Novel metaphors comprehension in a child with High-Functioning Autism Spectrum Disorders. A study on assessment and treatment

Until the first decade of the current millennium, the literature on metaphor comprehension highlighted typical difficulties in children with high-functioning Autism Spectrum Disorder (ASD). More recently, some scholars have devised special programs for enhancing the capability of understanding metaphors in these children. This article presents a case study based on a treatment aiming at enhancing novel metaphor comprehension in a high-functioning child with ASD. M.M., a pseudoacronym for an 8;10 year-old boy, diagnosed with high-functioning ASD, was first assessed with a metaphor comprehension test. This testing (at time TO) highlighted a rigid refusal of metaphors and a marked tendency toward literal interpretation. A baseline treatment (8 sessions of 45-60 min each, twice a week) was implemented, based on a series of recognition, denomination and emotion comprehension activities. M. M.'s metaphor comprehension was assessed a second time (Ti), followed by the experimental treatment (same duration and frequency as the first one), specifically focused on metaphor comprehension. Finally, a third assessment of metaphor comprehension took place (T2), followed by a last assessment 4 months later (follow-up, T3). The comparison between the performances at the metaphor comprehension test across the four assessments, from TO to T3, showed that the baseline treatment produced no effect at all, whereas a significant improvement appeared at T2, just after the experimental treatment, later confirmed at the follow up. Both quantitative and qualitative results showed an evident improvement in the way M.M. handled the semantic issues posed by the metaphors of the test, in line with the strategies he was taught during the treatmen

Beyond the literal meaning of words in children with klinefelter syndrome: two case studies

Literature on children with Klinefelter Syndrome (KS) points to general linguistic difficulties in both comprehension and production among other cognitive functions, and in the majority of cases, these coexist with an intellectual level within the norms. In these conditions, children having language delay generally engage in language therapy and are systematically monitored across ages. In this article, we present the profiles of two children with KS (47, XXY), aged 9.1 (Child S) and 13 (Child D), whose language development was assessed as adequate at age 3, and for this reason, did not receive any language treatment. At the present stage, their IQ, as measured by Wechsler Scales (Child S: 92; Child D: 101), is within the norm, but they both present marked weaknesses in pragmatic skills such as figurative language comprehension. The analysis of these two cases points to the need to go beyond global indexes of verbal abilities, as the same global index may mask a wide diversification of individual profiles. In addition, this study underlines the importance of monitoring the developmental trajectories of children like Child D and Child S, because weaknesses in pragmatic skills that are relevant for both academic achievement and social adaptation could emerge at later stages

A systematic review and meta-analysis of the effects of flavanol-containing tea, cocoa and apple products on body composition and blood lipids: exploring the factors responsible for variability in their efficacy

Several randomized controlled trials (RCTs) and meta-analyses support the benefits of flavanols on cardiometabolic health, but the factors affecting variability in the responses to these compounds have not been properly assessed. The objectives of this meta-analysis were to systematically collect the RCTs-based-evidence of the effects of flavanol-containing tea, cocoa and apple products on selected biomarkers of cardiometabolic risk and to explore the influence of various factors on the variability in the responses to the consumption of these products. A total of 120 RCTs were selected. Despite a high heterogeneity, the intake of the flavanol-containing products was associated using a random model with changes (reported as standardized difference in means (SDM)) in body mass index (−0.15, p < 0.001), waist circumference (−0.29, p < 0.001), total-cholesterol (−0.21, p < 0.001), LDL-cholesterol (−0.23, p < 0.001), and triacylglycerides (−0.11, p = 0.027), and with an increase of HDL-cholesterol (0.15, p = 0.005). Through subgroup analyses, we showed the influence of baseline-BMI, sex, source/form of administration, medication and country of investigation on some of the outcome measures and suggest that flavanols may be more effective in specific subgroups such as those with a BMI ≥ 25.0 kg/m2, non-medicated individuals or by specifically using tea products. This meta-analysis provides the first robust evidence of the effects induced by the consumption of flavanol-containing tea, cocoa and apple products on weight and lipid biomarkers and shows the influence of various factors that can affect their bioefficacy in humans. Of note, some of these effects are quantitatively comparable to those produced by drugs, life-style changes or other natural products. Further, RCTs in well-characterized populations are required to fully comprehend the factors affecting inter-individual responses to flavanol and thereby improve flavanols efficacy in the prevention of cardiometabolic disorders

SARS-CoV-2 infection in beta thalassemia: Preliminary data from the Italian experience

Patients with pre\u2010existent chronic morbidities are likely to be more severely affected by SARS\u2010Cov2 infection, but no data are available regarding Thalassemic Syndromes (TS). Note, TS and hemoglobin variants represent, according to WHO, one of the most frequent causes of anemia, affecting more than 7% of the world population.1 Thalassemic Syndromes are classified in either transfusion\u2010dependent thalassemia (TDT) or non\u2010transfusion\u2010dependent thalassemia (NTDT). Infectious complications, mainly from bacteria, constitute a common cause of mortality and morbidity in TS. Stress erythropoiesis, iron overload, splenectomy and adrenal insufficiency among others may contribute to increase susceptibility to infection.2 To verify the impact of SARS\u2010CoV\u20102 infection on TS, we set\u2010up a specific survey by electronic Case Report Form (eCRF).3 Inclusion criteria require at least 15\u2009days of follow\u2010up from either the onset of symptoms or SARS\u2010CoV2 positivity. The survey was approved by Ethics Committee and eCRF was shared with the Centers of Italian Hemoglobinopathies Network. The \u201cSociet\ue0 Italiana Talassemie ed Emoglobinopatie\u201d (SITE), has estimated the presence in Italy of approximately 5000 TDT and 1900 NTDT patients.3 As of 10 April 2020, 11 cases of TS and COVID\u201019 have been collected (see supplementary information). All the reported patients are in Northern Italy, where the rate of infection is higher, reflecting the national epidemiology. The mean age is 44\u2009\ub1\u200911\u2009years (range 31\u201061\u2009years) and 55% (6/11) are females. Ten patients are TDT, and one is NTDT. All the patients have thalassemia associated comorbidities, eight are splenectomized, and one patient (#9 in the supplementary table) has pulmonary hypertension treated with sildenafil. The likely source of infection has been detected in 55% (6/11) of cases: two had contacts with COVID\u201019 positive subjects, and four had occupational exposure (three are nurses working in hospital or assisted living facilities). Three patients were asymptomatic. One patient (#3 in supplementary information) was admitted for high fever and bone marrow hypoplasia, lymphopenia, and agranulocytosis (on treatment with deferiprone) and tested positive at the third swab. Six out of 11 were hospitalized, but no one required mechanical ventilation. The patient with more severe symptoms who required more intensive ventilation support with continuous positive airway pressure (CPAP) has a history of diffuse large B\u2010cell lymphoma, treated with chemotherapy in the previous year, currently in complete remission. Of the six people admitted to the hospital, only three received supposedly specific treatment for COVID\u201019: one hydroxychloroquine (HCQ), one HCQ plus ritonavir/darunavir, and one HCQ plus anakinra. Patient #3 did not receive HCQ due to concomitant therapy with amiodarone and an increased risk of life\u2010threatening arrhythmia. The clinical course ranged from 10 to 29\u2009days. Ten patients have clinically recovered and are on a daily remote phone call follow\u2010up. Splenectomy which was present in 8/11 patients did not seem to affect the clinical course. Of note, except for the patient with myelosuppression, no increase in blood requirement was observed. When luspatercept treatment was halted in the NTDT patient, hemoglobin fell from 110 to 82 g/L, a value similar to the pre\u2010luspatercept period. Neither death nor severe SARS or signs of cytokines storm were observed in these 11 subjects, which may be surprising, taking into account the mean age and the presence of severe comorbidities. Our data, although preliminary, do not indicate increased severity of COVID\u201019 in TS. A larger number of cases needs to be collected to define the impact of this new infection and its outcome in these fragile patients

Wastewater phytoremediation: genomic analysis and screening of green microalgae species for extracellular laccase activity.

Phytoremediation deals with the use of plants, or other green photosynthetic organisms, to reduce organic or inorganic pollutant in the environment, mainly waters and soils (Pivetz. B.E. 2001. EPA /540/S-01/500). Our research group is involved in studies regarding the use of plants for soil phytoremediation (Galante et al., 2005. Proc. SIGA Congress, L04) and, more recently, of unicellular green algae species (green microalgae) for wastewater treatments. Some microalgae species have been recently tested to degrade an array of pollutants such as phenols, polyphenolic aromatic compounds (PAH) and even hormones (Pollio et.al., 1994. Phytochemistry, 37:1269- 1272;. Pinto et.al., 2003. Biotechnol Lett., 25:1657-1659). It is worthy to note that about 2,500 species belong from Chlorophyceae, seldom living in contrasting habitat under severe environmental conditions. So far, a little has been done to exploit this genetic biodiversity bonanza; thus, few reports have been published on enzymes implicated in their degradative action (Semple et.al., 1996. Appl. Envr. Micr, 62:1265-1273). Since a wide collection of green microalgae species are available at the University of Naples, Department of Biological Science, recently we have started a research aimed to (a) find algae species with extracellular phenoloxidase enzymatic activity; (b) identify extracellular enzymes able to degrade xenobiotic like synthetic dyes and other PAHs; (c) clone and overexpress genes producing phenoloxidases in homologous and in heterologous systems, in order to use these enzymes primarily for phytoremediation of milling oil wastewaters. Among phenoloxidaes, we focused our interest on laccases (EC 1.10.3.2) that are phenol-oxidoreductases able to catalyze the oxidation of various aromatic compounds (particularly phenols) with the concomitant reduction of oxygen to water. Selected algae strains were grown in liquid culture at 22°C under continuous light conditions, starting with an inoculum of 0.1 OD. After ten days, the algal growth was measured as optical density at 600 nm. A screening was performed by detecting the laccase activity in the broth medium culture, deprived of algae cells, in the presence of 2,2-azino-bis 3-ethybenz-thiazoline-6-sulfonic acid (ABTS) at 420 nm. The laccase activity was referred to the polyphenol oxidase activity of Trametes versicolor; thus, each positive strain was assayed on industrial azo-dye Remazol Brilliant Blue R (RBBR) and on the natural phenol compound syringaldazine by kinetic analysis. Preliminary results, obtained comparing different species, showed a wide variation both within the same substrate and among the different microalgae. Microalgae strains able to produce and secrete laccase enzymes were further chosen for more detailed genetic studies. To clone phenoloxidase genes from those species, we have started a bioinformatics approach, on the basis of highly conserved coding sequences of laccases already isolated and sequenced from several higher plants. Primers drawn on the alignment of those sequences have been used to amplify genomic DNA

Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations

Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES in a cohort of 200 patients: 84 with isolated ID and 116 with ID and ASD. We identified 41 pathogenic variants with a detection rate of 22% (43/200): 39% in ID patients (33/84) and 9% in ID/ASD patients (10/116). Most of the causative genes are genes responsible for well-established genetic syndromes that have not been recognized for atypical phenotypic presentations. Two genes emerged as new candidates: CACNA2D1 and GPR14. In conclusion, this study reinforces the importance of ES in the diagnosis of ID/ASD and underlines that "reverse phenotyping" is fundamental to enlarge the phenotypic spectra associated with specific genes

International consensus guideline for reporting transmission electron microscopy results in the diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria)

Primary Ciliary Dyskinesia (PCD) is a heterogeneous genetic condition. European and North American diagnostic guidelines recommend transmission electron microscopy (TEM) as one of a combination of tests to confirm a diagnosis. However, there is no definition of what constitutes a defect or consensus on reporting terminology. The aim of this project was to provide an internationally agreed ultrastructural classification for PCD diagnosis by TEM. A consensus guideline was developed by PCD electron microscopy experts representing 18 centres in 14 countries. An initial meeting and discussion were followed by a Delphi consensus process. The agreed guideline was then tested, modified and retested through exchange of samples and electron micrographs between the 18 diagnostic centres. The final guideline a) Provides agreed terminology and a definition of class 1 defects which are diagnostic for PCD; b) Identifies class 2 defects which can indicate a diagnosis of PCD in combination with other supporting evidence; c) Describes features which should be included in a ciliary ultrastructure report to assist multidisciplinary diagnosis of PCD d) Defines adequacy of a diagnostic sample. This tested and externally validated statement provides a clear guideline for the diagnosis of PCD by TEM which can be used to standardise diagnosis internationally.</p

The 2019 and 2021 International Workshops on Alport Syndrome

In 1927 Arthur Cecil Alport, a South African physician, described a British family with an inherited form of kidney disease that affected males more severely than females and was sometimes associated with hearing loss. In 1961, the eponymous name Alport syndrome was adopted. In the late twentieth century three genes responsible for the disease were discovered: COL4A3, COL4A4, and COL4A5 encoding for the α3, α4, α5 polypeptide chains of type IV collagen, respectively. These chains assemble to form heterotrimers of type IV collagen in the glomerular basement membrane. Scientists, clinicians, patient representatives and their families, and pharma companies attended the 2019 International Workshop on Alport Syndrome, held in Siena, Italy, from October 22 to 26, and the 2021 online Workshop from November 30 to December 4. The main topics included: disease re-naming, acknowledging the need to identify an appropriate term able to reflect considerable clinical variability; a strategy for increasing the molecular diagnostic rate; genotype-phenotype correlation from monogenic to digenic forms; new therapeutics and new therapeutic approaches; and gene therapy using gene editing. The exceptional collaborative climate that was established in the magical medieval setting of Siena continued in the online workshop of 2021. Conditions were established for collaborations between leading experts in the sector, including patients and drug companies, with the aim of identifying a cure for Alport syndrome