Haploinsufficiency as a Foreground Pathomechanism of Poirer-Bienvenu Syndrome and Novel Insights Underlying the Phenotypic Continuum of CSNK2B-Associated Disorders.

CSNK2B encodes for the regulatory subunit of the casein kinase II, a serine/threonine kinase that is highly expressed in the brain and implicated in development, neuritogenesis, synaptic transmission and plasticity. De novo variants in this gene have been identified as the cause of the Poirier-Bienvenu Neurodevelopmental Syndrome (POBINDS) characterized by seizures and variably impaired intellectual development. More than sixty mutations have been described so far. However, data clarifying their functional impact and the possible pathomechanism are still scarce. Recently, a subset of CSNK2B missense variants affecting the Asp32 in the KEN box-like domain were proposed as the cause of a new intellectual disability-craniodigital syndrome (IDCS). In this study, we combined predictive functional and structural analysis and in vitro experiments to investigate the effect of two CSNK2B mutations, p.Leu39Arg and p.Met132LeufsTer110, identified by WES in two children with POBINDS. Our data prove that loss of the CK2beta protein, due to the instability of mutant CSNK2B mRNA and protein, resulting in a reduced amount of CK2 complex and affecting its kinase activity, may underlie the POBINDS phenotype. In addition, the deep reverse phenotyping of the patient carrying p.Leu39Arg, with an analysis of the available literature for individuals with either POBINDS or IDCS and a mutation in the KEN box-like motif, might suggest the existence of a continuous spectrum of CSNK2B-associated phenotypes rather than a sharp distinction between them.

'Too many BeEPs in our teens!' Behavioral and emotional problems in a large group of Italian adolescents.

BACKGROUND: One in six adolescents suffers from mental health problems. Despite the presence of general information on Italian adolescents' mental health, researches conducted with standardized assessment tools are scarce in the literature. We evaluated the prevalence of self-reported behavioral and emotional problems in a group of Italian adolescents and examined their relation to socio-demographical variables. METHODS: This population-based sampling survey was conducted on high school students aged 14-18 from urban areas of Rome and Latina. Participants completed Youth Self-Report (YSR) and a socio-demographic schedule to collect information on age, gender, type of school attended, socio-economic status, urbanicity. RESULTS: Final sample consisted of 1400 adolescents (38.61% male, mean age 16 years, s.d. 1.42). Prevalence of Internalizing Problems, Externalizing Problems and Total Problems was 29.55%, 18.34% and 24.13%. In our multivariable model, Internalizing Symptoms were not explained by sociodemographic variables while Externalizing Symptoms were explained by Male Gender [OR = 1.53 (1.14-2.06)], older age [OR = 2.06 (1.52-2.79)] and attending a Technical and Professional Institute [OR = 2.15 (1.53-3.02)], with an adjusted R2 = 4.32%. Total Problems were explained by School Type [Technical and Professional Institutes and Art and Humanities v. Grammar and Science School; OR respectively 1.93 (1.40-2.67) and 1.64 (1.08-2.47)], adjusted R2 = 1.94. CONCLUSIONS: The study provides, for the first time, evidence of a great prevalence of self-reported behavioral and emotional problems in a large sample of Italian adolescents, highlighting the role of different socio-demographic variables as risk factors for externalizing behaviors. Our results emphasize the urgent need for implementing prevention programs on mental health in adolescence.

Frequent Use of Emergency Departments by the Elderly Population When Continuing Care Is Not Well Established.

INTRODUCTION: The elderly, who suffer from multiple chronic diseases, represent a substantial proportion of Emergency Department (ED) frequent users, thus contributing to ED overcrowding, although they could benefit from other health care facilities, if those were available. The aim of this study was to evaluate and characterize hospital visits of older patients (age 65 or greater) to the ED of a university teaching hospital in Rome from the 1st of January to the 31st of December 2014, in order to identify clinical and social characteristics potentially associated with "elderly frequent users". MATERIAL AND METHODS: A retrospective study was performed during the calendar year 2014 (1st January 2014 - 31st December 2014) analyzing all ED admissions to the University Hospital of Rome Tor Vergata. Variables collected included age, triage code, arrival data, discharge diagnosis, and visit outcome. We performed a risk analysis using univariate binary logistic regression models. RESULTS: A total number of 38,016 patients accessed the ED, generating 46,820 accesses during the study period, with an average of 1.23 accesses for patient. The elderly population represented a quarter of the total ED population and had an increased risk of frequent use (OR 1.5: CI 1.4-1.7) and hospitalization (OR 3.8: CI 3.7-4). Moreover, they showed a greater diagnostic complexity, as demonstrated by the higher incidence of yellow and red priority codes compared to other ED populations (OR 3.1: CI 2.9-3.2). DISCUSSION: Older patients presented clinical and social characteristics related to the definition of "elderly frail frequent users". The fact that a larger number of hospitalizations occurred in such patients is indirect evidence of frailty in this specific population, suggesting that hospital admissions may be an inappropriate response to frailty, especially when continued care is not established. CONCLUSION: Enhancement of continuity of care, establishment of a tracking system for those who are at greater risk of visiting the ED and evaluating fragile individuals should be the highest priority in addressing ED frequent usage by the elderly.