Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer's disease

Amyloid beta (Aβ) is implicated in Alzheimer's disease (AD) as an integral component of both neural toxicity and plaque formation. Brains of the longest-lived rodents, naked mole-rats (NMRs) approximately 32 years of age, had levels of Aβ similar to those of the 3xTg-AD mouse model of AD. Interestingly, there was no evidence of extracellular plaques, nor was there an age-related increase in Aβ levels in the individuals examined (2–20+ years). The NMR Aβ peptide showed greater homology to the human sequence than to the mouse sequence, differing by only 1 amino acid from the former. This subtle difference led to interspecies differences in aggregation propensity but not neurotoxicity; NMR Aβ was less prone to aggregation than human Aβ. Nevertheless, both NMR and human Aβ were equally toxic to mouse hippocampal neurons, suggesting that Aβ neurotoxicity and aggregation properties were not coupled. Understanding how NMRs acquire and tolerate high levels of Aβ with no plaque formation could provide useful insights into AD, and may elucidate protective mechanisms that delay AD progression.     

Impact of COVID-19 lockdown on sleep quality in university students and administration staff

Journal of Neurology - In Italy, lockdown due to COVID-19 health emergency started on March 10 and partially ended on May 3rd, 2020. There was a significant increase of psychological distress and...     

The effect of desire thinking on facilitating beliefs in alcohol use disorder: An experimental investigation

Permissive beliefs relate to the acceptability of engaging in alcohol use in spite of obvious potential negative consequences. They are considered the most proximal and precipitating cognitive factor in the decision to use alcohol and/or the activation of strategies to obtain it. Recent research suggested that ‘desire thinking’ may be involved in the escalation of craving and addictive behaviours and can play a role in strengthening permissive beliefs. The current study tested whether the induction of desire thinking would have a stronger effect on rate of conviction in permissive beliefs compared to a control cognitive response in the form of neutral thinking and whether this effect would be specific for patients with alcohol use disorder (AUD). Thirty AUD patients and 30 social drinkers (SD) were randomly allocated to two thinking manipulation tasks (desire thinking and neutral thinking). Current permissive beliefs were measured before and after manipulation and after a resting phase. Findings showed that desire thinking increased the level of current permissive beliefs after manipulation relative to the neutral thinking condition for the AUD group but not for the SD group. This effect was not purely dependent on the concurrent level of perceived craving. This study supports a causal relationship between the induction of desire thinking and rate of conviction in permissive beliefs and highlights the relevance of targeting desire thinking in the treatment for AUD patients.     

Lengthier cryoablation and a bonus cryoapplication is associated with improved efficacy for cryothermal catheter ablation of supraventricular tachycardias in children

Introduction Cryoablation is an effective treatment for children with supraventricular tachycardias (SVT). The present study documents the effect of two different cryoablation protocols on acute and chronic success rates. Methods and results Fifty-three consecutive patients (age range, 5–20 years) were treated; patients 1 to 17 were treated by a standard ablation protocol and patients 18 to 53 were treated by a modified ablation protocol that required lengthier cryoablations plus delivery of a bonus cryoapplication to consolidate the acutely successful irreversible lesion created at intervention. Electrophysiological study (EPS) was performed with diagnostic catheters and cryoablations were performed with a 7FR 4 mm tip catheter (CryoCath Technologies). Acute endpoints for non-inducibility of atrioventricular nodal re-entrant tachycardia (AVNRT) by programmed atrial stimulation at baseline or during isoproterenol performed 30 min post procedure, as well as non-inducibility and conduction block over the accessory pathway (AP). The chronic endpoint was arrhythmia recurrence post intervention. No permanent cryo-related complications or adverse outcomes were reported. Acute success rates for patients 1 to 17 and 18 to 53 were 88 and 100%, respectively. The cumulative percentage of patients without arrhythmia recurrence at 12 month follow-up was significantly different at 73 and 90%, respectively. Conclusions Lengthier cryoablation delivery, approximating 7 min per cryoablation, increases the acute success rate at intervention. Moreover, these lengthier cryoablation deliveries plus a bonus cryoapplication to consolidate the acutely successful irreversible lesion created at intervention may also significantly improve the chronic success rate, while also maintaining an excellent safety profile for cryoablation treatment of children with SVT such as AVNRT and AP located near the AV junction.     

Common carotid intima-media thickness in growth hormone (GH)-deficient adolescents: a prospective study after GH withdrawal and restarting GH replacement

We prospectively investigated the risk of early atherosclerosis, by classical cardiovascular risk factors and intima-media thickness (IMT) at the common carotid arteries, in 23 adolescents diagnosed as GH deficient (GHD) during childhood and in 23 healthy sex-, age-, and BMI-matched controls. Measurements were performed in all subjects before stopping GH replacement. Because the diagnosis of GHD had been confirmed in 15 of the 23 adolescents, the protocol changed according to the diagnosis as follows: measurements were repeated after 6 months of GH withdrawal and 6 months of GH reinstitution in the 15 with GHD, and after 6 and 12 months of GH withdrawal, measurements were also taken in the eight non-GHD subjects. Serum IGF-I levels were in the normal range for age in all patients before GH withdrawal. When compared with controls, before GH withdrawal, GHD adolescents had reduced high-density lipoprotein cholesterol levels and increased total/high-density lipoprotein cholesterol ratio, fibrinogen, low-density lipoprotein cholesterol, and glucose levels; non-GHD adolescents had increased glucose, insulin, and homeostasis model assessment score. IMT at the common carotid arteries was similar in GHD and controls (0.52 +/- 0.03 vs. 0.55 +/- 0.06 mm; P = 0.23) and was higher in non-GHD than in controls (0.62 +/- 0.03 vs. 0.54 +/- 0.06 mm; P = 0.01). In GHD adolescents, 6 months of GH treatment withdrawal and 6 months of GH treatment reinstitution modified IGF-I levels, lipid profile, and insulin resistance but not IMT or systolic and diastolic peak velocities at the common carotid arteries. In non-GHD subjects, 12 months of GH treatment withdrawal significantly decreased IGF-I levels, IMT (to 0.54 +/- 0.06 mm; P < 0.001 vs. baseline), systolic and diastolic peak velocities, and improved insulin resistance. In conclusion, the discontinuation of GH in confirmed GHD adolescents is not followed by significant alterations of the common carotid arteries, despite the profound negative alterations of the lipid profile. In adolescents who were not confirmed to have GHD, IMT was increased while on GH therapy and normalized when they were taken off of GH.