SHANK3 controls maturation of social reward circuits in the VTA.

Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3, leads to a highly penetrant form of autism spectrum disorder. How SHANK3 insufficiency affects specific neural circuits and how this is related to specific symptoms remains elusive. Here we used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice. We identified dopamine (DA) and GABA cell-type-specific changes in excitatory synapse transmission that converge to reduce DA neuron activity and generate behavioral deficits, including impaired social preference. Administration of a positive allosteric modulator of the type 1 metabotropic glutamate receptors mGluR1 during the first postnatal week restored DA neuron excitatory synapse transmission and partially rescued the social preference defects, while optogenetic DA neuron stimulation was sufficient to enhance social preference. Collectively, these data reveal the contribution of impaired ventral tegmental area function to social behaviors and identify mGluR1 modulation during postnatal development as a potential treatment strategy

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Relationship between carotid intima-media thickness and non valvular atrial fibrillation type

Objective: Carotid intima-media thickness (cIMT) is a surrogate marker of subclinical atherosclerosis and it is able to predict both coronary and cerebral vascular events. No data exist on the association between cIMT and non valvular atrial fibrillation (NVAF) type. We conduct this study with the aim to analyze the association between abnormal cIMT and NVAF type. Methods: A cross-sectional study of the "Atrial fibrillation Registry for Ankle-brachial index Prevalence Assessment-Collaborative Italian Study (ARAPACIS)" has been performed. Among 2027 patients enrolled in the ARAPACIS, 673 patients, who underwent carotid ultrasound examination to assess cIMT, were included in the study. Results: Among the entire population, 478 patients (71%) had cIMT>0.90mm. Patients with an abnormal cIMT (>0.90mm) were significantly older and more likely hypertensive, diabetic and with a previous history of stroke than those with normal cIMT (≤0.90mm). These patients had more permanent/persistent NVAF and CHA2DS2-VASc score ≥ 2 (p<0.0001) compared to those with cIMT <0.90mm. Excluding all patients affected by previous cardiovascular disease, logistic regression analysis showed that independent predictors of abnormal cIMT were: age class 65-74 yrs. (p<0.001), age class ≥75 yrs. (p<0.001), arterial hypertension (p<0.001), calcium-channel blockers use (p<0.001) and persistent/permanent NVAF (p=0.001). Conclusion: Our findings show a high prevalence of abnormal cIMT in NVAF patients, reinforcing the concept that NVAF and systemic atherosclerosis are closely associated. Abnormal cIMT was particularly evident in persistent/permanent NVAF suggesting a more elevated atherosclerotic burden in patients with long-standing NVAF