Pubblicazioni su riviste internazionali

Abstract

Background
Based on the present global burden of oral diseases, unmet dental needs affect a more significant population worldwide. It is characterised by the need for dental care but receiving delayed or no care. The contributing factors include lack of knowledge about oral health, its consequences, and the availability of dental services. We need to find out the scale of the problem of unmet dental needs for the south Indian population. Therefore, the objective was to determine the relationship between the presence of oral disease and the quality of life-related to oral health using the OHIP-14 tool.

Methods
The unmet dental requirements of the south Indian population were determined using a cross-sectional questionnaire survey. Close-ended questions were used to obtain data from two investigators trained to record the answers from the patients. The data was collected using the OHIP-14 questionnaire, which consists of 14 items divided into seven domains with two questions each. Physical pain, psychological impairment, physical disability, psychological disability, social disability, and disability were all considered. An additional analysis of artificial neural network (ANN) was done.

Results
The response rate was 100 per cent. N = 1029 people replied to the questionnaire about their unmet dental needs. N = 497 (48.3%) were men, whereas N = 532 (51.7%) were women. The average age was 31.7811.72. As their current occupation, most of the included subjects (60.1%) were students. The respondents had no known personal habits and a mixed diet (94.93%). The average BMI was 24.022.59 (14-30.9). OHIP was present in 62.3% of the population. The average OHIP-14 severity score was 10.97. (8.54). The severity and degree of unmet dental need were substantial (p0.01) due to pain in the mouth/teeth/gums, malocclusion, and gum bleeding. The most common OHIP- 14 domains affected by unmet oral needs were psychological discomfort, psychological limitation, social limitation, and feeling handicapped. The analysis of ANN revealed that high OHIP scores were primarily attributed to dental caries, poor oral health, and dental aesthetics. 

Notes:

1 Nitte (Deemed to be University), Department of Periodontics, A B Shetty Institute of Dental Sciences, Mangalore, Karnataka, India
2 Department of Orthodontics and Dentofacial Orthopedics, Manav Rachna International Institute of Research and Studies (MRIIRS), Manav Rachna Dental College, Faridabad, Haryana, India
3 Nitte (Deemed to be University), Department of Oral Biology and Genomic Studies, A B Shetty Memorial Institute of Dental Sciences, Mangalore, Karnataka, India
4 Villa Santa Maria Institute, Tavernerio, Italy
5 School of Medicine, University of Madrid, Madrid, Spain
6 SC Chirurgia Maxillo-Facciale e Odontostomatologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy

Background: The correlation between food and Parkinson's disease (PD) showsthat the Mediterranean diet (MeD) brings positive benefits. Objective: To find thecorrelation between PD and food components in the various regions of Italy in 2016.Methods: The protein, fat, mineral and vitamin content of 275 foods belonging to 56distinct food categories were correlated with PD in terms of standardised mortalityratio (SMR). Data were computed for 19,500 families in 540 Italian municipalitiesfor 2016.
Life expectancy, demographic data and level of well-being were alsoanalysed. Stochastic and non-stochastic analyses (neural network mapping) wereused to compute the associations with PD. Results: The following results wereobtained by focusing on the food components deemed significant in both stochasticand non-stochastic analyses: Alcohol, saturated and monounsaturated fats, calciumand sodium were found to be causative or partially causative factors. Solublesugars, carbohydrates, starch, selenium and vitamin D were seen to be protectiveor partially protective.
The SMR of PD was significantly lower in Southern Italy thanin the North due to a lower consumption of causative foods and higher consumptionof protective ones. Furthermore, the lower gross domestic product (GDP) in theSouth may also have a significant effect. Conclusions: In 2016, the PD death rate inSouthern Italy was significantly lower than in the North. The food componentpattern that emerged in Southern regions was also significantly different: a lowerconsumption of causative food components and higher consumption of protectiveones together with a lower GDP and life expectancy. Using data on food expenditureand quantities enable us to track the correlation with PD SMR on an annual basis.

Notes:

1 Loyola University School of Medicine-Chicago
2 Villa Santa Maria Foundation, Tavernerio CO Italy
3 Mario Negri Institute Alumni Association, Milan Italy

A new pre-processing approach of EEG data to detect topological EEG features has been applied to a continuous segment of artifact-free EEG data lasting 10 minutes in ASCII format derived from 50 ASD children and 50 children with other Neuro-Psychiatric Disorders (NPD), matched for age and male/female ratios.

Each EEG is transformed in a triangular matrix of 171 values expressing all reciprocal Manhattan distances among the 19 electrodes of to the international 10-20 system. From this matrix, the minimum spanning tree (MST) is calculated. Electrode identification serial codes sorted according to the decreasing number of links in MST, and the number of links in MST are taken as input vectors for machine learning systems. 

Machine learning systems have been applied to build up a predictive model to distinguish between the two diagnostic classes (autism vs NPD) following a rigorous validation protocol.

The best machine learning system (KNN algorithm) obtained a global accuracy of 93.2% (92.37 % sensitivity and 94.03 % specificity) in differentiating ASD subjects from NPD subjects.

The results obtained in this study suggest that, thanks to the new pre-processing method introduced, there is the possibility to discriminate subjects with autism from subjects affected by other psychiatric disorders with a modest computational time reducing the information to 38 figures.

Notes:

1 Villa Santa Maria Foundation, Tavernerio, Italy
2 Belmont University, Nashville TN
3 Houston Neuroscience Brain Center, Houston, TX

The exposure to different form of beauty coming from visual art, music, nature, architecture, improves mental health and exerts neurotrophic effects on different parts of the brain. This in turn improves physical health, prolongs life expectancy, and reduces the risk of serious degenerative diseases such as Alzheimer’s and cancer. These beneficial actions would not be understandable and plausible if one did not accept the mind-body unity. The ‘hegemonic’ role of the brain in health and illness can be discerned, for example, in the effect of emotions on vital physiological parameters, in the relationships between stress and many medical-clinical pathologies, in the control exercised by the brain over the immune system reflecting also in the inhibition of tumour progression.

Notes:

Villa Santa Maria Foundation, Tavernerio, Italy.

The leisure-rehabilitation programs offered to children and adolescents with autism convey feelings like emotional, social, cognitive, and physical engagement, fun, adventure and sense of novelty. Each activity however has an intrinsic power to influence the emotional pattern in different ways. To define how each type of rehabilitation program can be expected to influence the psychological response di children and adolescent affected by autism; A Delphi study was carried out involving twelve Expert therapists. The aim is to have criteria to personalize the individual rehabilitation plan choosing a mix of activities with more appropriate emotional influence. We applied the Delphi procedure during a workshop with expert therapists (4 females - 1 male), with the aim of assessing the opinion of participants regarding the appropriateness of 11 types of leisure-rehabilitation activities in enhancing 7 types of psychological responses.
The activities with the highest potential for each psychological response were for dramatherapy emotional and cognitive engagement, team sports for social engagement and for fun, indoor climbing for physical engagement and for sense of adventure, for outdoor visits to museums sense of novelty. The top five activities with the highest overall impact (mean overall score > 7) were in decreasing order: indoor climbing, team sports, outdoor visits to common life environments, outdoor visits to parks and gardens, and dramatherapy. We hope that this Delphi exercise will help the carers of individuals with autism to choose and adapt possible leisure activities according to the specific needs of the subject, maximizing the potential benefit of rehabilitation.

Notes: 1 Villa Santa Maria Foundation, Tavernerio, Italy

The term “toe walking” describes walking on the toes with a lack of heel strike upon initiation of the stance phase of gait. In individuals with autism spectrum disorder (ASD), this phenomenon, or “tip-toe behavior” (TTB), can be present in a substantial proportion of subjects even during standing. In this study, we investigated TTB in 50 persons with ASD (age range 4–26 years). We evaluated TTB through an observational/report-based assessment protocol.
Subsequently, we employed a new structured video-based coding protocol based on standardized video recordings, focusing on static and dynamic conditions.
Finally, the findings of the two protocols were compared. Twenty-four subjects with TTB were identified and classified according to three functional groups: TTB1, present only during running (6 subjects); TTB2, present during walking and running (11 subjects); and TTB3, present during standing, walking, and running (7 subjects).
Moreover, we found that TTB3 subjects exhibited a significantly higher quantity of TTB compared with subjects in the TTB1 and TTB2 groups during both standing and walking tests. Additionally, a high quantity of TTB in the static test was found to be related to a high quantity of TTB in the dynamic test. Variables such as age, autism severity, intellectual disability, and gender were not significantly associated with the mean percent of TTB both in static and dynamic tests in multivariate analysis.
This structured video-based coding approach appears feasible and useful for assessing TTB in individuals with ASD and it has the potential to provide insights into TTB trajectories and aid in designing possible interventions.

Notes:

1 - School of Medicine and Surgery, University of Milano Bicocca, Milan, Italy
2 - Autism Research Unit, Villa S. Maria Foundation, Tavernerio (CO), Italy
3 - Department of Health Sciences, Section of Biostatistics, University of Genoa, Genoa, Italy

Background: The incidence of noncommunicable diseases (NCDs) has been rapidly ramped up worldwide. Hence, there is an urgent need to non-invasively detect NCDs possibly by exploiting saliva as a ‘liquid biopsy’ to identify biomarkers of the health status. Since, the absence of standardized procedures of collection/analysis and the lack of normal ranges makes the use of saliva still tricky, our purpose was to outline a salivary proteomic profile which features healthy individuals.

Methods: We collected saliva samples from 19 young blood donors as reference population and the proteomic profile was investigated through mass-spectrometry.

Results: We identified 1,004 proteins of whose 243 proteins were shared by all subjects. By applying a data clustering approach, we found a set of six most representative proteins across all subjects including Coronin-1A, F-actin-capping protein subunit alpha, Immunoglobulin J chain, Prosaposin, 78 kDa glucose-regulated protein and Heat shock 70 kDa protein 1A and 1B.

Conclusion: All of these proteins are involved in immune system activation, cellular stress responses, proliferation, and invasion thus suggesting their use as biomarkers in patients with NCDs.

Notes:

1 - Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
2 - Department of Human Science and Quality of Life Promotion, Telematic University San Raffaele, Rome, Italy
3 - Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
4 - Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
5 - Neurodegenerative Diseases Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
6 - Villa Santa Maria Foundation, Tavernerio, Italy
7 - Biological Resource Center, Department of Transfusion Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
8 - Department of Physics, Center for Complexity and Biosystems, University of Milan, Milan, Italy
9 - Department of Environmental Science and Policy, Center for Complexity and Biosystems, University of Milan, Milan, Italy
10 - SC Maxillo-Facial Surgery and Dentistry, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy

Background: Status epilepticus is a life-threatening condition that is defined as refractory (RSE) when the seizure activity continues despite treatment with benzodiazepine and a second appropriate treatment. Super refractory status epilepticus (SRSE) is an RSE that persists or recurs for ≥24 h. Few papers have reported the outcomes of pediatric patients affected by RSE and SRSE and treated with neuromodulation therapies. Vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. We present our findings of pediatric patients treated with VNS for RSE/SRSE.

Methods: We present a case series of seven consecutive pediatric patients treated with VNS for SRSE since 2012 by a single surgeon in Monza and Padua. A rapid titration was started soon after implantation. We considered electroclinical data before and after VNS implantation and at the last follow-up.

Results: We achieved the resolution of SRSE in five out of seven patients in a mean time of two weeks. At the last follow-up, these patients had a significant reduction of seizure burden without any relapse of SE.

Discussion and conclusions: Based on our limited findings, we discuss the potential role of VNS therapy in similar but distinct clinical contexts. For patients with drug-resistant epilepsy and RSE/SRSE, prompt VNS consideration is suggested, offering rapid responses and potentially reducing pharmacological load. Meanwhile, in NORSE/FIRES, we suggest early neuromodulation during the acute phase if standard treatments prove ineffective or not tolerated. This approach may leverage VNS's potential anti-inflammatory effects and neuromodulation, enhancing patient-specific treatments. Expanding case studies and prolonged follow-ups are recommended to strengthen these clinical insights.

Notes:

1 - Padua University Hospital, Padova, Italy
2 - Neurology and Neurophysiology Unit, Department of Women’s and Children’s Health, Padua University Hospital, Padova, Italy
3 - Epilepsy Unit, Villa Santa Maria SCS, Tavernerio, Como, Italy

Music listening is widely used in therapeutic music-based interventions across various clinical contexts. However, relating the diverse and overlapping musical elements to their potential effects is a complex task.
Furthermore, the considerable subjectivity of musical preferences and perceptual components of music, influenced by factors like cultural and musical background, personality structure of the user, and clinical aspects (in the case of diseases), adds to the difficulty.
This paper analyzes data derived from a previous randomized controlled study involving a healthy population (n = 320). The study aimed to induce relaxation through music listening experiences using both conventional and algorithmic approaches. The main goal of the current research is to identify potential relationships among the variables investigated during the experiment.
To achieve this, we employed the Auto Contractive Map (Auto-CM), a fourth-generation artificial neural network (ANN). This approach allows us to quantify the strength of association between each of the variables with respect to all others in the dataset.
The main results highlighted that individuals who achieved a state of relaxation by listening to music composed by Melomics-Health were predominantly over 49 years old, female, and had a high level of education and musical training. Conversely, for conventional (self-selected) music, the relaxing effect was correlated with the male population, aged less than 50 years, with a high level of education and musical training. Future studies conducted in clinical settings could help identify “responder” populations based on different types of music listening approaches.

Notes:

1 Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
2 Villa Santa Maria Foundation, Tavernerio, Italy
3 University of Trieste, Italy

BACKGROUND: Hip displacement (HD ) and dislocation in severe Cerebral Palsy (CP ) (GMFCS III , IV, V) are important causes of worsening disability and quality of life. Prevention must be started from the first months of life through screening programs and early treatments, both conservative and surgical. Evidence from Clinical Practice Guidelines also suggests the development of Care Pathways for good clinical practice. At the beginning of 2020 an interdisciplinary, multi-professional working group, composed of 26 members (including Physiatrists, Physiotherapist, Neuro-psychomotor Therapists and Orthopedists representing the respective Italian Scientific Societies) with the involvement of the FightTheStroke Foundation families’ association, was set up.

AIM: The aim of the multi-professional panel was the production of evidence-based recommendations for the Care Pathway “Prevention of Hip Displacement in children and adolescents with severe CP ” for best clinical practice implementation in our national context.

DESIGN: Clinical Care Pathway (Clinical Practice Guideline).

SETTING: Inpatient and outpatient.

POPULATION: C hildren with severe CP (GMFCS III -IV-V).

METHODS: The recommendations of this Care Pathway were developed using the American Academy for Cerebral Palsy and Developmental Medicine (AACPD M) guidelines for Care Pathways development and the Grading of Recommendations Assessment Development and Evaluation (GRAD E ADOLOP MENT) working group for adoption or adaption or de novo development of recommendations from high-quality guidelines. In 2020 a multidisciplinary working group (WG) developed four research questions on the prevention of hd on the following top-ics: screening, botulinum toxin treatment, postural management and preventive soft tissue surgery. a comprehensive review of the biomedical literature was performed on each question. Guidelines, systematic reviews and primary studies were retrieved through a top-down approach. References were screened according to inclusion criteria and quality was assessed by means of specific tools. A list of recommendations was then produced divided by intervention (screening programs, postural management, botulinum toxin, preventive surgery). in a series of meetings, the panel graduated recommendations using the GradE evidence to decision frameworks.

RESULTS: fifteen recommendations were developed: seven on screening programs, four on postural management strategies, one on botulinum toxin, and three on preventive surgery. Evidence quality was variable (from very low to moderate) and only a few strong recommendations were made.

CONCLUSIONS: in severe cp at high risk of hip dislocation, it is strongly recommended to start early hip surveillance programs. in our national context, there is a need to implement screening programs and dedicated Network teams. We also strongly recommend a comprehensive approach shared with the families and goal-oriented by integrating the different therapeutic interventions, both conservative and not, within screening programs.

CLINICAL REHABILITATION IMPACT: implementing a comprehensive multi-professional approach for the prevention of hip dislocation in severe CP.

NOTES:

1 - Pediatric Physical Medicine and Rehabilitation Unit, IRCCS Institute of Neurological Sciences, Bologna, Italy

 2 - Pediatric Physical Medicine and Rehabilitation Unit, IRCCS Ca’ Granda Ospedale Maggiore Polyclinic Hospital, Milan, Italy

3 - Children Rehabilitation Unit of S. M. Nuova Hospital, Azienda Unità Sanitaria Locale IRCCS di Reggio Emilia, Reggio Emilia, Italy

4 - Postgraduate Program in Clinical and Experimental Medicine, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

5 - Rehabilitation Area, AUSL Bologna, Bologna, Italy

6 - Pediatric Rehabilitation Area, AUSL Parma, Parma, Italy

7 - Child and Adolescent Neurology and Psychiatry Unit, ASST Lecco, Lecco, Italy

8 - Verte Physio Care, Carate Brianza, Monza-Brianza, Italy

9 - Pediatric Orthopedics and Traumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

10 - IRCCS Don Carlo Gnocchi Nonprofit Foundation, Milan, Italy

11 - UD GEE IRCCS Giannina Gaslini, Genoa, Italy

12 - UFS MIA Service of Rehabilitation, Azienda Usl Toscana Centro, Florence, Italy 

13 - Cardinal Ferrari Santo Stefano Rehabilitation Center, KOS Care, Fontanellato, Parma, Italy

14 - Villa Santa Maria Foundation, Tavernerio, Como, Italy

15 - School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

Well-being is a complex and multi-faceted concept, which covers several dimensions ranging from the physical to the psychological. It also includes the environment in which an individual lives and operates, playing a role in defining the concept of well-being. The influence of these possible well-being determinants – physical, psychological and environmental – may vary in relation to gender, providing in this way different possible outcomes and evidences in relation to health and social policies.
This article focuses on the impact of possible well-being determinants on the female and male genders in an attempt to illustrate the effective dimension of individual characteristics regarding employment, socio-economic status, civil status, overall health and education. In addition, the manuscript analyzes the influence of participation in social-related activities, given the pro-active role these play in the promotion of health and psychological condition.
The study is based on a 2018 survey of a statistically representative sample of the Italian population, which gathered information concerning the influence of several elements on individual subjective well-being. The analysis reveals a general agreement on how health status is one of the major detrimental risk factors for decreased psychological wellbeing in both genders. It also shows that cultural experiences act toward preventing well-being distress, particularly in females, leading to significant consequences in terms of promotion of individual subjective well-being.

Notes:

1 - Iulm University, Milan, Italy
2 - Fondazione Villa Santa Maria, Tavernerio (CO), Italy
3 - Free University Bozen, Italy

Culture and creative production have an important but somewhat elusive role in urban development. None of the many conceptual paradigms that have been proposed so far to explain it has turned out entirely satisfactory. We argue that the main reason behind this failure is the implicit linear thinking that informs all these approaches: namely, the idea that a few, major drivers explain urban development through a direct, clearly readable systemic impact.
Cities are complex socio-environmental systems whose functioning depends on the concurrent interaction of many different factors which cannot be reduced to the action of a few, simple causal forces. Failing to understand such complexity easily leads to dysfunctional urban governance approaches. In this paper, we analyze a database of 144 European cities as described by 58 variables belonging to different domains, as designed by a preliminary stage of the Cultural and Creative City Monitor (CCCM).
Our analysis builds on innovative machine learning techniques (PST) and on the Minimum Spanning Tree (MST) representation to map the structural interdependencies between the cultural and non-cultural sectors in cities with a strong cultural policy orientation. This toolbox carries considerable potential for precision cultural policies and data-driven urban governance strategies of the future.

Notes:

1 - Villa Santa Maria Foundation, Milan, Italy
2 - University of Chieti-Pescara, Italy
3 - ISPC-CNR, Naples, Italy
4 - MetaLAB (at) Harvard, Cambridge, MA, USA
5 - IULM University, Milan, Italy

Background:
The relationship between foods and cancers has been documented in many epidemiological and cohort studies of the Mediterranean Diet (MeD).

Objective:
Correlation between food expenditure in Italy and the prevalence of nine cancers: breast, prostate, colon, pancreas, TBL (throat-bronchial-lung), bladder in males and females, uterus, and ovaries, with a comparison of differences between Northern and Southern Italy.

Methods:
The expenditure of 19500 Italian families on the 56 most sold food categories was taken from ISTAT (Italian National Institute of Statistics) records for 2016. These data were then correlated with the prevalence of death from the nine above mentioned cancers in 2020. Stochastic and non-stochastic analyses were used to determine the correlations between foods and cancers.

Results:
None of the cancers showed identical protective or causative food patterns. The data confirmed the causative role of wine and the protective role of pasta, flour and sugar. Surprisingly fish and olive oil were found to be causative for some cancers. Southern Italy showed significantly lower prevalence of cancer due to a lower consumption of causative foods and higher consumption of protective ones.

Conclusion:
MeD has changed in Italy. Some causative and protective foods were found for all the cancers, but none had the same pattern. However, foods can be considered important co-factors in cancer development. Pasta, flour and sugar were shown to be protective for many cancers and, besides wine, some other foods, like olive oil and fish, were causative for some cancers. The correlation between food expenditure and disease seems to be a valid, simple research method.

Notes:

1 - Loyola University School of Medicine, Chicago
2 - Villa Santa Maria Foundation, Tavernerio, Italy
3 - Mario Negri Institute Alumni Association, Milan, Italy
4 - University of Milan, Italy
5 - University of Pavia, Italy

In determining the so-called “body burden”, hair has been widely accepted for assessing toxic element exposure. However, its role in assessing essential elements is controversial. This study investigates the possible relationship between hair minerals, metabolic syndrome (MetS) and cardiovascular (CV) risk in non-occupationally exposed subjects with overweight–obesity.

Ninetyfive voluntary participants (aged 51-12) were recruited in Northern Italy. Hair samples were collected and analysed via inductively coupled plasma mass spectrometry; the total toxicity index (TI) was calculated as well.

To evaluate cardiovascular risk factors in the presence or absence of MetS, the following factors were considered via the innovative artificial neural network (ANN) method Auto-CM: hair mineralograms (31 elements) and 25 variables including blood pressure, anthropometric parameters, insulin resistance and biochemical serum markers assessing inflammation. The
Framingham risk score, fatty liver index (FLI), visceral adiposity index and CV risk scores were also taken into consideration. As shown by the semantic map, which was subsequently confirmed by an activation and competition system (ACS), obesity parameters are strictly associated with CV risk factors, TI and inflammation; meanwhile, the single mineral elements seem to be unimportant.

Data obtained via ANN demonstrate that MetS may be at least partly mediated by altered mineral levels also in the presence of obesity and that waist circumference is a crucial point to be monitored rather than BMI alone. Furthermore, the mineral body burden is one of the important factors for CV risk.

Notes:

1 Occupational Health Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy
2 Villa Santa Maria Foundation, 22038 Tavernerio, Italy
3 Pediatric Nephrology and Dialysis, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
20122 Milan, Italy
4 Emergency Medicine Residency Program, Università Politecnica delle Marche, 60126 Ancona, Italy
5 Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, 60020 Ancona, Italy

Abstract: Background: Type 2 diabetes may be caused by some foods, which have been identified both in clinical practice and in prospective and epidemiological studies. Objective: To calculate the correlation between prevalence of death from type 2 diabetes and food expenditure for the main 56 categories of food sold in Italy. 

Methods: The food expenditure data were taken from the ISTAT (Istituto Italiano di Statistica) records that measure the spending of at least 19500 families in 540 municipalities in Italy on a yearly basis. The sample represents 6.3% of all Italian municipalities. The correlations were calculated using stochastic and non-stochastic (neural network) analyses. 

Results: Both types of analysis showed similar results. The correlations indicated sugars, fish and fresh tomatoes as causative of the disease, while yogurt, some fruits, canned fish and wine/liqueurs (with a moderate weekly consumption) emerged as protective. Significant differences were found between the northern and southern regions of Italy. A significantly lower prevalence of the disease was seen in northern regions due to a lower consumption of causative foods and higher consumption of protective foods. 

Conclusions: The results indicate that analysing food expenditure on a yearly basis may be a valid tool to determine the correlation between foods and type 2 diabetes. This method may be considered as an alternative to epidemiological and prospective clinical trials since it can be used to determine which foods may be causative of any disease very rapidly.

Notes:

1 - Loyola University School of Medicine, Chicago

2 - Villa Santa Maria Foundation, Tavernerio, Italy

3 - Mario Negri Institute Alumni Association, Milan, Italy

Background: According to the International Agency of Research on Cancer (IARC), the prevalence of breast cancer in women has been shown to be positively correlated with the consumption of red and processed meats. A number of other studies have suggested that dairy products and alcohol are causative, and that the Mediterranean diet is protective.

Objective: To correlate breast cancer with food expenditure in a sample of 19500 families in 540 Italian municipalities representing the 6.3 % of the total.

Methods: Expenditure on 56 of the most sold food categories were analysed. The ISTAT (Italian National Institute of Statistics) records from 2016 were compared with breast cancer deaths in 2019 to look for correlations. Stochastic analyses (multiple correlation, prediction profiler, and cluster and principal component analyses) and nonstochastic analyses (fourth generation neural networks) were used to determine correlations.

Results: Red and processed meats did not turn out to be causative of breast cancer in any of the analyses. On the contrary, pork was shown to be protective, as was sugar and pasta. Alcohol and, surprisingly, yogurt and fresh vegetables were found to be causative. In particular, the northern regions of Italy were shown to have a significantly higher prevalence of breast cancer deaths than all the other regions.

Conclusion: Our sales analysis of 56 different foods does not confirm the correlation between red and processed meats and breast cancer. Besides wine, other types of food, like yogurt and fresh vegetables, seem to be causative. Further studies are needed to confirm these findings.

Notes:

1.Department of Molecular Pharmacology and Therapeutics, Loyola University School of Medicine-Chicago, Piazza Novelli, Milan, Italy
2.Department of Epidemiology and Clinics Biostatistics, Mario Negri Institute Alumni Association, Milan, Italy
3.Irwin Labs, Strada Statale, 16, Bis 64 65010, Spoltore (PE), Italy
4.Villa Santa Maria Foundation, Tavernerio CO, Italy
5I.TS Nuove Tecnologie della Vita, Viale Europa, 15, 24125 Bergamo, Italy

Exposure to environmental stressors during pregnancy plays an important role in influencing subsequent susceptibility to certain chronic diseases through the modulation of epigenetic mechanisms, including DNA methylation. Our aim was to explore the connections between environmental exposures during gestation with DNA methylation of placental cells, maternal and neonatal buccal cells by applying artificial neural networks (ANNs).
A total of 28 mother–infant pairs were enrolled. Data on gestational exposure to adverse environmental factors and on mother health status were collected through the administration of a questionnaire. DNA methylation analyses at both gene-specific and global level were analyzed in placentas, maternal and neonatal buccal cells. In the placenta, the concentrations of various metals and dioxins were also analyzed.
Analysis of ANNs revealed that suboptimal birth weight is associated with placental H19 methylation, maternal stress during pregnancy with methylation levels of NR3C1 and BDNF in placentas and mother’s buccal DNA, respectively, and exposure to air pollutants with maternal MGMT methylation. Associations were also observed between placental concentrations of lead,
chromium, cadmium and mercury with methylation levels of OXTR in placentas, HSD11B2 in maternal buccal cells and placentas, MECP2 in neonatal buccal cells, and MTHFR in maternal buccal cells.
Furthermore, dioxin concentrations were associated with placental RELN, neonatal HSD11B2 and maternal H19 gene methylation levels. Current results suggest that exposure of pregnant women to environmental stressors during pregnancy could induce aberrant methylation levels in genes linked to several pathways important for embryogenesis in both the placenta, potentially affecting foetal development, and in the peripheral tissues of mothers and infants, potentially providing peripheral biomarkers of environmental exposure.

Notes:

1 Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy
2 Autism Research Unit, Villa Santa Maria Foundation, 22038 Tavernerio, Italy
3 Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna, Chemical Department, Via P. Fiorini 5, 40127 Bologna, Italy
4 Division of neonatology and NICU, Department of Clinical and Experimental Medicine, 56126 Pisa, Italy
5 Obstetrics and Gynecology Unit 1, Department of Experimental and Clinical Medicine, University of Pisa, 56126 Pisa, Italy
6 Obstetrics and Gynecology Unit 2, Pisa University Hospital, 56126 Pisa, Italy
7 First Division of Pathology, Department of Laboratory Medicine, Pisa University Hospital, 56126 Pisa, Italy
8 European Cancer and Environment Research Institute (ECERI), 1000 Brussels, Belgium
9 Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, AOU Cagliari, 09124 Cagliari, Italy
10 Department of Laboratory Medicine, Pisa University Hospital, 56126 Pisa, Italy

Abstract:

Although medical research has been performed predominantly on men both in preclinical and clinical studies, continuous efforts have been made to overcome this gender bias. Examining retrospectively 21 data sets containing sex as one of the descriptive variables, it was possible to verify how many times our AI protocol decided to keep gender information in the predictive model. The data sets pertained a vast array of diseases such as dyspeptic syndrome, atrophic gastritis, venous thrombosis, gastroesophageal reflux disease, irritable bowel syndrome, Alzheimer diseases and mild cognitive impairment, myocardial infarction, gastrointestinal bleeding, gastric cancer, hypercortisolism, AIDS, Covid diagnosis, extracorporeal membrane oxygenation in intensive therapy, among others. The sample size of these data sets ranged between 80 and 3147 (average 600). The number of variables ranged from 19 to 101 (average 41). Gender resulted to be part of the heuristic predictive model 19 out of 21 times. This means that also for highly adaptive and potent tools like Artificial Neural Networks, information on sex carries a specific value. The result of this study confirms the importance of gender information in building high performance predictive model in the field of Artificial Intelligence (AI). Therefore, also for AI, sex counts.

Notes:

Villa Santa Maria Foundation, Tavernerio, Italy

Abstract

Study objectives: Disorder of arousal (DOA) and sleep-related hypermotor epilepsy (SHE) are complex, often bizarre, involuntary sleep behaviors, whose differential diagnosis may be challenging because they share some clinical features, such as sleep fragmentation. Mounting evidence highlights the critical role of sleep in cognitive functions. Controversial findings are raised about the cognitive profile in SHE; however, no studies have investigated the cognitive profile in DOA. This study aimed to assess whether sleep instability affects cognitive functions in patients with SHE or DOA.

Methods: This study analyzed 11 patients with DOA, 11 patients with SHE, and 22 healthy controls (HC). They underwent full-night video polysomnography (vPSG) and comprehensive neuropsychological and behavioral evaluation. Differences in the variables of interest among the SHE group, DOA group, and their respective control groups were evaluated. The auto-contractive map (auto-CM) system was used to evaluate the strength of association across the collected data.

Results: The SHE group had reduced sleep efficiency and increased wake after sleep onset (WASO); both the SHE and DOA groups showed increased % of N2 and REM sleep compared to the HC group. Neuropsychological and behavioral evaluations showed a different cognitive profile in the SHE group with respect to the HC group. The auto-CM showed that Pittsburgh Sleep Quality Index (PSQI), Beck depression inventory (BDI), MWCST_PE, Epworth sleepiness scale (ESS), WASO, N1, and % REM were strictly correlated with SHE, whereas the SE and arousal index (AI) were strictly related to DOA.

Conclusions: Patients with SHE and DOA present different cognitive and psychiatric profiles, with subtle and selective cognitive impairments only in those with SHE, supporting the discriminative power of cognitive and psychiatric assessment in these two conditions.

Notes:

1 Sleep Disorder Center, Department of Public Health & Clinical and Molecular Medicine, University of Cagliari, 09042 Cagliari, Italy.
2 UOC Riabilitazione Funzionale e Neuroriabilitazione, Mater Olbia Hospital, 07026 Olbia, Italy.
3 ASL Cagliari, 09100 Cagliari, Italy.
4 Autism Research Unit, Villa Santa Maria Foundation, 22038 Tavernerio, Italy.
5 Unità di Neuropsichiatria dell'infanzia e dell'adolescenza, Dipartimento di Scienze Biomediche, Università di Cagliari & Ospedale Pediatrico, 09100 Cagliari, Italy.

Aim and methods: Artificial neural networks were used to unravel connections among blood gene methylation levels, sex, maternal risk factors and symptom severity evaluated using the Autism Diagnostic Observation Schedule 2 (ADOS-2) score in 58 children with autism spectrum disorder (ASD).

Results: Methylation levels of MECP2, HTR1A and OXTR genes were connected to females, and those of EN2, BCL2 and RELN genes to males. High gestational weight gain, lack of folic acid supplements, advanced maternal age, preterm birth, low birthweight and living in rural context were the best predictors of a high ADOS-2 score.

Conclusion: Artificial neural networks revealed links among ASD maternal risk factors, symptom severity, gene methylation levels and sex differences in methylation that warrant further investigation in ASD.

Notes:

1 Department of Translational Research & of New Surgical & Medical Technologies, University of Pisa
2 IRCCS Stella Maris Foundation, Calambrone, Pisa
3 Department of Clinical & Experimental Medicine, University of Pisa
4 Villa Santa Maria Foundation, Tavernerio, Como

Atypical sensory processing is frequently reported in persons with autism spectrum
disorders (ASD), and it is one of the described diagnostic criteria for ASD. There is also mounting literature supporting the presence of motor impairments in individuals with ASD. Among these motor signs, tip-toe behavior (TTB) is a possible clinical finding, but its etiology is not clearly understood.
It is suggested that TTB in ASD could be a sign of a sensory modulation impairment, but evidence is lacking and controversial. The main aim of this pilot study is to explore sensory features in a sample (4 females; 28 males) of children and adolescents with ASD (age range: 7–18).

All participants also presented Intellectual Disability. Participants were divided in two groups, matched for age and gender, on the basis of the presence or absence of TTB (16 ASD TTB group vs. 16 ASD NO-TTB group) and then evaluated by using the Short Sensory Profile. We found that both ASD groups tend to significantly present sensory-related behavioral symptoms, but ASD TTB individuals more frequently showed the specific pattern of “under responsive/seeks sensation” than ASD NO-TTB individuals.
These preliminary findings support that sensory-motor features might be taken into consideration when rehabilitation for TTB in children and adolescents with ASD is necessary.

Notes:

1 Autism Research Unit, Villa S. Maria Foundation, Tavernerio, Como, Italy
2 School of Medicine and Surgery, University of Milano Bicocca, Monza, Italy

Abstract

Background: 
Since one of the suggested mechanisms of action of VNS on epilepsy is the reduction of central inflammation, we carried out a comprehensive analysis of blood inflammatory markers in children considered for VNS surgery. Materials and methods: Five pediatric patients were studied. An extensive analysis of blood inflammatory markers was performed before surgery (T0) and six weeks after VNS implantation (T1). An epileptological outcome was obtained according to the McHugh score. 

Results: 
The variations of IgA, IgE, IgG, CD19, and PTX3 displayed a tendency toward a positive statistical correlation between T0 and T1. According to McHugh score, the patients were divided into Group 1 (i.e., Class I) and Group 2 (i.e., Classes II and III). IL-1β and PTX-3 tended to decrease more in Group 1, while TNF-α decreased in Group 2 (−56.65%) and slightly increased (+3.61%) in Group 1 at T1 without statistical correlation. 

Conclusions: 
The variation of IL-1β and PTX-3 seem to be related to a better outcome; thus, they are without statistical significance. A larger series of patients is needed to determine whether biochemical changes could relay with the clinical improvement of epilepsy.

Notes:

1 Academic Neurosurgery, Department of Neuroscience, University of Padova, Italy;

2 Department of Women’s and Children’s Health, University Hospital of Padova, Italy

3 Department of Pediatric Onco-Hematology, San Gerardo Hospital, Università degli Studi di Milano-Bicocca, Monza, Italy

4 Immunology and Cell Therapy, Centro Ricerca Tettamanti, Paediatric Clinic, University of Milan Bicocca, Monza, Italy

5 Neurosurgery Unit, San Gerardo Hospital, Monza, Italy

6 Epilepsy Unit, Villa Santa Maria, Child Care Center-Neuropsychiatric Rehabilitation Center, Tavernerio (CO), Italy

Wearable systems, or even more simply wearables, are a wide variety of body worn objects and accessories that in the last decade have been introduced in our availability. The aim of this paper is to propose a structured methodology to
conduct usability analysis with wearables and describe it through its application on a wearable system for water rehabilitation.
AQTIVO is a new corset co-design with users (patients and caregivers) and to validate its usability we carried out a test with 30 subjects and 10 caregivers in 2 water rehabilitation sites. The AQTIVO usability was very satisfactory. Young users. Indeed, it allowed new rehabilitation exercises (flotation, prone transfer). In adults, AQTIVO system improved the buoyancy task provided more support in dynamic tasks. Support from the caregiver was also reduced by using the brace in all subjects. Also the aesthetics was positively evaluated.

Notes:

1 Laboratory TeDH - Technology and Design for Healthcare, Department of Design,
and Sensibilab, Polo Territoriale di Lecco, Politecnico di Milano, Milan, Italy
2 IBFM – CN, Segrate, Milan, Italy
3 Casa di Cura Domus Salutis, Brescia, Italy
4 Istituto Villa Santa Maria, Como, Tavernerio, Italy
5 AUS Niguarda Onlus, Milan, Italy
6 Dipartimento di Scienza dei Materiali, Università degli Studi Milano-Bicocca, Milan, Italy
7 CNR-ICMATE, National Research Council of Italy, Lecco, Italy

Abstract: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Despite motor impairment is not currently included in the diagnostic criteria or evaluation of ASD, there is increasing evidence that subjects with ASD also have motor impairments, including gait alterations. Toe walking (TW) is a possible finding during gait observation in about 20% of subjects with ASD. TW persistence can contribute to a secondary shortening of the Achilles’ tendon. This systematic review aims to summarize the evidence about TW interventions in individuals with ASD. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations and was prospectively registered in the International Prospective Register of Systematic Reviews. The literature search was performed up to July, 24th 2020 on Medline (via PubMed), CINAHL, PsycINFO, The Cochrane Library, Google Scholar and Opengrey, from the inception of these databases. No restrictions regarding language, year of publication, and age of population were applied. Two reviewers independently screened titles and abstracts for eligibility; then independently screened full text of potentially eligible studies. A hand searching of the reference list of included studies was also performed. After the selection process, a total of 7 articles (all case reports) were included. Assessment of the studies’ completeness has been conducted using the CARE checklist. The studies considered a total sample of 11 subjects (11 males; age range of 4-9 years). Five studies assessed the effectiveness of behavioural interventions using acoustical feedback or tactile stimulus in addition to positive reinforcement. One study proposed serial casting, and the one evaluated the efficacy of a lymphatic drainage technique. In all 7 studies, a reduction of TW frequency has been reported. A follow-up assessment was conducted in 2/7 studies. There is a lack of high-quality studies with a sufficiently large and well-characterized sample to assess the effectiveness of treatments for TW in individuals with ASD. These findings strongly support the need for further research in this area.

Abstract

Background
Moving from the correlation between insulin-resistance and PCOS, metformin has been administered in some PCOS women improving ovulatory and metabolic functions and decreasing androgen levels. Inconsistency and unpredictability of response to metformin limit its extensive use. Aim of this study was to identify reliable predictors of response to metformin therapy for weight loss and reduction in plasma androgen levels using ANNs (artificial neural networks).

Methods
One hundred eight consecutive women with PCOS (ESHRE/ASRM 2003 Rotterdam criteria) treated with metformin 1500 mg/day, at inclusion and every 6 months underwent to a complete clinical, endocrine/metabolic assessment and ultrasonographic evaluation. Therapy outcomes were BMI reduction (≥1 kg/m2) in overweight/obese and free-androgen-index (FAI) decrease (≥1%) in hyperandrogenemic women. Semantic connectivity maps (SCMs) were obtained through Auto-CM, a fourth generation ANN, to compare patients’ baseline clinical features to the treatment outcomes. Multivariate logistic regression analysis was used to assess the major predictor in drop-out patients and the associated risk.

Results
At 6 months 54 out of 103 (52,4%) obese patients showed BMI reduction and 45 out of 89 (50,6%) hyperandrogenemic women showed FAI decrease. The further response rates at 12 months were 30,6 and 47%, respectively. SCMs showed a clear polarization for both the outcomes with elevated accuracy. Treatment responsiveness resulted strictly related to oligo-amenorrhea and hyperandrogenemia at baseline. In addition, lower serum testosterone levels at baseline were found to be the major predictor of treatment discontinuation.

Conclusions
In women with PCOS, menstrual pattern imbalance and ovarian androgens excess are the best predictors of metformin  esponse. They may pave the way for a rethinking of the criteria for evaluating hyperandrogenism in order to better define the large population included in the diagnosis of PCOS. Baseline plasma testosterone level can serve as a sensitive marker to predict treatment compliance.

Notes:

1 Reproductive Medicine Unit, Department of Mother and Child, San Paolo
Hospital Medical School, ASST Santi Paolo e Carlo, Milano, Italy
2 Istituto di Medicina Aerospaziale “A. Mosso”, Aeronautica Militare, Milano, Italy
3 Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
4 ”Aldo Ravelli” Research Center, Milano, Italy
5 Villa Santa Maria Foundation, Tavernerio, Italy
6 Gynecology and Obstetrics Unit, Department of Mother and Child, San Paolo Hospital Medical School, Department of Health Sciences, University of Milano, Milano, Italy

Abstract

Introduction: Accurate assessment of resting energy expenditure (REE) can guide optimal nutritional prescription in critically ill children. Indirect calorimetry (IC) is the gold standard for REE measurement, but its use is limited. Alternatively, REE estimates by predictive equations/formulae are often inaccurate. Recently, predicting REE with artificial neural networks (ANN) was found to be accurate in healthy children. We aimed to investigate the role of ANN in predicting REE in critically ill children and to compare the accuracy with common equations/formulae.

Study methods: We enrolled 257 critically ill children. Nutritional status/vital signs/biochemical values were recorded.
We used IC to measure REE. Commonly employed equations/formulae and the VCO2-based Mehta equation were estimated. ANN analysis to predict REE was conducted, employing the TWIST system.

Results: ANN considered demographic/anthropometric data to model REE. The predictive model was good (accuracy 75.6%; R2 = 0.71) but not better than Talbot tables for weight. After adding vital signs/biochemical values, the model became superior to all equations/formulae (accuracy 82.3%, R2 = 0.80) and comparable to the Mehta equation. Including IC-measured VCO2 increased the accuracy to 89.6%, superior to the Mehta equation.

Conclusions: We described the accuracy of REE prediction using models that include  emographic/anthropometric/clinical/metabolic variables. ANN may represent a reliable option for REE estimation, overcoming the inaccuracies of traditional predictive equations/formulae.

Notes:

1 Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
2 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Anestesia e Terapia Intensiva Donna-Bambino,
20122 Milan, Italy
3 Pediatric Intermediate Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
20122 Milan, Italy
4 Pediatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
5 Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital,
Boston, MA 02115, USA
6 Center for Nutrition, Boston Children’s Hospital, Boston, MA 02115, USA
7 Department of Anaesthesia, Harvard Medical School, Boston, MA 02115, USA
8 Villa Santa Maria Foundation, Neuropsychiatric Rehabilitation Center, Autism Unit, 22038 Tavernerio, Italy;
† These authors contributed equally to this work.

Notes:

1 Villa Santa Maria Foundation, Tavernerio (Como)
2 University of Milano-Bicocca

Background
Osteoporosis leads to bone fractures, burdened by high mortality and disability.
Our aim was to apply an artificial intelligence-based fragility fracture predictive model to different dual energy X-ray absorptiometry (DXA) parameters.

Methods
Retrospective approved multicentric study: 174 females without vertebral fractures at baseline were enrolled. All subjects performed spine X-ray, lumbar andfemoral DXA scan to assess bone mineral density (BMD) and bone strain index (BSI). Exams were performed at baseline and after a mean follow-up period of 3 years. The retrospective analysis was performed in the first two months of 2020. The occurrence of vertebral fracture was evaluated on x-rays at follow-up. Artificial Neural Network analysis (ANNs) selected relevant input data automatically (TWIST-system) constructing a semantic connectivity map (Auto Contractive Map) of the complex biological connections among the studied variables and the two conditions (fracture vs not fracture). A final list of 13 variables was included, considering both DXA-derived indices but also age, menopause status, weight and BMI.
Results
At follow-up, 69 women developed a vertebral fracture. TWIST system selected 9/13 available variables. ANNs reached a predictive accuracy of 79.56% with training testing procedure, with a sensitivity of 80.93% and a specificity of 78.18%. The semantic connectivity map highlighted BSI's role in predicting fracture risk: a high BSI value identified those women who did not experience further fragility fracture.
Conclusion
Artificial Intelligence is a useful method to analyse the complex osteoporotic system. Femoral BSI appears.

Note: 

1. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano.
2. BSE TECHNOLOGIC Srl, Torino.
3. IRCCS Istituto Ortopedico Galeazzi, Milano, Italy.
4. Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano.
5. Former: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Gastroenterology and
Digestive Endoscopy Unit, Milano.
6. Scuola di Specializzazione in Medicina Fisica e Riabilitativa, Università degli Studi di Milano.
7. IRCCS Policlinico San Donato, San Donato Milanese (Milano).
8. Institute of Endocrinology, Università Vita-Salute San Raffaele, Milano.
9. Villa Santa Maria Foundation, Tavernerio (Como).

Autism Spectrum Disorder (ASD) is a multicomplex disorder characterized by an umbrella of specific issues in the areas of social communication, restricted interests, and repetitive behaviors. The incidence of ASD is worldwide, and recent epidemiological data estimated it to be higher than 1/100.
Promising evidence-based interventions for core symptoms in children and adolescent have been developed in recent years. However, in addition to the core symptoms, ASD may have strong associations with other disorders and/or be associated with a plethora of behaviors and symptoms, such as those related to food selectivity and the consequent inadequate dietary intake.
Although some types of eating disturbances, such as food refusal, are also frequent in the general pediatric population, their prevalence appears to be significantly higher in ASD children, with rates ranging from 51% to 89%. There is evidence that children with ASD consume fewer fruits and vegetables and have a lower intake of calcium and protein, compared to their typically developing peers.
Moreover, children with ASD prefer foods with high carbohydrate, content such as white bread, pizza, cakes, cookies, ice-cream, or “fatty” foods. These foods are generally sweet, while on the contrary, bitter or sour tastes are more frequently rejected. This preference can cause a rise of blood glucose and triglycerides, resulting in overweight status and obesity, or endocrine disturbances such as diabetes, not to mention dental caries, since correct and constant oral hygiene is not always possible.
Additionally, children with ASD often have an inadequate intake of vitamin D, vitamin B12, vitamin C, calcium, zinc, and a lower consumption of dairies if compared with typically developed children. This means that food selectivity is not just a matter of taste, but it is, most of all, a matter of health.
Finally, children with ASD, because of false myths, sometimes undergo to non-intentional and dangerous dietary restrictions protocols (e.g., casein and/or gluten-free) based on non-evidence-based attempt to improve behavioral disturbances or gastrointestinal symptoms.

1 Department of Child Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, Pisa, Italy
2 Villa Santa Maria Foundation, Tavernerio, Como, Italy

Background: Several instruments have been proposed to investigate restricted, repetitive behaviors (RRBs) in individuals with Autism Spectrum Disorder (ASD). Systematic video obser-vations may overcome questionnaire and interview limitations to investigate RRBs. This study aimed to analyze stereotypic patterns through video-recordings and to determine the correlation between the number and appearance of RRBs to ASD severity;
Methods: Twenty health profes-sionals wearing a body cam recorded 780 specific-RRBs during everyday activities of 67 individu-als with ASD (mean age:14.2 ± 3.72 years) for three months. Each stereotypy was classified ac-cording to its complexity pattern (i.e., simple or complex) based on body parts and sensory chan-nels involved.
Results: The RRBs spectrum for each subject ranged from 1 to 33 different patterns (mean: 11.6 ± 6.82). Individuals with a lower number of stereotypies shown a lower ASD severity compared to subjects with a higher number of stereotypies (p=0.044). No significant differences were observed between individuals exhibiting simple (n=40) and complex patterns (n=27) of ste-reotypies on ASD severity, age, sex, and the number of stereotypes;
Conclusions: This study rep-resents the first attempt to systematically document expression patterns of RRBs with a da-ta-driven approach. This may provide a better understanding of the pathophysiology and man-agement of RRBs.

Notes:

1 Autism Research Unit, “Villa Santa Maria” Foundation, Tavernerio, Italy
2 Neurorehabilitation Research Laboratory, Department of Neurological and Rehabilitation Sciences, IRCSS San Raffaele Pisana, Rome, Italy
3 School of Medicine and Surgery, University of Milano Bicocca, Milano, Italy
4 School of Physical and Occupational Therapy, McGill University, Montreal, Canada
5 Department of Human Sciences and Promotion of the Quality of Life, San Raffaele University, Rome, Italy.

Abstract: Study objectives: PANS (Pediatric Acute Onset Neuropsychiatric Syndrome) is thought to be the result of several mechanisms and multiple etiologies, ranging from endocrine/metabolic causes to postinfectious autoimmune and neuroinflammatory disorders. Sleep disorders represent one of the most frequent manifestations of PANS, involving around 80% of patients. The present study describes the clinical and polysomnographic features in a group of PANS children identifying the relationships between sleep disorders and other PANS symptoms.
Methods: All participants underwent a clinical evaluation including polysomnography, cognitive assessment and blood chemistry examination. A data mining approach with fourth-generation Artificial Neural Networks has been used in order to discover subtle trends and associations among variables.
Results: Polysomnography showed abnormality in 17 out of 23 recruited subjects (73.9%). In particular, in accordance with AASM criteria, 8/17 children (47%) had ineffective sleep, 10/17 (58.8%) fragmented sleep, (47.1%) Periodic Limb Movement Disorder (PLMD) and 11/17 (64.7%) REM-Sleep Without Atonia (RSWA). Most patients had more than one sleep disorder. Notably, among the 19/23 patients diagnosed with Tic/Tourette Disorder, 8/19 (42.1%) show PLMD and 10/19 (52.6%) RSWA. Artificial Neural Network methodology and the Auto-Contractive Map exploited the links among the full spectrum of variables revealing the simultaneous connections among them,
facing the complexity of PANS phenotype.
Conclusion: Sleep disorders represent, for prevalence and impact on quality of life, a cardinal symptom in patients with PANS. Thus, considering the weight of sleep disorders on diagnosis and prognosis of PANS, we could consider the possibility of including them among the major diagnostic criteria.

The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole. The embryo-fetal period and the first two years of life (the so-called 'First 1000 Days') are the crucial time window for neurodevelopment. In particular, the interplay and the vicious loop between immune activation, gut dysbiosis, and mitochondrial impairment/oxidative stress significantly affects neurodevelopment during pregnancy and undermines the health of ASD people throughout life. Consequently, the most effective intervention in ASD is expected by primary prevention aimed at pregnancy and at early control of the main effector molecular pathways. We will reason here on a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach.

Background
Literature showed the effects of music therapy on behavioral disturbances, cognitive functions, and on quality of life in people with dementia. Especially, relational active music therapy approach is oriented to reduce behavioral disturbances increasing communication, especially non-verbal communication.
Objective
This study aimed at exploring the connection between the baseline characteristics of responders and the positive outcome of the intervention, but also the close relationship between the behavioral disturbances and the core of the therapeutic intervention (the relationship/communication improvement).
Method
Linear correlation index between input variables and the presence of a critical improvement of behavioral symptoms according Neuropsychiatric Inventory and a semantic connectivity map were used to determine, respectively, variables predictive of the response and complex connections between clinical variables and the relational nature of active music therapy intervention.
The dataset was composed of 27 variables and 70 patients with a moderate-severe stage of dementia and behavioral disturbances.
Results
Themain predictive factor is the Barthel Index, followed by NPI and some of its sub-items (mainly, Disinhibition, Depression, Hallucinations, Irritability, AberrantMotor Activity, and Agitation). Moreover, the semantic map underlines how the improvement in communication/relationship is directly linked to “responder” variable. “Responder” variable is also connected to “age,” “Mini Mental
State Examination,” and sex (“female”).
Conclusions
The study confirms the appropriateness of active music therapy in the reduction of behavioral disturbances and also highlights how unsupervised artificial neural networks models can support clinical practice in defining predictive factors and exploring the correlation between characteristics of therapeutic-rehabilitative interventions and related outcomes.

1 Music Therapy Research Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri, 27100, Pavia, Italy
2 Geriatric Department, Fondazione Istituto Ospedaliero di Sospiro, Sospiro, CR, Italy
3 Department of Mathematics and Geosciences, University of Trieste, Trieste, Italy
4 Villa Santa Maria Foundation, Tavernerio, CO, Italy

Background and Objective.
In 2 previous studies, we have shown the ability of special machine learning systems applied to standard EEG data in distinguishing children with autism spectrum disorder (ASD) from non-ASD children with an overall accuracy rate of 100% and 98.4%, respectively. Since the equipment routinely available in neonatology units employ few derivations,
we were curious to check if just 2 derivations were enough to allow good performance in the same cases of the above mentioned studies.
Methods.
A continuous segment of artifact-free EEG data lasting 1 minute in ASCCI format from C3 and C4 EEG channels present in 2 previous studies, was used for features extraction and subsequent analyses with advanced machine learning systems. A features extraction software package (Python tsfresh) applied to time-series raw data derived 1588 quantitative features. A special hybrid system called TWIST (Training with Input Selection and Testing), coupling an evolutionary algorithm named Gen-D and a backpropagation neural network, was used to subdivide the data set into training and testing sets as well as to select features yielding the maximum amount of information after a first variable selection performed with linear correlation index threshold.
Results.
After this intelligent preprocessing, 12 features were extracted from C3-C4 time-series of study 1 and 36 C3-C4 time-series of study 2 representing the EEG signature. Acting on these features the overall accuracy predictive capability of the best artificial neural network acting as a classifier in deciphering autistic cases from typicals (study 1) and other neuropsychiatric disorders (study 2) resulted in 100 % for study 1 and 94.95 % for study 2.
Conclusions.
The results of this study suggest that also a minor part of EEG contains precious information useful to detect autism if treated with advanced computational algorithms. This could allow in the future to use standard EEG from newborns to check if the ASD signature is already present at birth.

1 Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy
2 Bracco Imaging, Milan, Lombardia, Italy
3 Semeion Research Centre, Rome, Italy
4 Department of Mathematical and Statistical Sciences, University of Colorado, Denver, CO, USA

Background
The association of stereotypies and tics is not rare in children with severe autism spectrum disorder (ASD). The differential diagnosis between stereotypies and tics in this patient population can be difficult; however, it could be clinically relevant because of treatment implications.
Methods
A total of 108 video recordings of repetitive behaviors in young patients with stereotypies in the context of ASD were reviewed by a movement disorders expert and a trainee, in order to assess the prevalence of possible co-morbid tics. The Modified Rush Videotape Rating Scale (MRVS) was used to rate tic frequency and severity.
Results
Out of 27 patients with stereotypies (24 males; mean age 14 years), 18 (67%) reported possible tics. The most frequently observed tics were eye blinking, shoulder shrugging, neck bending, staring, and throat clearing. The mean MRVS score was 5, indicating mild tic severity. The only significant difference between patients with tics and patients without tics was the total number of stereotypies, which was higher in the subgroup of patients without tics (p = 0.01).
Conclusions
Expert review of video-recordings of repetitive behaviors in young patients with ASD and stereotypies suggests the possibility of a relatively high rate of co-morbid tics. These findings need to be integrated with a comprehensive clinical assessment focusing on the diagnostic re-evaluation of heterogeneous motor manifestations.

1 Child Neuropsychiatry Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
2 Department of Autism Research, “Villa Santa Maria” Child and Adolescent Neuropsychiatry Rehabilitation Unit, Tavernerio, CO, Italy
3 Michael Trimble Neuropsychiatry Research Group, University of Birmingham & BSMHFT, Birmingham, UK
4 School of Life & Health Sciences, Aston University, Birmingham, UK
5 Sobell Department of Motor Neuroscience & Movement Disorders, Institute of Neurology & University College London, London, UK
6 Department of Neuropsychiatry, National Centre for Mental Health, 25 Vincent Drive, Birmingham B15 2FG, UK

Background: Drug resistance to biologics in psoriasis therapy can occur – it may be acquired during a treatment or else present itself from the beginning. To date, no biomarkers are known that may reliably guide clinicians in predicting responsiveness to biologics. Biologics may pose a substantial economic burden. Secukinumab efficiently targets IL-17 in the treatment of psoriasis.
Objective: To assess the “fast responder” patient profile, predicting it from the preliminary complete blood count (CBC) and clinical examination.
Materials and Methods: From November 2016 to May 2017 we performed a multicenter prospective open label pilot study in three Italian reference centers enrolling bio-naive plaque psoriasis patients, undergoing the initiation phase secukinumab treatment (300mg subcutaneous at week 0,1,2,3,4). We define fast responders as patients having achieved at least PASI 75 at the end of secukinumab induction phase. Clinical and CBC data at week 0 and at week 4 were analyzed with linear statistics, principal component analysis, and artificial neural networks (ANNs), also known as deep learning. Two different ANNs were employed: Auto Contractive Map (Auto-CM), an unsupervised ANNs, to study how this variables cluster and a supervised ANNs, Training with Input Selection and Testing (TWIST), to build the predictive model.
Results: We enrolled 23 plaque psoriasis patients: 19 patients were responders and 4 were non-responders. 30 attributes were examined by Auto-CM, creating a semantic map for three main profiles: responders, non-responders and an intermediate profile. The algorithm yielded 5 of the 30 attributes to describe the 3 profiles. This allowed us to set up the predictive model. It displayed after training testing protocol an overall accuracy of 91.88% (90% for responders and 93,75% for non-responders).
Conclusions: The present study is possibly the first approach employing ANNs to predict drug efficacy in dermatology; a wider use of ANNs may be conducive to useful both theoretical and clinical insight.

Background: Reverse Transcription-Polymerase Chain Reaction (RT-PCR) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) diagnosis currently requires quite a long time span. A quicker and more efficient diagnostic tool in emergency departments could improve management during this global crisis. Our main goal was assessing the accuracy of artificial intelligence in predicting the results of RT-PCR for SARS-COV-2, using basic information at hand in all emergency departments.
Methods: This is a retrospective study carried out between February 22, 2020 and March 16, 2020 in one of the main hospitals in Milan, Italy. We screened for eligibility all patients admitted with influenza-like symptoms tested for SARS-COV-2. Patients under 12 years old and patients in whom the leukocyte formula was not performed in the ED were excluded. Input data through artificial intelligence were made up of a combination of clinical, radiological and routine laboratory data upon hospital admission. Different Machine Learning algorithms available on WEKA data mining software and on Semeion Research Centre depository were trained using both the Training and Testing and the K-fold cross-validation protocol.
Results: Among 199 patients subject to study (median [interquartile range] age 65 [46-78] years; 127 [63.8%] men), 124 [62.3%] resulted positive to SARS-COV-2. The best Machine Learning System reached an accuracy of 91.4% with 94.1% sensitivity and 88.7% specificity.
Conclusion: Our study suggests that properly trained artificial intelligence algorithms may be able to predict correct results in RT-PCR for SARS-COV-2, using basic clinical data. If confirmed, on a larger-scale study, this approach could have important clinical and organizational implications.

The recent SARS-CoV-2 pandemic behaved like a tsunami for many healthcare systems worldwide, as for example in the USA, India and Europe. Restricting the observation angle to the field of gastroenterology, a great number of new relevant clinical data have been produced in an exceedingly short period of time, such as the observation that the disease, originally considered as a respiratory illness, commonly features a variety of gastrointestinal intestinal symptoms and that the digestive system appears to be involved in disease pathogenesis [1 –3 ]. From the organizational site, endoscopy suites have been forced to suspend non-urgent procedures in order to re-allocate human resources to the care of COVID- 19 positive inpatients during the early phase of pandemic [4 –6 ] and are now planning how to gradually return to pre- COVID routine endoscopy activity [7 ]. The consequences of delaying the return to routine endoscopy are seriously impacting the health system; in the USA alone, a hypothetical suspension of elective endoscopy for 6 months is predicted to delay the diagnosis of over 2800 colorectal cancers and 22,000 adenomatous polyps with malignant potential [8 ]. The 6-month mortality rate for those eventually diagnosed with colorectal cancer is predicted to increase by 6.5% [9 ]. Nevertheless, the problem of re-starting nonurgent procedures while the COVID pandemic is ongoing with the need of maintaining protective measures and social distancing is present, the volume of procedures is going to overwhelm existing resources, resulting in a backlog of procedures. Thus, as Xiao et al. [10 ] propose in this issue of Digestive Diseases and Sciences , the policy of appropriately triaging and rescheduling endoscopic procedures, in particular screening and surveillance colonoscopy, should be based on specific and timely adopted new guidelines. Here probably lies one of the most important problems: which national or international guidelines should be adopted for the purpose? Recommendations have been changing rapidly and need to be updated, mainly due to the new development of worldwide sustained community transmission of COVID- 19 [11 ]; moreover, at least 21 specific recommendations are available for endoscopy during the COVID-19 pandemic elaborated by a pool of 93 international and national societies as identified in a recent review [12 ].
Xiao et al. adopted pre-COVID era guidelines, namely those of the US Multi-Society Task Force (USMSTF) published in 2017 [13 ] and updated in 2020 [14 ] as a guide to expanding access to endoscopy. In their single-center observational study of patients scheduled for open-access (OA) colonoscopy ordered by a primary physician over a six-week period during the COVID-19 pandemic, they found that up to one-fifth of colonoscopies can be rescheduled into a future year based on USMTSTF guidelines [14 ]. Interestingly enough, roughly 75% of these inappropriately scheduled colonoscopies were non-adherent to the above guidelines, whereas the remaining 25% was due to inappropriate use of family history by the primary care physician (PCP). Thus, the study confirms that: a) PCPs recommend repeat colonoscopy sooner than guidelines suggest [15 , 16 ]; and b) a significant proportion of open access colonoscopies for colorectal cancer prevention are indeed inappropriate, confirming the figure of nearly 8% according to a recent review by Kapila et al. [17 ]. Thus, the question arises of how to improve the use of OA colonoscopy for CRC screening and surveillance, since this might reduce the volume of procedures without delaying CRC detection. Xiao et al. suggest that this can be accomplished by incorporating guidelines at two points of care, namely following the index colonoscopy and in the PCP’s office. Nonetheless, as authors admit, often the PCP simply follows inappropriate recommendations provided by the endoscopist, suggesting lack of awareness or disagreement with existing guidelines. Indeed, predictors for poor adherence to guidelines have been carefully examined and suggested [18 ]. This pushes back to the general issue of how can effective guidelines be proposed and updated, with the conclusion that continuing education is mandatory, in particular in these times of rapidly changing clinical paradigms.

Notes:

1 Villa Santa Maria Foundation, Tavernerio, Italy
2 Division of Gastroenterology, ASST Bergamo Est, Seriate, BG, Italy

Background
About 20% of individuals with autism spectrum disorders (ASD) showed tip-toe behavior (TTB). This behavior may be related to a decreased ankle joint range of motion (ROM) in dorsiflexion. Physiologically, gastrocnemius (GM) and soleus (SM) muscles influence ankle ROM independently. However, no studies investigated the relationship between the amount of time individuals with ASD spend in TTB and GM and SM muscle lengths.

Objective
To evaluate the relationship between three mutually exclusive clinical patterns of TTB i.e., during standing, walking and running (TTB Class 1), or during walking and running (TTB Class 2), or only when running (TTB Class 3), and GM and SM muscle lengths.

Methods
Sixty-nine individuals with ASD (average age: 14.1 ± 3.6 years, 56 males) were enrolled. In a clinical setting, SM and GM muscle lengths of both legs were assessed through a manual goniometer. Measurements were performed by two trained assessors blinded to TTB classifications.

Results
Individuals with ASD classified as TTB Class 1 demonstrated a shortening of both GM and SM compared with NO-TTB and TTB Class 3 individuals.

Conclusions
Our results support the relationship between TTB severity and GM and SM shortening assessed by a decreased ankle joint ROM in dorsiflexion. Further studies are needed to determine the factors associated with TTB and decreased ankle ROM.

Notes:

1 Autism Research Unit, Villa Santa Maria Foundation, Via IV Novembre 15, Tavernerio, CO, Italy
2 School of Medicine and Surgery, University of Milano Bicocca, Milano, Italy
3 School of Physical & Occupational Therapy, McGill University, Montreal, Canada
4 Faculty of Human Development, Graduate School of Human Development and Environment, Kobe University, Japan
5 Human Health Sciences, Graduate School of Medicine, Kyoto University, Japan

The microbiota-gut-brain axis has been recently r cognized as a key modulator of neuropsychiatric health. In this framework, probiotics (recently named “psychobiotics”) may modify brain activity and function, possibly improving the behavioral profiles of children with Autism Spectrum Disorder (ASD). We evaluated the effects of probiotics on autism in a double-blind randomized,
placebo-controlled trial of 85 preschoolers with ASD (mean age, 4.2 years; 84% boys). Participants were randomly assigned to probiotics (De Simo e Formulation) (n=42) or placebo (n=43) for six months. Sixty-three (74%) children completed the trial. No differences between groups were detected on the primary outcome measure, the Total Autism Diagnostic Observation Schedule - Calibrated Severity Score (ADOS-CSS). An exploratory secondary analysis on subgroups of children with or without Gastrointestinal Symptoms (GI group, n= 30; NGI group, n=55) revealed in the NGI group treated with probiotics a significant decline in ADOS scores as compared to that in the placebo group, with a mean reduction of 0.81 in Total ADOS CSS and of 1.14 in Social-Affect ADOS CSS over six months. In the GI group treated with probiotics we found greater improvements in some GI symptoms, adaptive functioning, and sensory profiles than in the GI group treated with placebo. These results suggest potentially positive effects of probiotics on core autism symptoms in a subset of ASD children independent of the specific intermediation of the probiotic effect on GI symptoms. Further studies are warranted to replicate and extend these promising findings on a wider population with subsets of ASD patients which share targets of intervention on the microbiota-gut-brain axis.

Notes:

1 Fondazione Stella Maris (IRCCS), Italy,
2 Institute of Clinical Physiology, Italian National Research Council, Italy,
3 University of Pisa, Italy,
4 Department of Public Health and Infectious Diseases, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Italy,
5 Villa Santa Maria Foundation, Tavernerio, Italy

A sound postural system requires sensorimotor integration. Evidence suggests that individuals with Autism Spectrum Disorder (ASD) present sensorimotor integration impairments. The Physiological Profile Assessment (PPA) can be used to evaluate postural capacity assessing five physiological subsets (i.e., vision, reaction time, peripheral sensation, lower limb strength, balance); however, no studies applied the PPA in young individuals. Therefore, this study aimed to investigate the PPA in children and adolescents with ASD compared with age-matched typically developing (TD) individuals and examine the relationship between the PPA subset within the ASD and TD participants according to different age groups. Percentiles from the PPA were obtained from the TD children and adolescents (n = 135) for each test. Performances of the individuals with ASD (n = 18) were examined relative to the TD percentiles. ASD participants’ scores were above the 90th percentile (i.e., poor performance) in most sensory, motor and balance parameters. Performance in most of the PPA tests significantly improved with older age in the TD group but not in the ASD group. The study findings support the use of the PPA in TD children and adolescents while further research should investigate postural capacity in a larger ASD sample to enhance the understanding of sensorimotor systems contributing to compromised postural control.

Notes: 

1 School of Medicine and Surgery, University of Milano Bicocca, 20126 Milan, Italy
2 Autism Research Unit, “Villa Santa Maria” Foundation, 22038 Como, Italy
3 ASST Rhodense, Ospedale “G. Salvini”, 20024 Milan, Italy
4 Department of Physiotherapy, LUNEX International University of Health, Exercise and Sports, Differdange, 4671 Luxembourg, Luxembourg
5 Neuroscience Research Australia and School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW 2052, Australia
6 School of Physical and Occupational Therapy, McGill University, Montreal, QC H3G 1Y5, Canada
7 School of Physical Therapy and Athletic Training, Pacific University, Hillsboro, OR 97123, USA

The inaccuracy of resting energy expenditure (REE) prediction formulae to calculate energy metabolism in children may lead to either under- or overestimated real caloric needs with clinical consequences. The aim of this paper was to apply artificial neural networks algorithms (ANNs) to REE prediction. We enrolled 561 healthy children (2-17 years). Nutritional status was classified according to World Health Organization (WHO) criteria, and 113 were obese. REE was measured using indirect calorimetry and estimated with WHO, Harris-Benedict, Schofield, and Oxford formulae. The ANNs considered specific anthropometric data to model REE. The mean absolute error (mean ± SD) of the prediction was 95.8 ± 80.8 and was strongly correlated with REE values ( = 0.88). The performance of ANNs was higher in the subgroup of obese children (101 ± 91.8) with a lower grade of imprecision (5.4%). ANNs as a novel approach may give valuable information regarding energy requirements and weight management in children.

Few studies so far have focused on the duration of COVID- 19 detection in asymptomatic or pauci-symptomatic subjects1,2. In asymptomatic adults, the median time from the first positive test to the first of two consecutive negative tests ranges between 7 and 23 days. Only two case-report studies have concerned children, with a detectable virus for 10 days3 and for 17 days4.
There are multiple reports of prolonged viral shedding in peo- ple infected with SARS-CoV-2 but the presence of viral RNA on a test does not necessarily correlate with infectivity5–8.
The duration of quarantine required after clinical recovery to definitively prevent transmission is therefore uncertain.
We report a case of exceptionally high viral load and extremely slow SARS-CoV-2 RNA shedding in a toddler resident in Villa Santa Maria rehabilitation Institute, a well-known Nursing Home in the Lombardy region.
An Italian child with autism and severe intellectual disability, nine years old, resident in our Institute from 2018, on April 20th developed a cough and nasal discharge. On the evening of April 21st, a moderate fever (38.3 C°) was registered, disappearing on the morning of 22nd. All symptoms vanished from the 22nd after- noon.
At the objective examination, no clinical signs of lung involve- ment were noticed. The child underwent nose-pharyngeal swab for COVID-19 virus detection on April 24th.
Quantitative RT-PCR indicated a viral load corresponding to a Cycle Threshold(CT) value = 6 (10.5 log10 copies/mL). After this first swab other five repeated tests performed approximatively ev- ery two-three week confirmed the detection of COVID RNA with CT values of 29,30,36,26, 34 along the following twelve weeks (Fig. 1), till July 15th, date of the last positive swab. The subject was main- tained in isolation for all this period considering viral load levels potentially related to infectivity as those registered. The first nega- tive swab was registered on August 4th followed by a second neg- ative swab on August 6th. At this latter date a high specific IgG response was registered with S/CO titers (Log2) >10.
Throughout this period the subject remained asymptomatic. Blood examination tests revealed the presence of marked neu- tropenia (neutrophil count=930/ml) and a low percentage of CD4 helper lymphocytes (25%).
This case suggests that in pauci-symptomatic children excep- tionally high viral load can be detected and consequently the virus shedding can take a long duration, 82 days precisely. Careful mon- itoring with repeated tests at regular intervals checking CT values is important to establish the duration of the infectivity, which, as suggested by recent studies9,10 can be considered absent only with CT values above 34.

Notes: 1 Villa Santa Maria Foundation, Tavernerio, Italy 

Abstract: In this article we want to show the potential of an evolutionary algorithm called Topological Weighted Centroid (TWC). This algorithm can obtain new and relevant information from extremely limited and poor datasets. In a world dominated by the concept of big (fat?) data we want to show that it is possible, by necessity or choice, to work profitably even on small data. This peculiarity of the algorithm means that even in the early stages of an epidemic process, when the data are too few to have sufficient statistics, it is possible to obtain important information. 

To prove our theory, we addressed one of the most central issues at the moment: the COVID-19 epidemic. In particular, the cases recorded in Italy have been selected. Italy seems to have a central role in this epidemic because of the high number of measured infections. Through this innovative artificial intelligence algorithm, we have tried to analyze the evolution of the phenomenon and to predict its future steps using a dataset that contained only geospatial coordinates (longitude and latitude) of the first recorded cases. 

Once the coordinates of the places where at least one case of contagion had been officially diagnosed until February 26th, 2020 had been collected, research and analysis was carried out on: outbreak point and related heat map (TWC alpha); probability distribution of the contagion on February 26th (TWC beta); possible spread of the phenomenon in the immediate future and then in the future of the future (TWC gamma and TWC theta); how this passage occurred in terms of paths and mutual influence (Theta paths and Markov Machine). Finally, a heat map of the possible situation towards the end of the epidemic in terms of infectiousness of the areas was drawn up. The analyses with TWC confirm the assumptions made at the beginning.

Notes:

1 Semeion Research Center of Sciences of Communication, via Sersale, 117, 00128 Rome, Italy

2 University of Colorado at Denver, Department of Mathematical and Statistical Sciences, Denver, CO, US

3 Villa Santa Maria Foundation, Tavernerio (Como), Italy

Abstract: COVID-19 has heavily affected nursing homes for elderly people in Italy and particularly in the Lombardy region, causing uncount- able deaths. From the moment the pandemic slowly faded, there has been a pressing scientific and social need to define a limit of time and of viral load beyond which the positivity of RT-PCR loses its meaning, to reduce the isolation of the subjects in the nursing homes beyond the clinical and public health utility. 
While the decline in viral infectivity seems to decline in one or two weeks since symptom onset1-2 the RT-PCR positivity may per- sist for several weeks after the resolution of symptoms3-6. Since there is a minimal risk for persistently-positive recovered patients to shed infectious virus, many of them remain hospitalized, or in shelter-in-place, for a much longer time than necessary, with sig- nificant social distress and economic commitment. 
Few data are available so far in children and adolescent nursing homes regarding quantitative RT-PCR (qRT-PCR) registered during the COVID-19 pandemic. 
Fifty-two children and adolescents (41 males 11 females: mean age 14.8, range 6–18 years) affected by neuropsychiatric disorders and resident in Villa Santa Maria Rehabilitation Institute, a well- known nursing home in Lombardy region, underwent a series of qRT-PCR on nose-pharyngeal swabs from April 27 to July 4th, 2020. 
Thirty-two subjects had symptoms suggestive of COVID-19 infec- tion, like fever, cough, and or diarrhea while 20 were asymp- tomatic. Sixty-two percent of symptomatic subjects and 50% of asymptomatic subjects resulted positive to COVID-19 with a total of 30 positive cases (25 males - 5 females; mean age 14.1 years). 
Subjects showing positivity to the test were monitored through- out with repeated tests on a 1–2-week basis until the obtainment of two consecutive negative tests. We had to wait till July 4th to certify the negative turning of all subjects. 
Interesting details of viral load in the 30 subjects positive at RT-PCR were observed according to different subgroup characteris- tics. The initial viral load of 25 males was significantly higher than 5 females (median [IQR] males: 19 [14 – 23,5] vs. 27 [24–29], re- spectively; p = 0.01 by Mann-Whitney test). 
Initial viral load observed in 21 symptomatic subjects resulted substantially higher in comparison with 9 asymptomatic subjects (median [IQR] with symptoms: 20 [15 –27] vs. 22 [16.5–25], re- spectively; the difference anyway resulted statistically not signifi- cant (p = 0.8 Mann–Whitney test). The viral load at the first swab in 16 subjects who remained still positive at second swab was higher in comparison with 14 subjects who resulted negative at second swab. Also in this case the difference resulted statistically not significant (median CT[IQR] still positive: 19.5 [14.5 –23.7] vs. 22 [17.7–27], respectively (p = 0.4 Mann–Whitney test). 
Twenty subjects underwent more than two RT-PCR tests until permanent negative turning. 
Fig. 1 shows the oscillation of viral load in the subsequent 97 swabs, performed along 12 weeks after the first swab. A marked oscillation of viral load value was observed, also with negative swabs turning positive. 
This study shows that in children and adolescents found pos- itive at COVID-19 RT-PCR being resident in a nursing home the time required for a definitive disappearance of the virus from nose-pharyngeal swab can overcome two months. Along this pe- riod is possible to observe the existence of discrete oscillation in COVID-19 viral load count in line with the results of a recent Ital- ian study7. Given these findings, the WHO resolution for releasing COVID-19 patients from isolation seems reasonable to avoid unnec- essary social burden.

Notes: 1 Villa Santa Maria Institute, Tavernerio, Italy 2 Centro Diagnostico Italiano, Milano, Italy

In December 2019, a new potentially pandemic Coronavirus made its appearance in the province of Wuhan, China. From there, the epidemic began to spread to the rest of China, then to Asia and all over the world. Today, cases are reported in over one hundred countries, in Asia, Europe, North America, South America, Africa and Oceania. The feared transmission of the virus from human to human has been confirmed in all these regions and in Europe, also by asymptomatic subjects. It is difficult to understand why these data have long been underestimated, above all in the West Countries. Only on March 11th 2020 the WHO declared the pandemic alarm. To date, April 13th 2020, the confirmed cases in the world are 1.844.863 and the confirmed deaths 117.021 (20.465 in Italy vs. 3.351 recorded in China and 222 in South Korea). The situation appears particularly serious in Northern Italy, and more recently also in UK (11,329 deaths), France (14,946 deaths), Spain (17,489 deaths) and above all United States of America (21,972 deaths), with the number of cases doubling every day in Madrid and New York city. Italy has currently recorded 16.400 infected healthcare workers and 116 medical doctors dead. In this paper, we will try to explain why Italy has become the second epicenter of the world epidemics after China, and why the containment strategies and preventive measures adopted so far by the Italian government still do not seem to be sufficiently adequate in slowing the expansion of the COVID-19 outbreak.

Objectives: Paediatric acute onset neuropsychiatric syndrome (PANS) is a clinically heterogeneous disorder presenting with: unusually abrupt onset obsessive compulsive disorder (OCD) or severe eating restrictions, with at least two concomitant cognitive, behavioural, or affective symptoms such as anxiety, obsessive-compulsive behaviour,
irritability/depression. This study describes the clinical and laboratory variables of 39 children (13 female and 26 male) with a mean age at recruitment of 8.6 years (SD 3.1).

Methods: Using a mathematical approach based on Artificial Neural Networks, the putative associations between PANS working criteria, as defined at the NIH in July 2010 (Swedo et al. 2012), were explored by the Auto Contractive Map (Auto-CM) system, a mapping method able to compute the multi-dimensional association of strength of each variable with all other variables in predefined dataset.

Results: The PANS symptoms were strictly linked to one another on the semantic connectivity map, shaping a central “diamond” encompassing anxiety, irritability/Oppositional defiant disorder (ODD) symptoms, obsessive-compulsive symptoms, behavioural regression, sensory motor abnormalities, school performance deterioration, sleep disturbances, emotional lability/depression. The semantic connectivity map also showed the aggregation between PANS symptoms and laboratory and clinical variables. In particular, the emotional lability/depression resulted as a highly connected hub linked to autoimmune disease in pregnancy, allergic and atopic disorders and low Natural Killer percentage. Also anxiety symptoms were shown strongly related with recurrent infectious disease remarking the possible role of infections as a risk factor for PANS.

Conclusion: Our data mining approach shows a very specific constellation of symptoms having strong links to laboratory and clinical variables consistent with PANS feature.

Notes: 

1 Child & Adolescent Neuropsychiatry Unit, Department of Biomedical Sciences, University of Cagliari, & “G. Brotzu” Hospital Trust, Cagliari, Italy
2 Division of Child Neurology and Psychiatry, Department of Pediatrics, University of Messina. Messina, Italy
3 Division of Psychology, Department of Humanities and Social Sciences, University of Messina, Messina, Italy
4 Department of Cognitive Psychological Pedagogical Sciences and Cultural Studies, University of Messina, Messina, Italy
5 Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

Teriparatide is a bone-forming therapy for osteoporosis that increases bone quantity and texture, with uncertain action on bone geometry. No data are available regarding its influence on bone strain. To investigate teriparatide action on parameters of bone quantity and quality and on Bone Strain Index (BSI), also derived from DXA lumbar scan, based on the mathematical model finite element method. Forty osteoporotic patients with fractures were studied before and after two years of daily subcutaneous 20 mcg of teriparatide with dual X-ray photon absorptiometry to assess bone mineral density (BMD), hip structural analysis (HSA), trabecular bone score (TBS), BSI. Spine deformity index (SDI) was calculated from spine X-ray. Shapiro-Wilks, Wilcoxon and Student's t test were used for classical statistical analysis. Auto Contractive Map was used for Artificial Neural Network Analysis (ANNs). In the entire population, the ameliorations after therapy regarded BSI (-13.9%), TBS (5.08%), BMD (8.36%). HSA parameters of femoral shaft showed a worsening. Dividing patients into responders (BMD increase >10%) and non-responders, the first presented TBS and BSI ameliorations (11.87% and -25.46%, respectively). Non-responders presented an amelioration of BSI only, but less than in the other subgroup (-6.57%). ANNs maps reflect the mentioned bone quality improvements. Teriparatide appears to ameliorate not only BMD and TBS, but also BSI, suggesting an increase of bone strength that may explain the known reduction in fracture risk, not simply justified by BMD increase. BSI appears to be a sensitive index of TPD effect. ANNs appears to be a valid tool to investigate complex clinical systems.

Notes:

1 IRCCS Istituto Ortopedico Galeazzi, Milano, Italy.
2 Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano, Italy.
3 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UO Gastroenterologia ed Endoscopia Digestiva, Milano, Italy.
4 Villa Santa Maria Foundation, Centro di Riabilitazioni Neuropsichiatrica, UO Autismo, Tavernerio (CO), Italy.
5 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UO Endocrinologia, Milano, Italy.
6 IRCCS Istituto Auxologico, UO Endocrinologia e Malattie del Metabolismo, Milano, Italy.
7 A.O.U. Città della Salute e della Scienza di Torino, Presidio Molinette, Corso Bramante, Torino, Italy.
8 TECHNOLOGIC Srl, Lungo Dora Voghera, Torino, Italy.
9 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UO Medicina Nucleare, Milano, Italy.

Background and Objective: The translation of precision medicine in clinical practice will depend mostly from the possibility to make statistical inference at individual level, exactly positioning a new case in the taxonomy space (diagnosis) or in the time space (prognosis). As matter of the fact clinical epidemiology and medical statistics have not been suited to answer specific questions at the individual level. They focus on groups of individuals and not on single individuals. Classical statistics by definition needs samples to work, and samples by definition are always greater than one. This explains why for traditional statistics the single individual is a sort of moving and vague target to intercept. The objective of this paper is to show the feasibility of the use of potent machine learning system developed at Semeion Institute in approaching the problem of single individual statistics in a consistent and sound way.

Methods. Three cases studies relevant to different unsupervised machine learning systems are shown: a) the use of Self Organizing Maps to determine the confidence interval of a quality of life scale total score in seven new individual subjects having a group of 1000 individuals as reference data set; b) the use of the evolutionary algorithm “Pick and Squash Tracking” (PST) to cluster and discriminate patients affected by Barrett disease from those affected by simple gastroesophageal reflux disease, c) the use of Auto-CM system, a fourth generation artificial neural network, to map individual patients with and without acute myocardial infarction on the basis of genetic, clinical traits and classical risk factors. A further case study is described relying on the use of supervised machine learning systems, based on the concept of Fermi mathematics.

Results. The three unsupervised methods proved to be reliable and easily applicable to real world examples in term of readability, accuracy and reproducibility. The confidence interval related to seven new cases in the first case study allowed the clinician to identify easily the outlier. The accuracy of the map projection with PST algorithm in the second case study allowed an immediate visual evidence of the degree of membership of each individual subject to the two diagnostic classes. In the third case study the overall accuracy of clustering obtained by Auto-Cm system resulted to be 93%.The conceptual advantages obtainable are explained. The fourth method shows that is possible by using several independent classification models on the same individual to establish a degree of confidence of the prediction and therefore to overcome the dogma by which it is not possible to make a statistical inference when a sample is composed by just one subject.

Conclusions: Machine learning systems have the potential to allow the real translation of precision medicine philosophy in the real world.

Abstract: The gut microbiota is a complex and dynamic ecosystem with a strong influence on the host's health. Several factors can modify the gut's bacterial composition, often leading to the onset of intestinal dysbiosis. Therefore, it is essential not only to evaluate the quantitative bacterial changes occurring in the human microbiota but also to characterize relationships existing among all the microorganisms. This study aimed to evaluate the impact of bowel cleansing on the fecal microbiota network by highlighting differences between fecal microflora before and after colonoscopy, and luminal samples during colonoscopy. Fecal and luminal samples, previously analyzed by mean of Next-Generation Sequencing (NGS) for their bacterial abundance, were further processed by a method based on Artificial Neural Network (ANN) architecture. The bowel lavage had a strong effect on the intestinal microbiota network, leading to significant changes in the distribution of different bacterial hubs potentially involved in the microbiota homeostasis. Furthermore, the fecal and luminal microbiota showed a different bacterial network, characterized by distinct microbial hubs. In particular, the latter seemed to be rich in potentially pathogenic bacteria which, in physiological conditions, are counteracted by fecal microorganisms.

Background
Epithelial neoplasms of the scalp account for approximately 2% of all skin cancers and for about 10-20% of the tumors affecting the head and neck area. Radiotherapy is suggested for localized cutaneous squamous cell carcinomas (cSCC) without lymph node involvement, multiple or extensive lesions, for patients refusing surgery, for patients with a poor general medical status, as adjuvant for incompletely excised lesions and/or as a palliative treatment. To date, prognostic risk factors in scalp cSCC patients are poorly characterized.

Objective
To identify patterns of patients with higher risk of post-radiotherapy recurrence

Methods
A retrospective observational study was performed on scalp cSCC patients with histological diagnosis who underwent conventional radiotherapy (50-120 kV) (between 1996 and 2008, follow-up from 1 to 140 months, median 14 months). Out of the 79 enrolled patients, 22(27.8%) had previously undergone a surgery. Two months after
radiotherapy, 66(83.5%) patients achieved a complete remission, 6(7.6%) a partial remission, whereas 2(2.5%) proved non-responsive to the treatment and 5 cases were lost to follow-up. Demographical and clinical data were preliminarily analyzed with classical descriptive statistics and with principal component analysis. All data were then re-evaluated with a machine learning-based approach using a 4th generation artificial neural networks(ANNs)-based algorithm.

Results
ANNs analysis revealed four scalp cSCC profiles among radiotherapy responsive patients, not previously described: namely, 1) stage T2 cSCC type, aged 70-80 years; 2) frontal cSCC type, aged <70 years; 3) non-recurrent nodular or nodulo-ulcerated, stage T3 cSCC type, of the vertex and treated with >60 Grays (Gy); and 4) flat, occipital, stage T1 cSCC type, treated with 50-59 Gy. The model uncovering these four predictive profiles displayed 85.7% sensitivity, 97.6% specificity, and 91.7% overall accuracy.

Conclusions
Patient profiling/phenotyping with machine learning may be a new, helpful method to stratify patients with scalp cSCCs who may benefit from a RT-treatment.

Notes:

1 Phototherapy Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
2 Dermatology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico di Milano, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy
3 Young Dermatologists Italian Network, Centro Studi GISED, Bergamo, Italy
4 Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA
5 Fondazione Villa Santa Maria, Tavernerio, Como, Italy
6 Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USA
7 Clinical Dermatology Department, IRCCS S. Gallicano Dermatological Institute, Rome, Italy
8 School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
9 Ben Gurion University of the Negev, Beer Sheva Israel
^ Equally contributed as first authors.
† Equally contributed as last authors.

The aim of this study is to highlight the feasibility of an aesthetic experience in Museo Teatrale alla Scala in seventeen adolescents and adult subjects suffering from different forms of neuro-psychiatric diseases, guests of the Villa Santa Maria Institute, an Italian Rehabilitation Center.
The experience consisted in a guided tour in the museum coupled by an opera performance in the exedra room of the Museo Teatrale alla Scala, such as the adaptation of Mozart's Magic Flute. The measurement of the impact of this experience on psychological well-being, carried out through the use of a special analogue chromatic scale, allowed to establish a strong emotional impact with a statistically significant increase in the momentary psychological well-being in all three groups.
This pilot study confirms that art is able to stimulate parts of the brain that remain intact even after the onset of neuro-psychiatric diseases and that the measurement of temporary wellbeing is feasible even in the presence of cognitive deficit.

Notes:

*ICOM Italia
** Fondazione Villa Santa Maria – Tavernerio

Background: Metabolic syndrome (MetS) has been associated with colorectal adenomas and cancer. However, MetS definitions have changed over time, leading to a heterogeneity of patients included in previous studies and a substantial inextensibility of observations across time or eastern and western populations. Our aim was to evaluate the association of ‘harmonized’ criteria-defined MetS and its individual components with colorectal neoplasia and cancer in a western population.

Methods: In this multicenter, cross-sectional study, we prospectively evaluated consecutive outpatients who underwent open-access colonoscopy over a 3-month period. MetS was diagnosed according to the 2009 ‘harmonized’ criteria.

Results: Out of 5707 patients enrolled, we found 213 cancers (3.7%), 1614 polyps (28.3%), 240 nonpolypoid lesions (4.2%), 95 laterally spreading tumors (1.6%). Polyps presented histological low-grade dysplasia in 72.9% of samples, while in 9.8%, high-grade dysplasia or in situ carcinoma was present; dysplasia rates for nonpolypoid lesions were 66.2% (low-grade) and 2.9% (high-grade/in situ carcinoma), while for laterally spreading tumors, 29.6% and 37%, respectively. Overall, MetS prevalence was 41.6%. MetS correlated with both adenomas [odds ratio (OR): 1.76, 95% confidence interval (CI) 1.54–2.00] and cancer (OR: 1.92, 95% CI 1.42–

2.58). MetS was the only risk factor for such colonic lesions in subjects younger than 50 years. For all colonic neoplasia, we found MetS and not its individual components to be significantly associated.

Conclusions: MetS is risk factor for cancer and adenoma in Whites, especially when younger than 50 years. MetS patients might be considered as a high-risk population also in colorectal cancer screening programs.

NOTES: 

- Matteo Neri, Department of Medicine and Aging Sciences and Center of Aging Sciences and Translational Medicine (CeSI-MeT), ‘G.D.’ Annunzio University and Foundation, Chieti, Italy - Digestive Endoscopy and Gastroenterology Unit, ‘SS Annunziata’ University Hospital, Chieti, Italy 

- Angelo Milano and Konstantinos Efthymakis, Department of Medicine and Aging Sciences and Center of Aging Sciences and Translational Medicine (CeSI-MeT), ‘G.D.’ Annunzio University and Foundation, Chieti, Italy - Digestive Endoscopy and Gastroenterology Unit, ‘SS Annunziata’ University Hospital, Chieti, Italy

- Maria Antonia Bianco, Livio Cipolletta and Gianluca Rotondano, Division of Gastroenterology and Digestive Endoscopy Unit, Hospital ‘A Maresca’, Torre del Greco, Italy 

- Luigi Buri, Gastroenterology and Digestive Endoscopy Unit, Cattinara Hospital, Trieste, Italy

- Enzo Grossi, Villa Santa Maria Foundation, Como,Italy

- Francesco Tessari, Electronic Data Processing, Idea 99 Srl, Padova, Italy

Abstract: Background: Nutrition plays an important role in the aging process. Adherence to the Mediterranean diet (MedDiet) has been shown to be associated with lower rates of diseases. Cognitive status seems to be strongly interrelated with physical well-being, so that one influences the other. Physical performance measures are not only associated with clinical and subclinical age-related modifications, but are also able to predict disability, institutionalization, and mortality. 

Objective: To evaluate prospectively the associations between Mediterranean-Style Dietary Pattern Score (MSDPS), clinical characteristics, and cognition of the population sample of The TREVISO LONGEVA (TRELONG) Study, in Treviso, Italy. 

Methods: Global cognition, physical performance measures, MSDPS, and other clinical features were detected in 2010 in 82 men and 108 women. These characteristics were evaluated in relation to the physical performance measures identified 3.8 years later in 2013 in the same subjects, using a semantic connectivity map, through Auto-CM system, to grasp further and non-linear associations between variables which might remain, otherwise, undetected. Results: The Auto-CM system’s map shows a close association between better levels of global cognition and MSDPS in 2010 and higher physical performance in 2013. On the other hand, worse levels of global cognition and MSDPS in 2010 are associated with lower physical performance in 2013. 

Conclusion: The prevention models for successful aging may benefit from integrated programs that include cognitive, physical, and dietary interventions, since these aspects are mutually interrelated.

In the last 50 years, the worldwide trend concerning urbanization has been accompanied by the rural exodus toward urban and me- tropolitan areas. As mentioned from several studies and reports (United Nations, 2006 and 2010; Sørensen 2014; Lenzi & Perrucca, 2016), the percentage of those living in urban context rose over the 50% of the worldwide population, a percentage that reached almost the 75% within EU border.
The reason behind the growing interest in setting up in urban spaces is related to a wide range of direct influences and positive externalities generated by these areas on individual development, in comparison to rural ones. According to the literature on agglomeration economies, cities and urban areas are linked to benefits like higher productivity and wages, more learning opportunities and exchanges, higher rate of in- novation and creativity, more public services or other aspects that might positively influence individuals‘ development. If, on the one side, cities have become a major attractor for human development, on the other side this dynamic have also negative counterparts connected with different elements, the increased city size, the higher costs of living, the higher environmental costs (pollution or congestion), potential social conflicts. All these elements are threatening the individuals’ develop- ment, playing a role in choosing a place to live and work.
Starting from the 80s’ a large number of contributes concentrated on the perception of the individual quality of life within urban and rural contexts. Focusing the attention on the most economically developed countries, specifically in Europe, the quality of life has been increasing over the time when living in urban surroundings, this when considering both, subjective and objective well-being data. The gap between rural and urban in favor of urban areas can be explained with a lower level of opportunities in terms of e.g. access to public services, lower individual income, less employment opportunities, lower level of education and critical transport. If, at a first sight, it can be observed that conurbation, provides higher advantages in urban contexts, the size of those (vil- lages, town, cities and metropolises) matters in relation to the life sa- tisfaction, particularly in those realms not related to objective indicators such as education or income, but to subjective ones such as individual evaluation of their life or perceived quality of the environ- ment where they live. Towns and villages appear to be keener in sup- plying relational net and collaboration between residents than cities; a community feeling and a stronger social cohesion in these contexts brings toward a positive perception of individual well-being. Moreover, another aspect that might positively affect individual well-being it is the closeness to the natural environment, more frequent in small cities, town and rural areas in comparison with large cities and metropolitan areas. It is widely reported that living close to a natural space and using it for leisure activities promote a greater contribution to both physical and psychological individual well-being. Additional elements appear to be determinant such as the cultural supply, participation to voluntary, and community activities, which may prompt the activation of biolo- gical effects in individual and thus foster individual well-being.
The article aims to investigate the difference of individual psycho- logical well-being provided by living in rural and urban contexts, by enquiring the possible determinants related to both objective and sub- jective aspects. To this end, a cross-sectional survey was undertaken in the autumn of 2010 on a statistical representative sample (1500 polled) of residents living in both urban and rural areas in Italy. The survey has been modeled on the PGWBI (Psychological General Well-Being Index), an instrument specifically targeted to measure individual subjective well-being, used for the evaluation of the impact of different subjective well-being determinants. The questionnaire gathered a bounce of the main socio-demographic characteristics such as gender, age, education, income, diseases, employment, and civil status, which are listed as major objective well-being determinants in the well-being literature. Furthermore, information concerning other possible determinants re- lated to subjective dimension such as social and community involve- ment, cultural and leisure participation, sport activities, have been collected in order to provide a much comprehensive understanding of the influence of the different determinants on individual subjective well-being in relation to the size scale (urban vs. rural).

Notes:

a) Freie Universität Bozen – Libera Università di Bolzano
b) University of Bologna and Villa Santa Maria Institute, Tavernerio, Italy
c) Free University of Bolzano, IULM University, Milan, Italy

Background and Objective. 

In a previous study, we showed a new EEG processing methodology called Multi-Scale Ranked Organizing Map/Implicit Function As Squashing Time (MS-ROM/IFAST) performing an almost perfect distinction between computerized EEG of Italian children with autism spectrum disorder (ASD) and typically developing children. In this study, we assessed this system in distinguishing ASD subjects from children affected with other neuropsychiatric disorders (NPD). 
Methods. 
At a psychiatric practice in Texas, 20 children diagnosed with ASD and 20 children diagnosed with NPD were entered into the study. Continuous segments of artifact-free EEG data lasting 10 minutes were entered in MS-ROM/IFAST. From the new variables created by MS-ROM/IFAST, only 12 has been selected according to a correlation criterion. The selected features represent the input on which supervised machine learning systems (MLS) acted as blind classifiers. 
Results. 
The overall predictive capability in distinguishing ASD from other NPD cases ranged from 93% to 97.5%. The results were confirmed in further experiments in which Italian and US data have been combined. In this analysis, the best MLS reached 95.0% global accuracy in 1 out of 3 classes distinction (ASD, NPD, controls). This study demonstrates the value of EEG processing with advanced MLS in the differential diagnosis between ASD and NPD cases. The results were not affected by age, ethnicity and technicalities of EEG acquisition, confirming the existence of a specific EEG signature in ASD cases. To further support these findings, it was decided to test the behavior of already trained neural networks on 10 Italian very young ASD children (25-37 months). In this test, 9 out of 10 cases have been correctly recognized as ASD subjects in the best case. 
Conclusions. 
These results confirm the possibility of an early automatic autism detection based on standard EEG.

Notes: 1 - Villa Santa Maria Institute, Neuropsychiatric Rehabilitation Center, Autism Unit, Tavernerio (Como), Italy 2 - Semeion Research Centre of Sciences of Communication, Rome, Italy 3 - Department of Mathematical and Statistical Sciences, University of Colorado at Denver, CO, USA 4 - Tarnow Center for Self-Management, Houston, TX, USA

Notes:

1-Study Center of Young Dermatologists Italian Network (YDIN), GISED, Bergamo, Italy

2-Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy

3-Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy

4-School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy

5-Villa Santa Maria Foundation, Tavernerio, Italy

6-St. George's University School of Medicine, Grenada, West Indies

7-Department of Biomedical and Clinicl, Sciences (DIBIC), University of Milan, Milan, Italy

8-Respiratory Unit "Luigi Sacco" University Hospital; ASST Fatebenefratelli-SaccoMilan, Italy

9-Rheumatology Unit, University of Messina, Italy 10-Rheumatology Unit, "Luigi Sacco" University Hospital; ASST Fatebenefratelli-Sacco, Milan, Italy

Abstract: Objective 
Despite the increasing literature on the association of diabetes with inflammation, cardiovascular risk, and Vitamin D (25(OH)D) concentrations, strong evidence on the direction of causality between these factors is still lacking. This gap could 
be addressed by means of artificial neural networks (ANN) analysis 
Methods 
Retrospective observational study was carried out by means of an innovative data mining analysis –known as auto-contractive map (AutoCM)-, and semantic mapping 
followed by Activation and Competition System on data of workers referring to an occupational-health outpatient clinic Parameters analyzed included weight, height, waist circumference, BMI, percentage of fat mass, glucose, insulin, HbA1c, creatinine, total cholesterol, low and high density lipoprotein, triglycerides, uric acid, fibrinogen, homocysteine, CRP, diastolic and systolic blood pressure, and 25(OH)D. 
Results 
The study included 309 workers. Of these 23.6% were overweight or obese with rates of I, II and III level-obesity, respectively of 40.5%, 23.3% and 12.6%. All mean biochemical values were in normal range, except for T-Chol, HDL, LDL, CRP, and 
25(OH)D. HbAC1 was between 39-46 mmol/mol in 51.78%. 25(OH)D levels were sufficient in only 12.6%. Highest inverse correlation for hyperglycemia onset was with BMI and waste circumference, suggesting a protective role of 25(OH)D against their increase. Auto- CM processing and the semantic map evidenced direct association of 25(OH)D with high link strength (0.99) to low CRP levels and low HDL levels. Low 25(OH)D lead to changes in glucose which affected metabolic syndrome biomarkers, first of which HOMA index and blood glucose insulin, but not 25(OH)D. 
Conclusions 
The use of ANN suggests a key role of 25(OH)D respect to all considered metabolic parameters in the development of diabetes and evidences a causation between low 25(OH)D and high glucose concentrations.

Notes:

a Department of Preventive Medicine, Occupational Health Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

b Department of Clinical Chemistry and Microbiology, Bacteriology and Virology Units; Ospedale Maggiore Policlinico, Milan, ITALY

c Villa Santa Maria Foundation, Tavernerio, Italy

d Pediatric Nephrology & Dialysis, Milano Fondazione IRCCS Cà Grande Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy

e Pediatric Intermediate Care Unit, Department of Clinical and Community Health Sciences (DISCCO), Fondazione IRCCS Ospedale Cà Granda-Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy

f Semeion Research Centre of Sciences of Communication, Rome, Italy and University of Colorado, Denver, CO, USA

Motor disturbances have been widely observed in children with autism spectrum disorder (ASD), and motor problems are currently reported as associated features supporting the diagnosis of ASD in the current Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Studies on this issue reported disturbances in different motor domains, including both gross and fine motor areas as well as coordination, postural control, and standing balance. However, they failed to clearly state whether motor impairments are related to demographical and developmental features of ASD. Both the different methodological approaches assessing motor skills and the heterogeneity in clinical features of participants analyzed have been implicated as contributors to variance in findings. However, the non-linearity of the relationships between variables may account for the inability of the traditional analysis to grasp the core problem suggesting that the “single symptom approach analysis” should be overcome.
Artificial neural networks (ANNs) are computational adaptive systems inspired by the functioning processes of the human brain particularly adapted to solving non-linear problems. This study aimed to apply the ANNs to reveal the entire spectrum of the relationship between motor skills and clinical variables. 32 male children with ASD [mean age: 48.5 months (SD: 8.8); age range: 30-60 months] were recruited in a tertiary care university hospital. A multidisciplinary comprehensive diagnostic evaluation was associated with a standardized assessment battery for motor skills, the Peabody Developmental Motor Scale-Second Edition.
Exploratory analyses were performed through the ANNs. The findings revealed that poor motor skills were a common clinical feature of preschoolers with ASD, relating both to the high level of repetitive behaviors and to the low level of expressive language. Moreover, unobvious trends among motor, cognitive and social skills have been detected.
In conclusion, motor abnormalities in preschoolers with ASD were widespread, and the degree of impairment may inform clinicians about the severity of ASD core symptoms. Understanding motor disturbances in children with ASD may be relevant to clarify neurobiological basis and ultimately to guide the development of tailored treatments.

Notes:

1 Fondazione Stella Maris (IRCCS), Italy,
2 Autism Research Unit, Villa Santa Maria Scs, Italy,
3 Università degli Studi di Pisa, Italy

Abstract: Objective. Primary Sjögren’s syndrome (pSS) is a complex chronic systemic disorder, for which specific and effective therapeutic interventions are still lacking. In this era of precision medicine, there is a clear need for a better definition of disease phenotypes to foster the research of novel specific biomarkers and new therapeutic targets. 
The main objectives of this work are:1) to compare Auto Contractive Map (AutoCM), a data mining tool based on an artificial neural network (ANN) versus conventional Principal Component Analysis (PCA) in discriminating different pSS subsets and 2) to specifically focus on variables predictive of MALT-NHL development, assessing the previsional gain of the predictive models developed. 
Methods. Out of a historic cohort of 850 patients, we selected 542 cases of pSS fulfilling the AECG criteria 2002. Thirty-seven variables were analysed including: patient demographics, glandular symptoms, systemic features, biological abnormalities and MALT-NHLs. AutoCM was used to compute the association of strength of each variable with all other variables in the dataset. PCA was applied to the same data set. 
Results. Both PCA and AutoCM confirmed the associations between autoantibody positivity and several pSS clinical manifestations, highlighting the importance of serological biomarkers in pSS phenotyping. However, AutoCM allowed us to clearly distinguish pSS patients presenting with predominant glandular manifestations and no or mild extra-glandular features from those with a more severe clinical presentation. 
Out of 542 patients, we had 27 cases of MALT-NHLs. The AutoCM highlighted that, besides other traditional lymphoproliferative risk factors (i.e. salivary gland enlargement, low C4, leukocytopenia, cryoglobulins, monoclonal gammopathy, disease duration), rheumatoid factor was strongly associated to MALT-NHLs development. By applying data mining analysis, we obtained a predictive model characterised by a sensitivity of 92.5% and a specificity of 98%. If we restricted the analysis to the seven most significant variables, the sensitivity of the model was 96.2% and its specificity 96%. 
Conclusion. Our study has shed new light on the possibility of using novel tools to extract hidden, previously unknown and potentially useful information in complex diseases like pSS, facing the challenge of disease phenotyping as a prerequisite for discovering novel specific biomarkers and new therapeutic targets.

Notes: 1.Rheumatology Unit, University of Pisa

2.Villa Santa Maria Foundation, Tavernerio, Italy

Abstract: Artificial neural networks (ANNs) are a computational tool, based on highly non-linear mathematics models with potential applications in the prediction of osteoporotic fractures. 
Therefore, the present study aimed to evaluate the potential of ANNs analysis in the prediction of bone fragility fractures in post-menopausal women. ANNs prognostic performance in identifying vertebral morphometric deformity was compared with that of the widely used tool FRAX® in a sample of 587 Caucasian postmenopausal women underwent densitometry and morphometric analyses for the detection of vertebral fractures. 
The analysis of areas under the curve (AUCs) showed that sensitivity for ANNs (74%) almost doubled that found for FRAX ® (38%), with the latter presenting a specificity higher than the proposed tool (96 vs. 77%). Overall, ANN-based analysis was able to highlight high-risk patients with a global higher accuracy (74%) compared to that obtained by FRAX (67%). 
In conclusion, our data showed that compared to WHO’s algorithm ANNs had higher sensitivity in identifying vertebral deformity, thus suggesting a “promising role” in the prediction of osteoporotic fracture in postmenopausal women. However, further studies on larger sample are needed to definitely establish the clinical reliability of ANNs.

Notes: 1.Department of Morphology, Surgery and Experimental Medicine, Menopause and Osteoporosis Centre, University of Ferrara, Via Boschetto 29, 44124, Ferrara, Italy

2.Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, Via Borsari 46, 44121, Ferrara, Italy

3.Villa Santa Maria Foundation, Via IV Novembre, 22038 Tavernerio (CO), Italy

4.Department of Morphology, Surgery and Experimental Medicine, Section of Orthopedic Clinic, University of Ferrara, Via Aldo Moro 8, 44124, Cona, Ferrara, Italy

5.National Research Council, Neuroscience Institute, Aging Branch, via Giustiniani, 2, 35128, Padova, Italy

6.Department of Clinical and Experimental Medicine, Foggia University School of Medicine, Via L. Pinto, 1, Foggia, Italy

7.Department of Radiology, Scientific Institute Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy

Abstract: Many studies, focused on identifying new biomarkers for coronary artery disease (CAD) risk computation and monitoring, suggested a potential diagnostic role for fatty acids (FA). In the present study, we explored the potential diagnostic role of FA by using a data mining approach based on fourth generation artificial neural networks (ANN). Forty-one male subjects were enrolled. According to coronary angiography, 31 displayed CAD and 10 did not (non-CAD, control group). FA analysis was performed on plasma samples using a gas chromatography-mass spectrometry system and analyses were performed by an ANN method. The variables most closely related to CAD were low levels of alpha-linolenic acid, eicosapentaenoic acid, eicosatetraenoic and docosahexaenoic acids. High levels of 1,1-dimethoxyhexadecane, total dimethyl acetals and docosatetraenoic acid were related to non-CAD condition. This subset of variables, which were most closely correlated to the target diagnosis, achieved a consistent predictive rate. The average accuracy obtained was 76.5%, with 93% of sensitivity and 60% of specificity. The area under the ROC curve was equal to 0.79. In conclusion, our study highlighted the association between different plasma FA species, CAD and non-CAD conditions. The specific subset of variables could be of interest as a new diagnostic tool for CAD management.

Notes: *Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy

**Villa Santa Maria Institute, Tavernerio, Como, Italy

***Department of Cardiac Surgery, I.R.C.C.S. Policlinico San Donato, San Donato Milanese, Milan, Italy

****Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany

*****Service of Laboratory Medicine 1-Clinical Pathology, I.R.C.C.S. Policlinico San Donato, San Donato Milanese, Milan, Italy

Abstract: There is increasing evidence that autism spectrum disorder (ASD) subjects have also motor impairments. Toe walking (TW) is a phenomenon that can be found in ASD subjects during gait, even if this condition was found not to be necessarily related only to walking, since these children often also stand and run on their tiptoes. Since persistent TW in ASD subjects may contribute to secondary shortening of the Achilles’s tendon, it becomes important to have an assessment tool and/or outcome measure for both the clinical and rehabilitative settings. The aim of this systematic review is to critically evaluate and describe the methods employed to assess toe-walking in ASD subjects. 
The systematic review protocol was previously registered on PROSPERO. We conducted an extensive literature search in PubMed, CINAHL, PsycINFO, The Cochrane Library, and Scopus databases. There were no restrictions on the types of study design eligible for inclusion. Ten studies were included in the systematic review. Risk of bias of the included studies was conducted using the following instruments depending on the study types: STROBE Statement, Cochrane risk of bias tool, and CARE checklist. Almost all the included studies (8/10) proposed a TTB assessment only during walking. Nine out of ten of the included studies assessed TTB using a qualitative methodology. 
The results evidenced the heterogeneity of qualitative methods and a lack of a structured quantitative test to assess toe walking 
in ASD subjects.

Notes: *Autism Research Unit, Villa Santa Maria Foundation, Tavernerio (CO), Italy

**School of Medicine and Surgery – University of Milano Bicocca, Milan, Italy

***Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genoa, Genoa, Italy

Abstract: We provide an experimental evaluation of the impact of aesthetic experiences in terms of stress reduction (cortisol levels) and wellbeing increase. The test experience is a visit to the vault of the Sanctuary of Vicoforte, Italy. Data have been collected using a double step method. A structured interview in relation to the individual subjective well-being has been administered to a sample of 100 subjects. 
In addition, a sample of their saliva has been taken, and its cortisol level measured, before and after the experience, and likewise for momentary wellbeing measured on a Visual Analogous Scale. Subjects reported an average increase of 40% in wellbeing and a decrease of the 60% in the cortisol level. The recorded cortisol level values dropped on average well beyond the decrease normally associated to its circadian cycle. The modulating role of various variables has been appreciated, and profiling of the typical subjects who are wellbeing respondents/non-respondents and cortisol respondents/non-respondents has been carried out. 
We conclude that aesthetic experience seems to have a noticeable impact on individual physical and mental health. In both dominions, cultural participation intensity is significantly correlated to the response. The study underlines the potential of the arts and culture as a new platform for public health practices and new approaches to welfare policy design.

Notes: 1 Villa Santa Maria Institute, Tavernerio, Italy 2 IULM University, Milan, Italy 3 FBK-IRVAPP, Trento, Italy 4 Harvard University and MetaLAB (at) Harvard, Cambridge, MA, USA

Objective: The metabolic syndrome (MS) is a multifactorial disorder associated with a higher risk of developing cardiovascular diseases and type 2 diabetes. However, its pathophysiology and risk factors are still poorly understood. In this study, we investigated the associations among gender, psychosocial variables, job-related stress and the presence of MS in a cohort of obese Caucasian workers. 

Methods: A total of 210 outpatients (142 women, 68 men) from an occupational medicine service was enrolled in the study. Age, BMI, waist circumference, fasting glucose, blood pressure, triglycerides and HDL cholesterol were collected to define MS. In addition, we evaluated eating behaviors, depressive symptoms, and work-related stress. Data analyses were performed with an artificial neural network algorithm called Auto Semantic Connectivity Map (AutoCM), using all available variables. 

Results: MS was diagnosed in 54.4 and 33.1% of the men and women, respectively. AutoCM evidenced gender-specific clusters associated with the presence or absence of MS. Men with a moderate occupational physical activity, obesity, older age and higher levels of decision-making freedom at work were more likely to have a diagnosis of MS than women. Women with lower levels of decision-making freedom, and higher levels of psychological demands and social support at work had a lower incidence of MS but showed higher levels of binge eating and depressive symptomatology. 

Conclusion: We found a complex gender-related association between MS, psychosocial risk factors and occupational determinants. The use of these information in surveillance workplace programs might prevent the onset of MS and decrease the chance of negative long-term outcomes. 

Level of evidence Level V, observational study.

Notes: 1 Department of Preventive Medicine, Occupational Health Unit, Clinica del Lavoro Luigi Devoto, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico 2 Rehabilitation Medicine, IRCCS Istituto Auxologico Italiano, S. Giuseppe Hospital, Verbania, Italy 3 Department of Human and Social Sciences, University of Bergamo, Bergamo, Italy 4 Villa Santa Maria Foundation, Tavernerio, Italy 5 Laboratory of Clinical Chemistry and Microbiology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy 6 National Research Centre for the Working Environment, Copenhagen, Denmark 7 Sport Sciences, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark 8 Semeion Research Centre of Sciences of Communication, Rome, Italy 9 University of Colorado, Denver, CO, USA

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic. 

This study, carried out in two Italian Institutions, assesses the frequency of 27 potential autism risk factors related to pregnancy and peri- and postnatal periods by interviewing mothers who had children with autism, children with autism and one or two typically developing siblings, or only typically developing children. The clinical sample included three case groups: 73 children and adolescents with autism (Group A), 35 children and adolescents with autism (Group A1) having 45 siblings (Group B) and 96 typically developing children (Group C) matched for gender and age. Twenty-five out of 27 of risk factors presented a higher frequency in Group A in comparison with Group C and for nine of them a statistically significant difference was found. Twenty-one out of 27 of risk factors presented a higher frequency in Group A in comparison with Group B. A higher prevalence of environmental risk factors was observed in 11 risk factors in the Group A1 in comparison with Group B and for nine of them an odds ratio higher than 1.5 was found. For 13 factors there was a progressive increase in frequency going from Group C, B and A and a statistically higher prevalence of the mean number of stressful events per pregnancy was recorded in Group A when compared with Groups B and C. The 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 who are predisposed to have suboptimal pregnancies.

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.

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.

Notes:

1-Department of Developmental Neuroscience, IRCCS Stella Maris Foundation

2- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

3-Semeion Research Centre of Sciences of Communication, Rome, Italy

4-Department of Mathematical and Statistical Sciences, University of Colorado Denver, Denver, CO, USA

5-Autism Research Unit, Villa Santa Maria Institute, Tavernerio, Italy

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.

Human microbiota represents one of the most striking cultural revolution in medicine emerged in the last 20 years. Many studies have revealed how the complexity and dynamics of gut microbiota influences normal physiology and contribute to a variety of diseases ranging from obesity to atherosclerosis, allergy and severe neurological disorders. The latter topic is of particular relevance and really revolutionary and is specifically linked to the existence of so-called gut-brain axis: a physiological frame-work in which the gut microbiota communicates with the CNS and vice-versa through neural, endocrine and immune pathways. If this is true then is plausible to expect that the modulation gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders. Autism is definitely one of these disorders.
Autism encompasses a broad spectrum of heterogeneous neurodevelopmental disorders with a prevalence rate of 1:150 and a 4:1 male: female ratio, characterized by qualitative impairment in social communication area and restricted repetitive and stereo-typed patterns of behavior interests and activities.
The possibility that autism is the consequence of an imperfect development of gut flora is supported by a number of observations like: the frequent coexistence of gastrointestinal symptoms in autistic children; the appearance of the disease after an incidental antimicrobic therapy and the increased levels of urinary biomarkers of specific pathogens of clostridium spp. in the urine of autistic children.
SCFAs represent a group of compounds derived from the host microbiome that can induce widespread effects on gut, brain, and behavior, contribute to various neurological processes and are plausibly linked to ASDs.
Since the literature about the role played by intestinal dysbiosis in autism is increasing, we felt interesting to summarize the present evidences in this mini review.

Background: Coronary artery disease (CAD) is a multifactorial complex disease. The aim of the present study is to verify whether the personality traits in CAD are associated with coronary artery plaque (CAP) presence and severity in people with no history of cardiovascular disease.

Design: A cross-sectional monocenter study.

Methods: Seventy five individuals with no history of CAD underwent 64-slice computed tomography coronary angiography (CTCA) and were screened for traditional cardiac risk factors and for hostility, anger, and type D personality traits.

Results: In total, 48 patients (64%) had evidence of CAP, with mild (31%), moderate (33%), and severe (35%) coronary stenosis. Male sex, hypertension, being overweight, and number of cardiovascular risk factors increased the likelihood of CAP presence. Findings showed a significant difference between CAP presence vs. CAP absence for anger (26 vs. 30%, χ2 = 6.82) and type D personality (23 vs. 35%; χ2 = 8.23, P = 0.03), but not hostility (P > 0.05). Anger personality, and the type D subscale social inhibition, but not negative affectivity, were associated with an increased prevalence and severity of CAP. Univariate analysis confirms anger (odds ratio, OR = 1.38, 95% confidence interval, CI = 1.12-2.31), social inhibition (OR = 2.01, 95% CI = 1.81-2.93), 'negative affectivity by social inhibition' (OR = 1.24, 95% CI = 1.12-2.14), and type D personality (OR = 1.9, 95% CI = 1.11-2.03) as predictors of CAP presence. Moreover, multivariate analysis suggests social inhibition as also a unique CAP predictor (OR = 2.14, 95% CI = 1.89-2.96) after adjustment for having cardiac risk factors as a covariate.

Conclusion: The present data confirm the core role of traditional risk factors and suggest the primacy of social inhibition and anger personality traits in association with CAP presence and severity.

Background: 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.

Discussion: Results will have important implications for preventing psychological and physiological disease in older-aged women and for managing health-related costs for this population group.