An epidemiological investigation of high-risk infants for Respiratory Syncytial Virus infections: a retrospective cohort study.

BACKGROUND: Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context. METHODS: This retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described. RESULTS: A total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use. CONCLUSIONS: The assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future.

Physical activity and health-related quality of life in multiple myeloma survivors: the PROFILES registry.

OBJECTIVES: To investigate whether physical activity (PA) is associated with health-related quality of life (HRQOL) outcomes in multiple myeloma (MM) survivors up to 11 years after diagnosis. METHODS: We used data from the Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship registry. We included 175 MM survivors diagnosed between 1999 and 2009 as registered by the Netherlands Cancer Registry. Sixty-four per cent (n=112/175) of patients who received the questionnaires, completed the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-MY20. Patients were classified into two groups: physically active and not physically active patients. Univariable and multivariable linear regression models were used to evaluate associations between PA and HRQOL outcomes. RESULTS: Physically active patients reported a statistically significant higher global health status/HRQOL (p=0.001), lower fatigue (p=0.002) and fewer side effects of treatments (p=0.001), than not physically active patients. PA was not associated with psychological symptoms (ie, anxiety and depressive symptoms) (anxiety: p=0.139; depressive symptoms: p=0.073). Exploratory analyses performed on the other scales of the EORTC QLQ-C30 indicated statistically significant better outcomes in several functional and symptom subscales for physically active patients. CONCLUSIONS: These findings might contribute to a better understanding of the relationship between PA and disease specific HRQOL aspects in MM survivors. Prospective studies are warranted to further elucidate on the beneficial effects of PA on HRQOL outcomes of MM survivors.

Involvement of Phosphodiesterase 2A Activity in the Pathophysiology of Fragile X Syndrome.

The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in translational regulation of mRNAs that play key roles in synaptic morphology and plasticity. The functional absence of FMRP causes the fragile X syndrome (FXS), the most common form of inherited intellectual disability and the most common monogenic cause of autism. No effective treatment is available for FXS. We recently identified the Phosphodiesterase 2A (Pde2a) mRNA as a prominent target of FMRP. PDE2A enzymatic activity is increased in the brain of Fmr1-KO mice, a recognized model of FXS, leading to decreased levels of cAMP and cGMP. Here, we pharmacologically inhibited PDE2A in Fmr1-KO mice and observed a rescue both of the maturity of dendritic spines and of the exaggerated hippocampal mGluR-dependent long-term depression. Remarkably, PDE2A blockade rescued the social and communicative deficits of both mouse and rat Fmr1-KO animals. Importantly, chronic inhibition of PDE2A in newborn Fmr1-KO mice followed by a washout interval, resulted in the rescue of the altered social behavior observed in adolescent mice. Altogether, these results reveal the key role of PDE2A in the physiopathology of FXS and suggest that its pharmacological inhibition represents a novel therapeutic approach for FXS.

17ß-Estradiol modulates huntingtin levels in rat tissues and in human neuroblastoma cell line.

17ß-Estradiol (E2) exerts neurotrophic and neuroprotective functions in the brain. Here, E2-induced increased levels of huntingtin (HTT), a protein involved in several crucial neuronal functions is reported. E2 physiological concentrations up-regulate HTT in hippocampus and striatum of rats as well as in human neuroblastoma cells. This effect requires both nuclear and extra-nuclear estrogen receptor (ER)α activities. Intriguingly, HTT silencing completely prevents E2 protective effects against oxidative stress injury. In conclusion, these data indicate for the first time that HTT is an E2-inducible protein involved in the first steps of E2-induced signaling pathways committed to neuronal protection against oxidative stress.