Confirmation of mosaicism and uniparental disomy in amniocytes, after detection of mosaic chromosome abnormalities in chorionic villi

Chromosome mosaicism is detected in about 1-2% of chorionic villi samples (CVS), and may be due to a postzygotic nondisjunction event generating a trisomic cell line in an initially normal conceptus (mitotic origin) or the postzygotic loss of one chromosome in an initially trisomic conceptus (meiotic origin and trisomy rescue). Depending on the distribution of the abnormal cell line, the mosaic can be confined to the placenta (CPM) or generalised to the fetus (TFM, true fetal mosaicism). Trisomy rescue could theoretically be associated with a 33.3% probability of uniparental disomy (UPD) in the fetus. The aim of this study was to determine the risk of fetal involvement in a cohort of numerical and structural chromosome mosaics revealed in chorionic villi by means of combined direct and long-term culture analyses; we also determined the incidence of UPD associated with mosaic aneuploidies and supernumerary markers involving imprinted chromosomes. A total of 273 of a consecutive series of 15,109 CVS evaluated during a period of 5 years showed a mosaic condition in direct preparations and/or long-term cultures; confirmatory amniocentesis was performed in 203 cases. The abnormal cell line was extended to the fetus in 12.8% cases in terms of structural and numerical abnormalities involving autosomes and sex chromosomes; the risk of TFM varied and depended on the placental tissue distribution of the abnormal cell line. One of the 51 cases in which the mosaic involved an imprinted chromosome showed UPD, thus indicating a risk of 1.96%.     

Sudden cardiac death in younger adults: autopsy diagnosis as a tool for preventive medicine

Sudden death in children and younger adults can be caused by potentially heritable cardiovascular disorders, and the fatal outcome is often the first symptom in apparently healthy subjects. In these cases, a careful autopsy becomes the sole diagnostic tool to guide the clinical screening of the families. The aims of the present study were (1) to assess the pathological substrate of sudden cardiac death in children and younger adults (age, 1-40 years) in a large prospective series using strict morphological criteria; and (2) to perform cardiological assessment of the relatives of the deceased subjects with cardiomyopathies or structurally normal hearts, potentially consistent with a heritable cardiac disease. We studied 100 consecutive cases. Autopsy findings included coronary artery disease (30%, atherosclerotic in the majority of cases), cardiomyopathies (22%), and various cardiac abnormalities (28%). In the remaining 20% of cases, the presence of significant morphological abnormalities of the heart was ruled out. Twenty of 42 families in which the heart of the proband was either affected by a cardiomyopathy or failed to show significant structural abnormalities could be contacted and provided informed consent to cardiological assessment. A potentially inherited cardiac disease was diagnosed in 4 (20%). Molecular genetic analysis was restricted to 3 of these families and revealed a mutation in the ryanodine receptor type 2 gene (RyR2) in 1. Our results underline the implication of autopsy findings for relatives and the importance of cardiological screening of family members to uncover familial cardiomyopathies or genetic arrhythmias and to adopt the proper therapeutic and preventive strategies. Genetic testing is still time consuming and costly: accordingly, it should be restricted only to selected cases.     

The VADO approach in psychiatric rehabilitation: a randomized controlled trial

OBJECTIVE: This study investigated whether a specific structured planning and evaluation approach called VADO (in English, Skills Assessment and Definition of Goals) resulted in improved personal and social functioning among patients with chronic schizophrenia. METHODS: A total of 85 patients with chronic schizophrenia who were under a stable medication regimen were randomly allocated to the VADO-based intervention or to routine care; 78 completed the program. Interventions were carried out in nine Italian day treatment or residential rehabilitation facilities. Assessment at the beginning of the study and at the one-year follow-up included the Personal and Social Performance scale (PSP) and Brief Psychiatric Rating Scale Version 4.0 (BPRS). Clinically significant improvement was defined as an increase of at least 10 points on the PSP or a decrease of at least 20 percent on the BPRS total score. RESULTS: At baseline, average PSP scores in the experimental group and in the control group were 33.9+/-8.1 and 34.0+/-11.2, respectively (possible scores range from 1 to 100, with higher scores indicating better functioning). At six months, the score improved markedly in the experimental group (40.8+/-10.9) and minimal change was observed in the control group (35.3+/-11.6); the difference between groups was significant (difference of 6.9 points compared with 1.3 points; t=2.21, df=81, p<.05). At 12 months, the same trend was observed (difference of 12.0 points compared with 3.5 points), and the difference between groups was both statistically and clinically significant (t=2.99, df=75, p<.01). CONCLUSIONS: A statistically and clinically significant improvement in functioning was observed among patients treated with the VADO approach.     

Aesthetic improvements of radial forearm flap donor site by autologous fat transplantation

Despite its reliability, radial forearm (RF) flap is still affected by high donor site morbidity with poor cosmetic and functional outcomes after coverage with skin grafts. Having fat grafting demonstrated promising and effective filling and rejuvenating properties, we considered and tested it as a valuable alternative to dermal substitutes for the aesthetic improvement of RF flap donor site. Thirty-three patients with previous RF free flap reconstruction and poor donor site outcomes after full-thickness skin grafting to RF region were evaluated for secondary fat injection to improve outcomes. Objective and subjective assessments of results with standardized ultrasonographic soft tissue thickness measurements, cutaneous sensibility tests with the pressure-specified sensory device and scar assessment scale (POSAS) have been performed. Bivariate statistical analyses were performed comparing outcomes with contralateral healthy forearm. All cases showed significant improvement in soft tissue thickness (p< 0.031), cutaneous sensibility and scar appearance, with improved patient’s and observers’ scar assessment scores (<0.001). In conclusion, fat transplantation is an effective procedure that provided us with an adjunctive autologous layer in-between skin graft and underlying fascia, as well as a rejuvenating effect on skin and scars.     

Ex vivo effect of vascular wall stromal cells secretome on enteric ganglia

BACKGROUND Mesenchymal stromal cell(MSC)-based therapy is currently under study to treat inflammatory bowel diseases.MSC bioactive products could represent a valid alternative to overcome issues associated with systemic whole-cell therapies.However,MSC anti-inflammatory mechanisms differ between rodents and humans,impairing the reliability of preclinical models.AIM To evaluate the effect of conditioned medium(CM)derived from porcine vascular wall MSCs(pVW-MSCs)on survival and differentiation of porcine and guinea pig enteric ganglia exposed to lipopolysaccharide(LPS).METHODS Primary cultures of enteric ganglia were obtained by mechanic and enzymatic digestion of ileum resections from guinea pigs(Cavia porcellus)(GPEG)and pigs(Suus scrofa)(PEG).pVW-MSCs were derived by enzymatic digestion from vascular wall resections of porcine aorta and tested by immunoflowcytometry for MSC immune profile.Enteric ganglia were treated with increasing concentrations of LPS,CM derived by pVW-MSCs or a combination of CM and LPS 1μg/mL.Cell count and morphometric analysis of HuD positive neurons and glial fibrillary acidic protein positive glial cells were performed by immunofluorecent staining of cultured ganglia.RESULTS PEG showed a higher number of neurons compared to GPEG.Overall,CM exerted a protective role on LPS-treated enteric ganglia.CM in combination with LPS increased the number of glial cells per ganglion in both cultures evoking glial cells differentiation in porcine cultures.CONCLUSION These findings suggest an immunomodulating activity of pVW-MSCs mediators on the enteric nervous system in inflammatory conditions.     

Development and Validation of the Health of the Nation Outcome Scales-Residential Facility (HoNOS-RF)

The Health of the Nation Outcome Scale (HoNOS) (Lora et al. Epidemiol Psichiatr Soc 10(3):198–212, 2001) is widely used. However, clinicians have expressed concerns about its ability to describe severe mentally ill patients, as it does not consider some relevant clinical aspects. This study aims to develop and validate the HoNOS-Residential Facility (HoNOS-RF) in order to pursue a thorough assessment of patients admitted to psychiatric residential facilities (RFs). The final version of the HoNOS-RF was administered to 409 patients admitted to four RFs. Exploratory factor analysis, Cronbach’ alpha (α), Intraclass Correlation Coefficients (ICC) were used to assess construct validity, internal consistency and reliability, respectively. Concurrent criterion validity was assessed through correlations with the Brief Psychiatric Rating Scale-Expanded Version (BPRS-E) (Roncone et al. Acta Psychiatric Scand 100(3):229–36, 1999), Personal and Social Performance Scale (PSP) (Morosini et al. Acta Psychiatric Scand 101(4): 323–29, 2000), and comparisons across diagnostic groups. The final version of the HoNOS-RF consisted of 31 items, grouped into the following eight factors (overall explaining 55% of the total variability): personal and interpersonal functioning; environment; behavior and burden of care; cognitive function; somatic problems; anxiety-depression symptoms; psychotic symptoms; and other psychiatric symptoms. The scale showed high internal consistency (α?=?.807), and the correlations with PSP and BPRS-E ranged from adequate to moderate. The ICCs were in the excellent range for almost all items. These findings support the validity and the reliability of the HoNOS-RF, thus it may be a useful tool for the assessment of patients admitted to RFs, as it addresses clinical aspects that were mostly not included in the original version.