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  • Flores Mikkelsen posted an update 3 months, 2 weeks ago

    05 vs. GKCa and GKTe and p  less then  .01 vs. GKCaTe). PN density and IENFD were significantly correlated with Vβ (r = 0.55, p  less then  .01 and r = 0.54, p  less then  .01, respectively). IENFD was identified as a surrogate marker for the prediction of Vβ (cutoff value, 16.39). CONCLUSIONS The combination therapy of DPP4i and SGLT2i improved Vβ accompanied by PNs density and IENFD. IENFD was proportionally correlated with Vβ. Therefore, the prevention of DPN development may be concurrently beneficial for the preservation of Vβ in nonobese T2DM. Transcutaneous vagus nerve stimulation (tVNS) has been shown to promote inferences of emotional states based on eye-related information provided by facial expressions of emotions. Eye gaze direction can influence the allocation of attentional sources when processing facial emotional stimuli. Here we sought for further evidence indicating whether tVNS effects would be specific to emotional expressions or to gaze – both socially relevant stimuli – and whether they reflect the enhancement of attention. In two separate sessions receiving either active or sham tVNS, forty-three healthy young volunteers completed a Rapid Serial Visual Presentation task in which participants identified the gender of a target face (T1) with direct (salient social cue) or averted gaze (subtler social cue) with different emotional expressions or a neutral expression, and then judged the orientation of a landscape (T2) that appeared at different temporal lags after T1. Active tVNS, compared to sham stimulation, enhanced conditional T2 accuracy for both neutral and emotional faces and independently of the temporal lag, but only when gaze was directed at the participant. This suggests that tVNS modulates attention to a direct gaze (salient social cue) irrespective of the expressed emotion. We interpret that the effects of tVNS seem to reflect enhanced perception of gaze direction, which in turn attracts attention, making the observer more sensitive and increasing the impact of the socially relevant facial cue. We conclude that tVNS is a promising technique for enhancing social information processing in healthy humans. Since the 1980s, we have witnessed the rapid development of genetically modified mouse models of human diseases. A large number of transgenic and knockout mice have been utilized in basic and applied research, including models of neurodegenerative and neuropsychiatric disorders. To assess the biological function of mutated genes, modern techniques are critical to detect changes in behavioral phenotypes. We review the IntelliCage, a high-throughput system that is used for behavioral screening and detailed analyses of complex behaviors in mice. The IntelliCage was introduced almost two decades ago and has been used in over 150 studies to assess both spontaneous and cognitive behaviors. We present a critical analysis of experimental data that have been generated using this device. Memory transience is essential to gain cognitive flexibility. Recently, hippocampal neurogenesis is emerging as one of the mechanisms involved in the balance between persistence and forgetting. Social recognition memory (SRM) has its duration prolonged by neurogenesis. However, it is still to be determined whether boosting neurogenesis in distinct phases of SRM may favor forgetting over persistence. In the present study, we used enriched environment (EE) and memantine (MEM) to increase neurogenesis. SRM was ubiquitously prolonged by both, while EE after the memory acquisition did not favor forgetting. Interestingly, the proportion of newborn neurons with mature morphology in the dorsal hippocampus was higher in animals where persistence prevailed. Tat-beclin 1 Finally, one of the main factors for dendritic growth is the formation of cytoskeleton. We found that Latrunculin A, an inhibitor of actin polymerization, blunted the promnesic effect of EE. Altogether, our results indicate that the mechanisms triggered by EE to improve SRM are not limited to increasing the number of newborn neurons. Statins are effective inhibitors of cholesterol biosynthesis, largely used for prevention of cardiovascular diseases induced by hypercholesterolemia. However, their use in different clinical trials clearly indicate that the general benefits observed with statins are also related to effects beyond the cholesterol lowering. Increasing evidences suggest that some of these cholesterol-independent or “pleiotropic” effects of statins involve the interaction and modification of the membrane bilayers. In this manuscript, using a combined approach based on biophysical (electrochemical impedance spectroscopy on tethered bilayer lipid membranes) and biological methods (hemolysis on erythrocytes and immunocytochemistry on cancer cells), we demonstrate that lipophilic, but not hydrophilic statins are capable of reducing the damage caused by cholesterol-dependent cytolysins. This protection correlates with statins lipophilicity and capacity to interact with the lipid bilayer. Our data suggests lipophilic statins associate with membranes and interfere with the ability of cholesterol dependent cytolysins, to bind to membrane cholesterol. Evaluation of the capacity of statins to modulate cell membrane properties is essential for developing a correct therapeutic approach for cardiovascular diseases as well as for understanding the potential of this class of drugs as adjuvants for drug delivery. BACKGROUND & AIMS Chronic hepatitis B virus (HBV) infection is characterized by the presence of defective viral envelope proteins (hepatitis B surface antigen, HBsAg) and the duration of infection-most patients acquire the infection at birth or during the first years of life. We investigated the effects of these factors on patients’ lymphocyte and HBV-specific T-cell populations. METHODS We collected blood samples and clinical data from 243 patients with HBV infection (3-75 years old) in the United Kingdom and China. We measured levels of HBV DNA, HBsAg, HBeAg, and alanine aminotransferase; analyzed HBV genotypes; and isolated peripheral blood mononuclear cells (PBMC). In PBMC from 48 patients with varying levels of serum HBsAg, we measured 40 markers on nature killer (NK) and T cells by mass cytometry. PBMC from 189 patients with chronic infection and 38 patients with resolved infections were incubated with HBV peptide libraries, and HBV-specific T cells were identified by interferon gamma ELISpot assays or flow cytometry.

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