Structural brain anomalies in Cri-du-Chat syndrome: MRI findings in 14 patients and possible genotype-phenotype correlations.

INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings. PATIENTS AND METHODS: Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution. RESULTS: MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients. CONCLUSIONS: Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.

Fluid-structure interaction simulations outperform computational fluid dynamics in the description of thoracic aorta haemodynamics and in the differentiation of progressive dilation in Marfan syndrome patients.

Abnormal fluid dynamics at the ascending aorta may be at the origin of aortic aneurysms. This study was aimed at comparing the performance of computational fluid dynamics (CFD) and fluid-structure interaction (FSI) simulations against four-dimensional (4D) flow magnetic resonance imaging (MRI) data; and to assess the capacity of advanced fluid dynamics markers to stratify aneurysm progression risk. Eight Marfan syndrome (MFS) patients, four with stable and four with dilating aneurysms of the proximal aorta, and four healthy controls were studied. FSI and CFD simulations were performed with MRI-derived geometry, inlet velocity field and Young's modulus. Flow displacement, jet angle and maximum velocity evaluated from FSI and CFD simulations were compared to 4D flow MRI data. A dimensionless parameter, the shear stress ratio (SSR), was evaluated from FSI and CFD simulations and assessed as potential correlate of aneurysm progression. FSI simulations successfully matched MRI data regarding descending to ascending aorta flow rates (R 2 = 0.92) and pulse wave velocity (R 2 = 0.99). Compared to CFD, FSI simulations showed significantly lower percentage errors in ascending and descending aorta in flow displacement (-46% ascending, -41% descending), jet angle (-28% ascending, -50% descending) and maximum velocity (-37% ascending, -34% descending) with respect to 4D flow MRI. FSI- but not CFD-derived SSR differentiated between stable and dilating MFS patients. Fluid dynamic simulations of the thoracic aorta require fluid-solid interaction to properly reproduce complex haemodynamics. FSI- but not CFD-derived SSR could help stratifying MFS patients.

Decreased rotational flow and circumferential wall shear stress as early markers of descending aorta dilation in Marfan syndrome: a 4D flow CMR study.

BACKGROUND: Diseases of the descending aorta have emerged as a clinical issue in Marfan syndrome following improvements in proximal aorta surgical treatment and the consequent increase in life expectancy. Although a role for hemodynamic alterations in the etiology of descending aorta disease in Marfan patients has been suggested, whether flow characteristics may be useful as early markers remains to be determined. METHODS: Seventy-five Marfan patients and 48 healthy subjects were prospectively enrolled. In- and through-plane vortexes were computed by 4D flow cardiovascular magnetic resonance (CMR) in the thoracic aorta through the quantification of in-plane rotational flow and systolic flow reversal ratio, respectively. Regional pulse wave velocity and axial and circumferential wall shear stress maps were also computed. RESULTS: In-plane rotational flow and circumferential wall shear stress were reduced in Marfan patients in the distal ascending aorta and in proximal descending aorta, even in the 20 patients free of aortic dilation. Multivariate analysis showed reduced in-plane rotational flow to be independently related to descending aorta pulse wave velocity. Conversely, systolic flow reversal ratio and axial wall shear stress were altered in unselected Marfan patients but not in the subgroup without dilation. In multivariate regression analysis proximal descending aorta axial (p = 0.014) and circumferential (p = 0.034) wall shear stress were independently related to local diameter. CONCLUSIONS: Reduced rotational flow is present in the aorta of Marfan patients even in the absence of dilation, is related to aortic stiffness and drives abnormal circumferential wall shear stress. Axial and circumferential wall shear stress are independently related to proximal descending aorta dilation beyond clinical factors. In-plane rotational flow and circumferential wall shear stress may be considered as an early marker of descending aorta dilation in Marfan patients.

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

BACKGROUND: Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID). AIMS: Identification of genomic disorders in DD/ID. MATERIALS AND METHODS: We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs. RESULTS: We identified non-benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape. DISCUSSION AND CONCLUSION: We show how phenotypic and genetic analyses of array-CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects.

In silico analysis of the anti-hypertensive drugs impact on myocardial oxygen balance.

Hypertension is a very common pathology, and its clinical treatment largely relies on different drugs. Some of these drugs exhibit specific protective functions in addition to those resulting from blood pressure reduction. In this work, we study the impact of commonly used anti-hypertensive drugs (RAAS, [Formula: see text] and calcium channel blockers) on myocardial oxygen supply-consumption balance, which plays a crucial role in type 2 myocardial infarction. To this aim, 42 wash-out hypertensive patients were selected, a number of measured data were used to set a validated multi-scale cardiovascular model to subject-specific conditions, and the administration of different drugs was suitably simulated. Our results ascribe the well-known major cardioprotective efficiency of [Formula: see text] blockers compared to other drugs to a positive change of myocardial oxygen balance due to the concomitant: (1) reduction in aortic systolic, diastolic and pulse pressures, (2) decrease in left ventricular work, diastolic cavity pressure and oxygen consumption, (3) increase in coronary flow and (4) ejection efficiency improvement. RAAS blockers share several positive outcomes with [Formula: see text] blockers, although to a reduced extent. In contrast, calcium channel blockers seem to induce some potentially negative effects on the myocardial oxygen balance.

Fluid dynamics of heart valves during atrial fibrillation: a lumped parameter-based approach.

Atrial fibrillation (AF) consequences on the heart valve dynamics are usually studied along with a valvular disfunction or disease, since in medical monitoring, the two pathologies are often concomitant. Aim of the present work is to study, through a stochastic lumped-parameter approach, the basic fluid dynamics variations of heart valves, when only paroxysmal AF is present with respect to the normal sinus rhythm in absence of any valvular pathology. Among the most common parameters interpreting the valvular function, the most useful turns out to be the regurgitant volume. During AF, both atrial valves do not seem to worsen their performance, while the ventricular efficiency is remarkably reduced.

The error in neonatal intensive care: a multicenter prospective study.

AIM: During a nursing conference of the Northeaster Piedmont Neonatal Intensive and Subintensive Neonatal Units the error in pediatrics and neonatology was discussed and a follow-up work was proposed with the aim to understand how many, what type of errors and what kind of adverse event they cause in our clinical practice. METHODS: Through an anonymous "detection sheet" we detected the errors made between March 1 and April 30, 2010 in a NICU and 2 Subintensive therapies. The total number of patients was 166 for 2398 days of hospitalization. RESULTS: The total number of errors was 72, with a error of 0.43/patient. Forty-six patients had experienced at least 1 error (28% of patients) and more than a 16 (10% of our patients). There is a statistically significant correlation between days of hospitalization and the number of errors occurred (r=0.63 Sperman's correlation, P<0.01); 48% and 53% of the errors in the NICU and Subintensive CU were related to medication administration. CONCLUSION: The severe damage in the NICU was caused by errors more frequently related to vascular access while the only mistake that led to a serious incident in subintensive CU was determined by a monitoring error. Errors were most frequently attributed to inattention-distraction, less frequently have been attributed to a lack of experience or a state of excessive fatigue. The data of our study were made available to all staff in order to make operators more aware of the importance of working safely.

[What new fathers know, think and do: a survey about fathering's attitudes, beliefs and behaviors in a sample of 570 men just after the birth of their newborn]. / Cosa sanno, cosa pensano, cosa fanno i neo-papà: indagine su attitudini, conoscenze e comportamenti di 570 uomini rispetto al proprio ruolo paterno a poche ore dalla nascita del loro bambino.

AIM: The aim of this paper was to know and analyze information, attitudes and behaviors related with transformations occurring in men when they become fathers. METHODS: A self-administered questionnaire has been given out to all men whose newborns were born in the Hospitals located into Borgosesia, Ivrea, Novara, Verbania and Vercelli (Piedmont region in north west of the Italy) in the last quarter of 2006. The questionnaire was created ad hoc and filled out on the day of discharge; results underwent statistical analyses through SPSS system. RESULTS: For the duration of the research, out of 870 men who became fathers in the hospitals were involved in this study, 570 responded voluntarily to the self-administered questionnaire (65.6% of the total sample). They showed a lack of information about how to take care of their newborns and the emotional turmoil of women after delivery (58% think children are blind when they are born, 52% think it is better to breastfeed newborns at fixed times and 47% ignore that mothers can enter a depression state). Eighty-eight percent of respondents were in the delivery room to see their child's birth, 56% took a leave from job to stay with mother and child in the hospital and 58% of them report the intention to take an additional 2-3 days leave after coming home from the hospital; 27% had trouble sleeping during pregnancy and are afraid not to be good fathers for their child; 90% believe that their newborn will make them change life habits. Most of the new fathers had difficulties in sharing emotions and feelings related with their status of fathers-to-be with other men. Some of these results are significantly different in older fathers, fathers having their first child and fathers with a lesser level of education. CONCLUSION: During pregnancy and in the first months after their child is born, fathers-to-be and new fathers must be considered a potential target for educational interventions aiming at promoting their parenting information and reinforcing their positive attitudes and beliefs related with their fathering status.

Epistaxis in children under the age of two: possible marker of abuse/neglect? A retrospective study in North-Eastern Piedmont hospitals.

AIM: Epistaxis is an extremely common event at all ages; however, under two years of age epistaxis is a very rare event and recent studies carried out in Great Britain concern this event as related to possible non-accidental trauma. To date, no other studies carried out in Italy are available on this topic. METHODS: A file review of all cases of epistaxis occurred in children under the age of 2 who were admitted into the ED in our area over a period of two years was carried out. RESULTS: We have collected data concerning 10 cases of epistaxis occurred in children under 2 years of age with an incidence of 10.4 cases per 10000 accessions to the ED of children under the age of 2. Four of the cases had attendances for head injury or facial trauma. CONCLUSION: The results obtained are higher than the results of the British studies adopting the same methodology, but comparable to their surveillance data on the general population. Through the analysis of the collected data, two correlated assumptions have been made: a possible relationship between epistaxis and neglect, and a relation between epistaxis and domestic accidents.

[Congenital Milroy Oedema: a case report of a family]. / Edema congenito di Milroy. descrizione di una famiglia.

The authors describe the case of a newborn and their family with Nonne-Milroy disease (hereditary lymphedema type I), a genetic disease that is usually characterized by lymphedema, that most often affects the lower extremities or less frequently the back of the hands. We discuss etiology, inheritance pattern, differential diagnosis and follow-up.

[The Cri du Chat syndrome: a study on the quality of care]. / Sindrome del Cri du Chat: indagine sulla qualità dell' assistenza.

AIM: The Cri du Chat syndrome (SCdC / [OMIM #123450]) is a rare disease characterized by the deletion of the short arm of chromosome 5. The typical clinical features are the cat-like cry, microcephaly, a distinct facial phenotype and a severe psychomotor and mental retardation. The aim of this study was to provide an analysis on the data concerning the life quality and families assistance to whom have a child affected by Cri du Chat syndrome such as: the life's change of parents after the child's birth, the frequency of treatments, the collaboration between family and center of reference. METHODS: We have also analyzed the improvement obtained, the type of school attended, the aide and the time spent at home in postprimary education. Through a questionnaire sent to 100 families, we have been picked up information on 76 patients. RESULTS: These families have to adapt to the reality of a child with a rare genetic disorder for which there are no pharmacological or surgical therapies. CONCLUSION: Therefore, it seems important to give information and tips for dealing with the disease and the early start of rehabilitation and educational therapy.

Duplication of the pituitary stalk in a patient with a heterozygous deletion of chromosome 14 harboring the thyroid transcription factor-1 gene.

Magnetic resonance imaging of the hypothalamic-pituitary region revealed a duplication of the pituitary stalk in a patient with a heterozygous deletion of chromosome 14 harboring the thyroid transcription factor-1 gene.

Vitamin D at term of pregnancy and during lactation in white and black women living in Northern Italy.

AIM: Evaluate the vitamin D serum status in a population of white and black mothers who live in the same geographic area of northern Italy (45 degrees 8' N of latitude) and its correlation with vitamin D serum concentrations of the respective newborns at birth, at 2 and 12 months. METHODS: Twelve white woman-infant pairs and 12 black woman-infant pairs were recruited from January through March 2006. The study population had no pre-existing disease and delivered at term of pregnancy (37-41 weeks of gestational age). Only black infants were given vitamin D supplementation from birth to 1 year of age. RESULTS: Eleven black and 12 white women had low vitamin D serum levels at term of pregnancy. Similarly, black and white newborns were both vitamin D deficient at birth. After 12 months white women re-gained physiological vitamin D serum levels, whereas black women maintained a status of vitamin D deficiency. Black newborns who were given supplementation showed lower vitamin D serum concentrations as compared with white newborns at 1 year of age. CONCLUSION: These data showed that all the women living in the same region of northern Italy without any supplementation are equally vitamin D deficient at term of pregnancy regardless of their skin pigmentation. Consequently, every woman should be supplied with additional vitamin D during pregnancy and lactation, though such supplementation seems to exert the most beneficial effects in black women.

Lack of improvement in the modality of beta2 administration in pediatric departments: survey in Piedmont and Aosta Valley.

AIM: In recent years many consensus conferences of scientific societies have reaffirmed the advantages of metered dose inhalator (MDI) and spacer administration compared to classic aerosol in acute asthma and maintenance therapy. Faced with a more than convincing documentation, the practitioners have shown a controversial attitude concerning this type of administration. At the same time, as a general acceptance of its superiority there is an inexplicable lack of use. METHODS: This survey was carried out in 2006 and it involved pediatric hospital wards in Piedmont and Aosta Valley to evaluate the use of spacers in acute asthma in hospitalised children undergoing treatment. These results were compared to those obtained from another survey carried out in 2008 using identical questionnaires in the same departments in order to evaluate the implementation of such a practice. RESULTS: In the two years between one survey and the other no increase in the use of MDI and spacer has been detected, but, on the contrary, a consistent decrease. CONCLUSION: Notwithstanding the amount of evidence concerning its superiority compared to nebulisers MDI and spacer is not commonly used for asthma therapy yet. A "promotional" multidisciplinary intervention could play a determining role in the implementation of such a practice.

[Sleeping in the supine position in the ASL 11 region of Piemonte. Assessment of the efficacy of a promotional campaign]. / Dormire sulla schiena nell'asl 11--regione Piemonte Valutazione dell'efficacia di una campagna promozionale.

OBJECTIVES: To record the prevalence of the sleeping position of sucklings living in the ASL 11-Regione Piemonte; to make an information campaign about the utility of sleeping in the supine position (most important protection factor against the SIDS); to find out its efficacy for a short or long time. METHODS: During the first two months of 2002 all the parents coming to the consulting rooms for the compulsory vaccinations of their 3 and 5 months old babies have been interviewed about the position of their babies during sleep. The same recording has been made in the first two months of 2003 and 2004. During 2002 various consciousness campaigns have been made, above all for medical operators of hospital nurseries and of Mother-and-Child Departments and Prevention Departments in ASL 11 area. RESULTS: Before the consciousness campaign the percentage of 3 months old sucklings sleeping in the supine position was 62,3% and 55% for the 5 months old suckings; after the campaign the percentage has grown to 77,4% for 3 months old sucklings and 74,5% for 5 months old sucklings during 2003 and during 2004 the percentage has grown to 80,3% and 74,2%, respectively. CONCLUSIONS: A simple and not expensive but capillary consciousness and information campaign addressed to medical operators has obtained valid and statistically relevant results in a short time.