Urinary polyomavirus infections in neurodevelopmental disorders

We have recently reported enhanced frequencies of polyomavirus infection in post-mortem brain tissue of autistic patients compared to controls. To further explore potential contributions to neurodevelopmental disorders by polyomaviruses, we have employed specie-specific TaqMan assays to assess the prevalence and titres of BKV, JCV and SV40 inthe urines of 87 patients with autism spectrum disorder, 84 controls matched by sex and age with the autistic sample, 15 subjects with Down syndrome and 13 fragile X individuals. Prevalence rates of urinary BKV infection were significantly greater in Down syndrome and fragile X patients compared to autistic and control individuals (

Clinical and neurobiological indices of the developmental trajectories of autism in preschool age

This thesis collects doctoral studies about developmental trajectories of autism in preschooler age and clinical and neurobiological indices of the different outcomes observed. The work has been organized into five parts. In particular, the first report regards a review study on the new diagnostic classification of Autism Spectrum Disorders (hereinafter referred to as ASD) in DSM-5. The second work is a collection of doctoral studies about diagnostic stability of ASD between 3 and 5 years of age. According to this study, Autistic Disorder (herein after referred to as AD) diagnosis is more stable than Pervasive Developmental Disorder Not Otherwise Specified (hereinafter referred to as PDD-NOS); the amount and type of treatment are not strictly related to the outcome; upon their first evaluation at about 3 y.o., ADOS Calibrated Severity Score (CSS), but not non verbal IQ (nvIQ), may be hypothesized to be a predictive factor of the outcome in ASD children. The third study has been carried out with the collaboration of The Italian Autism Network (ITAN) study, a large national multi-centric project initiated by SmithKline Foundation with the aim of collecting biological materials (DNA, RNA, plasma and lymphoblastoid cell lines) and clinical and functional data from ASD probands in order to test whether some genetic markers already scrutinized in Autism Studies are actually associated with ADSs in a newly collected Italian ASD cohort. A significant association was found for two of seven markers: rs4307059 T allele and rs35678 TC genotype located at loci previously associated with social and verbal communication skills. The fourth study has been carried out in collaboration with Prof. Persico’s research group (Child and Adolescent Neuro Psychiatry Unit at the University "Campus Bio-Medico" of Rome). It is a multi-centric study in which urinary levels of p-cresol have been found to be significantly higher in 59 non-syndromic autistic children than in 59 tightly age- and sex-matched controls. Moreover, p-cresol levels have been found to be significantly higher in female autistic children if compared to males, in more severely affected autistic children regardless of their sex, and in children who experienced regressive onset. In the fifth and last work we have studied 36 autistic subjects of whom we have collected data on developmental clinical profiles and urinary samples, thus analyzing the concentrations of total urinary p-cresol. The aims of this study are not only to confirm an elevation of this toxic compound in ASD children, but also to check for correlations between p-cresol levels on the one hand, and the clinical phenotypes and developmental profiles on the other hand

Parental perspectives on psychiatric comorbidity in preschoolers with autism spectrum disorders receiving publicly funded mental health services

An increased prevalence of psychiatric comorbidity (PC) in individuals with Autism Spectrum Disorders (ASD) is consistently reported. While several studies have examined PC in school-aged children, adolescents and adults with ASD, investigations on PC in preschoolers are less common. In this study, we explore the prevalence and the type of PC in a sample of 989 preschoolers with ASD through the DSM-Oriented Scales (DOS) of the Child Behavior Checklist (CBCL 1½-5) and their possible links with the core features of ASD and cognitive functioning. Results indicated that 37.8% of the sample had at least one PC in addition to ASD; these subjects displayed significantly higher Total score (p = 0.02) and Social Affect score (p = 0.003) on the ADOS-based calibrated severity scores (CSS), as well as lower (p ≤ 0.0001) performance IQ (pIQ) compared to ASD individuals without PC. As far as the specific DOS, Affective Problems (AP) were detected in 23.4% of the whole sample, ADHD Problems (ADHD) in 17.3%, Anxiety Problems (AXP) in 16.7%, and Oppositional Problems (OP) in 7.9%. These different comorbidities were isolated in 195 subjects (Mono-comorbid group: 19.7% of the whole sample), while 179 subjects (18.1% of the whole sample) had two or more types of PC (Multi-comorbid group). One-way ANOVA revealed that subjects with multi-comorbidity have statistically significant lower pIQ and higher Total score and Social Affect score on CSS-ADOS. Specific differences for each type of comorbidity and gender differences were also discussed. Taken together, results indicate a considerable presence of PC in preschoolers with ASD that should be accurately considered during the assessment and diagnosis process in order to plan a tailored intervention based not only on core symptoms of ASD, but also on comorbid psychiatric condition since preschool age

Gut to brain interaction in Autism Spectrum Disorders: A randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters

Background: A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a "gut-brain axis" disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx®) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD. Methods: A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns. Discussion: The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD. Trial registration: ClinicalTrials.gov Identifier: NCT02708901. Retrospectively registered: March 4, 2016

Serological screening for Celiac Disease in 382 pre-schoolers with Autism Spectrum Disorder

Background: Recent investigations suggest a possible common genetic background between Autism Spectrum Disorders (ASD) and Celiac Disease (CD). However, studies regarding this association are scarce and often limited by the small sample sizes and/or large heterogeneity among ASD groups in terms of demographic and clinical features. The present study aims to investigate the overall CD prevalence (biopsy proven-CD patients plus screening detected tTG and EMA positive cases) in a large population of pre-schoolers with ASD referred to a tertiary care University Hospital. Methods: We retrospectively collected data about 382 children (mean age: 46.97 ± 13.55 months; age-range: 18-72 months) consecutively diagnosed as ASD (according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria) over the period 2010-2013, and who performed a serological CD screening. Results: The overall CD prevalence was 2.62%, which is statistically significant higher to that reported in the Italian paediatric population (p = 0.0246). Half of these children had no symptoms or risk factors related to CD when they performed the serological screening. Conclusions: If replicated, these data suggest the importance of regular screening for CD in young patients with ASD, and are of relevance for clinical and public health

Sex Differences in Autism Spectrum Disorder: An Investigation on Core Symptoms and Psychiatric Comorbidity in Preschoolers

Findings regarding sex differences in autism spectrum disorder (ASD), as far as core symptoms and psychiatric comorbidities (PC) are concerned, are inconsistent, inconclusive, or conflicting among studies. The lower prevalence of ASD in females than in males and the age and intelligence quotient (IQ) heterogeneity among samples made it difficult to investigate these differences. This case–control study tries to deepen the impact of sex differences on core symptoms of autism and PC in 214 preschoolers with ASD (mean age, 45.26) without impairment in non-verbal IQ (nvIQ ≥70). A total of 107 ASD females (mean age, 44.51 ± 13.79 months) were matched one by one with 107 males (mean age, 46.01 ± 13.42 months) for chronological age (±6 months) and nvIQ (±6 points). We used the Autism Diagnostic Observation Schedule 2 (ADOS-2) and the Child Behavior Checklist (CBCL) 1.5–5 to explore autism severity and PC. The results highlight that ASD females did not significantly differ from ASD males regarding the severity of autism. Statistically significant lower levels of emotionally reactive (p = 0.005, η2 = 0.04), anxious-depressed (p = 0.001, η2 = 0.05), internalizing problems (p = 0.04, η2 = 0.02), and DSM-Oriented Scales anxiety problems (p = 0.02, η2 = 0.04) in ASD females than in ASD males were also detected. Our findings of no difference in the autism severity and lower internalizing problems in females than males with ASD extend the knowledge of autism in females during preschool years. Compared to other similar studies on this topic, we can state that these results are not supported by differences in nvIQ between sexes nor by the presence of cognitive impairment. It confirms the need for clinicians to consider sex differences when describing autism psychopathology

Parental Perspectives on Psychiatric Comorbidity in Preschoolers With Autism Spectrum Disorders Receiving Publicly Funded Mental Health Services

An increased prevalence of psychiatric comorbidity (PC) in individuals with Autism Spectrum Disorders (ASD) is consistently reported. While several studies have examined PC in school-aged children, adolescents and adults with ASD, investigations on PC in preschoolers are less common. In this study, we explore the prevalence and the type of PC in a sample of 989 preschoolers with ASD through the DSM-Oriented Scales (DOS) of the Child Behavior Checklist (CBCL 1½-5) and their possible links with the core features of ASD and cognitive functioning. Results indicated that 37.8% of the sample had at least one PC in addition to ASD; these subjects displayed significantly higher Total score (p = 0.02) and Social Affect score (p = 0.003) on the ADOS-based calibrated severity scores (CSS), as well as lower (p ≤ 0.0001) performance IQ (pIQ) compared to ASD individuals without PC. As far as the specific DOS, Affective Problems (AP) were detected in 23.4% of the whole sample, ADHD Problems (ADHD) in 17.3%, Anxiety Problems (AXP) in 16.7%, and Oppositional Problems (OP) in 7.9%. These different comorbidities were isolated in 195 subjects (Mono-comorbid group: 19.7% of the whole sample), while 179 subjects (18.1% of the whole sample) had two or more types of PC (Multi-comorbid group). One-way ANOVA revealed that subjects with multi-comorbidity have statistically significant lower pIQ and higher Total score and Social Affect score on CSS-ADOS. Specific differences for each type of comorbidity and gender differences were also discussed. Taken together, results indicate a considerable presence of PC in preschoolers with ASD that should be accurately considered during the assessment and diagnosis process in order to plan a tailored intervention based not only on core symptoms of ASD, but also on comorbid psychiatric condition since preschool age

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

L’autismo nel DSM-5

Negli ultimi 10 anni è stato condotto dagli esperti DSM-5 un intenso lavoro di revisione della letteratura e dei dati disponibili allo scopo di giungere a una nuova classificazione dei Disturbi dello Spettro Autistico che fosse affidabile e valida sia per gli scopi clinici che di ricerca. Obiettivo: Descrivere i nuovi criteri DSM-5 per l’autismo e discutere le motivazioni sottostanti alle modifiche apportate rispetto alla precedente versione del manuale. Metodologia: Vengono presi in esame i principali quesiti inerenti la nosologia dell’autismo che i revisori hanno affrontato con particolare riferimento ai “core domain” del disturbo, all’eliminazione del ritardo del linguaggio dai criteri diagnostici, alla scelta di una unica categoria diagnostica, alle relazioni tra il nuovo sistema di classificazione e i recenti progressi in campo neurobiologico. Discussione: vengono commentate le novità nella classificazione DSM 5 dell’autismo rispetto alle precedenti classificazioni ma anche i quesiti che restano ancora aperti e i successivi orientamenti della ricerca in questo campo