Management of Infants with Brief Resolved Unexplained Events (BRUE) and Apparent Life-Threatening Events (ALTE): A RAND/UCLA Appropriateness Approach.

Unexpected events of breath, tone, and skin color change in infants are a cause of considerable distress to the caregiver and there is still debate on their appropriate management. The aim of this study is to survey the trend in prevention, decision-making, and management of brief resolved unexplained events (BRUE)/apparent life-threatening events (ALTE) and to develop a shared protocol among hospitals and primary care pediatricians regarding hospital admission criteria, work-up and post-discharge monitoring of patients with BRUE/ALTE. For the study purpose, a panel of 54 experts was selected to achieve consensus using the RAND/UCLA appropriateness method. Twelve scenarios were developed: one addressed to primary prevention of ALTE and BRUE, and 11 focused on hospital management of BRUE and ALTE. For each scenario, participants were asked to rank each option from '1' (extremely inappropriate) to '9' (extremely appropriate). Results derived from panel meeting and discussion showed several points of agreement but also disagreement with different opinion emerged and the need of focused education on some areas. However, by combining previous recommendations with expert opinion, the application of the RAND/UCLA appropriateness permitted us to drive pediatricians to reasoned and informed decisions in term of evaluation, treatment and follow-up of infants with BRUE/ALTE, reducing inappropriate exams and hospitalisation and highlighting priorities for educational interventions.

Development of Psychological Problems Among Adolescents During School Closures Because of the COVID-19 Lockdown Phase in Italy: A Cross-Sectional Survey.

Background: Previous studies have shown that during COVID-19 pandemic, mainly due to the imposed lockdown, significant psychological problems had emerged in a significant part of the population, including older children and adolescents. School closure, leading to significant social isolation, was considered one of the most important reasons for pediatric mental health problems. However, how knowledge of COVID-19 related problems, modification of lifestyle and age, gender and severity of COVID-19 pandemic had influenced psychological problems of older children and adolescents has not been detailed. To evaluate these variables, a survey was carried out in Italy. Methods: This cross-sectional survey was carried out by means of an anonymous online questionnaire administered to 2,996 students of secondary and high schools living in Italian Regions with different COVID-19 epidemiology. Results: A total of 2,064 adolescent students (62.8% females; mean age, 15.4 ± 2.1 years), completed and returned the questionnaire. Most of enrolled students showed good knowledge of COVID-19-related problems. School closure was associated with significant modifications of lifestyle and the development of substantial psychological problems in all the study groups, including students living in Regions with lower COVID-19 incidence. However, in some cases, some differences, were evidenced. Sadness was significantly more frequent in females (84%) than males (68.2%; p < 0.001) and in the 14-19-year-old age group than the 11-13-year-old age group (79.2% vs. 70.2%; p < 0.001). Missing the school community was a significantly more common cause of sadness in girls (26.5% vs. 16.8%; p < 0.001), in southern Italy (26.45% vs. 20.2%; p < 0.01) and in the 14-19-year-old group (24.2% vs. 14.7%; p < 0.001). The multivariate regression analysis showed that male gender was a protective factor against negative feelings (p < 0.01), leading to a decrease of 0.63 points in the total negative feelings index. Having a family member or an acquaintance with COVID-19 increased the negative feelings index by 0.1 points (p < 0.05). Conclusions: This study shows that school closures because of the COVID-19 pandemic outbreak was associated with significant lifestyle changes in all the students, regardless of age and gender. Despite some differences in some subgroups, the study confirms that school closure can cause relevant mental health problems in older children and adolescents. This must be considered as a reason for the maintenance of all school activities, although in full compliance with the measures to contain the spread of the pandemic.

Reasons and pathways of first-time consultations at child and adolescent mental health services in Italy: an observational study.

BACKGROUND: An increasing number of young people have made contact with the Child and Adolescent Mental Health Services (CAMHS). However, only a small proportion of the population with emotional problems, actually seek specialized care. Research concerning the help-seeking process and pathways to care of a clinical sample could help to develop effective health policies to facilitate access to specialized care. AIM: To analyze the access pattern for CAMHS, reasons of contact and care pathways of a consecutive sample of first-time patients. Our aim was to analyze the association between source of referral, socio-demographic and clinical variables. METHODS: Standardized assessment instruments and information concerning access patterns and care pathways were collected from 399 patients at first-time contact with CAMHS in a Northern Italian Region. RESULTS: Most patients were referred to CAMHS by school teachers (36 %) or health professionals (32 %), while only 17 % of the parents sought help by themselves. School issues (50 %) and emotional problems (17 %) were the most frequent reasons for contact. The proportion of first-time contacts with no diagnosis of mental disorder at their first consultation did not differ by source of referral. Parents of children who did not receive a clinical diagnosis of mental disorders described them as "psychosocially impaired" and their condition as "clinically severe" likewise parents of patients who received a psychiatric diagnosis. Patients with externalizing problems were more frequently referred by the parents themselves, while youth with internalizing problems were more often referred through health professionals. Families with non-traditional structures (adoptive, foster care, mono-parental) were more likely to consult CAMHS directly, while immigrant youth were more often referred by teachers. CONCLUSION: Socio-demographic and clinical characteristics can affect pathways to care. To improve early access to care for children and adolescents with ongoing mental disorders, a plan for proper action addressed to teachers and health professionals may well be important. This would improve their ability to recognize emotional and behavioral problems and use proper referral pathways, while informative intervention addressed to non-Italian families should inform them about the functioning and the mission of CAMHS.

Design and synthesis of novel sulfonamide-containing bradykinin hB(2) receptor antagonists. Synthesis and structure-relationships of α,α-tetrahydropyranylglycine.

A series of α,α-cycloalkylglycine sulfonamide compounds of general formula 1 has previously been identified by our group as selective human B(2)(hB(2)) receptor antagonists. Here we report the in vitro and in vivo BK antagonist activity of a further evolution of the series, consisting in compounds of the general formula 2, containing either an alkyl piperazine or a 4-alkyl piperidine ring bearing various positively charged groups (R'). These studies unexpectedly revealed quite a flat nanomolar/subnanomolar SAR for the binding affinity, while differences were seen in the in vitro functional activities. We propose that variations in the residence time may explain these results.

Alkyl piperidine and piperazine hydroxamic acids as HDAC inhibitors.

We report here the strategy used in our research group to find a new class of histone deacetylase (HDAC) inhibitors. A series of N-substituted 4-alkylpiperazine and 4-alkylpiperidine hydroxamic acids, corresponding to the basic structure of HDAC inhibitors (zinc binding moiety-linker-capping group) has been designed, prepared, and tested for HDAC inhibition. Linker length and aromatic capping group connection were systematically varied to find the optimal geometric parameters. A new series of submicromolar inhibitors was thus identified, which showed antiproliferative activity on HCT-116 colon carcinoma cells.

Fragment-based approach to drug lead discovery: overview and advances in various techniques.

In the last 20 years the advent of new technologies, such as high-throughput screening (HTS) and combinatorial chemistry, has produced new tools for the discovery of biologically active molecules. In the past decade, fragment-based drug discovery has emerged as a more rational and focused approach that concentrates on the quality, rather than the quantity, of hits and leads. The principles behind this strategy are different from those that represented the basis of conventional HTS. The starting point of this approach is always a small chemical entity (typically MW 150-200), a fragment, with low affinity for the selected target. Fragments should satisfy key features such as diversity, reduced structural complexity, aqueous solubility and availability. Because of their small size, they occupy a smaller region of chemical space if compared with classical HTS compounds; hence, fragment libraries provide a good diversity with a relatively low number of compounds. Classical biochemical assays are often not suitable to detect the low binding affinities involved, so some well known biophysical techniques, such as nuclear magnetic resonance and x-ray, have been opportunely modified in order to render them able to perform the task. When selecting fragments suitable for subsequent optimization, a useful parameter has been introduced, the ligand efficiency, which is defined as the free energy of binding divided by the non-hydrogen atom count. Once selected, a fragment must undergo a heavy elaboration to improve binding affinity, at the same time acquiring drug-like properties. There are two main ways to go on at this point. The most common one is the so-called 'fragment evolution', consisting of a stepwise and systematic addition of chemical functionalities to the starting fragment core, together with a continuous feedback for pharmacological and physicochemical properties. The second one, less common but with great potential, is 'fragment linking': when two or more fragment hits are found to bind in adjacent regions of the target protein, they can be linked through appropriate spacers to rapidly produce a single molecule with much higher binding affinity. Two representative case histories are described: Abbott's ABT 518, an MMP (matrix metalloproteinase) inhibitor, and Eli-Lilly's LY-517717, an inhibitor of factor Xa serine protease. In addition, a list of molecules claimed to be derived from fragment approach and currently undergoing clinical trials is presented.

Giancarlo Rastelli: the scientist, the man.

Doctor Giancarlo Rastelli graduated from the University of Parma, Italy (cum laude) in July 1957, and in 1961, moved to the Mayo Clinic, Rochester, New York. The name of Dr. Rastelli is recognized worldwide for the classification of the atrioventricular (AV) canal and for the procedure relating to the anatomical repair of transposition of the great arteries (TGA) with ventricular septal defect (VSD) and pulmonary stenosis (PS). The most extraordinary aspect of his successful research work was that it was mostly done during the five years when Dr. Rastelli was fighting against his fatal illness. He died at the age of 36 years. Dr. Rastelli's fame as a scientist now belongs to the history of medicine.

Descending thoracic aorta to left pulmonary artery fistula after stent implantation for acquired left pulmonary artery stenosis.

This is a case report of a Fontan patient with previous Potts anastomosis who underwent stent implantation for left pulmonary artery stenosis. At follow-up the patient developed a fistula between the descending thoracic aorta and the left pulmonary artery at the site of the stent. This represents a late complication of stent placement.