Clinical characterization of a 6-year-old patient with autism and two adjacent duplications on 10q11.22q11.23. a case report

Autism is a neurodevelopmental disorder presenting in the first 3 years of life. Deficits occur in the core areas of social communication and interaction and restricted, repetitive patterns of behavior, interests or activities. The causes of autism are unknown, but clinical genetic studies show strong evidence in favor of the involvement of genetic factors in etiology. Molecular genetic studies report some associations with candidate genes, and candidate regions have emerged from several genome-wide linkage studies. Here, we report a clinical case of autism in a 6-year-old boy with double duplication on 10q11.22q11.23 with ASD (Autism Spectrum Disorder), intellectual disability, developmental delay, hypotonia, gross-motor skills deficit, overgrowth and mild dysmorphic features. In the literature, only five cases of ASD with 10q11.21q11.23 duplication are reported. This is the first extensive clinical description of an ASD subject with 10q11.22q11.23 duplication. Our findings suggest that 10q11.21q11.23 microduplication could represent a copy number variant that predisposes to autism

Impact of sleep disorders on behavioral issues in preschoolers with autism spectrum disorder

BackgroundSleep disorders are one of the most common problems in children with Autism Spectrum Disorder (ASD). However, they often tend to be underdiagnosed and incorrectly treated in clinical practice. This study aims to identify sleep disorders in preschool children with ASD and to explore their relationship with the core symptoms of autism, the child's developmental and cognitive level as well as the psychiatric comorbidities. MethodsWe recruited 163 preschool children with a diagnosis of ASD. The Children's Sleep Habits Questionnaire (CSHQ) assessed sleep conditions. Multiple standardized tests were used to evaluate intellectual abilities, the presence of repetitive behaviors (through the Repetitive Behavior Scale-Revised), as well as the emotional-behavioral problems and the psychiatric comorbidities (through the Child Behavior Checklist -CBCL 1(1/2)-5). ResultsThe results showed that poor disorders had consistently higher scores in all areas assessed by the CSHQ and on the CBCL across all domains. The correlational analysis showed that severe sleep disorders were associated with higher scores in internalizing, externalizing, and total problems at the CBCL syndromic scales, and in all DSM-oriented CBCL subscales. Moreover, we found that the association between sleep disorders and restricted and repetitive behaviors (RRBs) is explained by the anxiety-related symptoms. ConclusionBased on these findings, the study recommends that screening for sleep problems followed by early intervention should constitute a routine part of clinical practice for children with ASD

Clinical Characterization of a 6-Year-Old Patient with Autism and Two Adjacent Duplications on 10q11.22q11.23. A Case Report

Autism is a neurodevelopmental disorder presenting in the first 3 years of life. Deficits occur in the core areas of social communication and interaction and restricted, repetitive patterns of behavior, interests or activities. The causes of autism are unknown, but clinical genetic studies show strong evidence in favor of the involvement of genetic factors in etiology. Molecular genetic studies report some associations with candidate genes, and candidate regions have emerged from several genome-wide linkage studies. Here, we report a clinical case of autism in a 6-year-old boy with double duplication on 10q11.22q11.23 with ASD (Autism Spectrum Disorder), intellectual disability, developmental delay, hypotonia, gross-motor skills deficit, overgrowth and mild dysmorphic features. In the literature, only five cases of ASD with 10q11.21q11.23 duplication are reported. This is the first extensive clinical description of an ASD subject with 10q11.22q11.23 duplication. Our findings suggest that 10q11.21q11.23 microduplication could represent a copy number variant that predisposes to autism

Neurodevelopmental outcome of Italian preterm ELBW infants: an eleven years single center cohort

Abstract Background Preterm extremely low birth weight infants (ELBWi) are known to be at greater risk of developing neuropsychiatric diseases. Identifying early predictors of outcome is essential to refer patients for early intervention. Few studies have investigated neurodevelopmental outcomes in Italian ELBWi. This study aims to describe neurodevelopmental outcome at 24 months of corrected age in an eleven-year single-center cohort of Italian ELBWi and to identify early risk factors for adverse neurodevelopmental outcomes. Methods All infants born with birth weight < 1000 g and admitted to the Neonatal Intensive Care Unit of the “Fondazione IRCCS Policlinico San Matteo” hospital in Pavia, Italy, from Jan 1, 2005 to Dec 31, 2015 were eligible for inclusion. At 24 months, Griffiths’ Mental Developmental Scales Extended Revised (GMDS-ER) were administered. Neurodevelopmental outcome was classified as: normal, minor sequelae (minor neurological signs, General Quotient between 76 and 87), major sequelae (cerebral palsy; General Quotient ≤ 75; severe sensory impairment). Univariate and multivariate multinomial logistic regression models were performed to analyze the correlation between neonatal variables and neurodevelopmental outcome. Results 176 ELBWi were enrolled (mean gestational age 26.52 weeks sd2.23; mean birthweight 777.45 g sd142.89). 67% showed a normal outcome at 24 months, 17% minor sequelae and 16% major sequelae (4.6% cerebral palsy on overall sample). The most frequent major sequela was cognitive impairment (8.52%). In the entire sample the median score on the Hearing-Speech subscale was lower than the median scores recorded on the other subscales and showed a significantly weaker correlation to each of the other subscales of the GMDS-ER. Severely abnormal cUS findings (RRR 10.22 p 0.043) and bronchopulmonary dysplasia (RRR 4.36 p 0.008) were independent risk factors for major sequelae and bronchopulmonary dysplasia for minor sequelae (RRR 3.00 p 0.018) on multivariate multinomial logistic regression. Conclusions This study showed an improvement in ELBWI survival rate without neurodevelopmental impairment at 24 months compared to previously reported international cohorts. Cognitive impairment was the most frequent major sequela. Median scores on GMDS-ER showed a peculiar developmental profile characterized by a selective deficit in the language domain. Severely abnormal cUS findings and bronchopulmonary dysplasia were confirmed as independent risk factors for major sequelae

Patients with acute coronary syndrome show oligoclonal T-cell recruitment within unstable plaque: evidence for a local, intracoronary immunologic mechanism

Background\u2014Recent studies indicate that T-cell activation may play an important role in the pathophysiology of acute coronary syndromes (ACS). However, although those studies detected T-cell expansion in peripheral blood cells, demonstration of specific T-cell expansion within the plaque of patients with ACS is lacking. The present study aims to address whether a specific, immune-driven T-lymphocyte recruitment occurs within the unstable plaque of patients with ACS. Methods and Results\u2014We simultaneously examined the T-cell repertoire using CDR3 size analysis both in coronary plaques (obtained by directional atherectomy) and in peripheral blood of patients with either ACS (n*11) or chronic stable angina (n*10). Unstable plaques showed a 10-fold increase in T-cell content by quantitative PCR. Using spectratyping analysis, we found several specific T-cell clonotype expansions only in unstable plaque from each patient with ACS, indicating a specific, antigen-driven recruitment of T cells within unstable lesions. Conclusions\u2014For the first time, T-cell repertoire was investigated directly into coronary plaques; using this approach, we demonstrate that coronary plaque instability in the setting of ACS is associated with immune-driven T-cell recruitment, specifically within the plaque

Patients with acute coronary syndrome show oligoclonal T-cell recruitment within unstable plaque: evidence for a local, intracoronary immunologic mechanism.

Background—Recent studies indicate that T-cell activation may play an important role in the pathophysiology of acute coronary syndromes (ACS). However, although those studies detected T-cell expansion in peripheral blood cells, demonstration of specific T-cell expansion within the plaque of patients with ACS is lacking. The present study aims to address whether a specific, immune-driven T-lymphocyte recruitment occurs within the unstable plaque of patients with ACS. Methods and Results—We simultaneously examined the T-cell repertoire using CDR3 size analysis both in coronary plaques (obtained by directional atherectomy) and in peripheral blood of patients with either ACS (n*11) or chronic stable angina (n*10). Unstable plaques showed a 10-fold increase in T-cell content by quantitative PCR. Using spectratyping analysis, we found several specific T-cell clonotype expansions only in unstable plaque from each patient with ACS, indicating a specific, antigen-driven recruitment of T cells within unstable lesions. Conclusions—For the first time, T-cell repertoire was investigated directly into coronary plaques; using this approach, we demonstrate that coronary plaque instability in the setting of ACS is associated with immune-driven T-cell recruitment, specifically within the plaque

Suitability of North Star Ambulatory Assessment in young boys with Duchenne muscular dystrophy

The aim of this study was to establish the suitability of the North Star Ambulatory Assessment for use in young boys with Duchenne muscular dystrophy.We studied 147 typically developing and 144 boys affected by Duchenne muscular dystrophy between the ages of 3 and 5 years. More than 85% of the typically developing boys by the age of 4 years had full scores on all the items with total scores ≥33/34. Before the age of 4 years more than 15% of the typically developing boys did not achieve full scores on all the items. Some items, such as standing on one leg, showed significant improvement with age. In contrast, other activities were rarely achieved even in the older boys. Even if there was a progressive increase in scores with age, both total and individual item scores in Duchenne were still far from those obtained in the typically developing children of the same age. Our findings suggest that the North Star Ambulatory Assessment can be reliably used at least from the age of 4 years. Longitudinal natural history data studies are needed to assess possible changes over time and the possible effect of early steroids

Vascular risk factors in glaucoma: The results of a national survey

Graefe's Archive for Clinical and Experimental Ophthalmology Volume 245, Issue 6, 1 June 2007, Pages 795-802 Vascular risk factors in glaucoma: The results of a national survey (Article) Orzalesi, N.a , Rossetti, L.a, Omboni, S.b, Sborgia, C.c, Vetrugno, M.c, Cantatore, F.c, Campos, E.d, Baldi, A.d, Quaranta, L.e, Serra, A.f, Zucca, I.f, Mura, M.f, Malocci, M.f, Uva, M.g, Longo, A.g, Lombardo, A.g, Scorcia, G.h, Moschettini, R.h, Gallenga, P.E.i, Mastropasqua, L.i, Ciancaglini, M.i, Carpineto, P.i, Lobefalo, L.i, Perri, P.j, Paduano, B.j, Alfieri, G.k, Menchini, U.k, Campana, F.k, Giansanti, F.k, Delle Noci, N.l, Balducci, F.l, Calabria, G.m, Saccà, S.m, Sanna, G.m, Camicione, P.m, Mastromarino, A.m, Balestrazzi, E.n, Di Staso, S.n, Ferreri, G.o, D’Andrea, A.o, Orzalesi, N.p, Rossetti, L.p, Fogagnolo, P.p, Mazzolani, F.p, Brancato, R.q, Carassa, R.q, Bettin, P.q, Fiori, M.q, Guerra, R.r, Martini, E.r, Scarale, G.r, Campi, L.r, Bonavolontà, G.s, Rinaldi, E.s, Di Meo, A.s, Fusco, R.s, Dorigo, M.T.t, Doro, D.t, Grgic, V.t, Lodato, G.u, Morreale Bubella, D.u, Signorelli, F.u, Gandolfi, S.v, Trimarchi, F.w, Milano, G.w, Fiore, C.x, De Carolis, A.x, Sbordone, G.x, Nardi, M.y, Bartolomei, M.P.y, Figus, M.y, Guidi, G.y, Scullica, L.z, Salgarello, T.z, Colotto, A.z, Bucci, M.G.aa, Cerulli, L.aa, Manni, G.L.aa, Centofanti, M.aa, Parravano, M.aa, Scuderi, G.aa, Nucci, C.aa, Carta, F.ab, Pinna, A.ab, Caporossi, A.ac, Frezzotti, P.ac, Grignolo, F.ad, Brogliatti, B.ad, Rolle, T.ad, Ravalico, G.ae, Vattovani, O.ae, Tritto, D.ae, Canziani, T.ae, Marchini, G.af, Marraffa, M.af, OPTIME Study Group (Osservatorio sulla Patologia glaucomatosa, Indagine Medico Epidemiologica)ag, CONPROSO (Collegio Nazionale dei Professori Ordinari di Scienze Oftalmologiche)ah Hide additional authors a Department of Medicine, Surgery and Odontology, University of Milan, San Paolo Hospital, Milan, Italy b Docleader Srl, Somma Lombardo, VA, Italy c University of Bari, Italy View additional affiliations View references (52) Abstract Background The role of vascular risk factors in glaucoma is still being debated. To assess the importance of vascular risk factors in patients with primary open-angle glaucoma (POAG), data from the medical history of 2,879 POAG patients and 973 age-matched controls were collected and analyzed. Methods Design: observational survey. Setting: 35 Italian academic centers. Study population: POAG patients and age-matched controls. In order to reduce bias consecutive patients were included. Observation procedures: data concerning vascular risk factors were collected for all patients with a detailed questionnaire. A complete ophthalmological examination with assessment of intraocular pressure (IOP), visual field, optic disc, and systemic blood pressure was performed. Main outcome measures: the ESH-ESC (European Society of Hypertension-European Society of Cardiology) guidelines were used to calculate the level of cardiovascular risk. Crude and adjusted estimates of the odds ratios (OR) were calculated for all cardiovascular risk factors in POAG and controls. Results The study included 2,879 POAG patients and 973 controls. POAG cases had a significantly higher systolic and diastolic blood pressure (p=0.001) and systolic perfusion pressure (p=0.02) as compared with controls. Also mean IOP was significantly higher in the POAG group (p=0.01), while diastolic perfusion pressure was not significantly different in the two groups. Myopia was more prevalent in the POAG group (23 vs 18%, p=0.005) as well as a positive family history for glaucoma (26 vs 12%, p= 0.004). POAG patients tended to have a higher cardiovascular risk than controls: 63% of glaucoma cases vs 55% of controls (OR: 1.38, p=0.005) had a “high” or “very high” cardiovascular risk. Conclusions The level of cardiovascular risk was significantly higher in glaucoma patients than in controls. © Springer-Verlag 2006

MEDICAL SCIENCE. GISSI-2: A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction

A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1\ub75 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12 500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study was the combined estimate of death plus severe left ventricular damage. 12 490 patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA alone, tPA plus heparin). No specific differences between the two thrombolytic agents were detected as regards the combined end-point (tPA 23\ub71%; SK 22\ub75%; relative risk 1\ub704, 95% Cl 0\ub795-1\ub713), nor after the addition of heparin to the aspirin treatment (hep 22\ub77%, no hep 22\ub79%; RR 0\ub799, 95% Cl 0\ub791-1\ub708). The outcome of patients allocated to the four treatment groups was similar with respect to baseline risk factors such as age, Killip class, hours from onset of symptoms, and site and type of infarct. The rates of major in-hospital cardiac complications (reinfarction, post-infarction angina) were also similar. The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0\ub75%, SK 1\ub70%, RR 0\ub757, 95% Cl 0\ub738-0\ub785; hep 1\ub70%, no hep 0\ub76%, RR 1\ub764, 95% Cl 1\ub709-2\ub745), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8\ub78% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI. \ua9 1990