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Transgender and gender-diverse (TGD) individuals continue to experience harassment and discrimination across various aspects of life, significantly impacting their physical and mental health. The scarcity of data on their general health, particularly regarding dietary habits, remains a challenge in developing effective healthcare strategies for this population. To address this gap, we analyzed selected dietary habits, physical activity (PA), and body mass index (BMI) among Italian TGD adults compared to the Italian general population (IGP). An online anonymous survey was conducted via the Computer Assisted Web Interviewing technique from June 2020 to June 2021. Participants were enrolled through clinical centers and TGD organizations. Data from 959 TGD adults were analyzed using chi-squared tests and logistic regression models. Key findings indicated that approximately 70% of TGD individuals consumed fewer servings of fruit and vegetables (FV) than recommended (five or more servings per day). Although red meat consumption was lower overall, a greater percentage of TGD individuals reported consuming more than three servings per week. Additionally, 58% of TGD participants indicated that they did not engage in any PA, compared to 36% of the IGP. Notably, significant differences in BMI were identified, with higher rates of overweight and obesity among TGD individuals assigned female at birth. These results underscore the urgent need for tailored nutritional guidelines and inclusive public health strategies to meet the specific health needs of the Italian TGD population. Expanding access to targeted interventions could contribute to improving overall well-being in this marginalized group.

ABSTRACTHealthcare workers (HCWs) are the target population for vaccination against coronavirus disease (COVID-19) as they are at a high risk of exposure and transmission of pathogens to patients. Neutralizing antibodies developed after COVID-19 vaccination decline within few months of vaccination. Several factors, including age and sex, can affect the intensity, efficacy, and duration of immune response to vaccines. However, sex-specific analyses of humoral responses to COVID-19 vaccines are lacking. This study aimed to evaluate sex-based differences in anti-S/RBD (Receptor Binding Domain) responses at three different time points after the second dose of mRNA COVID-19 vaccine in HCWs in relation to age, and to investigate the role of sex hormones as potential markers of response. Anti-S/RBD levels after two doses of the mRNA vaccine were collected from 521 HCWs naïve to COVID-19, working at two Italian Clinical Centers. Multiple regression analysis was applied to evaluate the association between anti-S levels and sex, age, and plasma levels of sex hormones. Significantly higher anti-S/RBD response to the COVID-19 vaccination was found in female HCWs, and a significant and more abrupt decline in response with time was observed in women than that in men. A novel, positive association of testosterone plasma levels and higher anti-S levels in male HCWs was found, suggesting its potential role as sex specific marker in males. In conclusion, understanding the sex-based differences in humoral immune responses to vaccines may potentially improve vaccination strategies and optimize surveillance programs for HCWs.

Background: Cognitive functions represent foundational factors for mental health and quality of life (QoL). In Tourette syndrome (TS), psychiatric comorbidities are common and have been inconsistently reported to affect the cognition and QoL of patients, while the role of tic disorder duration has not been yet explored. Methods: To examine how comorbidities and TS duration may influence cognition and QoL, N = 80 children with TS (6–16 years) were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Standardized questionnaires were used to assess the presence and severity of TS main comorbidities and QoL. Data were interpreted using linear correlations, regression, and mediation analysis. Results: Depression and attention-deficit/hyperactivity disorder (ADHD) symptoms accounted for poorer cognitive performance. Anxiety oppositely predicted better cognitive performance, while no significant role for obsessive compulsive disorder (OCD) was observed. Disease duration was associated with lower total IQ, verbal reasoning, and working memory abilities. Depression, anxiety, and TS duration also deeply influenced QoL measures. Conclusions: TS common comorbidities have a differential impact on the cognitive abilities of children and adolescents, which translates into a complex influence on their perceived QoL. A longer clinical history of tics was related to worse cognitive outcomes, which prompts further consideration of disease duration in both clinical and research settings involving children and adolescents.

Abstract The serotonin-transporter-linked promoter region (5-HTTLPR) has been widely investigated as contributing to depression vulnerability. Nevertheless, empirical research provides wide contrasting findings regarding its involvement in the etiopathogenesis of the disorder. Our hypothesis was that such discrepancy can be explained considering time as moderating factor. We explored this hypothesis, exploiting a meta analytic approach. We searched PubMed, PsychoINFO, Scopus and EMBASE databases and 1096 studies were identified and screened, resulting in 22 studies to be included in the meta-analyses. The effect of the 5-HTTLPR x stress interaction on depression risk was found to be moderated by the following temporal factors: the duration of stress (i.e. chronic vs. acute) and the time interval between end of stress and assessment of depression (i.e. within 1 year vs. more than 1 year). When stratifying for the duration of stress, the effect of the 5-HTTLPR x stress interaction emerged only in the case of chronic stress, with a significant subgroup difference (p = 0.004). The stratification according to time interval revealed a significant interaction only for intervals within 1 year, though no difference between subgroups was found. The critical role of time interval clearly emerged when considering only chronic stress: a significant effect of the 5-HTTLPR and stress interaction was confirmed exclusively within 1 year and a significant subgroup difference was found (p = 0.01). These results show that the 5-HTTLPR x stress interaction is a dynamic process, producing different effects at different time points, and indirectly confirm that s-allele carriers are both at higher risk and more capable to recover from depression. Overall, these findings expand the current view of the interplay between 5-HTTLPR and stress adding the temporal dimension, that results in a three-way interaction: gene x environment x time.

IntroductionItaly is one of the high-income countries hit hardest by Covid-19. During the first months of the pandemic, Italian healthcare workers were praised by media and the public for their efforts to face the emergency, although with limited knowledge and resources. However, healthcare workers soon had to face new challenges at a time when the national health system was working hard to recover. This study focuses on this difficult period to assess the impact of the COVID-19 pandemic on the mental health of Italian healthcare workers.Materials and MethodsHealthcare workers from all Italian regions [n = 5,502] completed an online questionnaire during the reopening phase after the first wave lockdown. We assessed a set of individual-level factors (e.g., stigma and violence against HCWs) and a set of workplace-level factors (e.g., trust in the workplace capacity to handle COVID-19) that were especially relevant in this context. The primary outcomes assessed were score ≥15 on the Patient Health Questionnaire-9 and score ≥4 on the General Health Questionnaire-12, indicators of clinically significant depressive symptoms and psychological distress, respectively. Logistic regression analyses were performed on depressive symptoms and psychological distress for each individual- and workplace-level factor adjusting for gender, age, and profession.ResultsClinically significant depressive symptoms were observed in 7.5% and psychological distress in 37.9% of HCWs. 30.5% of healthcare workers reported having felt stigmatized or discriminated, while 5.7% reported having experienced violence. Feeling stigmatized or discriminated and experiencing violence due to being a healthcare worker were strongly associated with clinically significant depressive symptoms [OR 2.98, 95%CI 2.36–3.77 and OR 4.72 95%CI 3.41–6.54] and psychological distress [OR 2.30, 95%CI 2.01–2.64 and OR 2.85 95%CI 2.16–3.75]. Numerous workplace-level factors, e.g., trust in the workplace capacity to handle COVID-19 [OR 2.43, 95%CI 1.92–3.07] and close contact with a co-worker who died of COVID-19 [OR 2.05, 95%CI 1.56–2.70] were also associated with clinically significant depressive symptoms. Similar results were found for psychological distress.ConclusionsOur study emphasizes the need to address discrimination and violence against healthcare professionals and improve healthcare work environments to strengthen the national health system's capacity to manage future emergencies.

Reactive astrogliosis is one of the pathological hallmarks of prion diseases. Recent studies highlighted the influence of several factors on the astrocyte phenotype in prion diseases, including the brain region involved, the genotype backgrounds of the host, and the prion strain. Elucidating the influence of prion strains on the astrocyte phenotype may provide crucial insights for developing therapeutic strategies. Here, we investigated the relationship between prion strains and astrocyte phenotype in six human- and animal-vole-adapted strains characterized by distinctive neuropathological features. In particular, we compared astrocyte morphology and astrocyte-associated PrPSc deposition among strains in the same brain region, the mediodorsal thalamic nucleus (MDTN). Astrogliosis was detected to some extent in the MDTN of all analyzed voles. However, we observed variability in the morphological appearance of astrocytes depending on the strain. Astrocytes displayed variability in thickness and length of cellular processes and cellular body size, suggesting strain-specific phenotypes of reactive astrocytes. Remarkably, four out of six strains displayed astrocyte-associated PrPSc deposition, which correlated with the size of astrocytes. Overall, these data show that the heterogeneous reactivity of astrocytes in prion diseases depends at least in part on the infecting prion strains and their specific interaction with astrocytes.

ObjectiveTo evaluate the clinical effectiveness of online remote behavior therapy, compared with face-to-face therapy in reducing tics and co-occurring disorders associated with the tics in a sample of youths with Tourette Syndrome.DesignA randomized controlled trial. TS patients were randomized to receive face-to-face or online remote behavior therapy.Participants40 children aged between 9 and 16 years affected by Tourette Syndrome.ResultsOnline remote and face-to-face behavior therapy are equally effective in the treatment of tics and co-occurring disorders in children and adolescents affected by Tourette Syndrome. Both groups showed an improvement in the severity of tics, obsessive-compulsive symptoms, and anxiety symptoms, as assessed by neuropsychological findings. Online remote behavior therapy was more effective for reducing depressive symptoms than face-to-face behavior therapy.ConclusionsOnline remote behavior therapy is a promising tool for behavioral therapies for patients with Tourette Syndrome and may represents an alternative treatment option.

Metabolic syndrome (MetS) represents one of the greatest challenges to public health given its serious consequences on cardiovascular diseases and type 2 diabetes. A carbohydrate-restricted, low-fat diet is the current therapy for MetS. Natural mineral waters (NMWs) are known to exert beneficial effects on human health. Our primary objective was to shed light on the potential therapeutic properties of NMWs in MetS. A total of 125 C57BL/6 male and female mice were included in the study. Of these, 10 were left untreated. They were fed a standard diet with tap water throughout the study period, and stayed healthy. The remaining 115 mice were initially fed a high-calorie diet (HCD) consisting of a high-fat feed (60% of energy from fat) with 10% fructose in tap water, served ad libitum over a period of 4 months to induce MetS (the MetS induction phase). Mice were then randomly divided into six treatment groups and a control group, all of which received a low-calorie diet (LCD), but with a different kind of drinking water, for 2 months (the treatment phase). Five groups were each treated with a different kind of NMW, one group by alternating the five NMWs, and one group – the control group – was given tap water. Body weight and blood biochemistry were monitored over the 6-month trial. After 4 months, male and female mice on HCD developed obesity, hypercholesterolaemia and hyperglycaemia, although gains in body weight, total cholesterol, and blood glucose in males were greater than those observed in females (P < 0.0001). When combined with an LCD, the NMWs rich in sulphate, magnesium and bicarbonate, and the minimally mineralised one were the most effective in reducing the blood levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, and glucose. Sex differences emerged during both the MetS induction phase and the treatment phase. These results suggest that NMWs rich in specific macronutrients, such as bicarbonate, sulphate and magnesium, and minimally mineralised water, in combination with an LCD, may contribute to controlling blood lipid and glucose levels in subjects with MetS. Further studies are needed to confirm these results and to extend them to humans.

Maternal infections during pregnancy and the consequent maternal immune activation (MIA) are the major risk factors for autism spectrum disorder (ASD). Epidemiological evidence is corroborated by the preclinical models in which MIA leads to ASD-like behavioral abnormalities and altered neuroinflammatory profiles, with an increase in pro-inflammatory cytokines and microglial markers. In addition to neuroinflammatory response, an abnormal expression of endogenous retroviruses (ERVs) has been identified in neurodevelopmental disorders and have been found to correlate with disease severity. Our aim was to evaluate the transcriptional profile of several ERV families, ERV-related genes, and inflammatory mediators (by RT real-time PCR) in mouse offspring of both sexes, prenatally exposed to polyinosinic:polycytidylic acid (Poly I:C), a synthetic double-stranded RNA molecule targeting TLR-3 that mimics viral maternal infection during pregnancy. We found that prenatal exposure to Poly I:C deregulated the expression of some ERVs and ERV-related genes both in the prefrontal cortex (PFC) and hippocampus, while no changes were detected in the blood. Interestingly, sex-related differences in the expression levels of some ERVs, ERV-related genes, and inflammatory mediators that were higher in females than in males emerged only in PFC. Our findings support the tissue specificity of ERV and ERV-related transcriptional profiles in MIA mice.

We are very honoured by the collaboration we had with the editorial staff of Brain Sciences for the realization of the special issue “Epidemiology of ASD Services: Unmet Need, Barriers and Innovative Solutions” [...]

Promoting a healthy diet, mainly in youths, is the most effective action to prevent and fight dietary excesses and nutritional imbalance in the population. MaestraNatura (MN) is an innovative nutritional education program aimed at promoting a healthy lifestyle in first-level secondary school students. The study evaluated the effectiveness of the MN program in improving knowledge in students following the MN program (MN group) with respect to a control group (CO group) undergoing a “traditional” nutritional education path. To this end, the nutrition knowledge of the two groups was assessed by three multi-choice questionnaires. The results showed a significant improvement in knowledge (p < 0.001) in the MN group with respect to the CO group for all the questionnaires. Furthermore, the students’ ability to transfer the principles of nutrition guidelines to the real context of daily meals was determined by asking the MN group to create a weekly food plan before (T0) and after (T1) the completion of the MN program. The MN group demonstrated improved performance in organizing the weekly menu plan at T1 with respect to T0 (p = 0.005). In conclusion, the MN nutritional education program appears to be an effective tool for improving knowledge and skills on nutritional issues, especially in those students with a lower starting level of knowledge and ability.

Remote methods for data collection allow us to quickly collect large amounts of data, offering several advantages as compared to in-lab administration. We investigated the applicability of an online assessment of motor, cognitive, and communicative development in 4-month-old infants based on several items of the Bayley Scales of Infant Development, 3rd edition (BSID-III). We chose a subset of items which were representative of the typical developmental achievements at 4 months of age and that we could administer online with the help of the infant’s caregiver using materials which were easily available at home. Results showed that, in a sample of infants tested live (N = 18), the raw scores of the BSID-III were significantly correlated with the raw scores of a subset of items corresponding to those administered to a sample of infants tested online (N = 53). Moreover, for the “online” participants, the raw scores of the online assessment did not significantly differ from the corresponding scores of the “live” participants. These findings suggest that the online assessment was to some extent comparable to the live administration of the same items, thus representing a viable opportunity to remotely evaluate infant development when in-person assessment is not possible.

During the early stages of the coronavirus disease 2019 (COVID-19) pandemic in Italy, an online survey was launched via a local patient advocacy website to investigate mental health issues in children and adolescents with Tourette syndrome (TS). Respondents were parents, who were asked to report on their child's general health, tics, comorbidities/problems, pharmacological treatment/psychotherapy, symptom variations, and daily routine, as well as on their family's health and work experiences during the pandemic. Two hundred thirty-eight people participated in the survey, 203 females and 35 males. Our findings indicate that, in the time window of 4–6 weeks after the beginning of the COVID-19-related lockdown, 67% of individuals with TS developed a relevant worsening of the overall clinical condition as rated by their parents. An improvement or no variation of the clinical picture was reported in 20.5 and 6.7% of cases, respectively. Most worsened symptoms included tics, hyperactivity, rage attacks, obsessions/compulsions, and anxiety. Of the subjects experiencing a clinical worsening, the majority (51.76%) showed variations across two to five symptom domains. No association was found between symptom variation and family demographics or health and economic issues specifically related to the lockdown. The current COVID-19 pandemic is exerting a considerable impact on the mental health of young individuals with TS by worsening both tics and emotional and behavioral symptoms.

The organisms of most domains of life have adapted to circadian changes of the environment and regulate their behavior and physiology accordingly. A particular case of such paradigm is represented by some types of host-pathogen interaction during infection. Indeed, not only some hosts and pathogens are each endowed with their own circadian clock, but they are also influenced by the circadian changes of the other with profound consequences on the outcome of the infection. It comes that daily fluctuations in the availability of resources and the nature of the immune response, coupled with circadian changes of the pathogen, may influence microbial virulence, level of colonization and damage to the host, and alter the equilibrium between commensal and invading microorganisms. In the present review, we discuss the potential relevance of circadian rhythms in human bacterial and fungal pathogens, and the consequences of circadian changes of the host immune system and microbiome on the onset and development of infection. By looking from the perspective of the interplay between host and microbes circadian rhythms, these concepts are expected to change the way we approach human infections, not only by predicting the outcome of the host-pathogen interaction, but also by indicating the best time for intervention to potentiate the anti-microbial activities of the immune system and to weaken the pathogen when its susceptibility is higher.

Overall, the present pilot study provides detailed information on clinical management for Autism Spectrum Disorder (ASD) referral and diagnosis processes that are mandatory for child and adolescent mental health management. The analysis of ASD management, even if carried out on a selected sample of Child and Adolescent Mental Health (CAMH) units, represents a good approximation of how, in Italian outpatient settings, children and adolescents with ASD are recognised and eventually diagnosed. One of the aims of the study was to verify the adherence of Italian CAMH units to international recommendations for ASD referral and diagnosis and whether these processes can be traced using individual chart reports. Overall, the analysis evidenced that Italian CAMH units adopt an acceptable standard for ASD diagnosis, although the reporting of the ASD managing process in the individual chart is not always accurate. Furthermore, data collected suggest some improvements that CAMH units should implement to fill the gap with international recommendations, namely, establishing a multidisciplinary team for diagnosis, improving the assessment of physical and mental conditions by the use of standardised tools, implementing a specific assessment for challenging behaviours that could allow timely and specific planning of intervention.

Abstract Five patients with paroxysmal nocturnal haemoglobinuria and thrombotic complications under oral antithrombotic treatment with vitamin K antagonist were switched to receive the direct oral anticoagulant rivaroxaban an factor Xa inhibitor. In all five patients haematological and biochemical parameters and adverse events were evaluated for a period of twelve months. Therapy with rivaroxaban was well tolerated in all cases and one patient showed a significant reduction of bleeding and transfusion requirement. All patients obtained a significant reduction in days of hospitalization with a consequent improvement in their quality of life after rivaroxaban treatment.

Background: The Quantitative Checklist for Autism in Toddlers (Q-CHAT) is parent-report screening questionnaire for detecting threshold and sub-threshold autistic features in toddlers. The Q-CHAT is a dimensional measure normally distributed in the general population sample and is able to differentiate between a group of children with a diagnosis of autism and unselected toddlers.Objectives: We aim to investigate the psychometric properties, score distribution, and external validity of the Q-CHAT in an Italian clinical sample of young children with autism versus children with developmental delay and typically developing children.Method: N = 126 typically developing children (TD), n = 139 children with autism, and n = 50 children presenting developmental delay (DD) were administered the Q-CHAT. Standardized measures of cognitive functions, language, and behaviors were also obtained.Results: The Q-CHAT scores were normally distributed and demonstrated adequate internal consistency and good item to total score correlations. The mean Q-CHAT score in the autism group was significantly higher than those found in the DD sample and TD children. No difference on the mean Q-CHAT score between DD and TD children was found. The accuracy of the Q-CHAT to discriminate between autism and TD was very good. Two different cut-points (27 and 31, respectively) maximized sensitivity and specificity for autism versus TD and DD, respectively. Finally, higher Q-CHAT scores were correlated with lower language and social communication skills.Conclusions: In clinical settings, the Q-CHAT demonstrated good psychometric properties and external validity to discriminate autism children not just from children with typical development but also from children with developmental delay.

Background and Objectives: Feeding problems occur more frequently among children with Autism spectrum disorder (ASD). The aim of this study was to analyse eating difficulties of ASD children through the direct observation of the caregiver-child co-regulation system.Methods: We compared 60 ASD children with a control group of 50 typically developing Italian children on the Scale for the Assessment of Feeding Interaction (SVIA). The Brief Autism Mealtime Behaviour Inventory (BAMBI) was used to define the presence of an eating disorder.Results: The ASD group showed higher scores on all dimensions of the SVIA compared to the control group. The SVIA and the BAMBI showed significant correlations. In a second step, the ASD sample was divided into two subgroups, children with and without feeding difficulties. The comparison between the ASD subgroups with the control group on the SVIA scales showed significant differences on all dimensions. Finally, significant differences emerged between the two ASD subgroups in three SVIA dimensions.Conclusion: These data suggest the importance of direct observation of feeding in the assessment of children with ASD. The SVIA seems to be able to point out some feeding difficulties in these subjects and to discriminate ASD with and without an eating disorder. Critical aspects of the application of SVIA to autistic children are discussed.

MaestraNatura is an innovative nutrition education program aimed at both enhancing awareness about the importance of a healthy food–lifestyle relationship and the ability to transfer the theoretical principles of nutrition guidelines to everyday life. The educational contents of the program resulted from the analysis of the answers to a questionnaire submitted to students aged 6–13 in order to assess their degree of knowledge about nutritional facts. Educational paths were specifically designed and implemented to address the main knowledge gaps identified through the analysis of the answers and were then tested for teachers’ satisfaction in a sample of 56 schools in the north, centre, and south of Italy, involving 790 classes, 600 teachers, and 15,800 students. The results showed an approval rating from teachers from 90% to 94%. Said paths were designed for primary (6–10 years old) and first-level secondary (11–13 years old) school students. In addition, in a pilot study carried out in nine Educational Institutes located in an area close to Rome (Lazio region), a specific path was tested for effectiveness in increasing students’ knowledge about fruit and vegetables by conducting questionnaires before (T0) and after (T1) the didactic activities. Results showed a significant increase in right answers at T1 with respect to T0 (z = 2.142, p = 0.032). Fisher’s exact probability test showed an answer variability depending on the issue considered. In conclusion, this work could be considered as a first necessary step toward the definition of new educational program, aimed at increasing food literacy and favouring a healthier relationship with food, applicable in a widespread and effective manner, also outside of Italy.

In the past two decades, several screening instruments were developed to detect toddlers who may be autistic both in clinical and unselected samples. Among others, the Quantitative CHecklist for Autism in Toddlers (Q-CHAT) is a quantitative and normally distributed measure of autistic traits that demonstrates good psychometric properties in different settings and cultures. Recently, machine learning (ML) has been applied to behavioral science to improve the classification performance of autism screening and diagnostic tools, but mainly in children, adolescents, and adults. In this study, we used ML to investigate the accuracy and reliability of the Q-CHAT in discriminating young autistic children from those without. Five different ML algorithms (random forest (RF), naïve Bayes (NB), support vector machine (SVM), logistic regression (LR), and K-nearest neighbors (KNN)) were applied to investigate the complete set of Q-CHAT items. Our results showed that ML achieved an overall accuracy of 90%, and the SVM was the most effective, being able to classify autism with 95% accuracy. Furthermore, using the SVM–recursive feature elimination (RFE) approach, we selected a subset of 14 items ensuring 91% accuracy, while 83% accuracy was obtained from the 3 best discriminating items in common to ours and the previously reported Q-CHAT-10. This evidence confirms the high performance and cross-cultural validity of the Q-CHAT, and supports the application of ML to create shorter and faster versions of the instrument, maintaining high classification accuracy, to be used as a quick, easy, and high-performance tool in primary-care settings.

The prevalence of Autism Spectrum Disorder (ASD) has increased dramatically in recent decades, supporting the claim of an autism epidemic. Systematic monitoring of ASD allows estimating prevalence and identifying potential sources of variation over time and geographical areas. At present, ASD prevalence estimates are available worldwide, coming either from surveillance systems using existing health and educational databases or from population studies specifically performed. In the present article, we present a review of the ASD prevalence estimates published since 2014. Data confirm a high variability in prevalence across the world, likely due to methodological differences in case detection, and the consistent increase of prevalence estimates within each geographical area.

ContextThe existing literature on the treatment of pediatric chronic tic disorder (CTD) and Tourette syndrome (TS) indicates that both behavioral therapy (BT) and pharmacotherapy (PT) are effective for reducing symptoms.ObjectiveTo evaluate the efficacy of BT compared to psychoeducation (PE) or PT for reducing tics and co-occurring symptoms and for improving quality of life (QoL) in a sample of youths with CTD and TS.DesignA 10 weeks, 2 sites (Catania, Rome) randomized controlled trial. Participants were randomized to receive one of the following treatments: BT, PE, or PT.Participants110 outpatients aged between 8 and 17 years affected by CTD or TS.ResultsPatients in the BT and PT groups showed a significant reduction in the severity of tic symptoms, while the PE group did not show any improvement. PT was more effective for reducing obsessive compulsive symptoms than BT, while PE group did not show any improvement. Both BT and PT groups showed an improvement in most QoL domains, whereas no differences were found in the PE group.ConclusionsBT is as effective as pharmacological therapy in the treatment of tic disorders in children and adolescents, thus offering an alternative to medications for CTD and TS.

A significant body of evidence supports the multifactorial etiology of neurodevelopmental disorders (NDDs) affecting children. The present review focuses on early exposure to environmental chemicals as a risk factor for neurodevelopment, and presents the major lines of evidence derived from epidemiological studies, underlying key uncertainties and research needs in this field. We introduce the exposome concept that, encompassing the totality of human environmental exposures to multiple risk factors, aims at explaining individual vulnerability and resilience to early chemical exposure. In this framework, we synthetically review the role of variable gene backgrounds, the involvement of epigenetic mechanisms as well as the function played by potential effect modifiers such as socioeconomic status. We describe laboratory rodent studies where the neurodevelopmental effects of environmental chemicals are assessed in the presence of either a “vulnerable” gene background or adverse pregnancy conditions (i.e., maternal stress). Finally, we discuss the need for more descriptive and “lifelike” experimental models of NDDs, to identify candidate biomarkers and pinpoint susceptible groups or life stages to be translated to large prospective studies within the exposome framework.

Brain damage of various aetiologies can lead to different disorders of consciousness (DOC), varying from coma to vegetative, to minimally conscious states. Each state is characterised by a different degree of wakefulness, awareness, pain sensitivity and is differentially handled with respect to treatment, ethical considerations and end-of-life decisions. Thus, its correct identification is crucial while devising or modulating appropriate treatment strategies. Actually, the main coma scales cannot always accurately determine the state of consciousness of an individual, while other tools (e.g. imaging techniques) present a certain degree of uncertainty. A complementary approach may be constituted by a 24-hour observation of patients, for a sufficient period of days, using an ad hoc behavioural scale, further correlated with physiological and pharmacological parameters measured on patients. The method herein described might help recognising the presence of consciousness of the different DOC patients, and thus discerning a vegetative from a minimally conscious state.

Introduction: Motor stereotypies represent a typical example of the difficulty in distinguishing non-clinical behaviors (physiological and transient) from symptoms or among different disorders (primary stereotypies, associated with Autistic Spectrum Disorder (ASD), Intellectual Disabilities, genetic syndromes, sensory impairment). The aim of this study was to obtain an accurate assessment on the relationship between stereotypies and neurodevelopmental disorders.Methods: We studied 23 children (3 girls) aged 36 to 95 months, who requested a consultation due to the persistence or increased severity of motor stereotypies. None of patients had a previous diagnosis of ASD. The assessment included the Motor Severity Stereotypy Scale (MSSS), the Repetitive Behavior Scale-Revised (RBS-R), the Raven’s Colored Progressive Matrices (CPM), the Child Behavior Checklist for ages 1 ½ -5 or 4-18 (CBCL), the Social Responsiveness Scale (SRS) and the Autism Diagnostic Observation Schedule- Second edition (ADOS 2). Results: All patients were showing motor stereotypies for periods of time varying from 6 to 77 months. The MSSS showed each child had a limited number of stereotypies; their frequency and intensity were mild. The interference of stereotypies was variable; the impairment in daily life was mild. The RBS-R scores were positive for the subscale of Stereotypic behaviors in all children. Moreover, several children presented other repetitive behaviors, mainly Ritualistic behavior and Sameness behavior. All patients showed a normal cognitive level. The CBCL evidenced behavioral problems in 22% of the children: Internalizing problems, Attention and Withdrawn were the main complaints. On the SRS, all but one of the tested patients obtained clinical scores in the clinical range for at least one area. On the ADOS 2, four patients obtained scores indicating a moderate level of ASD symptoms, four had a mild level and fifteen showed no or minimal signs of ASD.Discussion: Motor stereotypies in children with normal cognitive level represent a challenging diagnostic issue for which a finely tailored assessment is mandatory in order to define a precise developmental profile. Thus, careful and cautious use of standardized tests is warranted to avoid misdiagnosis. Furthermore, it is hard to consider motor stereotypies, even the primary ones, exclusively as a movement disorder.

The FISE (Federazione Italiana Sport Equestri) Pindar is a multicentre research project aimed at testing the potential effects of therapeutic riding on schizophrenic patients. Twenty-four subjects with a diagnosis of schizophrenia were enrolled for a 1 year-treatment involving therapeutic riding sessions. All subjects were tested at the beginning and at the end of treatment with a series of validated test batteries (BPRS and 8 items-PANSS). The results discussed in this paper point out an improvement in negative symptoms, a constant disease remission in both early onset and chronic disease subjects, as well as a reduced rate of hospitalization.

Mating success is linked to reproductive success in males, but parameters influencing it are poorly known. The relationships between lifetime mating success (LMS), fluctuating asymmetry (FA), body size (SIZE), reproductive period (RP) and emergence date (MD) of males of Cercion lindeni were investigated. Males were marked and photographed in their pre-reproductive period, and their matings monitored. RP was assumed to be the period between the MD and the last sighting of each individual. Three different FA measures and the size of each individual were determined. The results showed that the individuals not present at the pond during the reproductive period had a higher FA (but not for meristic characters) than those present. For those individuals actually involved in reproductive activity, LMS was only positively correlated with RP, which was negatively related with MD, and this with SIZE.

In mice behavioral response to pain is modulated by social status. Recently, social context also has been shown to affect pain sensitivity. In our study, we aimed to investigate the effects of interaction between status and social context in dyads of outbred CD-1 male mice in which the dominance/submission relationship was stable. Mice were assessed for pain response in a formalin (1% concentration) test either alone (individually tested-IT), or in pairs of dominant and subordinate mice. In the latter condition, they could be either both injected (BI) or only one injected (OI) with formalin. We observed a remarkable influence of social context on behavioral response to painful stimuli regardless of the social status of the mice. In the absence of differences between OI and IT conditions, BI mice exhibited half as much Paw-licking behavior than OI group. As expected, subordinates were hypoalgesic in response to the early phase of the formalin effects compared to dominants. Clear cut-differences in coping strategies of dominants and subordinates appeared. The former were more active, whereas the latter were more passive. Finally, analysis of behavior of the non-injected subjects (the observers) in the OI dyads revealed that dominant observers were more often involved in Self-grooming behavior upon observation of their subordinate partner in pain. This was not the case for subordinate mice observing the pain response of their dominant partner. In contrast, subordinate observers Stared at the dominant significantly more frequently compared to observer dominants in other dyads. The observation of a cagemate in pain significantly affected the observer's behavior. Additionally, the quality of observer's response was also modulated by the dominance/submission relationship.

BackgroundThe significance of behavioral neuroscience and the validity of its animal models of human pathology largely depend on the possibility to replicate a given finding across different laboratories. Under the present test and housing conditions, this axiom fails to resist the challenge of experimental validation. When several mouse strains are tested on highly standardized behavioral test batteries in different laboratories, significant strain x lab interactions are often detected. This limitation, predominantly due to elevated within-group variability observed in control subjects, increases the number of animals needed to address fine experimental questions. Laboratory rodents display abnormal stress and fear reactions to experimental testing, which might depend on the discrepancy between the stability of the neonatal environment and the challenging nature of the adult test and housing conditions.Methodology/principal findingsStimulating neonatal environments (e.g. brief maternal separations, increased foraging demands or maternal corticosterone supplementation) reduce stress and fear responses in adulthood. Here we tested whether reduced fearfulness associated with experimental testing would also reduce inter-individual variation. In line with our predictions, we show that a moderate elevation in neonatal corticosterone through maternal milk significantly reduces fear responses and inter-individual variability (average 44%) in adult mouse offspring.Conclusions/significanceWe observed reduced variation in pain perception, novelty preference, hormonal stress response and resistance to pathogen infection. This suggests that the results of this study may apply to a relatively broad spectrum of neuro-behavioral domains. Present findings encourage a reconsideration of the basic principles of neonatal housing systems to improve the validity of experimental models and reduce the number of animals used.