Impulsive, Disinhibited Behavior-Dining in a Restaurant.

Dining in a restaurant with a loved one who has dementia can be an ordeal, especially if the expectations of the caregiver do not match those of the patient and the restaurant environment is not suitable for patients with dementia. The size of the dining area, lighting, background music or noise, décor of the room, number of customers, variety of the items on the menu, number of plates and cutlery on the table, in addition to flowers, candles, and other decorations on the table are all potent distractors. There are so many stimuli; the patient can be overwhelmed with information overload and not able to focus on the main purpose of the event: have dinner and especially enjoy the other person's company. In this case scenario, we present a 62-year-old man diagnosed with behavioral variant frontotemporal dementia (bvFTD). His daughter "invited" him to have dinner with her at a very fancy restaurant to celebrate her promotion at work. Unfortunately, whereas the evening started very well, it had a catastrophic ending. We discuss what went wrong in the patient/daughter interaction and how the catastrophic ending could have been avoided or averted.

Fisetin provides antidepressant effects by activating the tropomyosin receptor kinase B signal pathway in mice.

Depression has been associated with a low-grade chronic inflammatory state, suggesting a potential therapeutic role for anti-inflammatory agents. Fisetin is a naturally occurring flavonoid in strawberries that has anti-inflammatory activities, but whether fisetin has antidepressant effects is unknown. In this study, we exposed mice to spatial restraint for 2 weeks with or without treatment with fisetin. Immobility time in the forced swimming and tail suspension test after this restraint increased in the untreated group, but this increase did not occur in the fisetin group. We administered fisetin to Abelson helper integration site-1 (Ahi1) knockout mice, which have depressive phenotypes. We found that fisetin attenuated the depressive phenotype of these Ahi1 knockout mice. We further investigated the potential mechanism of fisetin's antidepressant effects. Because TrkB is a critical signaling pathway in the mechanisms of depression, we examined whether phosphorylated TrkB was involved in the antidepressant effects of fisetin. We found that fisetin increased phosphorylated TrkB level without altering total TrkB; this increase was attenuated by K252a, a specific TrkB inhibitor. Taken together, our results demonstrated that fisetin may have therapeutic potential for treating depression and that this antidepressant effect may be mediated by the activation of the TrkB signaling pathway.

Exogenous Adipokine Peptide Resistin Protects Against Focal Cerebral Ischemia/Reperfusion Injury in Mice.

Previous studies have demonstrated that plasma resistin levels were increased in patients with acute ischemic stroke. However, the role of resistin after ischemic brain injury is still unclear. In this study, we investigated the protective effects of resistin on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that resistin (i.c.v.) significantly reduced infarct volume and improved neurological deficits after 45 min of ischemia and 24 h of reperfusion. Furthermore, our data demonstrate that intraperitoneal administration of resistin (10 µg/kg body weight) also had protective effects on infarct volume, indicating the crossing of resistin through the impaired BBB after ischemia injury. Resistin treatment reduced cleaved protein level of Poly(ADP-ribose)polymerase-1 (PARP-1), a marker of cellular apoptosis, showing the anti-apoptotic activity of resistin. Resistin increased the level of phosphorylated Akt after ischemic brain injury. The neuroprotective effect of resistin was partially reversed by a PI3K inhibitor wortmannin, demonstrating that the PI3K/Akt signal pathway is involved in the anti-apoptotic mechanisms of resistin. Finally, we found that resistin treatment improved neurological function recovery at 14 days after treatment, including balance ability and muscle strength. Given these findings, resistin may have therapeutic potential for the treatment of stroke.

ß-arrestin 2 attenuates cardiac dysfunction in polymicrobial sepsis through gp130 and p38.

Sepsis is an exaggerated systemic inflammatory response to persistent bacteria infection with high morbidity and mortality rate clinically. ß-arrestin 2 modulates cell survival and cell death in different systems. However, the effect of ß-arrestin 2 on sepsis-induced cardiac dysfunction is not yet known. Here, we show that ß-arrestin 2 overexpression significantly enhances animal survival following cecal ligation and puncture (CLP)-induced sepsis. Importantly, overexpression of ß-arrestin 2 in mice prevents CLP-induced cardiac dysfunction. Also, ß-arrestin 2 overexpression dramatically attenuates CLP-induced myocardial gp130 and p38 mitogen-activated protein kinase (MAPK) phosphorylation levels following CLP. Therefore, ß-arrestin 2 prevents CLP-induced cardiac dysfunction through gp130 and p38. These results suggest that modulation of ß-arrestin 2 might provide a novel therapeutic approach to prevent cardiac dysfunction in patients with sepsis.