Higher fresh fruit intake relates to larger grey matter volumes in areas involved in dementia and depression: A UK Biobank study.

The benefits of consuming fruits and vegetables are widely accepted. While previous studies suggest a protective role of fruits and vegetables against a variety of diseases such as dementia and depression, the biological mechanisms/effects remain unclear. Here we investigated the effect of fruit and vegetable consumption on brain structure. Particularly on grey matter (GM) and white matter (WM) volumes, regional GM volumes and subcortical volumes. Cross-sectional imaging data from UK Biobank cohort was used. A total of 9925 participants (Mean age 62.4 ± 7.5 years, 51.1 % men) were included in the present analysis. Measures included fruit and vegetable intake, other dietary patterns and a number of selected lifestyle factors and clinical data. Brain volumes were derived from structural brain magnetic resonance imaging. General linear model was used to study the associations between brain volumes and fruit/vegetable intakes. After adjusting for selected confounding factors, salad/raw vegetable intake showed a positive association with total white matter volume, fresh fruit intake showed a negative association with total grey matter (GM) volume. Regional GM analyses showed that higher fresh fruit intake was associated with larger GM volume in the left hippocampus, right temporal occipital fusiform cortex, left postcentral gyrus, right precentral gyrus, and right juxtapositional lobule cortex. We conclude that fruit and vegetable consumption seems to specifically modulate brain volumes. In particular, fresh fruit intake may have a protective role in specific cortical areas such as the hippocampus, areas robustly involved in the pathophysiology of dementia and depression.

Mannose Binding Lectin, S100 B Protein, and Brain Injuries in Neonates With Perinatal Asphyxia.

Perinatal asphyxia triggers an acute inflammatory response in the injured brain. Complement activation and neuroinflammation worsen brain damage after a systemic ischemia/reperfusion insult. The increase of mannose binding lectin (MBL) during asphyxia may contribute to the brain damage, via activation of the complement lectin pathway. The possible role of MBL2 gene variants in influencing the severity of post-asphyxia brain injuries is still unexplored. This retrospective study included 53 asphyxiated neonates: 42 underwent therapeutic hypothermia (TH) and 11 did not because they were admitted to the NICU later than 6 h after the hypoxic insult. Blood samples from TH-treated and untreated patients were genotyped for MBL2 gene variants, and biomarker plasma levels (MBL and S100 B protein) were measured at different time points: during hypothermia, during rewarming, and at 7-10 days of life. The timing of blood sampling, except for the T1 sample, was the same in untreated infants. Highest (peak) levels of MBL and MBL2 genotypes were correlated to neuroimaging brain damage or death and long-term neurodevelopmental delay. MBL2 wild-type genotype was associated with the highest MBL levels and worst brain damage on MRI (p = 0.046) at 7-10 days after hypoxia. MBL increased in both groups and S100B decreased, slightly more in treated than in untreated neonates. The progressive increase of MBL (p = 0.08) and to be untreated with TH (p = 0.08) increased the risk of brain damage or death at 7-10 days of life, without affecting neurodevelopmental outcomes at 1 year. The effect of TH on MBL plasma profiles is uncertain.

Propofol and fentanyl sedation for laser treatment of retinopathy of prematurity to avoid intubation.

BACKGROUND: Despite the optimization of neonatal assistance, severe retinopathy of prematurity (ROP, stage III-IV) remains a common condition among preterm infants. Laser photocoagulation usually requires general anesthesia and intubation, but extubation can be difficult and these infants often affected by chronic lung disease. We retrospectively evaluated the clinical charts of 13 neonates that were sedated with propofol in association with fentanyl for the laser treatment of ROP. This protocol was introduced in our unit to avoid intubation and minimize side effects of anesthesia and ventilation. METHODS: Propofol 5% followed by a bolus of fentanyl was administered as sedation during laser therapy to 13 preterm infants, affected by ROP stage III-IV. Propofol was initially infused as a slow bolus of 2-4 mg/kg and then continuously during the entire procedure, at 4 mg/kg/hour, increasing the dosage to 6 mg/kg/hour if sedation was not achieved. A laryngeal mask was placed and patients were ventilated with a flow-inflating resuscitation bag. RESULTS: Thirteen neonates were treated allowing to perform surgery without intubation. Only 4/13 (30.8%) of infants required minimal respiratory support during and/or after surgery. Heart rate after the intervention was higher than that at the beginning while remaining in the range of normal values. Blood pressures before, during and after surgery were similar. No episodes of bradycardia nor hypotension were recorded. Laser treatment was always successful. CONCLUSION: The good level of anesthesia and analgesia achieved sustains the efficacy of sedation with propofol during laser photocoagulation to avoid intubation and mechanical ventilation during and after the procedure.

Practices and Perceptions of Family Centered Care among Healthcare Providers: A Cross-sectional Study in a Pediatric Hospital.

PURPOSE: This study aimed to: (1) investigate the extent to which Family Centered Care (FCC) principles are currently applied in clinical practice by healthcare providers working in inpatient units; (2) evaluate the extent to which FCC principles are perceived as necessary; and (3) examine the associations between FCC principles and socio-demographic and job characteristics of participants. Design and Methods A cross-sectional study was conducted at a large pediatric hospital using the Italian version of the FCC Questionnaire Revised (FCCQ-R). Univariate and multivariate analyses were performed. RESULTS: Data from 469 healthcare providers were used for analysis. Scores for the FCC daily practices (Current activities) were significantly lower than those for their perceived necessity (Necessary activities) (p < .001). Participants who were male, younger, with work experience >20 years and working in rehabilitation reported a significantly higher perception of Current activities of FCC than others. The older and the more educated the participants, the greater was the perceived necessity of FCC activities. Female, older, and less experienced participants employed by the hospital but not working in the rehabilitation setting perceived a greater gap between Necessary and Current activities of FCC. CONCLUSIONS: Scores for the Current and Necessary activities of FCC were lower than those reported in other studies. The lower scores in the Current activities and the significant gap can be due to organizational barriers or lack of skills, but the lower scores in the Necessary activities should be interpreted as a deficit of knowledge about FCC. PRACTICE IMPLICATIONS: There is a need for further education about FCC in order to increase its perceived relevance in clinical practice.

Outpatient parents' views on shared-decision-making at an Italian children's hospital.

Information is lacking on what parents in southern European countries know and how they view clinical shared-decision-making (SDM) for their children. This survey assesses general parental views on SDM and patient-physician SDM relationships in an Italian paediatric outpatients' clinic. In a 3-month cross-sectional survey, we enrolled 458 consecutive native and foreign Italian-speaking parents bringing their children to our public hospital for various reasons. Parents completed an anonymous questionnaire exploring their general views on SDM, including what doctor-patient relationship predominates today, and what approach reassures them most. Multivariate logistic regression analysed outcome data from parental questionnaire answers. Results are reported as percentages, odds ratios (OR) and 95% confidence intervals (CI). Multivariate logistic regression showed that 440 parents (96.1%) appreciated SDM, 245 (53.5%) preferred SDM for choosing children's treatment, 126 (27.5%) answered that SDM is the predominant relationship today, and most parents 275 (60.0%) felt reassured by SDM. More native than foreign Italian-speaking parents preferred SDM (97.0 vs 89.7%, OR = 3.8; 95% CI = 1.4-10.8). Highly-educated parents preferred SDM for choosing their child's therapy (57.9 vs 34.1%, OR = 2.7; 95% CI = 1.6-4.4) and this approach reassured them (64.3 vs 41.2%, OR = 2.5; 95% CI = 1.6-4.1). In conclusion, parents bringing children to an Italian outpatient clinic, especially highly-educated parents, wish to be offered SDM and find it reassuring. These findings should encourage paediatricians working in a challenging multicultural environment to change their physician-centred approach and engage parents in tailored SDM strategies.

Bacterial sepsis in neonates: Single centre study in a Neonatal intensive care unit in Bosnia and Herzegovina.

OBJECTIVE: The aim of the study was to evaluate the incidence, mortality, risk factors, aetiology and the susceptibility to antibiotics of the bacteria responsible for sepsis. MATERIAL AND METHODS: A single centre, prospective, observational study, involving 200 neonates admitted over 12 months to the NICU of the University Children's Hospital, Tuzla, Bosnia and Herzegovina. RESULTS: The crude incidence of all neonatal sepsis was 68.0% (136/200) and that of late-onset sepsis (LOS) was 48.5% (97/200), yelding an incidence density of LOS of 41.6/1000 patient days. LOS represented the most frequent infection and was significantly more frequent than early-onset sepsis (EOS) (71.3% versus 28.7% p<0.001). The overall mortality was 14.0%, and 18.4% among infected neonates. Risk factors associated with LOS were: mechanical ventilation, intravascular catheter, surgical procedures, birth weight ≤1500 g, gestational age ≤ 28 weeks and Apgar score ≤ 3 at 5 minutes. Culture proven sepsis developed in 43.4% of neonates. Klebsiella pneumoniae and Enterococcus faecalis were the predominant bacteria. Gram-negative bacteria were susceptible to amikacin, imipenem and meropenem; gram-positive bacteria to vancomycin and amikacin. CONCLUSION: Neonatal sepsis in our NICU showed a high incidence rate, and gram-negative bacteria were predominant. Low gestational age, mechanical ventilation and an intra-vascular catheter were significantly associated with sepsis. It is necessary to develop a multidisciplinary approach for routine surveillance of nosocomial infections, to improve the asepsis of therapeutic procedures, and to implement the more appropriate use of antibiotics.

Effectiveness of an improvement programme to prevent interruptions during medication administration in a paediatric hospital: a preintervention-postintervention study.

OBJECTIVE: To assess the effectiveness of an improvement programme to reduce the number of interruptions during the medication administration process in a paediatric hospital. DESIGN AND METHODS: A prestudy-post study design was used to monitor nursing interruptions during medication cycles in a paediatric hospital. Interruptions were reported on an observation sheet (MADOS-P) adapted to the paediatric context. SETTING: A 600-bed tertiary paediatric research hospital in Italy. INTERVENTION: The interventions included a yellow sash worn by nurses during medication cycles, a yellow-taped floor area indicating the 'No interruption area', visual notices in the medication areas, education sessions for healthcare providers and families, patient and parent information material. RESULTS: 225 medication cycles were observed before the intervention (T0) and 261 after the intervention (T1). The median of interruptions occurring in each cycle decreased significantly from baseline to postintervention (8.0 vs 2.0, p=0.002), as the rate ratios (interruptions/patient post-pre ratio: 0.34; interruptions/medication post-pre ratio: 0.37; interruptions/hour of medication cycle post-pre ratio: 0.53, p<0.001). During preintervention, the main causes of interruptions were 'other patients' (19.9%), 'other nurses' (17.2%) and 'conversation' (15.7%); during postintervention, they were 'other nurses' (26.1%), 'conversation' (18.2%) and 'other patients' (17.4%). CONCLUSIONS: This bundle of interventions proved to be an effective improvement programme to prevent interruptions during medication administration in a paediatric context.

Role of right ventricular three-dimensional electroanatomic voltage mapping for arrhythmic risk stratification of patients with corrected tetralogy of Fallot or other congenital heart disease involving the right ventricular outflow tract.

BACKGROUND: The post-surgical history of repaired congenital heart disease (rCHD), in particular tetralogy of Fallot (TOF), is often complicated by sudden death. Electrical myocardial abnormalities could be a substrate for malignant ventricular arrhythmias. METHODS AND RESULTS: 146 patients with TOF or other rCHD involving a subpulmonary right ventricle, considered to be at high arrhythmic risk, underwent right ventricular (RV) electroanatomic voltage mapping (EVM). Maps showed endocardial scars (<0.5mV) in all cases, mainly involving the RV outflow tract (n=141, 96.6%). In 28 cases (19.2%), other areas were involved. Total scar extension, expressed as % of total endocardial area, was significantly higher in patients with QRS ≥180ms [4.5% (±2.5) vs 2.8% (±2.4), p=0.014], left and right ventricular systolic dysfunction [4.5% (±3.2) vs 2.8% (±2.3), p=0.016 and 3.5% (±3.0) vs 2.6% (±1.9), p=0.03, respectively], premature ventricular contractions (PVCs) [3.2% (±2.6) vs 2.2% (±1.8), p<0.05], exercise-induced PVCs [3.8% (±2.4) vs 2.6% (±2.2), p=0.01], previous shunt [4.0% (±2.7) vs 2.6% (±2.2), p=0.01] and reintervention [4.2% (±3.2) vs 2.6% (±2.0), p=0.008]. Scar size also showed a positive correlation with duration of post-surgical follow-up (ρ=0.01), age at correction (ρ=0.01) and absolute QRS duration (ρ=0.05). CONCLUSIONS: Patients with rCHD involving the right ventricle show electrical scars with variable distribution, not necessarily matching with sites of surgical lesions. Scar extension correlates with some of the risk factors for life-threatening arrhythmias in CHD, such as prolonged QRS. Thus EVM could be considered an additional tool in the assessment of risk stratification in this particular population.

Accuracy of Bedside Paediatric Early Warning System (BedsidePEWS) in a Pediatric Stem Cell Transplant Unit.

Hospital mortality in children who undergo stem cell transplant (SCT) is high. Early warning scores aim at identifying deteriorating patients and at preventing adverse outcomes. The bedside pediatric early warning system (BedsidePEWS) is a pediatric early warning score based on 7 clinical indicators, ranging from 0 (all indicators within normal ranges for age) to 26. The aim of this case-control study was to assess the performance of BedsidePEWS in identifying clinical deterioration events among children admitted to an SCT unit. Cases were defined as clinical deterioration events; controls were all the other patients hospitalized on the same ward at the time of case occurrence. BedsidePEWS was retrospectively measured at 4-hour intervals in cases and controls 24 hours before an event (T4-T24). We studied 19 cases and 80 controls. The score significantly increased in cases from a median of 4 at T24 to a median of 14 at T4. The proportion of correctly classified cases and controls was >90% since T8. The area under the curve receiver operating characteristic was 0.9. BedsidePEWS is an accurate screening tool to predict clinical deterioration in SCT patients.

Exploring the Relationship between Family Functioning and Psycho-Pathology in a Sample in the Pediatric Age.

The purpose of this study was to investigate differences in family functioning between families with clinical subjects in paediatric age and families taken from the Italian population. To this aim we used the Family Adaptability and Cohesion Evaluation Scale (FACES). Participants were children diagnosed with a psychopathology, recruited into the psychiatry department in a Paediatric Hospital of Rome. A total of 106 families participated in the study. The non-pathological sample is composed by 2,543 parents in different age periods of the life-cycle. Results showed significant differences in family functioning between pathological and non-pathological samples. Specifically, families from the pathological sample (particularly the ones who experienced eating disorders) were more frequently located in extreme or mid-range regions of Olson's circumplex model (p < .001). These findings suggest some considerations that can be useful in therapeutic works with families in a clinical setting. Critical aspects and clinical applications are discussed.

High prevalence of nickel allergy in an overweight female population: a pilot observational analysis.

CONTEXT: In our Allergy Unit, we incidentally observed that a low Nickel diet, prescribed for delayed allergy to Nickel sulfate, reduced body mass index (BMI) and waist circumference in overweight patients. OBJECTIVES: This pilot cross-sectional analysis was undertaken to compare the prevalence of Nickel allergy of overweight individuals versus the general population. We also had the chance to report the efficacy of a low Nickel diet on BMI and waist circumference in Nickel-sensitive overweight subjects. METHODS: Eighty-seven overweight subjects, with a BMI > 26 Kg/m2, were consecutively enrolled in a health prevention program, and screened for the presence of Nickel allergy. The enrolled population was mostly females (72/87) (82.8%). Forty-three overweight women and two men showed a Nickel allergy and started a low Nickel diet. After 6-months of dieting, 24 overweight allergic women could be traced and changes in BMI and waist circumference were calculated. MAIN OUTCOME MEASUREMENTS: Prevalence of Nickel allergy in overweight. RESULTS: Prevalence of Nickel allergy in overweight female was 59.7%, compared with a prevalence rate of 12.5% in the general population. A significant reduction in BMI was observed in 24 out of 43 overweight females with Nickel allergy after 24 weeks of a low Nickel diet. Relative to baseline, mean BMI decrease was 4.2 ± 0.5 (P < 0.001) and the mean decline in waist circumference was 11.7 ± 0.6 cm (P < 0.001). CONCLUSIONS: This pilot observational analysis showed a substantially higher prevalence of Nickel allergy among overweight females, especially those with metabolic syndrome and fatty liver disease. A normocaloric low Nickel diet was effective in reducing BMI in this population. Further research is strongly needed to confirm these preliminary findings.

A systematic review of hospital foodservice patient satisfaction studies.

The quality of hospital foodservice is one of the most relevant items of health care quality perceived by patients and by their families. Patient satisfaction is considered a way of measuring the quality of services provided. The purpose of this study was to retrieve and review the literature describing patient satisfaction with hospital foodservices. The systematic review was conducted on three electronic archives, PubMed, Excerpta Medica Database, and the Cumulative Index to Nursing and Allied Health Literature (1988 through 2012), to search for any articles reporting patient satisfaction with hospital foodservices. A total of 319 studies were identified. After removing duplicates, 149 abstracts were reviewed, particular attention being given to the presence of a description of the tool used. Thirty-one articles were selected and the full texts were reviewed. Half the studies (n=15) were performed in North America. Patient satisfaction scores were generally high, with some variation among hospitals and different modes of food delivery that was investigated through intervention studies. Qualitative studies were also reported (ethnographic-anthropologic methods with interviews and focus groups). Quantitative tools were represented by questionnaires, some of which relied on previous literature and only a few were validated with factorial analysis and/or Cronbach's α for internal consistency. Most analyses were conducted assuming a parametric distribution of results, an issue not primarily tested. More studies on the quality of hospital foodservice have been carried out in North America than in Europe. Also, a variety of tools, most of which have not been validated, have been used by the different investigating facilities.

Predictive validity of the Italian parental questionnaire for developmental evaluation at age 4 (QS4-G).

AIM: To examine whether the results at 4 years of age of the developmental questionnaire QS4-G can predict the outcome of cognitive, neuropsychological and academic abilities 4-6 years later. The QS4-G is a validated parental questionnaire designed for the screening and surveillance of the neuropsychological and behavioural developmental status of 4-year-olds (93 questions). METHODS: Longitudinal prospective study on a subsample of the QS4-G validation original sample was conducted. According to previous results, the sample was divided into two groups: 'at risk' and 'not at risk'. Sensitivity, specificity, accuracy and likelihood ratios were assessed and referred to outcomes. RESULTS: Thirty-five children were classified as 'not at risk' and 16 as 'at risk'. There were significant associations between past QS4-G score and cognitive, neuropsychological and academic abilities 4-6 years later. With the same cut-off identified at the first cross-sectional study, sensitivity and specificity for difficulties in cognitive development were 90% and 83% while in the neuropsychological abilities 62% and 90%, respectively. A lower predictive validity was found for difficulties in academic abilities (sensitivity 43%, specificity 86%). QS4-G specific area scores showed significant correlations with related academic tests at follow-up (rho range: 0.404-0.565, P < 0.005). CONCLUSIONS: QS4-G shows good predictive validity for cognitive development and neuropsychological abilities. The risk of false negatives for academic abilities can be reduced by analysing the specific area results of QS4-G, which show good correlations with related tests at follow-up.

Focal seizures versus epileptic spasms in children with focal cortical dysplasia and epilepsy onset in the first year.

PURPOSE: Focal cortical dysplasia (FCD) has been recognized as one of the most frequent causes of drug resistant epilepsy, especially in children. In infancy, onset of FCD-related epilepsy is substantially characterized by epileptic spasms (ES) or focal seizures. Which elements pertaining to the FCD are responsible for the onset of one type of seizure over the other is still unclear. Purpose of our study was to compare the characteristics of FCDs in terms of lateralization and site in patients with epileptic spasms versus patients with focal seizures. METHODS: We retrospectively reviewed data from 41 patients with FCD related epilepsy with onset during the first 14 months of life. Seizure semeiology and drug resistance were analyzed, as were age at onset and FCD site and lateralization. RESULTS: Twenty-one children had focal seizures, 11 had ES and nine had focal seizures followed by ES. Mean age at onset was respectively 8.2, 5.1 and 1.8 months. Drug resistance was present in respectively 38.5%, 34.6% and 26.9% of children. Among patients with only ES, 90.9% had an exclusively frontal FCD localization, versus 42.9% of patients with focal seizures and 11.1% of patients with focal seizures followed by ES. FCD lateralization was right sided respectively in 47.6%, 81.8% and 66.7% of patients. CONCLUSIONS: Frontal lobe localization of FCDs was closely associated with ES (p=0.001). Moreover we also found that patients with focal seizures followed by ES had a significantly earlier age at onset compared to patients with focal seizures only (p<0.001). The association between ES and right-sided FCD lateralization, even if numerically suggestive, did not reach statistical significance (p=0.16). There was no significant association between seizure type and drug resistance (p=0.08).

Are parents of children hospitalized with severe community-acquired pneumonia more satisfied with care when physicians allow them to share decisions on the antibiotic route?

CONTEXT AND OBJECTIVE: Despite convincing evidence that oral and injected amoxicillin have equal efficacy in children with severe community-acquired pneumonia (CAP), hospitalized children often receive injected antibiotics. To investigate whether shared decision-making (choosing the antibiotic route) influences parental satisfaction. DESIGN, SETTING AND PARTICIPANTS: In a one-year questionnaire-based study, we enrolled consecutive children hospitalized for CAP. At admission, all children's parents received a leaflet on CAP. Parents arriving during the daytime were assigned to a shared group and could choose the antibiotic route, those admitted at other times were assigned to an unshared group for whom physicians chose the antibiotic route. Shared group parents answered anonymous questionnaire investigating why they chose a specific route. Parents in both groups answered another anonymous questionnaire at discharge assessing perceived satisfaction with care. MAIN OUTCOME MEASURE: Parents' satisfaction with perceived medical information as assessed by data from a questionnaire. RESULTS: Of the 95 children enrolled, more children's parents were assigned to the unshared than the shared group (77 vs. 18). Of the 18 children's parents in the shared group, 14 chose the oral antibiotic route mainly to avoid painful injections. Doctors explanations were considered better in the shared than in the unshared group (P = 0.02). DISCUSSION AND CONCLUSIONS: The larger number of children's parents assigned to the unshared group reflects paediatricians' reluctance to offer shared-decision making. Well-informed parents prefer oral antibiotic therapy for children with severe CAP. Allowing parents choose the antibiotic route respects parents' wishes, reduces children's pain and improves satisfaction.

Exploring the relationship between family functioning and psycho-pathology in a sample in the pediatric age

The purpose of this study was to investigate differences in family functioning between families with clinical subjects in paediatric age and families taken from the Italian population. To this aim we used the Family Adaptability and Cohesion Evaluation Scale (FACES). Participants were children diagnosed with a psychopathology, recruited into the psychiatry department in a Paediatric Hospital of Rome. A total of 106 families participated in the study. The nonpathological sample is composed by 2,543 parents in different age periods of the life-cycle. Results showed significant differences in family functioning between pathological and non-pathological samples. Specifically, families from the pathological sample (particularly the ones who experienced eating disorders) were more frequently located in extreme or mid-range regions of Olson’s circumplex model (p < .001). These findings suggest some considerations that can be useful in therapeutic works with families in a clinical setting. Critical aspects and clinical applications are discussed (AU)

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MBL2 gene polymorphisms increase the risk of adverse neurological outcome in preterm infants: a preliminary prospective study.

BACKGROUND: As described in animal models, the lectin-complement pathway is central to the propagation of ischemia-reperfusion injuries in many tissues, including the brain. Similarly, it might affect the genesis of brain damage in preterm infants. MBL2 gene single-nucleotide polymorphisms (SNPs), regulating mannose-binding lectin (MBL) serum levels, could predict the risk of adverse neurological outcome in these infants. METHODS: To evaluate the association between SNPs of the MBL2 gene and long-term neurological outcomes in preterm infants, 75 infants (gestational age (GA) ≤ 32 wk) were observed in a prospective longitudinal study and assessed by clinical and instrumental exams at 12 and 24 mo of corrected age (CA). They were genotyped for the promoter polymorphism -221 and for the exon-1 variant alleles (at codons 52, 54, and 57) of the MBL2 gene. RESULTS: The MBL2 exon-1 OO genotype was more frequent in children with an adverse neurological outcome (5/35; 7%) than in controls (0/40; 0%), P = 0.045. The risk of intraventricular hemorrhage in carriers of the genotype OO was marked, without reaching statistical significance (odds ratio: 8.67; 95% confidence interval: 0.87-86.06; P = 0.07). CONCLUSION: Preterm infants who are carriers of MBL2 exon-1 OO genotype are exposed to an increased risk of adverse neurological outcomes.

Cognitive findings and behavior in children and adolescents with phenylketonuria.

OBJECTIVE: The primary aim of this study was to assess cognitive development, in particular that of executive functions (EFs), and behavioral findings for patients with early treated phenylketonuria (PKU). Furthermore, we evaluated the relationships of our findings with plasma levels of Phe and adherence to dietary prescriptions. METHODS: A cross-sectional design was adopted. Patients who had early treated PKU, who were older than 4 years, and who were regularly seen by a physician were enrolled in the study. Cognitive development was assessed with Wechsler Scales appropriate to the chronological age of subjects in the study. Executive functions were assessed using the Tower of London test, and behavioral findings were quantified with the Child Behavior Checklist. RESULTS: Thirty-five patients were enrolled (mean age 11.5 years, SD ± 6.2). The mean Full Scale intelligence quotient was in the normal range (93.4 ± 17.4), without significant difference between the verbal intelligence quotient (mean, 94.3 ± 16.1) and performance intelligence quotient (mean, 93.9 ± 18.0). The majority of patients showed a deficit within the EF domain of cognitive abilities (mean lower than 1.8 SD of the normal mean), 8 of them showing a score <2 SD lower than the normal mean. Internalizing problems were also observed in 12 patients (38.7%) and were higher in adherent patients and in patients with a lower intelligence quotient. CONCLUSION: After early diagnosis and treatment of PKU, residual problems can be found in EFs of patients not achieving satisfactory Phe levels, while scores of internalizing behaviors were higher in compliant patients.

The immunosuppressive effect of mesenchymal stromal cells on B lymphocytes is mediated by membrane vesicles.

The immunomodulatory properties of mesenchymal stromal cells are the subject of increasing interest and of widening clinical applications, but the reproducibility of their effects is controversial and the underlying mechanisms have not been fully clarified. We investigated the transfer of membrane vesicles, a recently recognized pathway of intercellular communication, as possible mediator of the interaction between mesenchymal stromal cells and B lymphocytes. Mesenchymal stromal cells exhibited a strong dose-dependent inhibition of B-cell proliferation and differentiation in a CpG-stimulated peripheral blood mononuclear cell coculture system. We observed that these effects could be fully reproduced by membrane vesicles isolated from mesenchymal stromal cell culture supernatants in a dose-dependent fashion. Next, we evaluated the localization of fluorescently labeled membrane vesicles within specific cell subtypes both by flow cytometry and by confocal microscopy analysis. Membrane vesicles were found to be associated with stimulated B lymphocytes, but not with other cell phenotypes (T lymphocytes, dendritic cells, natural killer cells), in peripheral blood mononuclear cell culture. These results suggest that membrane vesicles derived from mesenchymal stromal cells are the conveyors of the immunosuppressive effect on B lymphocytes. These particles should be further evaluated as immunosuppressive agents in place of the parent cells, with possible advantages in term of standardization, safety, and feasibility.