Gut mobilization improves behavioral symptoms and modulates urinary p-cresol in chronically constipated autistic children: A prospective study

Chronic constipation is common among children with ASD and is associated with more severe hyperactivity, anxiety, irritability, and repetitive behaviors. Young autistic children with chronic constipation display higher urinary, and foecal concentrations of p-cresol, an aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic behaviors, while blunting social interaction. This study was undertaken to prospectively assess the behavioral effects of gut mobilization in young autistic children with chronic constipation, and to verify their possible correlation with urinary p-cresol. To this aim, 21 chronically constipated autistic children 2–8 years old were evaluated before (T0), 1 month (T1), and 6 months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity. Gut mobilization yielded a progressive and highly significant decrease in all behavioral symptoms over the 6-month study period. Urinary p-cresol levels displayed variable trends not significantly correlated with changes in behavioral parameters, mainly increasing at T1 and decreasing at T2. These results support gut mobilization as a simple strategy to ameliorate ASD symptoms, as well as comorbid anxiety and hyperactivity, in chronically constipated children. Variation in p-cresol absorption seemingly provides limited contributions, if any, to these behavioral changes. Further research will be needed to address the relative role of reduced abdominal discomfort following mobilization, as compared to specific modifications in microbiome composition and in gut bacteria-derived neuroactive compounds

Hypermethioninemia in Campania: Results from 10 years of newborn screening

In the last years tandem mass spectrometry (MS/MS) has become a leading technology used for neonatal screening purposes. Newborn screening by MS/MS on dried blood spot samples (DBS) has one of its items in methionine levels: the knowledge of this parameter allows the identification of infant affected by homocystinuria (cystathionine β-synthase, CBS, deficiency) but can also lead, as side effect, to identify cases of methionine adenosyltransferase (MAT) type I/III deficiency. We started an expanded newborn screening for inborn errors of metabolism in Campania region in 2007. Here we report our ten years experience on expanded newborn screening in identifying patients affected by hypermethioninemia. During this period we screened approximately 77,000 infants and identified two cases: one case of classical homocystinuria and one patient affected by defect of MAT I/III. In this paper we describe these patients and their biochemical follow-up and review the literature concerning worldwide newborn screening reports on incidence of CBS and MAT deficiency

[Surgical treatment of caval obstructions]

The vena cava is the seat of obstructive disorders for which direct reparative surgery may sometimes become necessary. S.C.S. is mainly caused by neoplastic invasions or, in the case of the inferior vena cava, by progression of phlebothrombosis of the lower limbs. Prosthesis or autologous substitution and thrombointimectomy are specifically indicated in the two cases respectively. The two methods are described in detail and exemplified through the authors' personal cases consisting in an inferior caval thrombointimectomy and four superior caval by passes. It is concluded that surgical procedures are effective when the primitive disorder can be dominated and the thrombosis is not excessively extensive

Application of a site-specific DNA excision strategy for marker gene removal during gene transfer in Vitis spp.

Site-specific DNA excision strategy for marker gene removal was exploited for gene transfer into grape. Nicotiana benthamiana leaf sections and embryogenic calli of V. vinifera (\u2018Chardonnay\u2019 and \u2018Brachetto\u2019) were co-cultured with Agrobacterium tumefaciens carrying the chemically-inducible pX6 vector with the Green Fluorescent Protein gene (GFP). This vector provides a reliable system for marker gene (nptII) excision, based on Cre/loxP and regulated by 17- -estradiol. Transgenic cultures were selected on kanamycin, and plantlets were regenerated. Preliminary molecular assays showed the transfer of the GFP gene into the plant genome. After induction on different concentrations and exposition time on 17- -estradiol, observations at the fluorescence stereomicroscope showed the expected GFP gene expression. To exploit the effectiveness of this strategy for achieving Pathogen Derived Resistance, the GFP gene was replaced with a sequence of the GVA virus coat protein gene in sense and antisense orientation for transcription of a hairpin RNA (pX6-pKcpGVA). Gene transfer experiments on tobacco and grapes produced plantlets containing the foreign genes

Acceptability of the transitional wearable companion “+me” in children with autism spectrum disorder: A comparative pilot study

+me is an experimental interactive soft toy, looking like a panda, developed for young children. When touched on the paws or head (inputs), the toy can emit attractive responses such as colored lights and amusing sounds (outputs). +me is wirelessly connected to a control tablet through which an adult caregiver can modify its input-output contingencies so as to produce different, rewarding response patterns using the same device. Given these features, we propose +me as a potential novel tool to support the therapy of Autism Spectrum Disorder (ASD). The allure of the device could be exploited to capture the attention and encourage the social interaction of toddlers during play activities with therapists. In this pilot study, +me was tested on two small groups of children aged 30–48 months, one group diagnosed with ASD and the second with Communication Disorder, a condition that often presents—especially at an early age—overlapping symptoms with ASD. The proposed play activities aimed to foster simple imitative behaviors and stimulate the engagement of the children. The results were compared with those of a previous test run on Typically Developed children. Preliminary observations, based on the analysis of video recordings, suggest that, on average, +me is able to encourage a positive engagement and that different groups tend to manifest some different behaviors

TRIM8 modulates p53 activity to dictate cell cycle arrest

p53 is a central hub in controlling cell proliferation. To maintain genome integrity in response to cellular stress, p53 directly regulates the transcription of genes involved in cell cycle arrest, DNA repair, apoptosis and/or senescence. An array of post-translational modifications and protein-protein interactions modulates its stability and activities in order to avoid malignant transformation. However, to date, it is still not clear how cells decide their own fate in response to different types of stress. Here we describe that the human TRIM8 protein, a member of the TRIM family, is a new modulator of the p53-mediated tumor suppression mechanism. We show that under stress conditions, such as UV exposure, p53 induced the expression of TRIM8, which, in turn, stabilized p53, leading to cell cycle arrest and reduction of cell proliferation through enhancement of CDKN1A (p21) and GADD45 expression. TRIM8 silencing reduced the capacity of p53 to activate genes involved in cell cycle arrest and DNA repair in response to cellular stress. Concurrently, TRIM8 overexpression induced the degradation of the MDM2 protein, the principal regulator of p53 stability. Co-immunoprecipitation experiments showed that TRIM8 physically interacted with p53, impairing its interaction with MDM2. Altogether, our results reveal a previously unknown regulatory pathway controlling p53 activity and suggest TRIM8 as a novel therapeutic target to enhance p53 tumor suppressor activity