feelings, suicidal ideation, excessive weeping, and reduced facial expressions. Suicidal ideation was the only factor independently and significantly associated with higher VCI in the multivariable linear regression model., Discussion: Suicidal ideation was significantly and independently associated with higher verbal comprehension, indicating that depressed juveniles with better verbal ability may be at a greater risk of showing suicidal ideation., 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 © 2024 Trasolini, Serra, Iannoni, Andracchio, Apicella, Maglio, Menghini and Vicari.)

Advancements in early diagnosis and paediatric cardiac surgery have improved the long-term survival of patients with congenital heart disease, necessitating a thorough assessment of their health-related quality of life (HRQoL). This study aimed to assess HRQoL in paediatric patients with coarctation of the aorta (CoA) (both as reported by patients and caregivers), and to evaluate associated factors. Patients aged 5-18 years diagnosed with CoA and their parents were enrolled at Bambino Gesù Children's Hospital between September 2016 and December 2017. Socio-demographic characteristics were recorded using a family form, and the Pediatric Quality of Life Inventory (PedsQL) 3.0 cardiac module was used to evaluate HRQoL. Clinical data were retrieved from medical chart reviews. In this observational study, sixty-five pediatric patients (39 males, median [IQR] age 12 [9-14]) with CoA and their parents (65 mothers and 65 fathers) were enrolled. These patients exhibited overall good HRQoL. Mothers reported significantly lower total HRQoL scores compared to patient self-reports ( p  = .037), as well as treatment anxiety ( p  = .033), and cognitive problems ( p  = .021). Pediatric patients with CoA perceived their HRQoL better than their mothers did. Female sex and older age were associated with lower HRQoL scores.

Background: Sharing and fairness are important prosocial behaviors that help us navigate the social world. However, little is known about how and whether individuals with Williams Syndrome (WS) engage in these behaviors. The unique phenotype of individuals with WS, consisting of high social motivation and limited social cognition, can also offer insight into the role of social motivation in sharing and fairness when compared to typically developing (TD) individuals. The current study used established experimental paradigms to examine sharing and fairness in individuals with WS and TD individuals., Methods: We compared a sample of patients with WS to TD children (6-year-olds) matched by mental age (MA) on two experimental tasks: the Dictator Game (DG, Experiment 1, N = 17 WS, 20 TD) with adults modeling giving behaviors used to test sharing and the Inequity Game (IG, Experiment 2, N = 14 WS, 17 TD) used to test fairness., Results: Results showed that the WS group behaved similarly to the TD group for baseline giving in the DG and in the IG, rejecting disadvantageous offers but accepting advantageous ones. However, after viewing an adult model giving behavior, the WS group gave more than their baseline, with many individuals giving more than half, while the TD group gave less. Combined these results suggest that social motivation is sufficient for sharing and, in particular, generous sharing, as well as the self-focused form of fairness. Further, individuals with WS appear capable of both learning to be more generous and preventing disadvantageous outcomes, a more complex profile than previously known., Conclusions: In conclusion, the present study provides a snapshot into sharing and fairness-related behaviors in WS, contributing to our understanding of the intriguing social-behavioral phenotype associated with this developmental disorder., (© 2024. The Author(s).)

The co-occurrence Oppositional Defiant Disorder (ODD) in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) has been associated to difficulties in regulating adverse states, elevated functional impairment, deficits in Executive Functions and high risk for psychopathology. Recent studies have shown that ODD is a negative predictor of a positive response to methylphenidate (MPH) treatment for ADHD symptoms in children and adolescents and that patients with a diagnosis of comorbid ADHD and ODD are less likely to respond favorably to pharmacological treatment with MPH. We conducted a naturalistic study to understand the clinical characteristics of drug-naïve children and adolescents with ADHD that influence the response to MPH by measuring the effect on attention. Specifically, we investigated whether a single dose of MPH differently affects the performance of 53 children and adolescents with ADHD with or without ODD comorbidity. In addition, participant characteristics such as symptom severity, functional impairment, and associated behavioral and emotional symptoms at baseline were examined to better understand what aspects affect the response to MPH. We found that a single dose of MPH improved the attention of children and adolescents with ADHD without ODD more than those with comorbid ADHD and ODD, resulting in reduced reaction times. Our findings indicated that children and adolescents with comorbid ADHD and ODD and those with ADHD alone did not exhibit differences in measures of attention prior to taking MPH, nor in demographic variables (age, intelligence quotient, gender), clinical characteristics related to symptom severity, and adaptive behaviors. However, we observed differences between the two groups in certain behavioral aspects, including the Dysregulation Profile and disruptive behaviors. Assessing symptoms in combination with the presence of ADHD can be beneficial in determining which individuals would derive the greatest benefits from treatment., Competing Interests: The authors have no financial or proprietary interests in any material discussed in this article., (Copyright: © 2024 D’Aiello et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The current study aimed (1) to provide an analysis of the frequency and prevalence of sleep disturbances in a large Italian sample of children and adolescents with ASD, detecting specific predictors of the presence/absence of sleep disorders, (2) to examine the phenomenon of co-sleeping within a subgroup of participants with ASD. A total of 242 children and adolescents with ASD (194 males, mean age 5.03 ± 3.15 years) were included. After the diagnostic procedure, caregivers were requested to complete the Sleep Disturbance Scale for Children (SDSC) to assess sleep disorders among participants. The presence of co-sleeping was investigated in a subgroup of 146 children and adolescents with ASD. An elevated or clinically relevant global score for sleep disorders (≥ 60) was found in 33% of participants. The most prevalent sleep disorder in our group was related to difficulties with sleep onset and sleep maintenance (~ 41% of cases). Sleep disturbances were predicted by higher intelligence quotient (IQ)/developmental quotient (DQ), increased internalizing problems, and elevated parental stress. The subgroup of participants engaged in co-sleeping (N = 87) were younger and had lower IQ/DQ scores, reduced adaptive functioning, and diminished psychological wellbeing than the non-co-sleeping group. Our findings are consistent with the current literature highlighting that insomnia is the most widespread sleep problem associated with ASD. The relationship between IQ/DQ and sleep alterations is a crucial topic that deserves additional research. Future studies should assess sleep by objective measures such as EEG topography to better understand the mechanisms underlying sleep alterations in this neurodevelopmental disorder., (© 2024. The Author(s).)

Background: The SMARCB1 gene encodes a subunit of the BRG1-Associated Factor (BAF) complex, and mutations in this gene have been linked to Coffin-Siris Syndrome (CSS) type 3. CSS is characterized by a range of developmental disabilities, facial dysmorphic features, and feeding difficulties. There's been noted genotype-phenotype correlation in CSS, with cases involving SMARCB1 mutations often exhibiting more severe language impairment and intellectual disability. Method: We conducted a review of reported CSS type 3 cases and presented the first instance of CSS associated with a SMARCB1 variant wherein the patient exhibited normal intelligence and only mild selective neuropsychological deficits. The patient underwent evaluation for feeding challenges, growth delay, and dysmorphic features during their second year of life. Subsequently, CSS diagnosis was confirmed due to a de novo heterozygous c.568C > T (p.Arg190Trp) variant in the SMARCB1 gene. Due to learning difficulties, the patient underwent a comprehensive neuropsychological assessment, which was related to the retrospective reconstruction of her medical and developmental history. Results: The patient demonstrated normal intelligence and adaptive functioning, with specific deficits in arithmetic and selective difficulties in verbal learning and long-term memory. Feeding difficulties and language delay observed in early childhood showed significant improvement over time. Discussion: We discuss this case in relation to previously reported CSS type 3 cases, emphasizing neuropsychological aspects. It's evident that neuropsychological features of CSS can vary among affected individuals, highlighting the importance of personalized support and interventions tailored to specific cognitive and emotional needs by healthcare professionals. Our case suggests avenues for future research to identify specific modifiers of phenotypic expression to explain variability in intellect among patients and pinpoint potential targets for gene therapy.

Williams syndrome (WS) and Down syndrome (DS) are two neurodevelopmental disorders with distinct genetic origins characterized by mild to moderate intellectual disability. Individuals with WS or DS exhibit impaired hippocampus-dependent place learning and enhanced striatum-dependent spatial response learning. Here, we used the Weather Prediction Task (WPT), which can be solved using hippocampus- or striatum-dependent learning strategies, to determine whether individuals with WS or DS exhibit similar profiles outside the spatial domain. Only 10% of individuals with WS or DS solved the WPT. We further assessed whether a concurrent memory task could promote reliance on procedural learning to solve the WPT in individuals with WS but found that the concurrent task did not improve performance. To understand how the probabilistic cue-outcome associations influences WPT performance, and whether individuals with WS or DS can ignore distractors, we assessed performance using a visual learning task with differing reward contingencies, and a modified WPT with unpredictive cues. Both probabilistic feedback and distractors negatively impacted the performance of individuals with WS or DS. These findings are consistent with deficits in hippocampus-dependent learning and executive functions, and reveal the importance of congruent feedback and the minimization of distractors to optimize learning in these two populations., (© 2024 The Authors. Developmental Psychobiology published by Wiley Periodicals LLC.)

Purpose: The aim of the present review is to analyze dynamic interactions between nutrigenomics, environmental cues, and parental influence, which can all lead to children's neophobic reactions and its persistence in time., Methods: We reviewed studies available on electronic databases, conducted on children aged from birth to 18 years. We also considered official websites of Italian Institutions, providing advice on healthy eating during infancy., Results: Modern day societies are faced with an eating paradox, which has severe and ever-growing implications for health. In face of a wider availability of healthy foods, individuals instead often choose processed foods high in fat, salt and sugar content. Economic reasons surely influence consumers' access to foods. However, there is mounting evidence that food choices depend on the interplay between social learning and genetic predispositions (e.g., individual eating traits and food schemata). Neophobia, the behavioral avoidance of new foods, represents an interesting trait, which can significantly influence children's food refusal. Early sensory experiences and negative cognitive schemata, in the context of primary caregiver-child interactions, importantly contribute to the priming of children's food rejection., Conclusions: As neophobia strongly affects consumption of healthy foods, it will be relevant to rule definitively out its role in the genesis of maladaptive food choices and weight status in longitudinal studies tracking to adulthood and, in meanwhile, implement early in life effective social learning strategies, to reduce long-term effects of neophobia on dietary patterns and weight status., Level of Evidence: Level II, controlled trials without randomization., (© 2024. The Author(s).)

Background: Developmental Dyslexia (DD) is a brain-based developmental disorder causing severe reading difficulties. The extensive data on the neurobiology of DD have increased interest in brain-directed approaches, such as transcranial direct current stimulation (tDCS), which have been proposed for DD. While positive outcomes have been observed, results remain heterogeneous. Various methodological approaches have been employed to address this issue. However, no studies have compared the effects of different transcranial electrical stimulation techniques (e.g., tDCS and transcranial random noise stimulation, tRNS), on reading in children and adolescents with DD., Methods: The present within-subject, double-blind, and sham-controlled trial aims to investigate the effects of tDCS and hf-tRNS on reading in children and adolescents with DD. Participants will undergo three conditions with a one-week interval session: (A) single active tDCS session; (B) single active hf-tRNS session; and (C) single sham session (tDCS/hf-tRNS). Left anodal/right cathodal tDCS and bilateral tRNS will be applied over the temporo-parietal regions for 20 min each. Reading measures will be collected before and during each session. Safety and blinding parameters will be recordered., Discussion: We hypothesize that tRNS will demonstrate comparable effectiveness to tDCS in improving reading compared to sham conditions. Additionally, we anticipate that hf-tRNS will exhibit a similar safety profile to tDCS. This study will contribute novel insights into the effectiveness of hf-tRNS, expediting the validation of brain-based treatments for DD., 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. The reviewer AC declared a shared affiliation with the author SV to the handling editor at the time of review., (Copyright © 2024 Battisti, Lazzaro, Varuzza, Vicari and Menghini.)

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a higher prevalence in male than in female participants. Recent studies have hypothesized the presence of different phenotypes in male and female participants with ASD. The present study aims to assess possible sex differences in cognitive and adaptive functioning, symptomatology of ASD, and psychopathological comorbidities in a large sample of children and adolescents with ASD., Methods: The study included a total of 2,146 children and adolescents diagnosed with ASD, comprising 1785 boys (mean age 7.12 ± 3.69 years) and 361 girls (mean age 6.25 ± 3.30 years). The age of the participants ranged from 1.35 to 19.05 years (mean age 9.98 ± 3.64). The study sought to include all children and adolescents diagnosed with Autism or ASD., Results: Present results showed that girls with ASD had lower IQs than boys but similar adaptive functioning. The severity of symptoms of ASD was greater in boys than in girls, as were scores on psychopathological measures. With increasing age, boys with ASD showed greater impairment in social communication skills than girls and increased psychopathological comorbidities. Older girls showed fewer restricted and repetitive behaviors., Discussion: Exploring phenotypic differences in children and adolescents with ASD fosters an understanding of subtle diagnostic facets that may go unrecognized, allowing for increasingly individualized and tailored interventions., 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 © 2024 Di Vara, Guerrera, Menghini, Scibelli, Lupi, Valeri and Vicari.)

This perspective review aims to explore the potential neurobiological mechanisms involved in the application of transcranial Direct Current Stimulation (tDCS) for Down syndrome (DS), the leading cause of genetically-based intellectual disability. The neural mechanisms underlying tDCS interventions in genetic disorders, typically characterized by cognitive deficits, are grounded in the concept of brain plasticity. We initially present the neurobiological and functional effects elicited by tDCS applications in enhancing neuroplasticity and in regulating the excitatory/inhibitory balance, both associated with cognitive improvement in the general population. The review begins with evidence on tDCS applications in five neurogenetic disorders, including Rett, Prader-Willi, Phelan-McDermid, and Neurofibromatosis 1 syndromes, as well as DS. Available evidence supports tDCS as a potential intervention tool and underscores the importance of advancing neurobiological research into the mechanisms of tDCS action in these conditions. We then discuss the potential of tDCS as a promising non-invasive strategy to mitigate deficits in plasticity and promote fine-tuning of the excitatory/inhibitory balance in DS, exploring implications for cognitive treatment perspectives in this population., 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 © 2024 Faralli, Fucà, Lazzaro, Menghini, Vicari and Costanzo.)

Objectives: Modic type 1 changes (MC1) are vertebral endplate bone marrow (BM) lesions observed on magnetic resonance images in sub-populations of chronic low back pain (CLBP) patients. The etiopathogenesis remains unknown and treatments that modify the underlying pathomechanisms do not exist. We hypothesized that two biological MC1 subtypes exist: a bacterial and a non-bacterial. This would have important implications for developing treatments targeting the underlying pathomechanisms., Methods: Intervertebral disc (IVD) samples adjacent to MC1 (n ​= ​34) and control (n ​= ​11) vertebrae were collected from patients undergoing spinal fusion. Cutibacterium acnes ( C.acnes ) genome copy numbers (GCNs) were quantified in IVD tissues with 16S qPCR, transcriptomic signatures and cytokine profiles were determined in MC1 and control BM by RNA sequencing and immunoassay. Finally, we assessed if C.acnes GCNs are associated with blood plasma cytokines., Results: IVD tissues from control levels had <870 ​ C.acnes GCNs/gram IVD. MC1-adjacent IVDs had either "low" (<870) or "high" (>870) C.acnes GCNs. MC1 patients with "high" C.acnes GCNs had upregulated innate immune cell signatures (neutrophil, macrophage/monocyte) and pro-inflammatory cytokines related to neutrophil and macrophage/monocyte function in the BM, consistent with a host defense against bacterium. MC1 patients with "low" C.acnes GCNs had increased adaptive immune cell signatures (T-and B-cell) in the BM and elevated IL-13 blood plasma levels., Conclusion: Our study provides the first evidence for the existence of bacterial ( C.acnes "high") and non-bacterial ( C.acnes "low") subtypes in MC1 patients with CLBP. This supports the need for different treatment strategies., Competing Interests: OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, AbbVie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant and Topadur. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143). Co-founder of CITUS AG. SD is an inventor of the patent of Aclarion., (© 2024 The Author(s).)

The evidence shows that the COVID-19 pandemic dramatically increased the number of urgent psychiatric consultations for children and adolescents in hospital emergency departments (EDs). However, what needs to be further investigated are the characteristics of psychiatric hospitalization in children and adolescents admitted to the Child and Adolescent Neuropsychiatry Unit wards in EDs. Specifically, this retrospective study aimed to examine changes in (i) the number of inpatients and (ii) the distribution of psychopathological disorders and self-injurious behaviors in our Child and Adolescent Neuropsychiatry Unit ward during the COVID-19 lockdown in Italy (March-June 2020; October 2020-January 2021) compared with the same months of previous years. We found a significantly lower number of inpatients during the first four quarantine months than the first four reference months and a higher number of inpatients during the second four quarantine months than the second four reference months. Additionally, we found an increased frequency of mood disorders, non-suicidal self-injurious behavior, and suicidal ideation during the COVID-19 lockdown compared to the reference periods. Our findings underline the need to develop psychological healthcare services for future emergency periods in order to identify and treat psychological distress in children and adolescents early, reducing the risk of psychiatric hospitalization.

Background: Lateral discoid meniscus accounts for most meniscal tears in children 10 years of age and younger. The role of bony morphology in discoid meniscus has been previously studied in a limited capacity using radiographs., Purpose: To use magnetic resonance imaging to measure features of the femoral condyles and tibial plateaus in patients with discoid meniscus to assess potential determinants of symptoms and subsequent surgery and to compare with matched controls to investigate age-related changes in bony features., Study Design: Cross-sectional study; Level of evidence, 3., Methods: After institutional review board approval, detailed morphology of the femoral condyles and tibial plateau was measured in 177 patients (3-18 years of age; 56% female) with confirmed lateral discoid meniscus. Measurements from 269 participants (3-18 years of age; 55% female) with asymptomatic knees were used as controls. Two-way analysis of variance with Holm-Šídák post hoc was used to compare measurements between discoid menisci and matched controls. Independent t tests were used to compare aspects of bony morphology within the discoid meniscus cohort., Results: Compared with controls, patients with a lateral discoid meniscus had a larger bicondylar width and notch width (7- to 10-year-old and 15- to 18-year-old age groups; P < .05), larger tibial plateau width (11- to 14-year-old and 15- to 18-year-old age groups; P < .001), and smaller lateral ( P < .02) and coronal ( P < .02) tibial slopes across all age groups. Among patients with a discoid meniscus, larger bicondylar width, larger tibial plateau width, larger notch width, and a flatter lateral femoral condyle were associated with pain ( P < .005) and lateral meniscal tears ( P < .02). Larger notch width and notch width index were also associated with subsequent surgery ( P < .05)., Conclusion: There are clinically significant abnormalities in bony morphology in patients with a discoid meniscus, including larger femoral condyles and tibial plateaus and a flatter tibial plateau. Additionally, femoral size, femoral curvature, and tibial plateau size may influence the likelihood of knee pain, meniscal tear, and need for surgery. These findings highlight the importance of bony morphology in discoid meniscus pathophysiology in children and adolescents. Such measurements may also aid radiographic detection of discoid meniscus and guide decisions regarding the timing of potential surgical intervention., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: D.E.K. is a paid consultant for Miach Orthopaedics and DePuy Synthes and receives education support from Kairos Surgical. B.E.H. has received education payments from Arthrex, Kairos Surgical, and Pylant and is a consultant and stock owner for Imagen Technologies. M.S.K. has received consulting fees and royalties from OrthoPediatrics and Ossur; royalties from El Secier and Wolters Kluwer; speaking fees from Smith & Nephew; and support for education from Kairos Surgical Inc. A.M.K. is a paid consultant of Miach Orthopaedics. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Current psychological and pharmacological treatments for Anorexia Nervosa (AN) provide only moderate effective support, and there is an urgent need for research to improve therapies, especially in developing age. Non-invasive brain stimulation has suggested to have the potential to reducing AN symptomatology, via targeting brain alterations, such as hyperactivity of right prefrontal cortex (PFC). We suppose that transcranial direct current stimulation (tDCS) to the PFC may be effective in children and adolescents with AN., Methods: We will conduct a randomized, double blind, add-on, placebo-controlled trial to investigate the efficacy of tDCS treatment on clinical improvement. We will also investigate brain mechanisms and biomarkers changes acting in AN after tDCS treatment. Eighty children or adolescent with AN (age range 10-18 years) will undergo treatment-as-usual including psychiatric, nutritional and psychological support, plus tDCS treatment (active or sham) to PFC (F3 anode/F4 cathode), for six weeks, delivered three times a week. Psychological, neurophysiological and physiological measures will be collected at baseline and at the end of treatment. Participants will be followed-up one, three, six months and one year after the end of treatment. Psychological measures will include parent- and self-report questionnaires on AN symptomatology and other psychopathological symptoms. Neurophysiological measures will include transcranial magnetic stimulation (TMS) with electroencephalography and paired pulse TMS and repetitive TMS to investigate changes in PFC connectivity, reactivity and plasticity after treatment. Physiological measures will include changes in the functioning of the endogenous stress response system, body mass index (BMI) and nutritional state., Discussion: We expect that tDCS treatment to improve clinical outcome by reducing the symptoms of AN assessed as changes in Eating Disorder Risk composite score of the Eating Disorder Inventory-3. We also expect that at baseline there will be differences between the right and left hemisphere in some electrophysiological measures and that such differences will be reduced after tDCS treatment. Finally, we expect a reduction of endogenous stress response and an improvement in BMI and nutritional status after tDCS treatment. This project would provide scientific foundation for new treatment perspectives in AN in developmental age, as well as insight into brain mechanisms acting in AN and its recovery. Trial registration The study was registered at ClinicalTrials.gov (ID: NCT05674266) and ethical approval for the study was granted by the local research ethics committee (process number 763&#95;OPBG&#95;2014)., (© 2023. The Author(s).)

Background: The COVID-19 pandemic had a major impact on the mental health and well-being of children with neurodevelopmental conditions (NDCs) and of their families worldwide. However, there is insufficient evidence to understand how different factors (e.g., individual, family, country, children) have impacted on anxiety levels of families and their children with NDCs developed over time., Methods: We used data from a global survey assessing the experience of 8043 families and their children with NDCs (mean of age (m) = 13.18 years, 37% female) and their typically developing siblings (m = 12.9 years, 45% female) in combination with data from the European Centre for Disease Prevention and Control, the University of Oxford, and the Central Intelligence Agency (CIA) World Factbook, to create a multilevel data set. Using stepwise multilevel modelling, we generated child-, family- and country-related factors that may have contributed to the anxiety levels of children with NDCs, their siblings if they had any, and their parents. All data were reported by parents., Results: Our results suggest that parental anxiety was best explained by family-related factors such as concerns about COVID-19 and illness. Children's anxiety was best explained by child-related factors such as children's concerns about loss of routine, family conflict, and safety in general, as well as concerns about COVID-19. In addition, anxiety levels were linked to the presence of pre-existing anxiety conditions for both children with NDCs and their parents., Conclusions: The present study shows that across the globe there was a raise in anxiety levels for both parents and their children with NDCs because of COVID-19 and that country-level factors had little or no impact on explaining differences in this increase, once family and child factors were considered. Our findings also highlight that certain groups of children with NDCs were at higher risk for anxiety than others and had specific concerns. Together, these results show that anxiety of families and their children with NDCs during the COVID-19 pandemic were predicted by very specific concerns and worries which inform the development of future toolkits and policy. Future studies should investigate how country factors can play a protective role during future crises., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form and declare the following activities and relationships: Dr Bölte discloses that he has in the last three years acted as an author, consultant, or lecturer for Medice and Roche. He receives royalties for textbooks and diagnostic tools from Hogrefe, Kohlhammer, Reinhardt and Liber. Bölte is a partner of NeuroSupportSolutions International AB. Dr Poustka served in an advisory or consultancy role for infectopharm and Roche and received speaker’s fee by Infectopharm, Takeda, and Medice. She received royalties from Hogrefe, Kohlhammer and Schattauer. Dr Zander receives royalties from Hogrefe. Dr Hardan served in an advisory or consultancy role for IAMA Therapeutics, Beaming Health, and As You Are. He also has equity in Quadrant BioSciences and I-SCAN., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD., Methods: After completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH., Results: Our results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual-spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS., Discussion: In conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms., 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 © 2023 D’Aiello, Lazzaro, Battisti, Pani, Di Vara, De Rossi, Pretelli, Costanzo, Vicari and Menghini.)

Smaller anterior cruciate ligament (ACL) size in females has been hypothesized to be a key contributor to a higher incidence of ACL tears in that population, as a lower cross-sectional area (CSA) directly corresponds to a larger stress on the ligament for a given load. Prior studies have used a mid-length CSA measurement to quantify ACL size. In this study, we used magnetic resonance imaging to quantify the CSA along the entire length of the intact ACL. We hypothesized that changes in the ACL CSA along its length would have different patterns in males and females. We also hypothesized that changes in ACL CSA along its length would be associated with body size or knee size with different associations in females and males. MR images of contralateral ACL-intact knees of 108 patients (62 females, 13-35 years) undergoing ACL surgery were used to measure the CSA along the ACL length, using a custom program. For both females and males, the largest CSA was located at 37%-39% of ACL length from the tibial insertion. Compared to females, males had a significantly larger CSA only within the distal 41% of the ACL (p < 0.001). ACL CSA was associated with patient height and weight in males (r > 0.3; p < 0.05), whereas it was associated with intercondylar notch width in females (r > 0.3; p < 0.05). These findings highlight the importance of standardizing the location of measurement of ACL CSA., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Collagen organization of the anterior cruciate ligament (ACL) can be evaluated using T 2 * relaxometry. However, T 2 * mapping requires manual image segmentation, which is a time-consuming process and prone to inter- and intra- segmenter variability. Automating segmentation would address these challenges. A model previously trained using Constructive Interference in Steady State (CISS) scans was applied to T 2 * segmentation via transfer learning. It was hypothesized that there would be no significant differences in the model's segmentation performance between T 2 * and CISS, structural measures versus ground truth manual segmentation, and reliability versus independent and retest manual segmentation. Transfer learning was conducted using 54 T 2 * scans of the ACL. Segmentation performance was assessed with Dice coefficient, precision, and sensitivity, and structurally with T 2 * value, volume, subvolume proportions, and cross-sectional area. Model performance relative to independent manual segmentation and repeated segmentation by the ground truth segmenter (retest) were evaluated on a random subset. Segmentation performance was analyzed with Mann-Whitney U tests, structural measures with Wilcoxon signed-rank tests, and performance relative to manual segmentation with repeated-measures analysis of variance/Tukey tests (α = 0.05). T 2 * segmentation performance was not significantly different from CISS on all measures (p > 0.35). No significant differences were detected in structural measures (p > 0.50). Automatic segmentation performed as well as the retest on all segmentation measures, whereas independent segmentations were lower than retest and/or automatic segmentation (p < 0.023). Structural measures were not significantly different between segmenters. The automatic segmentation model performed as well on the T 2 * sequence as on CISS and outperformed independent manual segmentation while performing as well as retest segmentation., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Introduction: Attention deficit hyperactivity disorder (ADHD) has been associated with difficulties in regulating aversion states, high functional impairment, and a high risk of psychopathology across the lifespan. ADHD is clinically heterogeneous, with a wide spectrum of severity and associated symptoms. Clinical characteristics need to be carefully defined in different periods of life as ADHD course, symptoms, and comorbidities may fluctuate and change over time. Adolescence usually represents the transition from primary to secondary education, with a qualitative and quantitative change in environmental and functional demands, thus driving symptoms' change., Methods: In order to characterize age-related clinical features of children (<11 years) and adolescents (≥11 years) with ADHD, we conducted a naturalistic study on 750 children and adolescents assessed for ADHD at our Neuropsychiatry Unit over the course of 3 years (2018-2020)., Results: We found that ADHD symptoms were significantly higher in children than adolescents. More importantly, we found worse global functioning, lower adaptive skills, higher levels of anxiety and depressive symptoms, somatic complaints, emotional dysregulation, social problems, and aggression in adolescents, despite a lower severity of ADHD-specific symptoms., Conclusion: These results should be confirmed in longitudinal observational studies of adequate sample size in order to reliably describe a potential course characterized by worsening of functioning, reduction in ADHD-specific symptoms and increase in general psychopathology during the transition from childhood to adolescence., 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 © 2023 De Rossi, D’Aiello, Pretelli, Menghini, Di Vara and Vicari.)

This study investigated the prevalence and distribution of psychiatric comorbidities in a group of 472 children and adolescents with ASD aged 3-18 years. We examined differences in age, sex, IQ, adaptive skills, and ASD symptom severity by comparing participants with ASD (ASD group) with participants with ASD and a psychiatric disorder (ASD/PSY group). Overall, 32.2% of participants had a comorbid psychiatric condition. Attention deficit/hyperactivity disorder (ADHD) was the most frequent diagnosis among preschoolers (20.4%); among school-age children, ADHD and anxiety/obsessive-compulsive disorders were the most frequent conditions (21% and 10.6%, respectively); finally, adolescents exhibit higher prevalence of anxiety/obsessive-compulsive disorders (21.8%). The ASD/PSY group showed a higher percentage of males, they were older and showed lower adaptive skills than the group with ASD; moreover, their mothers exhibited higher stress levels than mothers of participants in the ASD group. The comparison between age groups in participants within ASD/PSY group revealed that preschoolers had lower IQ than school-age children and adolescents, and worse adaptive skills, more repetitive behaviors, and restricted interests than adolescents. This study highlights the importance of an accurate diagnosis of psychiatric comorbidities in children and adolescents with ASD, also considering individual and family impairment.

Increasing evidence shows that children with Communication Disorders (CDs) may show gross, fine, and visual-motor difficulties compared to children with typical development. Accordingly, the present study aims to characterize gross, fine and visual-motor skills in children with CDs, distinguishing children with CDs into three subgroups, i.e., with Language Disorders (LD), Speech Sound Disorders (SSD), and LD + SSD. In Experiment 1, around 60% of children with CDs (4 to 7 years; 21 with LD, 36 with SSD, and 90 with LD + SSD) showed clinical/borderline scores in balance skills, regardless of the type of communication deficit. However, children with LD, SSD, and LD + SSD did not differ in gross and fine motor skills. In Experiment 2, a higher percentage of children with CDs (4 to 7 years; 34 with LD, 62 with SSD, 148 with LD + SSD) obtained clinical/borderline scores in Visual Perception skills. Moreover, children with LD + SSD performed significantly worsen in Visual Perception and Fine Motor Coordination skills compared to children with SSD only. Our results underlined that CDs are generally associated with gross motor difficulties and that visual-motor difficulties are related to the type of communication deficit. Paying earlier attention to the motor skills of children with CDs could help clinicians design effective interventions.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most prevalent neurodevelopmental disorder diagnosed in the scholar age. It is associated with significant impairment in global functioning, and in moderate/severe presentations the outcome is critically dependent on pharmacological optimization of the multi-modal treatment. Methylphenidate (MPH) is the first-choice pharmacological treatment in children and adolescents with ADHD, with substantial evidence of significant efficacy and effectiveness on global functioning and symptoms' severity. There is some evidence supporting a few clinical and socio-demographic variables as predictors of pharmacological treatment prescription in children with ADHD independently of ADHD symptoms severity. However, it is warranted to investigate clinical and general psychopathological characteristics potentially associated with negative outcomes and the need for pharmacological treatment to inform appropriate prescription strategies. In this context, we compared 268 children and adolescents who were prescribed MPH (ADHD/MPH) for the first time after their first diagnostic assessment at our center, and 444 children and adolescents with ADHD (ADHD/noMPH) who were recommended non-pharmacological evidence-based interventions alone. ADHD/MPH group had higher severity of non-ADHD psychopathological symptoms compared to the ADHD/noMPH group, as documented by higher scores on the Child Behavior Checklist (CBCL) subscales, higher severity of ADHD symptoms, lower average IQ and lower adaptive levels independently of IQ. More specifically, beside externalizing symptoms, also internalizing symptoms were significantly higher in the ADHD/MPH group. The presence of significant non-ADHD psychopathology should be considered as a clinical factor associated with the need for MPH prescription in children and adolescents with ADHD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Sensory processing disorders (SPDs) can be described as difficulty detecting, modulating, interpreting, and/or responding to sensory experiences. Because SPDs occur in many individuals with autism spectrum disorder and in other populations with neurodevelopmental disorders, it is important to distinguish between typical and atypical functioning in sensory processes and to identify early phenotypic markers for developing SPDs. This review considers different methods for diagnosing SPDs to outline a multidisciplinary approach useful for developing valid diagnostic measures. In particular, the advantages and limitations of the most commonly used tools in assessment of SPDs, such as caregiver reports, clinical observation, and psychophysical and neuroimaging studies, will be reviewed. Innovative treatment methods such as neuromodulation techniques and virtual reality will also be suggested.

Background: The transition of teaching from in-person to Distance Learning (DL) due to the COVID-19 pandemic led to negative effects on students' psychological wellbeing and academic achievement. The worst consequences have been experienced by students with so-called special educational needs , as well as by their parents. However, very little emphasis has been placed on the effects of DL in students with Specific Learning Disorders (SLD). The present work aimed to evaluate the effects of DL during the COVID-19 lockdown in Italian students with SLD and in their parents., Methods: An online survey was administered to 92 students with SLD and their parents after the COVID-19 lockdown. The survey consisted of four sections: participants' demographic information; perceived stress related to general aspects (i.e., social and family determinants) as well as specific aspects related to DL; attitudes and feelings toward DL; and academic grades before and after DL., Results: Students with SLD perceived stress mainly from social isolation/distancing and DL ( p always ≤ 0.0001), especially from online classes and oral exams ( p always ≤ 0.0001). Students who did not benefit from appropriate accommodations (i.e., individualized teaching and learning methods) during DL perceived 3 times more DL-related stress than those who used them as in-person learning (OR = 3.00, CI 95%: 1.24-7.28, p = 0.015). Girls perceived more stress from online lessons (OR = 0.40, CI 95%: 0.16-0.96, p = 0.04) and use of devices (OR = 0.33, CI 95%: 0.14-0.80, p = 0.015) than boys. Negative feelings (less motivation, reduced ability to understand lessons, interact, and stay focused) and positive feelings (less anxiety and more self-confidence with its own rate of learning) toward DL emerged. Higher academic grades also was observed after DL ( p ≤ 0.0001). Lastly, strong and positive correlations emerged between students' and parents' perceived stress during DL ( p always < 0.001)., Implications: The present study prompts special considerations for students with special educational needs not only when providing conventional instruction, but especially when it is necessary to suddenly modify teaching approaches., 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 Battisti, Lazzaro, Varuzza, Vicari and Menghini.)

Background: The cross-sectional area (CSA) of the anterior cruciate ligament (ACL) and reconstructed graft has direct implications on its strength and knee function. Little is known regarding how the CSA changes along the ligament length and how those changes vary between treated and native ligaments over time., Hypothesis: It was hypothesized that (1) the CSA of reconstructed ACLs and restored ACLs via bridge-enhanced ACL restoration (BEAR) is heterogeneous along the length. (2) Differences in CSA between treated and native ACLs decrease over time. (3) CSA of the surgically treated ACLs is correlated significantly with body size (ie, height, weight, body mass index) and knee size (ie, bicondylar and notch width)., Study Design: Cohort study; Level of evidence, 2., Methods: Magnetic resonance imaging scans of treated and contralateral knees of 98 patients (n = 33 ACL reconstruction, 65 BEAR) at 6, 12, and 24 months post-operation were used to measure the ligament CSA at 1% increments along the ACL length (tibial insertion, 0%; femoral insertion, 100%). Statistical parametric mapping was used to evaluate the differences in CSA between 6 and 24 months. Correlations between body and knee size and treated ligament CSA along its length were also assessed., Results: Hamstring autografts had larger CSAs than native ACLs at all time points ( P < .001), with region of difference decreasing from proximal 95% of length (6 months) to proximal 77% of length (24 months). Restored ACLs had larger CSAs than native ACLs at 6 and 12 months, with larger than native CSA only along a small midsubstance region at 24 months ( P < .001). Graft CSA was correlated significantly with weight (6 and 12 months), bicondylar width (all time points), and notch width (24 months). Restored ACL CSA was significantly correlated with bicondylar width (6 months) and notch width (6 and 12 months)., Conclusion: Surgically treated ACLs remodel continuously within the first 2 years after surgery, leading to ligaments/grafts with heterogeneous CSAs along the length, similar to the native ACL. While reconstructed ACLs remained significantly larger, the restored ACL had a CSA profile comparable with that of the contralateral native ACL. In addition to size and morphology differences, there were fundamental differences in factors contributing to CSA profile between the ACL reconstruction and BEAR procedures., Registration: NCT02664545 (ClinicalTrials.gov identifier)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: this study received funding support from the Translational Research Program at Boston Children’s Hospital, the Children’s Hospital Orthopaedic Surgery Foundation, the Children’s Hospital Sports Medicine Foundation, the Football Players Health Study at Harvard University, and the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grants R01-AR065462 and R01-AR056834). M.M.M. is a founder, paid consultant, and equity holder in Miach Orthopaedics, which was formed to work on upscaling production of the BEAR scaffold. M.M.M. maintained a conflict-of-interest management plan that was approved by Boston Children’s Hospital and Harvard Medical School during the conduct of the trial, with oversight by both conflict-of-interest committees and the institutional review board of Boston Children’s Hospital, as well as the US Food and Drug Administration. B.C.F. is an assistant editor for The American Journal of Sports Medicine and the spouse of M.M.M., with the inherently same conflicts. A.M.K. is a paid consultant for Miach Orthopaedics and maintained a conflict-of-interest management plan that was approved by Boston Children’s Hospital and Harvard Medical School during the conduct of the trial, with oversight by both conflict-of-interest committees and the institutional review board of Boston Children’s Hospital. For the BEAR Trial Team, D.E.K., L.J.M., and Y.-M.Y. all have disclosures as listed in the American Academy of Orthopaedic Surgeons database, none of which is related to this current project or technology. These include educational payments from Kairos Surgical (D.E.K., Y.-M.Y.). L.J.M. also has received hospitality payments from various companies. B.P. has manufactured the scaffolds used in the trials at Boston Children’s Hospital and is a paid consultant and equity holder in Miach Orthopaedics at this time, as he assists with transfer of the manufacturing process to the contract manufacturing organization that Miach has engaged to do the manufacturing. N.S. has manufactured scaffolds used in the trials at Boston Children’s Hospital and is a paid consultant for Miach Orthopaedics. B.P. and N.S. maintain a conflict-of-interest management plan that was approved by Boston Children’s Hospital and Harvard Medical School during the conduct of the trial, with oversight by both conflict-of-interest committees and the institutional review board of Boston Children’s Hospital. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Developmental Dyslexia (DD) significantly interferes with children's academic, personal, social, and emotional functioning. Nevertheless, therapeutic options need to be further validated and tested in randomized controlled clinical trials. The use of transcranial direct current stimulation (tDCS) has been gaining ground in recent years as a new intervention option for DD. However, there are still open questions regarding the most suitable tDCS protocol for young people with DD. The current crossover study tested the effectiveness of a short and intensive tDCS protocol, including the long-term effects, as well as the influence of age and neuropsychological processes at baseline on reading improvements. Twenty-four children and adolescents with DD were randomly assigned to receive active tDCS during the first slot and sham tDCS during the second slot or vice versa. Five consecutive daily sessions of left anodal/right cathodal tDCS set at 1 mA for 20 min were administered over the parieto-occipital regions. Reading measures (text, high frequency word, low frequency word, and non-word lists) and neuropsychological measures (visual-spatial and verbal working memory, phoneme blending, and rapid automatized naming tasks) were collected before, immediately after, 1 week and 1 month later the treatment. Our results showed that only the active tDCS condition improved non-word reading speed immediately after and 1 month later the end of the treatment compared with baseline. In addition, the improvement in non-word reading speed was significantly correlated with age and with neuropsychological measures (verbal working memory and phoneme blending) at baseline but only in the active tDCS condition. The current crossover study contributed to enforce previous effects of tDCS, including long-term effects, on non-word reading speed and to understand the effect of age and neuropsychological processes on reading outcomes. Our findings showed that tDCS could be a low-cost and easy-to-implement treatment option with long-term effects for children and adolescents with DD., 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 Battisti, Lazzaro, Costanzo, Varuzza, Rossi, Vicari and Menghini.)

The Strengths and Difficulties Questionnaire (SDQ) is a worldwide questionnaire used for the early identification of behavioural/emotional symptoms in children and adolescents with neuropsychiatric disorders. Although its prognostic power has been studied, it has not yet been tested whether SDQ: (i) can identify pathognomonic symptoms across a variety of neurodevelopmental and neuropsychiatric disorders, (ii) can capture emotional and behavioural problems associated with the main diagnosis, as well as shared transdiagnostic dimensions, and (iii) can detect changes in symptomatology with age. The present study evaluated nearly 1000 children and adolescents overall with Global Developmental Delay (GDD), Intellectual Disability (ID), Language Disorder (LD), Specific Learning Disorder (SLD), Autism Spectrum Disorder (ASD), Attention Deficit/Hyperactivity Disorder (ADHD), Mood Disorder (MD), Anxiety Disorder (AD), and Eating Disorders (ED). We found that SDQ: (i) can identify the core symptoms in children with ASD, ADHD, MD, and AD via specific subscales; (ii) can capture the associated emotional and behavioural symptoms in children with LD, GDD, ID, SLD, and ED; and (iii) can detect changes in the symptomatology, especially for GDD, LD, ASD, ADHD, and AD. SDQ is also able to recognise the transdiagnostic dimensions across disorders. Our results underscore the potential of SDQ to specifically differentiate and identify behavioural/emotional profiles associated with clinical diagnosis.

Sleep disturbances may be a significant source of distress for children with neurodevelopmental disorders, and consequently also for their families. Crucially, sleep disturbances might be influenced by comorbidity. Attention deficit hyperactivity disorder (ADHD) and specific learning disorder (SLD) often co-occur, and consequently, investigating sleep disturbances in children with comorbidity of ADHD and SLD is essential. Our study aimed at detecting sleep difficulties in a group of 74 children with ADHD, 78 children with SLD, and 76 children with ADHD and SLD by using the Sleep Disturbances Scale for Children. The results showed that sleep difficulties emerge more clearly in children with comorbid ADHD and SLD compared to children with only ADHD or SLD. These sleep difficulties were not due to differences in ages and behavioral/emotional problems. In conclusion, evaluating sleep disturbances is important when assessing and managing children with ADHD, SLD, and particularly with the two comorbid conditions, to better understand their difficulties and develop tailored interventions.

Objective: High incidence of sleep problems in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) has been described. Mindfulness meditation has emerged as a novel approach to sleep disturbances and insomnia remediation. This preliminary study tested the efficacy of Mindfulness-Oriented Meditation (MOM) training on sleep quality and behavioral problems in children with ADHD., Design: Twenty-five children with ADHD aged 7-11 years underwent two programs three times per week for eight-weeks: the MOM training (15 children) and an Active Control Condition (10 children)., Main Outcome Measures: Objective and subjective measures of sleep quality and behavioral measures were collected before and after the programs., Results: Positive effects on sleep and behavioral measures were found only in the MOM group., Conclusion: Although they are preliminary, our results indicate that MOM training is a promising tool for ameliorating sleep quality and behavioral manifestations in ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inappropriate levels of attention, hyperactivity, and impulsivity that interfere with individual functioning. The international guidelines recommend targeting ADHD-related neurochemical brain abnormalities by intervening via drug treatment, such as methylphenidate (MPH), as first choice. Drug treatments are usually associated with a huge amount of cost for families and the healthcare system, suspension for low compliance, poor long-term efficacy, and side effects. Transcranial direct current stimulation (tDCS) has been suggested as a possible noninvasive means to safely manipulate brain activity and, in turn, improve behavior and cognition in developmental ages. Several studies have shown that tDCS has the potential to improve ADHD-related cognitive deficits, but the effect of tDCS compared with MPH has never been evaluated. The aim of the present within-subject, sham-controlled, randomized proof-of-concept study is to demonstrate the positive effect of one-session anodal tDCS analogous to the MPH drug on inhibitory control and working memory in children and adolescents with ADHD. We strongly believe that this study protocol will serve to accelerate research into low-cost, drug-free, feasible interventions for ADHD.

Atypical development of numerical cognition (dyscalculia) may increase the onset of neuropsychiatric symptoms, especially when untreated, and it may have long-term detrimental social consequences. However, evidence-based treatments are still lacking. Despite plenty of studies investigating the effects of transcranial electrical stimulation (tES) on numerical cognition, a systematized synthesis of results is still lacking. In the present systematic review (PROSPERO ID: CRD42021271139), we found that the majority of reports (20 out of 26) showed the effectiveness of tES in improving both number (80%) and arithmetic (76%) processing. In particular, anodal tDCS (regardless of lateralization) over parietal regions, bilateral tDCS (regardless of polarity/lateralization) over frontal regions, and tRNS (regardless of brain regions) strongly enhance number processing. While bilateral tDCS and tRNS over parietal and frontal regions and left anodal tDCS over frontal regions consistently improve arithmetic skills. In addition, tACS seems to be more effective than tDCS at ameliorating arithmetic learning. Despite the variability of methods and paucity of clinical studies, tES seems to be a promising brain-based treatment to enhance numerical cognition. Recommendations for clinical translation, future directions, and limitations are outlined.

Background: Common variable immunodeficiency (CVID) is a complex, predominantly antibody deficiency usually diagnosed between 20−40 years. Few data about elderly patients are reported in the literature. Our aim was to evaluate the clinical phenotypes of elderly patients with CVID. Method: A retrospective analysis of adult patients with CVID was performed in our Referral Centre, focusing on the main differences between “older” patients (≥65 years at the diagnosis) and “younger” patients (<65 years). Results: The data from 65 younger and 13 older patients followed up for a median period of 8.5 years were available. At diagnosis, recurrent infections represented the only clinical manifestation in 61% and 69% of younger and older patients, respectively. The incidence of autoimmune diseases was higher in elderly patients compared with younger ones (30 vs. 18%, respectively). During the follow-up, the incidence of autoimmune disorders and enteropathy increased in the younger patients whereas neoplasia became the most prevalent complication in the elderly (38%). All patients received a replacement therapy with immunoglobulin, with good compliance. Conclusion: CVID occurrence in elderly patients is rarely described; therefore, the clinical characteristics are not completely known. In our series, neoplasia became the most prevalent complication in the elderly during the follow-up. In elderly patients, 20% SCIg was as safe as in the younger ones, with good compliance. A genetic analysis is important to confirm the diagnosis, identify specific presentations in the different ages, clarify the prognosis and guide the treatment. Future clinical research in this field may potentially help to guide their care.

Background: Childhood Apraxia of Speech is a severe and persistent clinical subtype of Speech Sound Disorder. Given the difficulties in the acquisition, programming and control of the movements underlying speech and the slowdown in a wide range of non-linguistic skills, the difficulty in implicit learning of sequential information could play a role in the disorder, contributing to understand its etiopathological mechanisms and behavioral manifestations., Aims: The present study was aimed at investigating implicit learning in children with Childhood Apraxia of Speech., Methods and Procedures: Twenty-five children with Childhood Apraxia of Speech, aged between 4 and 12 years, were matched for IQ and age to a control group of 25 typically developing children. Implicit learning of participants was assessed by Serial Reaction Time Task., Outcome and Results: Children with Childhood Apraxia of Speech did not show implicit learning, as documented by the absence of differences between reaction times in the sequenced block and the random block, usually considered as a measure of implicit learning effect., Conclusion and Implications: Our results underline an implicit learning deficit in children with Childhood Apraxia of Speech, supporting the concept of a disorder not only confined to the speech domain, but also involving non-linguistic skills, in a composite and complex picture., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Methylphenidate (MPH) is the treatment of first choice for developmental ADHD. To date, no reliable method to predict how patients will respond to MPH exists and conflicting results are reported on clinical characteristics of responders. The present study aims to give a more precise characterization of the patients who will respond best to MPH to help clinicians in defining the treatment plan. Age, neuropsychological functioning (i.e., attention and working memory), and behavioral/emotional symptoms of 48 drug-naïve children and adolescents with ADHD (42 boys and 6 girls, age-range 6-16 years, mean age 10.5 ± 2.5 years, mean IQ 101.3 ± 11.2) were studied to assess how these different characteristics affected a single-dose MPH response. Four hierarchical linear regression models were used to explore whether age, neuropsychological measures at baseline, and behavioral/emotional symptoms could predict attention and working memory measures after a single-dose MPH administration. We found that improvement in attention and working memory was predicted by age, neuropsychological measures at baseline, and severity of ADHD symptoms. No behavioral and emotional symptoms predicted single-dose MPH response with the exception of conduct symptoms.

Cerebellar agenesis is an extremely rare condition characterized by a near complete absence of the cerebellum. The pathogenesis and molecular basis remain mostly unknown. We report the neuroradiological, molecular, neuropsychological and behavioral characterization of a 5-year-old girl, with cerebellar agenesis associated with parietal and peri-Sylvian polymicrogyria, followed-up for 10 years at four time points. Whole exome sequencing identified two rare variants in CSMD1 , a gene associated with neurocognitive and psychiatric alterations. Mild intellectual impairment, cerebellar ataxia and deficits in language, memory and executive functions, with relatively preserved adaptive and psychopathological domains, were initially showed. Phonological awareness and verbal memory declined at 11 years of age, and social and anxiety problems emerged. Adaptive and psychopathological characteristics dramatically worsened at 15 years. In summary, the developmental clinical outcome showed impairment in multiple cognitive functions in childhood, with a progressive decline in cognitive and adaptive abilities and the emergence of psychopathological symptoms in adolescence. The observed phenotype could be the result of a complex interplay between cerebellar abnormality, brain malformation and the relations with CSMD1 variants. These findings may provide insights into the developmental clinical outcomes of a co-occurrence between rare brain malformation and rare genetic variants associated to neurodevelopmental disorders.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder in school-age children, and it is usually associated with a significant impairment in global functioning. Traditionally, boys with ADHD are more likely to be referred for clinical assessments due to a higher prevalence of externalizing symptoms. However, as regards gender-related differential clinical characteristics between boys and girls with ADHD, further investigation is warranted in light of conflicting results found in currently available literature. In fact, a more precise clinical characterization could help increase appropriate diagnoses and treatment planning. In this context, we carried out a retrospective observational study on 715 children and adolescents diagnosed with ADHD from 2018 to 2020 at our center, in order to describe their gender-related clinical characteristics. Boys displayed higher average IQs, but they were comparable to girls in functional impairments and adaptive skills. Girls displayed higher scores on the Attention Problems subscale of the CBCL 6-18 and on several CPRS-R:L subscales, suggesting higher general ADHD symptom severity. Boys showed higher scores on CBCL 6-18 subscales, such as withdrawn/depressed, internalizing, and obsessive-compulsive problems. In conclusion, girls showed more severe ADHD features and lower IQ in clinically referred settings, while boys showed more internalizing problems and obsessive-compulsive symptoms.

Background: Little is known about sex-based differences in anterior cruciate ligament (ACL) tissue quality in vivo or the association of ACL size (ie, volume) and tissue quality (ie, normalized signal intensity on magnetic resonance imaging [MRI]) with knee anatomy., Hypothesis: We hypothesized that (1) women have smaller ACLs and greater ACL normalized signal intensity compared with men, and (2) ACL size and normalized signal intensity are associated with age, activity levels, body mass index (BMI), bicondylar width, intercondylar notch width, and posterior slope of the lateral tibial plateau., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Knee MRI scans of 108 unique ACL-intact knees (19.7 ± 5.5 years, 62 women) were used to quantify the ACL signal intensity (normalized to cortical bone), ligament volume, mean cross-sectional area, and length. Independent t tests were used to compare the MRI-based ACL parameters between sexes. Univariate and multivariate linear regression analyses were used to investigate the associations between normalized signal intensity and size with age, activity levels, BMI, bicondylar width, notch width, and posterior slope of the lateral tibial plateau., Results: Compared with men, women had significantly smaller mean ACL volume (men vs women: 2028 ± 472 vs 1591 ± 405 mm 3 ), cross-sectional area (49.4 ± 9.6 vs 41.5 ± 8.6 mm 2 ), and length (40.8 ± 2.8 vs 38.1 ± 3.1 mm) ( P < .001 for all), even after adjusting for BMI and bicondylar width. There was no difference in MRI signal intensity between men and women (1.15 ± 0.24 vs 1.12 ± 0.24, respectively; P = .555). BMI, bicondylar width, and intercondylar notch width were independently associated with a larger ACL ( R 2 > 0.16, P < .001). Younger age and steeper lateral tibial slope were independently associated with shorter ACL length ( R 2 > 0.03, P < .04). The combination of BMI and bicondylar width was predictive of ACL volume and mean cross-sectional area ( R 2 < 0.3). The combination of BMI, bicondylar width, and lateral tibial slope was predictive of ACL length ( R 2 = 0.39). Neither quantified patient characteristics nor anatomic variables were associated with signal intensity., Conclusion: Men had larger ACLs compared with women even after adjusting for BMI and knee size (bicondylar width). No sex difference was observed in signal intensity, suggesting no difference in tissue quality. The association of the intercondylar notch width and lateral tibial slope with ACL size suggests that the influence of these anatomic features on ACL injury risk may be partially explained by their effect on ACL size., Registration: NCT02292004 and NCT02664545 (ClinicalTrials.gov identifier)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study received funding support from the Translational Research Program at Boston Children’s Hospital, the Children’s Hospital Orthopaedic Surgery Foundation, the Children’s Hospital Sports Medicine Foundation, Boston Children’s Hospital Faculty Council, the Football Players Health Study at Harvard University (funded by a grant from the National Football League Players Association), and the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grants R01-AR065462 and R01-AR056834). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Medical School, Harvard University or its affiliated academic healthcare centers, the National Football League Players Association, Boston Children’s Hospital, or the National Institutes of Health. M.M.M. is a founder, paid consultant, and equity holder in Miach Orthopaedics, which was formed to work on upscaling production of the BEAR scaffold. M.M.M. has also received honoraria from the Musculoskeletal Transplant Foundation. B.C.F. is a paid associate editor for The American Journal of Sports Medicine and the spouse of M.M.M. with the inherently same conflicts. A.M.K. is a paid consultant for Miach Orthopaedics. D.K. and Y.-M.Y. have received education payments from Kairos Surgical. B.P. has manufactured the scaffolds used in the trials at Boston Children’s Hospital and is a paid consultant and equity holder in Miach Orthopaedics. N.S. has manufactured scaffolds used in the trials at Boston Children’s Hospital and is a paid consultant for Miach Orthopaedics. M.M.M., A.M.K., B.P., and N.S. maintained a conflict-of-interest management plan that was approved by Boston Children’s Hospital and Harvard Medical School during the conduct of the trial, with oversight by both conflict-of-interest committees and the institutional review board of Boston Children’s Hospital. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2021.)

Revolving Door (RD) is a frequent phenomenon afflicting children and adolescents with psychiatric diagnoses. Nevertheless, risk factors for RD are still a matter of debate. To better understand RD phenomenon, we conducted a retrospective study on 224 children and adolescents (165 females and 59 males, aged 6-16 years) with a psychiatric hospitalization, taking the multiple risk factors together. At this aim, 108 patients with multiple hospitalizations and 116 patients with only one hospitalization were compared on demographic characteristics, clinical conditions, psychiatric ward stay, and post-discharge management factors. More than half of psychiatric patients were readmitted within three months of discharge. RD patients presented greater severity of illness, needed longer stays, and were more frequently placed in residential facilities than non-RD patients. Non-suicidal self-injurious and adoption were the main predictors of RD. Clinical instruments that detected behavioural and emotional symptoms, suicidal ideation severity, and level of impairment of the person's functioning were useful to identify patients at high risk for RD. In conclusion, our findings pointed out that several risk factors have to be considered to better understand and, in the future, prevent RD phenomenon.

Numbers are everywhere, and supporting difficulties in numerical cognition (e.g., mathematical learning disability (MLD)) in a timely, effective manner is critical for their daily use. To date, only low-efficacy cognitive-based interventions are available. The extensive data on the neurobiology of MLD have increased interest in brain-directed approaches. The overarching goal of this study protocol is to provide the scientific foundation for devising brain-based and evidence-based treatments in children and adolescents with MLD. In this double-blind, between-subject, sham-controlled, randomized clinical trial, transcranial random noise stimulation (tRNS) plus cognitive training will be delivered to participants. Arithmetic, neuropsychological, psychological, and electrophysiological measures will be collected at baseline (T0), at the end of the interventions (T1), one week (T2) and three months later (T3). We expect that tRNS plus cognitive training will significantly improve arithmetic measures at T1 and at each follow-up (T2, T3) compared with placebo and that such improvements will correlate robustly and positively with changes in the neuropsychological, psychological, and electrophysiological measures. We firmly believe that this clinical trial will produce reliable and positive results to accelerate the validation of brain-based treatments for MLD that have the potential to impact quality of life.

Individuals with autism spectrum disorder (ASD) usually manifest heterogeneous impairments in their higher cognitive functions, including their implicit memory (IM) and explicit memory (EM). However, the findings on IM and EM in youths with ASD remain debated. The aim of this study was to clarify such conflicting results by examining IM and EM using two comparable versions of the Serial Reaction Time Task (SRTT) in the same group of children and adolescents with ASD. Twenty-five youths with high-functioning ASD and 29 age-matched and IQ-matched typically developing youths undertook both tasks. The ability to implicitly learn the temporal sequence of events across the blocks in the SRTT was intact in the youths with ASD. When they were tested for EM, the participants with ASD did not experience a significant reduction in their reaction times during the blocks with the previously learned sequence, suggesting an impairment in EM. Moreover, the participants with ASD were less accurate and made more omissions than the controls in the EM task. The implications of these findings for the establishment of tailored educational programs for children with high-functioning ASD are discussed.

Given the pleiotropic nature of coding sequences and that many loci exhibit multiple disease associations, it is within non-coding sequence that disease-specificity likely exists. Here, we focus on joint disorders, finding among replicated loci, that GDF5 exhibits over twenty distinct associations, and we identify causal variants for two of its strongest associations, hip dysplasia and knee osteoarthritis. By mapping regulatory regions in joint chondrocytes, we pinpoint two variants (rs4911178; rs6060369), on the same risk haplotype, which reside in anatomical site-specific enhancers. We show that both variants have clinical relevance, impacting disease by altering morphology. By modeling each variant in humanized mice, we observe joint-specific response, correlating with GDF5 expression. Thus, we uncouple separate regulatory variants on a common risk haplotype that cause joint-specific disease. By broadening our perspective, we finally find that patterns of modularity at GDF5 are also found at over three-quarters of loci with multiple GWAS disease associations.

Pyrocystis lunula is a unicellular bioluminescing dinoflagellates. While the mechanisms and genes underlying bioluminescence and luciferase synthesis are understood in many bioluminescing clades, it remains unknown in dinoflagellates. We took advantage of merging long and short reads to provide here a de novo assembly of P. lunula transcriptome. A total of 975 million filtered paired-end reads were obtained and assembled into 155,716 contigs corresponding to putative transcripts that were functionally annotated. This dataset will be valuable for improving our understanding of protist's biology and is accessible via NCBI BioProject (PRJNA727555)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2021 The Author(s).)

Event-based prospective memory (PM) was investigated in children with Attention deficit/hyperactivity disorder (ADHD), using a novel experimental procedure to evaluate the role of working memory (WM) load, attentional focus, and reward sensitivity. The study included 24 children with ADHD and 23 typically-developing controls. The experimental paradigm comprised one baseline condition (BC), only including an ongoing task, and four PM conditions, varying for targets: 1 Target (1T), 4 Targets (4T), Unfocal (UN), and Reward (RE). Children with ADHD were slower than controls on all PM tasks and less accurate on both ongoing and PM tasks on the 4T and UN conditions. Within the ADHD group, the accuracy in the RE condition did not differ from BC. A significant relationship between ADHD-related symptoms and reduced accuracy/higher speed in PM conditions (PM and ongoing trials), but not in BC, was detected. Our data provide insight on the adverse role of WM load and attentional focus and the positive influence of reward in the PM performance of children with ADHD. Moreover, the relation between PM and ADHD symptoms paves the road for PM as a promising neuropsychological marker for ADHD diagnosis and intervention.