Screening for developmental disorders in 3- and 4-year-old italian children: a preliminary study

BACKGROUND: The "Osserviamo" project, coordinated by the Municipality of Rome and the Department of Pediatrics and Child Neuropsychiatry of Sapienza University, aimed to validate an Italian version of the Ages and Stages Questionnaire-3 and to collect, for the first time in Italy, data on developmental disorders in a sample of 4,000 children aged 3 and 4 years. The present paper presents the preliminary results of the "Osserviamo" project. METHODS: 600 parents of children between 39 and 50 months of age (divided in two age stages: 42 and 48 months) were contacted from 15 kindergarden schools. RESULTS: 23.35% of the whole sample scored in the risk range of at least one developmental area of the Ages and Stages Questionnaire-3rd Edition (ASQ-3) and 7.78% scored in the clinical range. Specifically, 23.97% of the children in the 42-month age stage scored in the risk range and 5.79% scored in the clinical range. Males scored lower than females in the fine motor skills and personal-social development domains. Moreover, 22.79% of the children in the 48-month age stage scored in the risk range, while 9.55% scored in the clinical range. Males scored lower than females in fine motor skills. CONCLUSION: Italian validation of the ASQ-3 and recruitment of all 4,000 participants will allow these data on the distribution of developmental disorders to be extended to the general Italian pediatric population. One main limitation of the study is the lack of clinical confirmation of the data yielded by the screening programme, which the authors aim to obtain in later stages of the study

Classical and quantum Big Brake cosmology for scalar field and tachyonic models

We study a relation between the cosmological singularities in classical and quantum theory, comparing the classical and quantum dynamics in some models possessing the Big Brake singularity - the model based on a scalar field and two models based on a tachyon-pseudo-tachyon field . It is shown that the effect of quantum avoidance is absent for the soft singularities of the Big Brake type while it is present for the Big Bang and Big Crunch singularities. Thus, there is some kind of a classical - quantum correspondence, because soft singularities are traversable in classical cosmology, while the strong Big Bang and Big Crunch singularities are not traversable.Comment: final version, to appear in Phys. Rev.

Deliveries by caesarean sections on request of women: legal-medical evidence

Introduction: In Italy the use of caesarean delivery has a rising trend moving away from European standards appeared on Euro-Peristat on maternal and child health, presenting the highest percentage of use of this procedure with significant regional differences. This study have analyzed the most recent data of a Sicilian reality about normal delivery and caesarean sections carried out in a hospital situated in Messina (Italy). Materials and methods: A total number of 1,573 medical records from 1st January 2011 to 31st December 2013 were analyzed and data gathered were statistically examined to describe general and specific parameters of the sample making use of Epi Info 7.1.4 software (CDC Atlanta – USA). Chi-square test was used to show any statistic differences among studied population. Results: Overall data showed that were carried out 38.27% of spontaneous deliveries, 7.06% of induced labor, and 54.67% of caesarean deliveries. There were no significant statistical differences between recourse to caesarean section and vaginal delivery in relation to nationality, age, level of education and/or work. The enrolled group, based on the parameters examined, was divided into appropriate caesarean section, in 79.49% of cases, inappropriate in 7.20% (mother’s request) and unjustified in 13.31% (with no indication, incomplete medical record). An examination of the anesthetic medical records showed that the caesarean section was considered to be urgent in 31.74% of the cases; however in 17.92% of these cases there is no information in the medical records justifying the use of emergency procedures. Conclusion: The reported data from the study that we conducted, lead to medical-legal and juridical considerations, especially as regards the use of caesarean delivery on the woman request. The complexity of the phenomenon requires the development of a variety of intervention strategies, not only for issues related to the reduction of health care costs, but also with regard to the clinical risk management and medical legal aspects related to the several profiles of professional responsibility

A wearable heart rate measurement device for children with autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by early impairment in social and communication domains and autonomic nervous system unbalance. This study evaluated heart rate (HR) as a possible indicator of stress response in children with ASD as compared to children with language disorder (LD). Twenty-four patients [mean age = 42.62 months; SD = 8.14 months,12 with ASD (10 M/2F) and 12 with LD (8 M/4F)] underwent clinical [Leiter International Performance Scale-Revised, Autism Diagnostic Observation Schedule, second edition (ADOS-2)] and physiological evaluation (HR monitoring) during five interactive activities, while wearing an HR measurement device. IQ (ASD:IQ = 103.33 ± 12.85 vs. LD:IQ = 111.00 ± 8.88, p = 0.103) and fluid reasoning on the Leiter-R Scale were within the normal range in all subjects. Increased HR during the third activity (ADOS-2 bubble play) significantly correlated with autistic symptoms (r = 0.415; p = 0.044), while correlations between ADOS-2 total score and HR during the first activity (ADOS-2 free play; r = 0.368; p = 0.077), second activity (Leiter-R figure ground subscale; r = 0.373, p = 0.073), and fifth activity (ADOS-2 anticipation of a routine with objects; r = 0.368; p = 0.076) did not quite reach statistical significance. Applying a linear regression model, we found that the ADOS-2 total score significantly influenced HR variations (p = 0.023). HR monitoring may provide a better understanding of the stress-provoking situations for children with ASD. Furthermore, it could help clinicians detect the impact of the stressful condition on the autistic core and adress treatment strategy

Biologic drugs in chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a condition defined by the presence of recurrent urticaria, angioedema, or both, which persist for more than six weeks in duration and occurs in the absence of an identifiable trigger. Both children and adults can develop CSU, although it is more common in adults and in women than in men, with a peak occurrence in the third to fifth decades of life. It imposes a significant burden on patients, families and healthcare systems. The goal of therapy in patients with CSU is to achieve a level of symptom control and improvement in quality of life that is acceptable to the patient, while minimizing therapy-related side effects. The recent introduction of biologic drugs has changed the management of the disease. This work aims to provide a narrative review of the current state of biological therapy and the promising drugs under development for CSU

Dynamic Response Characteristics in Variable Stiffness Soft Inflatable Links

© Springer Nature Switzerland AG 2019. In soft robotics, there is the fundamental need to develop devices that are flexible and can change stiffness in order to work safely in the vicinity of humans. Moreover, these structures must be rigid enough to withstand the force application and accuracy in motion. To solve these issues, previous research proposed to add a compliance element between motor and load – Series Elastic Actuators (SEAs). This approach benefits from improved force control and shock tolerance due to the elasticity introduced at joint level. However, series compliance at the joint level comes at the cost of inferior position controllability and additional mechanical complexity. In this research, we move the elastic compliance to the link, and evaluate the characteristics of variable stiffness soft inflatable links. The detailed investigation of the dynamic behaviour of inflatable link takes into consideration different internal pressures and applied loads. Our results demonstrate that the use of soft inflatable links leads to good weight lifting capability whilst preserving compliance which is beneficial for safety critical applications

Proton-irradiated breast cells: molecular points of view

Breast cancer (BC) is the most common cancer in women, highly heterogeneous at both the clinical and molecular level. Radiation therapy (RT) represents an efficient modality to treat localized tumor in BC care, although the choice of a unique treatment plan for all BC patients, including RT, may not be the best option. Technological advances in RT are evolving with the use of charged particle beams (i.e. protons) which, due to a more localized delivery of the radiation dose, reduce the dose administered to the heart compared with conventional RT. However, few data regarding proton-induced molecular changes are currently available. The aim of this study was to investigate and describe the production of immunological molecules and gene expression profiles induced by proton irradiation. We performed Luminex assay and cDNA microarray analyses to study the biological processes activated following irradiation with proton beams, both in the non-tumorigenic MCF10A cell line and in two tumorigenic BC cell lines, MCF7 and MDA-MB-231. The immunological signatures were dose dependent in MCF10A and MCF7 cell lines, whereas MDA-MB-231 cells show a strong pro-inflammatory profile regardless of the dose delivered. Clonogenic assay revealed different surviving fractions according to the breast cell lines analyzed. We found the involvement of genes related to cell response to proton irradiation and reported specific cell line- and dose-dependent gene signatures, able to drive cell fate after radiation exposure. Our data could represent a useful tool to better understand the molecular mechanisms elicited by proton irradiation and to predict treatment outcome

Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP)

Introduction: Post-marketing surveillance activities (namely pharmacovigilance) are crucial to favor the early detection of unexpected adverse events (AEs) and/or serious adverse reactions (SAEs). Indeed, spontaneous reporting of AEs has been demonstrated to underestimate the number of events in different clinical settings. Aim of the present study is to report the preliminary data of a Regional (Calabria, Italy) Pharmacovigilance Program (CBPP) aimed at improving AEs' reporting associated with biologics use in rheumatology. Materials and methods: We developed a simple, cost-effective pharmacovigilance program based on regular training sessions for physicians (stimulated reporting), periodical phone calls by a clinical pharmacologist aimed at identifying new events and stimulating self-awareness and encouraging reporting to the physician during the subsequent follow-up visit for minor AEs. To test this approach, all consecutive patients undergoing treatment with one biologic agent at eight rheumatology centers during a two-years period were invited to participate. Collected AEs were compared to the number of AEs spontaneously reported for the same molecules in the same centers before starting the protocol. Results: During the study period, 399 patients (245 females; mean age: 58 \ub1 11 years) were started on treatment with biologics for active RA (n = 211, 52.9%), PsA (n = 119, 29.8%) or AS (n = 69, 17.3%) at eight rheumatology centers. A total of 125 AEs (31.3%) and 9 SAEs (2.3%) were reported during the two-years study period. In the control cohort (comprising 368 consecutive patients started on treatment with bDMARDs during a two-years period before CBPP study) only 42 (11.4%) AEs and no SAEs were reported (p < 0.0001). The most common AEs were injection site reactions and skin disorders. Conclusions: In conclusion, our study provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology

A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies-associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss-of-function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD-box RNA helicase in neurological function

A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function.

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies-associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss-of-function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD-box RNA helicase in neurological function