Titolo: Pregnancy risk factors related to autism: an Italian case-control study in mothers of children with ASD, their siblings and of typically developing children (2018)
Autore: Enzo Grossi, Lucia Migliore, Filippo Muratori
Info: Submitted to DOHAD Journal
The aim of this study was to assess the frequency of twenty-six potential risk factors for autism related to pregnancy and peri-post natal period derived from a careful interview about pregnancy and peri/post history of mothers having had both one child with autism and one or two typically developing siblings observed in two Institutions in Italy adopting the same protocol. The clinical sample included a cases group of 73 autistic children and adolescents (Group A) (mean age 8.22, S.D. 6.35). Thirty five of them (Group A 1) had 45 siblings (Group B) who represented an internal control group, while 96 typically developing children (group C) matched for gender and age represented an external control group. Almost all (25 out of 27) factors on study presented an higher frequency in group A. A statistically significant difference was found for nine factors, which were all more frequent in autistic group in comparison with typicals group. A higher prevalence of environmental risk factors was observed in 11 out of 12 risk factors in A1 group in comparison with group B (siblings) (sign test: p< 0.003.The relative small sample size precluded the reach of statistical significance. A statistically higher prevalence of the mean number of stressful events per pregnancy was recorded in the group A when compared to group B and C. The above results suggest that environmental, incidental phenomena and Stressful life events can influence pregnancy outcome in predisposed subjects, pointing out a possible threshold effect in women predisposed to suboptimal pregnancies.
Titolo: The role of carboxy-terminal cross-linking telopeptide of type I collagen, dual x-ray absorptiometry bone strain and Romberg test in a new osteoporotic fracture risk evaluation: A proposal from an observational study. (2018)
Autore: Fabio M Ulivieri, Luca P Piodi, Enzo Grossi, Luca Rinaudo, Carmelo Messina, Anna P Tassi, Marcello Filopanti, Anna Tirelli, Francesco Sardanelli
The consolidated way of diagnosing and treating osteoporosis in order to prevent fragility fractures has recently been questioned by some papers, which complained of overdiagnosis and consequent overtreatment of this pathology with underestimating other causes of the fragility fractures, like falls. A new clinical approach is proposed for identifying the subgroup of patients prone to fragility fractures. This retrospective observational study was conducted from January to June 2015 at the Nuclear Medicine-Bone Metabolic Unit of the of the Fondazione IRCCS Ca' Granda, Milan, Italy. An Italian population of 125 consecutive postmenopausal women was investigated for bone quantity and bone quality. Patients with neurological diseases regarding balance and vestibular dysfunction, sarcopenia, past or current history of diseases and use of drugs known to affect bone metabolism were excluded. Dual X-ray absorptiometry was used to assess bone quantity (bone mineral density) and bone quality (trabecular bone score and bone strain). Biochemical markers of bone turnover (type I collagen carboxy-terminal telopeptide, alkaline phosphatase, vitamin D) have been measured. Morphometric fractures have been searched by spine radiography. Balance was evaluated by the Romberg test. The data were evaluated with the neural network analysis using the Auto Contractive Map algorithm. The resulting semantic map shows the Minimal Spanning Tree and the Maximally Regular Graph of the interrelations between bone status parameters, balance conditions and fractures of the studied population. A low fracture risk seems to be related to a low carboxy-terminal cross-linking telopeptide of type I collagen level, whereas a positive Romberg test, together with compromised bone trabecular microarchitecture DXA parameters, appears to be strictly connected with fragility fractures. A simple assessment of the risk of fragility fracture is proposed in order to identify those frail patients at risk for osteoporotic fractures, who may have the best benefit from a pharmacological and physiotherapeutic approach.
Titolo: The Role of Trabecular Bone Score and Hip Geometry in Thalassemia Major: A Neural Network Analysis (2017)
Autore: Marina Baldini, Enzo Grossi, Maria Domenica Cappellini, Carmelo Messina, Alessia Marcon, Elena Cassinerio, Lorena Airaghi, Giuseppe Guglielmi and Fabio Massimo Ulivieri*
Info: British Journal of Research ISSN 2394-3718
Osteopathy in thalassemia is a very heterogeneous condition; severity depends on multiple factors, interacting through nonlinear mechanisms. Classic statistics have limitations when applied to the study of such highly complex relationships. Currently, an alternative approach of analysis is represented by the artificial neural networks (ANNs), powerful mathematical tools, increasingly applied to analyze multifactorial databases, as considered more appropriate than classic statistics. We adopted this specialized mathematical method to 76 thalassemia major (TM) patients. In all of them dual energy X-ray
absorptiometry (DXA) was performed to measure bone mineral density, and two recent developments were included: trabecular bone score, evaluating bone microarchitecture, and hip structural analysis, evaluating hip geometry.
The relationships between bone status and endocrine, hematologic, and clinical parameters were investigated. Using a particular ANN (Auto Contractive Map algorithm), the strength of inter-variable association was defined and a connectivity map generated, visually representing the main connections among the entered variables. Iron status indices (ferritin, liver iron
concentration) emerged as the most important variables, dividing the map into two sectors, with parameters indicating satisfactory bone condition in the upper, those indicating poor condition in the lower, near the variable “fractures”. The Auto Contractive Map highlighted the key role of bone quantity, bone geometry, and microarchitecture in defining thalassemic bone condition.
Among numerous available indices, high femoral bone mineral density and low cross-sectional moment of inertia emerged as the gold standard to classify thalassemic patients for prognostic and therapeutic purposes.
Titolo: Role of the Human Breast Milk-Associated Microbiota on the Newborns’ Immune System: A Mini Review (2017)
Autore: Marco Toscano, Roberta De Grandi, Enzo Grossi and Lorenzo Drago*
Info: Frontiers in Microbiology, 25 October 2017
The human milk is a rich and complete nourishment that is essential for the correct development of the infant’s organism (Ballard and Morrow, 2013).
The first milk produced by mothers after the delivery is called colostrum and it is biochemically and functionally different from the mature milk (Castellote et al., 2011). Colostrum, indeed, contains high concentration of lactoferrin, Immunoglobulin A (IgA), leukocytes and specific developmental factors, and a low amount of lactose, potassium and calcium, underlying its immunological functions rather than nutritional (Kulski and Hartmann, 1981; Pang and Hartmann, 2007).
From 5 days to 2 weeks postpartum, there is the production of transitional milk which shares some characteristics of colostrum, although its main function is to support newborns at nutritional level (Henderson et al., 2008; Nommsen-Rivers et al., 2012).
Finally, 2 weeks after the delivery the milk can be considered as mature and its composition tends to be stable over the time, even if slight variations can occur during lactation (Ballard and Morrow, 2013). The main components of human milk are: (i) macronutrients, such as protein, fat and lactose, which concentration depends on the stage of lactation and maternal characteristics; (ii) micronutrients, including vitamins A, B1, B2, B12 and D that vary in human milk in relation to maternal diet and body stores; (iii) growth factor, which are strongly active on the endocrine system, nervous system, vasculature and intestinal tract; (iv) immunological factors, which are essential to defend the newborn from inflammation and infection, and for this reason, the early milk is rich in immune components that can support infants in the first delicate stages of their life; (v) the microbiota, which comprises more than 200 different bacterial species with a pivotal role in the formation of the newborn’s first gut microbiota (Drago et al., 2017).
The aim of the present Mini Review is to highlight the specific and fundamental role of human milk-associated bacteria in modulating and influencing the newborns’ immune system during their life.
Titolo: Impact of delivery mode on the colostrum microbiota composition (2017)
Autore: Marco Toscano, Roberta De Grandi, Diego Giampietro Peroni, Enzo Grossi, Valentina Facchin, Pasquale Comberiati and Lorenzo Drago.
Info: BMC Microbiology (2017) 17:205
Background
Breast milk is a rich nutrient with a temporally dynamic nature. In particular, numerous alterations in
the nutritional, immunological and microbiological content occur during the transition from colostrum to mature
milk. The objective of our study was to evaluate the potential impact of delivery mode on the microbiota of
colostrum, at both the quantitative and qualitative levels (bacterial abundance and microbiota network).
Methods
Twenty-nine Italian mothers (15 vaginal deliveries vs 14 Cesarean sections) were enrolled in the study.
The microbiota of colostrum samples was analyzed by next generation sequencing (Ion Torrent Personal Genome
Machine). The colostrum microbiota network associated with Cesarean section and vaginal delivery was evaluated
by means of the Auto Contractive Map (AutoCM), a mathematical methodology based on Artificial Neural Network
(ANN) architecture.
Results
Numerous differences between Cesarean section and vaginal delivery colostrum were observed. Vaginal
delivery colostrum had a significant lower abundance of Pseudomonas spp., Staphylococcus spp. and Prevotella spp.
when compared to Cesarean section colostrum samples. Furthermore, the mode of delivery had a strong influence
on the microbiota network, as Cesarean section colostrum showed a higher number of bacterial hubs if compared
to vaginal delivery, sharing only 5 hubs. Interestingly, the colostrum of mothers who had a Cesarean section was
richer in environmental bacteria than mothers who underwent vaginal delivery. Finally, both Cesarean section and
vaginal delivery colostrum contained a greater number of anaerobic bacteria genera.
Conclusions
The mode of delivery had a large impact on the microbiota composition of colostrum. Further
studies are needed to better define the meaning of the differences we observed between Cesarean section and
vaginal delivery colostrum microbiota.
Titolo: Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder (2017)
Autore: Łucja Bieleninik (1), Monika Geretsegger (1), Karin Mössler (1), Jörg Assmus (1), Grace Thompson (2), Gustavo Gattino (3,4), Cochavit Elefant (5), Tali Gottfried (6), Roberta Igliozzi (7), Filippo Muratori (7,8), Ferdinando Suvini (7), Jinah Kim (9), Mike
Info: JAMA - The Journal of the American Medical Association, 2017; 318(6): 525-535
Importance
Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication.
Objective
To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD.
Design, Setting, and Participants
Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016.
Interventions
Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents’ concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child’s focus of attention, to help children develop affect sharing and joint attention.
Main Outcomes and Measures
The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months.
Results
Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14.08 to 13.23 in the music therapy group and from 13.49 to 12.58 in the standard care group (mean difference, 0.06 [95% CI, −0.70 to 0.81]; P = .88), with no significant difference in improvement. Of 20 exploratory secondary outcomes, 17 showed no significant difference.
Conclusions and Relevance
Among children with autism spectrum disorder, improvisational music therapy, compared with enhanced standard care, resulted in no significant difference in symptom severity based on the ADOS social affect domain over 5 months. These findings do not support the use of improvisational music therapy for symptom reduction in children with autism spectrum disorder.
Trial Registration
isrctn.org Identifier: ISRCTN78923965
Titolo: Diagnosis of autism through EEG processed by novel artificial adaptive systems: a proof of concept pilot study (2017)
Autore: Enzo Grossi, Chiara Olivieri & Massimo Buscema
Info: Computer Methods and Programs in Biomedicine 142 (2017) 73–79
Background
MS-ROM/I-FAST is a new, complex algorithm used for blind classification of the original EEG tracing of each subject. This is accomplished by recording and analyzing a few minutes of their EEG without artifacts removing. A proof of concept study well equipped with cross-validation techniques previously published showed accuracy values ranging from 94%-98% in discerning subjects with Mild Cognitive Impairment and/or Alzheimer’s Disease from healthy elderly people. Since ASD is known to show deviant patterns in simple resting state EEG recordings, this supports the idea that the atypical organization of the cerebral cortex present in autism should result in an EEG signature open to detection through potent analytical systems like Artificial Neural networks (ANNs.)
Aim of the study
The aim of the study is to assess how effective this methodology distinguishes ADS subjects from typically developing ones.
Methods
Fifteen definite ASD subjects (13 males; 2 females; age range 7-14; mean value = 10.4) and ten typically developing subjects ( 4 males; 6 females; age range 7-12; mean value 9.2 ) were included in the study. Patients received independent Autism diagnoses according to DSM-V criteria, then subsequently confirmed by a qualified psychiatrist at Villa Santa Maria, where the patients reside, using the ADOS scale (overall severity score had a range from a minimum of 4 to a maximum of 10 points, average = 7.9). No autistic child was affected by genetic conditions and/or cerebral malformations documented by neuroimaging and epilepsy. A continuous segment of artefact-free EEG data lasting 60 s was used to compute multi-scale entropy values and for subsequent analyses. A Multi-scale ranked organizing map (MS-ROM), based on the self-organizing map (SOM) neural network, coupled with the TWIST system (an evolutionary system able to select predictive features) created an invariant features vector input of EEG on which supervised machine learning systems acted as blind classifiers.
Results
After MS-ROM/I-FAST preprocessing, the overall predictive capability of different machine learning systems in deciphering autistic cases from normal ones resulted extremely good reaching also perfect distinction with specific classifiers. These results were obtained at different times in separate experiments performed on the same training and testing subsets. The similarities among the ANN weight matrixes measured with apposite algorithms were not affected by the age of the subjects. This suggests that the ANNs do not read age-related EEG patterns, but rather invariant features related to the brain’s underlying disconnection signature.
Conclusion
This pilot study seems to open up new avenues for the development of non-invasive diagnostic testing for the early detection of ASD.rumors and disappointments at media level, while the third problem is specifically felt by Pharmaceutical Companies and Institutional Review Boards releasing the clearance for first in man trials.
Titolo: Assessment of presentation patterns, clinical severity and sensorial mechanism of tip-toe behavior in ASD children: a cohort observational study (2017)
Autore: Giulio Valagussa, Luca Trentin, Valeria Balatti, Enzo Grossi
Info: Autism Research 2017
We assessed presentation patterns, clinical severity and sensorial mechanism of tip-toe behavior (TTB ), more commonly known as toe walking , in a cohort of ASD subjects in two studies. The first study includes 69 consecutive ASD subjects (57 males, 12 females, mean age = 14 years – 3.7 SD) under observation at our institute. A therapist assessed the presence of TTB during standing, walking and running using direct observation and an interview of the main caregiver living with the children was conducted. The prevalence of TTB was 32%. We found three clinical presentation patterns of TTB: 1) present while standing, walking and running (45.5%), 2) present when walking and running (18.4%) or 3) present only when running (36.4%). TTB subjects were more frequently non-verbal than subjects without TTB (72.7% vs 44.6% - p= 0.03). On the other hand, no significant difference in ASD severity according to the ADOS scale was found between TTB and non-TTB subjects. In the second study, carried out in a subgroup of 14 ASD subjects (7 TTB and 7 non-TTB), we show that acting upon a soft floor surface (foam mats) made a substantial difference in reducing the phenomenon. TTB is a frequent phenomenon in individuals with ASD and may occur in three mutually exclusive modalities, which ultimately defines what is commonly known as toe walking. The presence of TTB seems correlated to the severity of language delay. Foot contact on soft surfaces reduces TTB both during static and/or dynamic tasks. Further evaluation is needed to clarify the potential pathophysiological implications of this phenomenon.
Titolo: Inequalities in access to biological treatments for psoriasis: Results from the Italian Psocare Registry (2016)
Autore: Luigi Naldi, Simone Cazzaniga, Marco Di Mercurio, Enzo Grossi, Antonio Addis
Info: British Journal of Dermatology Accepted manuscript online: 14 December 2016
Background: Limited evidence is available on the impact of socioeconomic factors in drug prescriptions for psoriasis.
Objectives: To investigate factors influencing prescription of conventional versus biological treatment for psoriatic patients, based on the Psocare registry with a special focus on socioeconomic factors.
Methods: This was a cross-sectional study evaluating the baseline data of patients included in the Italian Psocare Registry. All of the consecutive adult patients with a diagnosis of chronic plaque psoriasis (Ps) or psoriatic arthritis and who were prescribed a systemic treatment for Ps at the participating centres were included in this study. Univariate and multivariate analyses of the baseline factors associated with a biologics prescription were performed.
Results: From September 2005 to September 2009, 12,838 patients were identified. A multivariate analysis revealed that, among other factors, completing a level of education higher than lower secondary school and being employed as a manager or a professional were independent factors associated with a biologics prescription at entry in the registry. Additional analyses on the association between these two variables and a severe Ps condition (i.e., psoriasis area and severity index [PASI] score > 20) revealed a significant increasing trend of severe disease towards lower educational attainment, while unemployed patients were more likely to have a more severe condition as compared to the other categories of workers.
Conclusions: We documented inequalities of drug prescriptions for Ps in Italy, with a trend towards a higher frequency of prescription for more expensive biologics in higher socio-economic sectors of the population.
Titolo: Monitoring food selectivity in a group of children with autism spectrum disorders with direct observation: a comparative observational feasibility study (2016)
Autore: Enzo Grossi, Sara Melli, Marina Norsi
Info: Scientific Times Journal of Paediatrics, Volume 1 Issue 1
Food selectivity is a fairly common issue with children who have an autism spectrum disorder (ASD)’.
Few studies based on direct observation of feeding behavior in youths with ASD are available in the literature.In this study we explore and monitor food selectivity by directly observing eating behaviors with a standardized protocol in a sample of10 children and adolescents with ASD residing at our rehabilitation institution comparing to 10 children and adolescents affected by mild-moderate mental retardation residing in the same institution. Carefully detailed food records for a 20 day period were analyzed.Subjects with ASD resulted significantly more selective than controls (lunch p = 0.016, dinner p = 0.042). Furthermore, the observed subjects with ASD had a bimodal distribution of weight percentiles ( 6 kids were < 25 % weight percentile. 2 kids > 75% weight percentile) while the control group revealed normal body weight distribution. We found a negative correlation between: food selectivity and duration of stay ( R = - 0.5848 ), as well as food selectivity and age ( R = - 0.6437 ), but a positive correlation between food refusal and disease severity measured with Autism Diagnostic Observation Scale (ADOS-
2) ( R = 0.4441 ).
Our data confirm the feasibility of a direct observation monitoring protocol for feeding behavior importance of food selectivity in subjects affected by ASD. Younger children are more selective than
older ones and the duration of institutional residency seems to positively impact this behavior pattern. Lastly, the severity of ASD symptoms resulted directly proportional to nutritional fixation severity
Titolo: SPSd - A New Rating Scale for Psychological Distress in Adolescence: a Validation Study on a Nationwide Italian Cohort Of 31,661 Adolescents (2016)
Autore: Enzo Grossi, Gabriele Manella, Giovanni Pieretti, Bruno Genetti, Milena Sperotto, Paolo Vian
Info: Psychological Distress, Nova Science Publishers Inc 2016
In this paper we present a new rating scale for adolescent psychological distress based on an Italian population study carried out in a cohort of 31,661 adolescents, and analyzed with Rasch Analysis in addition to the traditional tests.
The Italian epidemiological survey on drug use in the school population was conducted by the Department of Anti Drug Policies in the first six months of 2014. It was based on a methodology of the European Monitoring Centre for Drugs and the Drug Addiction (EMCDDA - European School Survey Project on Alcohol and Other Drugs - ESPAD). The questionnaire and the survey procedures were taken from ESPAD and adjusted modified in order to address the specific characteristics of to the Italian school system.
The total population sample consisted on 31,661 15-19 years old students who attended Italian public high schools.
Among the items in the source scale we have selected nine items belonging to three dominions (Energy, Emotional Stability, Impulsivity and Risk-Taking) from which we expected the maximal indirect relation to wellbeing state and therefore as complement, to distress. To evaluate the psychometric properties of distress scale we carried out the homogeneity analysis or internal consistency of the scale, using the Cronbach's alpha coefficient, and analysis of the validity of the scale, using the Gamma coefficient of Goodman and Kruskal - index rank correlation. The data dimensionality was explored using Rasch Analysis and factor analysis.
The Cronbach's alpha obtained considering all items was to 0.694, making it quite satisfactory and meeting the standards criteria of acceptability. Rasch analysis confirmed the items validity and that the items distribution remains in the area of the tolerance defined.
A very good distribution emerges with a complete absorption of possible values along the scale range; neither ceiling or floor effect is observed.
Whereas the level of distress measured by the scale is higher the lower the score detected, it is observed a significantly higher level of distress in females than in males (52.59 vs 59.61).
For all psychotropic substances analyzed,significantly higher levels of distress in consumers than non-consumers have been found. In addition,the level of distress as measured by the scale appears to increase going from users of “soft” drugs to users of “hard” drugs: - 57.18 is the mean value obtained in the distress scale from the group of students who say they have never used any illegal drug; - 53.00 is the mean value obtained in the distress scale from the group of students who report use of cannabis at least once in their life; - 50.18 is the mean value obtained in the distress scale from the group of students who report use of cocaine at least once in their life; - 47.95 is the mean value obtained in the distress scale from the group of students who report use of heroin at least once in their life. This survey has detected several factors/conditions associated to the use of substances, which can be considered a reliable proxy of psychological distress: family background seems to be very important as well as the relationship with parents; this emerged as regards the presence of rules on behavior outside the home, the quality of relationships with prominent adult figures (particularly the father), their leadership role, and the family harmony.
Titolo: Psychological Interventions to Reduce Distress and Improve Quality of Life in Families with Autistic Children (2016)
Autore: Cristina Zarbo, Angelo Compare, Sara Melli, Enzo Grossi
Info: Psychological Distress, Nova Science Publishers Inc 2016
The experience of childbirth and becoming a parent can become particularly distressing when newborn has a severe chronic disability, like Autism Spectrum Disorder (ASD). Families with autistic children face an overload of their adaptive capacities and crisis situations that can in turn lead to various negative psychological consequences on each parent, the couple, children, and the whole family. Indeed, parents of autistic children show high incidence of psychological distress and mental disorders (e.g., anxiety disorders, depressive symptoms). Evidence suggests that parents of children with ASD may benefit of comprehensive and flexible psychological interventions to reduce parental distress and promote the wellbeing and improve the quality of life of the family.
Titolo: Mental Stress in Parents and Siblings of Autistic Children: Review of the Literature and Original Study of the Related Psychological Dimensions (2016)
Autore: Sara Melli, Enzo Grossi, Cristina Zarbo, Angelo Compare
Info: Psychological Distress, Nova Science Publishers Inc 2016
Parental mental stress is clinically common in families of autistic children and adversely affects the care of the child. Moreover, parents of autistic children frequently experience feelings of guilt, maladaptive coping styles, a lack of ability to forgive themselves and variations in mindfulness. However,it is unclear which of these dimensions is predominant in these families and their pattern of association with other components of this complex picture. While most notable in parents, this is also true of healthy siblings who intrinsically perceive more responsibility and often receive less attention than their afflicted brothers or sisters. The evidence available in the literature on the topic is quite controversial, revealing both positive and negative effects deriving from growing up with ASD siblings.
Demographic and psychological information on mental stress, feelings of guilt, ability to forgive, mindfulness and coping styles were collected through clinical interviews and self-report questionnaires in parents and siblings of autistic children. Artificial Neural Networks (Auto-CM system) were applied to parents data to highlight the associations among the variables under investigation.
Predominant dimensions in parents of autistic children indcluded low feelings of guilt, high levels of forgiveness and low levels of maladaptive coping responses. These three main dimensions were strictly related among themselves. While high parental mental stress was strictly related to high parental distress subscales, to high maladaptive coping styles, and to low self-forgiveness ability, conversely, low mental stress appeared to be marginal in relation to the other psychological dimensions.
This behavior is typical of complex nonlinear systems. The severity of the ASD was not related to parental psychological dimensions. The ADOS scores, both low and high, were in fact marginal in the connectivity map in relation to the other dimensions.
In siblings, the average distress scores level was extremely high irrespectively of ASD severity or family size. About one third of them were at risk of developing major depression. Distress appeared to be mainly related to difficulties in building a meaningful relationship with the ASD child and in managing the child’s behavioral problems. In conclusione the interplay of psychological factors related to stress in parents and siblings of ASD children is complex. Understanding these relationships is the starting point to activating and enhancing parental resources essential to the wellbeing of both children and caregivers.
Titolo: Artificial Neural Networks Link One-Carbon Metabolism to Gene-Promoter Methylation in Alzheimer's Disease (2016)
Autore: Enzo Grossi, Andrea Stoccoro, Pierpaola Tannorella, Lucia Migliore, Fabio Coppedè
Info: Journal Alzheimer Disease Jul 1;53(4):1517-22. doi: 10.3233/JAD-160210.
Background: There is increasing interest in DNA methylation studies in Alzheimer’s disease (AD), but little is still known
concerning the relationship between gene-promoter methylation and circulating biomarkers of one-carbon metabolism in
patients.
Objective: To detect the connections among circulating folate, homocysteine (hcy) and vitamin B12 levels and promoter
methylation levels of PSEN1, BACE1, DNMT1, DNMT3A, DNMT3B, and MTHFR genes in blood DNA.
Methods:We applied a data mining system called Auto Contractive Map to an existing database of 100 AD and 100 control
individuals.
Results: Low vitamin B12 was linked to the AD condition, to low folates, and to high hcy. Low PSEN1 methylation was
linked to low folate levels as well as to low promoter methylation of BACE1 and DNMTs genes. Low hcy was linked to
controls, to high folates and vitamin B12, as well as to high methylation levels of most of the studied genes
Conclusions: The present pilot study suggests that promoter methylation levels of the studied genes are linked to circulating
levels of folates, hcy, and vitamin B12.
Titolo: Gut to brain interaction in Autism Spectrum Disorders. Role of probiotics on clinical, biochemical and neurophysiological parameters: a randomized controlled trial. (2016)
Autore: Elisa Santocchi, Letizia Guiducci, Francesca Fulceri, Lucia Billeci, Emma Buzzigoli, Fabio Apicella, Sara Calderoni, Enzo Grossi, Maria Aurora Morales, Filippo Muratori.
Info: BMC Psychiatry 16:183
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: GI symptoms; autism symptoms severity; affective and behavioral comorbid symptoms; plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; 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. Registered 4 March 2016.
Key words
Autism Spectrum Disorders (ASD), Gut-brain axis, endophenotype, probiotic Vivomixx®, quantitative electroencephalography (QEEG), phtalates.
Titolo: Microbiota Network and Mathematic Microbe Relation in Colostrum and Mature Milk of two different geographic areas: Italy versus Burundi (2016)
Autore: Lorenzo Drago, Marco Toscano, Roberta De Grandi, Enzo Grossi, Ezio Maria Padovani, Diego Peroni
Info: ISME Journal advance online publication 16 December 2016;
Human milk is essential for the initial development of newborns, as it provides all nutrients and vitamins, such as vitamin D, and it represents a great source of commensal bacteria. Here we explore the microbiota network of colostrum and mature milk of Italian and Burundian mothers. In both populations, by studying colostrum and mature milk microbiota with a new methodology based on an Artificial Neural Network (ANN) architecture, the Auto Contractive Map (AutoCM), it has been showed a different bacterial network, as diverse microbial hubs and central hubs have been observed in these samples. Interestingly, the Italian and Burundian mature milk showed a greater abundance of anaerobe intestinal bacteria if compared with colostrum samples, corroborating the hypothesis that intestinal microorganisms are able to reach the mammary glands by mean of dendritic cells and CD18+. In conclusion, the microbiota of human milk is a dynamic and complex ecosystem that not only differs between different populations, but it changes also during the transition from colostrum to mature milk. Finally, the association of complex mathematic systems such as ANN and AutoCM to metagenomics analysis represents an innovative approach to investigate in detail specific bacterial
interactions in biological samples.
Titolo: Unexpected improvement in core autism symptoms after long term treatment with probiotics (2016)
Autore: Enzo Grossi, Delia Dunca, Sara Melli & Vittorio Terruzzi
Info: SAGE Open Medical Case Reports Volume 4: 1– 5
Background
Many studies report the existence of so-called gut-brain axis: a physiological framework in which the gut microbiota communicates with the CNS and vice-versa through neural, endocrine and immune pathways. If this is true, then it is plausible to expect that the modulation gut microbiota may be a tractable strategy in developing novel therapeutics for complex CNS disorders. Autism is definitely one of these disorders.
Objectives
To report the case of a 12 year old boy with ASD and severe cognitive disability in which an unexpected improvement of autistic core symptoms was observed after four months of probiotic treatment.
Method
The case study refers to a 12 year old boy with ASD, severe cognitive disability and gastrointestinal disturbances attending the Villa Santa Maria Institute in resident care since 2009. The boy was first diagnosed with Pervasive Developmental Disorder (PDD) at the age of two. Later on ASD Diagnosis was made according to DSM-V criteria and was confirmed by the ADOS-2 assessment (Autism Diagnostic Observation Schedule).
In February 2014, a probiotic treatment was prescribed to control gastrointestinal symptoms (VSL#3, a product with lyophilized Bifidobacteria, Lactobacilli and Streptococci), which lasted four months.
The diet was consistently followed throughout the entire period and treatment compliance was ensured by a careful supervision. No other dietary supplements containing probiotics or prebiotics or antibiotics was administered during the treatment and follow-up period.
The rehabilitation program already in place, based on behavior, communication, psychomotor therapy, individualized Education Plan/School Services and parents involvement, was regularly maintained.
Improvement in ASD symptoms already became apparent and clinically evident from the few weeks after starting the probiotic treatment.
The ADOS-2 assessment was repeated six times over the October 2013-March 2015 period (twice before starting the treatment, twice during (after month 1 and month 4) and twice after treatment interruption.
Results
The probiotic treatment reduced the severity of abdominal symptoms as expected. While the Restricted Repetitive Behaviors domain scores did not change, an unexpected improvement of the Autistic core symptoms did occur. The Social Affect Domain Score of ADOS improved, going from 20 to 18 after two months of treatment, with a further 1 point reduction during the following two months. The severity level 17 remained stable during the follow up period.
Conclusions
The appropriate use of probiotics merits further research, which hopefully will open new avenues in the fight against ASD.
Titolo: Predictors of Response to Long-Term Cholinesterase Inhibitors Treatment of Alzheimer Disease: Data Mining from Tredem Registry (2016)
Autore: Maurizio Gallucci , Pierpaolo Spagnolo, Maria Aricò, Enzo Grossi
Info: Journal Alzheimer Disease Vol. 50 969-979
Abstract.
Background: the pharmacological treatment of Alzheimer Disease is based largely on cholinesterase inhibitors.
Objective: to investigate whether or not some non-pharmacological and contextual factors measured prior to starting treatment such as past occupation, lifestyles, marital status, degree of autonomy and cognitive impairment, living alone or with others, the degree of brain atrophy are associated with a better response to cholinesterase inhibitors treatment.
Methods: Eighty-four Alzheimer’s disease (AD) and six AD with cerebrovascular disease (AD + CVD) outpatients of Treviso Dementia (TREDEM) Registry, with an average cholinesterase inhibitors treatment length of four years, were considered. The outpatients had undergone a complete evaluation and some non-pharmacological and contextual factors were collected. We defined responder a patient with a delta score T0 – T1 equal or inferior to 2.0 points per year of MMSE and a non-responder a patient with a delta score T0 – T1 superior to 2.0 points per year. In order to identify hidden relationships between variables related to response and non-response, we use a special kind of artificial neural network called Auto-CM, able to create a semantic connectivity map of the variables considered in the study.
Results: a higher cognitive profile, a previous intellectual work, healthier lifestyles, being married and not living alone, a higher degree of autonomy and lower degree of brain atrophy at baseline resulted to affect the response to long term ChEI therapy.
Conclusion: non-pharmacological and contextual factors appear influence the effectiveness of treatment with ChEI in the long term.
Titolo: Pregnancy risk factors in autism: a pilot study with artificial neural networks (2016)
Autore: Enzo Grossi, Federica Veggo, Antonio Narzisi, Angelo Compare, Filippo Muratori
Info: Pediatric Research; Pediatr Res. 2016 Feb;79(2):339-47. doi: 10.1038/pr.2015.222. PubMed PMID: 26524714.
Background:
Autism is a multi-factorial condition where a single risk factor can unlikely provide comprehensive explanation for the disease origin. Moreover, due to the complexity of risk factors interplay, traditional statistics is often unable to explain the core of the problem due to the strong inherent non-linearity of relationships. The aim of this study was to assess the frequency of twenty-seven potential risk factors related to pregnancy and peri-post natal period.
Methods:
The mothers of of forty-five autistic children and of 68 typical developing children completed a careful interview. 24 siblings of 19 autistic children formed an internal control group.
Results:
A higher prevalence of potential risk factors was observed in twenty-two and fifteen factors in external control and internal control group respectively. For six of them, the difference in prevalence was statistically significant. Specialized Artificial Neural Networks (ANNs) discriminated between autism and control subjects with 80.19% global accuracy.
Conclusions:
Pregnancy factors play an important role in autism development. ANNs are able to build up a predictive model, which could represent the basis for a diagnostic screening tool.
Titolo: Data Mining of Determinants of Intrauterine Growth Retardation Revisited Using Novel Algorithms Generating Semantic Maps and Prototypical Discriminating Variable Profiles (2015)
Autore: Massimo Buscema, Enzo Grossi, Luisa Montanini, Maria E. Street
Info: Plos One 7th July 2015
Objectives:
Intra-uterine growth retardation is often of unknown origin, and is of great interest as a “FetalOrigin of Adult Disease” has been now well recognized. We built a benchmark based upon a previously analysed data set related to Intrauterine Growth Retardation with 46 subjectsdescribed by 14 variables, related with the insulin-like growth factor system and pro-inflammatorycytokines, namely interleukin -6 and tumor necrosis factor -α.
Design and Methods:
We used new algorithms for optimal information sorting based on the combination of twoneural network algorithms: Auto-contractive Map and Activation and Competition System. Auto-Contractive Map spatializes the relationships among variables or records by constructinga suitable embedding space where ‘closeness’ among variables or records reflects accurately their associations. The Activation and Competition System algorithm insteadworks as a dynamic non linear associative memory on the weight matrices of other algorithms, and is able to produce a prototypical variable profile of a given target.
Results:
Classical statistical analysis, proved to be unable to distinguish intrauterine growth retardationfrom appropriate-for-gestational age (AGA) subjects due to the high non-linearity of underlying functions. Auto-contractive map succeeded in clustering and differentiatingcompletely the conditions under study, while Activation and Competition System allowed to develop the profile of variables which discriminated the two conditions under study betterthan any other previous form of attempt. In particular, Activation and Competition System showed that ppropriateness for gestational age was explained by IGF-2 relative gene expression, and by IGFBP-2 and TNF-α placental contents. IUGR instead was explained by IGF-I, IGFBP-1, IGFBP-2 and IL-6 gene expression in placenta.
Conclusions:
This further analysis provided further insight into the placental key-players of fetal growthwithin the insulin-like growth factor and cytokine systems. Our previous published analysis could identify only which variables were predictive of fetal growth in general, and identified only some relationships.
Titolo: Networks in Coronary Heart Disease Genetics as a Step towards Systems Epidemiology. (2015)
Autore: Fotios Drenos, Enzo Grossi, Massimo Buscema, Steve E Humphries
Info: Plos One May 7, 2015
We present the use of innovative machine learning techniques in the understanding of Coronary Heart Disease (CHD) through intermediate traits, as an example of the use of this class of methods as a first step towards a systems epidemiology approach of complex diseases genetics. Using a sample of 252 middle-aged men, of which 102 had a CHD event in 10 years follow-up, we applied machine learning algorithms for the selection of CHD intermediate phenotypes, established markers, risk factors, and their previously associated genetic polymorphisms, and constructed a map of relationships between the selected variables. Of the 52 variables considered, 42 were retained after selection of the most informative variables for CHD. The constructed map suggests that most selected variables were related to CHD in a context dependent manner while only a small number of variables were related to a specific outcome. We also observed that loss of complexity in the network was linked to a future CHD event. We propose that novel, non-linear, and integrative epidemiological approaches are required to combine all available information, in order to truly translate the new advances in medical sciences to gains in preventive measures and patients care.
Titolo: Age-, Adiposity- and Insulin-Related Changes in Urinary Di-(2-Ethylhexyl) Phthalate Metabolites (2015)
Autore: Arianna Smerieri, Chiara Testa, Pietro Lazzeroni, Francesca Nuti, Enzo Grossi, Silvia Cesari, Luisa Montanini, Giuseppe Latini, Sergio Bernasconi, Anna Maria Papini, Maria E. Street.
Info: Plos One 10: 2. 02
Background and objectives:
Phthalates might be implicated with obesity and insulin sensitivity. The aim of this study was to evaluate the levels of primary and secondary metabolites of DEHP in urine in obese and normal-weight subjects both before and during puberty, and to investigate their relationships with auxological parameters and indexes of insulin sensitivity.
Methods:
DEHP metabolites (MEHP, 6-OH-MEHP, 5-oxo-MEHP, 5-OH-MEHP, and 5-CX-MEHP), were measured in urine by RP-HPLC-ESI-MS. Traditional statistical analysis and a data mining analysis through the Auto-CM system, a fourth generation artificial neural network (ANN), were able to offer an insight of the complex biological connections between the studied variables.
Results:
The data showed changes in DEHP metabolites in urine, related with obesity, onset of puberty, and presence of insulin resistance. Changes in urine metabolites were related with age, height and weight, waist circumference and waist to height ratio, thus to fat distribution. In addition, clear relationships in both obese and normal-weight subjects were detected among MEHP, its products of oxidation and measurements of insulin sensitivity (insulin, fasting glucose to insulin ratio, HOMA-IR index, and whole body insulin sensitivity index).
Conclusions:
It remains to be elucidated whether exposure to phthalates per se is actually the risk factor or if the ability of the body to metabolize phthalates is actually the key point. Further studies that span from conception to elderly subjects besides further understanding of DEHP metabolism are warranted to clarify these aspects.
Titolo: Which are the better outcome predictors in preschoolers with autism who respond positively at the treatment as usual (TAU) ? Insights from an observational study using Artificial Neural Networks (2015)
Autore: Antonio Narzisi, Filippo Muratori, Massimo Buscema, Sara Calderoni, Enzo GrossiIRCCS Stella Maris Foundation - Department of Developmental Neuroscience, University of Pisa, Pisa, Italy, Semeion Research Center, Rome, Italy, 4Department of Mathematical
Info: NEUROPSYCHIATRIC DISEASES AND TREATMENTS Vol 11 pp 1587—1599 2015
In Italy Treatment As Usual (TAU) for autism spectrum disorders (ASD) is composed of specific treatments performed by child neuropsychiatric services and of school inclusion with individual support teacher. The Artificial Neural Networks (ANNs) have never been used in order to study the effects of treatment in ASD. Auto Contractive Map (Auto-CM) is a special kind of ANNs able to find out consistent trends and associations among variables creating a semantic connectivity map. The matrix of connections, visualized through minimum spanning tree filter takes into account non linear associations among variables and captures connection schemes among clusters. Objectives: The main aim is to use Auto-CM in order to identify key variables to discriminate among responders versus no responders at TAU. Methods: 56 preschoolers with ASD aged between 24 and 48 months were recruited at different centers in Italy. They were evaluated by blind researchers at baseline and after six months using a multi-informant assessment protocol. All children were referred to community providers for available interventions. Results: At T1, the severity of autism measured through ADOS improved in 62% of involved children (Response) while it was the same or worse in 37% of 56 (No Response). The application of the the Semeion ANNs overcome the 85% of global accuracy (Sine–Net almost reaching 90%). Consequently, some of the tested algorithms were able to find a good correlation between some variables and TAU outcome. The semantic connectivity map obtained with the application of the Auto-CM system showed results that clearly indicated that ‘Response’ can be visually separated from the ‘No Response’ cases. Particularly it was possible to visualize a Response area characterized by’ Parents Involvement high’ and ‘MacArthur Expressive low’. No Response area resulted strongly connected only with ‘Parents Involvement low’. Conclusions: The ANN model that was used in this study appears to be a promising tool for the identification of the variables involved in the positive of negative response to TAU in autism.
Titolo: L'apporto dell'arte, della religione e della comunicazione nella "cura" delle persone con disturbi dello spettro autistico (2014)
Autore: Marina Norsi
Info: Dolentium Hominum n. 86
L'apporto della religione e dell'arte nella cura dei bambini autistici viene analizzata basandosi sui dati riportati nella letteratura e sull'esperienza degli ultimi 10 anni nelle strutture terapeutiche(nidi e asili) in Israele. L'influenza della religione nell'accettare la diagnosi ed affrontare la cura dell'autismo puo' essere positiva(accettazione della malattia come espressione della volonta' Divina) o negativa(malattia come punizione divina per i dubbi dei genitori nei confronti di Dio) . I dati riportati in letteratura confermano che il supporto delle organizzazioni religiose e dei ministri del culto sono di grande aiuto: diminuiscono lo stress e lo stato di ansia delle famiglie. L'arte terapia usata ormai in tutto il mondo come terapia complementare ha vantaggi rispetto alle terapie convenzionali:e' un mezzo di comunicazione non verbale, viene accettata dai bambini in modo positivo e non minaccioso,potenzia il contatto di sguardo, potenzia l'apprendimento di colori, forme geometriche, oggetti. Sono stati descritti in modo particolareggiato esempi concreti dell'uso dell'arte terapia e pratiche religiose nella stesura dei programmi cognitivi, educativi nelle strutture terapeutiche per bambini autistici.
Titolo: The Role of Intestinal Dysbiosis in the Pathogenesis of Autism: Minireview (2014)
Autore: Enzo Grossi & Vittorio Terruzzi
Info: International Journal of Microbiology & Advanced Immunology (IJMAI) 2: 201
Autism spectrum disorder is a complex neurodevelopmental disease where gastrointestinal disturbance is commonly reported. Here we review the evidence suggesting that gut microbota my play a role in this disease and summarize comparative studies we found in international literature on the topic. Discussion of results, methodology of the data collection, bias of selection and behavioral interferences lead to the conclusion that changes in the gut microbiota is a significant piece of autism spectrum disorder but further studies are needed to understand this pathogenetic role.
Titolo: Personality traits, cardiac risk factors, and their association with presence and severity of coronary artery plaque in people with no history of cardiovascular disease. (2014)
Autore: Angelo Compare, Paula M C Mommersteeg, Francesco Faletra, Enzo Grossi, Elena Pasotti, Tiziano Moccetti, Angelo Auricchio
Coronary artery disease (CAD) is a complex, multifactorial disease in which personality seems to play a role but with no definition in combination with other risk factors. Objective: To explore the nonlinear and simultaneous pathways between traditional and personality traits risk factors and coronary stenosis by Artificial Neural Networks (ANN) data mining analysis. Method: Seventy-five subjectswere examined for traditional cardiac risk factors and personality traits.Analyseswere based on a new data mining method using a particular artificial adaptive system, the autocontractive map (AutoCM). Results: Several traditional Cardiovascular Risk Factors (CRF) present significant relations with coronary artery plaque (CAP) presence or severity. Moreover, anger turns out to be the main factor of personality for CAP in connection with numbers of traditional risk factors. Hidden connection map showed that anger, hostility, and the Type D personality subscale social inhibition are the core factors related to the traditional cardiovascular risk factors (CRF) specifically by hypertension. Discussion: This study shows a nonlinear and simultaneous pathway between traditional risk factors and personality traits associated with coronary stenosis in CAD patients without history of cardiovascular disease. In particular, anger seems to be the main personality factor for CAP in addition to traditional risk factors.
Titolo: PAHA study: Psychological Active and Healthy Aging: psychological wellbeing, proactive attitude and happiness effects of whole-body vibration versus Multicomponent Training in aged women: study protocol for a randomized controlled trial. (2014)
Autore: Angelo Compare, Cristina Zarbo, Elena Marín, Alessia Meloni, Jacobo A Rubio-Arias, Rosendo Berengüí, Enzo Grossi, Edo Shonin, Gianmaria Martini, Pedro E Alcaraz
Evidence demonstrates that physical exercise and psychological wellbeing are closely interlinked, particularly in older-aged women. However, research investigating how different forms of exercise influence mental health in older-aged women is underdeveloped. Methods/design: A randomized controlled trial (N = 300) will assess the relative effectiveness of two different exercise programs (whole-body vibration and Multicomponent Training) for improving psychological wellbeing in older-aged women. The following outcomes will be assessed at three time points (that is, pre, post, and follow-up): psychological wellbeing, proactive attitude, quality of life, and happiness.
