Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome

Tuberous sclerosis complex (TSC) and Peutz-Jeghers syndrome (PJS) are dominantly inherited benign tumor syndromes that share striking histopathological similarities. Here we show that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the gene mutated in TSC. Like TSC2, LKB1 inhibits the phosphorylation of the key translational regulators S6K and 4EBP1. Furthermore, we show that LKB1 activates TSC2 through the AMP-dependent protein kinase (AMPK), indicating that LKB1 plays a role in cell growth regulation in response to cellular energy levels. Our results suggest that PJS and other benign tumor syndromes could be caused by dysregulation of the TSC2/mTOR pathway.     

Pilot study of a visitor volunteer programme for community elderly people receiving home health care

There is a need to evaluate community support programmes for elderly people. In this randomized control trial (RCT), we determined the effectiveness of 'friendly visitors' in a volunteer programme of a visiting nurses organization in Southern Ontario, Canada. The Volunteer Friendly Visitor Programme was developed to support elderly people receiving homemaking and nursing care in the community. Volunteers are screened, trained, interviewed and matched to homebound elderly clients for general interest, visit expectations and personality. Volunteers spend three to four hours on average per week with clients socializing in mutually agreed-upon ways. The nursing staff identified clients who were lonely for this additional support. These newly-referred clients were randomly allocated to receive a friendly visitor or not for six weeks. Those receiving the volunteer visitor improved in life satisfaction and two social support measures: worth and social integration. Thus, the addition of volunteer visitors to planned homemaking and nursing care made a difference for elderly in the community.     

Quantitative assessment of choriocapillaris flow deficits in eyes with macular neovascularization

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate choriocapillaris flow deficits (CC FD) in a group of eyes with Type 3 macular neovascularization (MNV) versus a...     

Multifocal nivolumab immune-related adverse effects during asymptomatic SARS-CoV-2 infection: causality or casuality?

Neurological Sciences -     

MDMA induces EPSP-Spike potentiation in rat ventral hippocampus in vitro via serotonin and noradrenaline release and coactivation of 5-HT4 and beta1 receptors.

It is well documented that N-methyl-3,4-methylenedioxyamphetamine (MDMA, ecstasy) releases brain serotonin (5-HT; 5-hydroxytryptamine), noradrenaline (NE; norepinephrine), and dopamine, but the consequent effect on brain functioning remains elusive. In this study, we characterized the effects of MDMA on electrically evoked responses in the ventral CA1 region of a rat hippocampal slice preparation. Superfusion with MDMA (10 microM, 30 min) increased the population spike amplitude (PSA) by 48.9+/-31.2% and decreased population spike latency (PSL) by 103+/-139 mus (both: mean+/-SD, n=123; p<0.0001, Wilcoxon test), without affecting field excitatory postsynaptic potential (fEPSP). This effect persisted for at least 1 h after MDMA washout; we have called this EPSP-spike potentiation (ESP) by MDMA, ESP MDMA. Antagonism of GABAergic transmission did not prevent ESP MDMA, suggesting that an increase in excitability of pyramidal cells underlies this MDMA action. Block of serotonin transporter (SERT) with citalopram or 5-HT depletion with (+/-)-p-chlorophenylalanine pretreatment partially inhibited the ESP MDMA. Block of both SERT and NE transporter prevented ESP MDMA, indicating its dependence on release of both 5-HT and NE. ESP MDMA is produced by simultaneous activation of 5-HT4 and beta1 receptors, with a predominant role of 5-HT4 receptors. Block of both 5-HT4 and beta1 receptors revealed an inhibitory component of the MDMA action mediated by 5-HT1A receptor. The concentration range of MDMA which produced ESP MDMA (1-30 microM) corresponds to that commonly reached in human plasma following the ingestion of psychoactive MDMA doses, suggesting that release of both 5-HT and NE, and consequent ESP MDMA may underlie some of the psychoactive effects of MDMA in humans.