Recent studies indicated that hyperactivity of the hypothalamopituitary-adrenal system is a considerable risk factor for the precipitation of affective disorders, most notably of major depression. The mechanism by which this hyperactivity eventually leads to clinical symptoms of depression is unknown. In the present animal study, we tested one possible mechanism, i.e., that long-term exposure to high corticosterone levels alters functional responses to serotonin in the hippocampus, an important area in the etiology of depression. Rats were injected daily for 3 weeks with a high dose of corticosterone; electrophysiological responses to serotonin were recorded intracellularly from CA1 pyramidal neurons in vitro. We observed that daily injections with corticosterone gradually attenuate the membrane hyperpolarization and resistance decrease mediated by serotonin-1A receptors. We next used single-cell antisense RNA amplification from identified CA1 pyramidal neurons to resolve whether the functional deficits in serotonin responsiveness are accompanied by decreased expression levels of the serotonin-1A receptor. It appeared that expression of serotonin-1A receptors in CA1 pyramidal cells is not altered; this result was supported by in situ hybridization. Expression of corticosteroid receptors in the same cells, particularly of the high-affinity mineralocorticoid receptor, was significantly reduced after long-term corticosterone treatment. The present findings indicate that prolonged elevation of the corticosteroid concentration, a possible causal factor for major depression in humans, gradually attenuates responsiveness to serotonin without necessarily decreasing serotonin-1A receptor mRNA levels in pyramidal neurons. These functional changes may occur by a posttranscriptional mechanism or by transcriptional regulation of genes other than the serotonin-1A receptor gene itself. mineralocorticoid receptor ͉ glucocorticoid receptor ͉ intracellular recording ͉ single-cell antisense RNA amplification ͉ in situ hybridization C orticosteroid hormones are secreted from the adrenal glands in a circadian pattern (1). In rats, corticosterone circulates in low amounts in the morning and at high concentrations in the evening. Temporary elevations in the level occur after stressful events. Corticosteroids can enter the brain and bind to two intracellular receptor subtypes (2): the mineralocorticoid receptor (MR; K d Ϸ 0.5 nM) and the glucocorticoid receptor (GR; K d Ϸ 5 nM). Because of the difference in affinity, changes in plasma corticosterone concentration alter the relative MR͞GR occupation. Low levels of corticosterone mainly activate brain MRs, whereas high levels at the circadian peak or during stress activate GRs along with MRs (3-5). Electrophysiological studies in CA1 hippocampal neurons, which coexpress MR and GR, have shown that selective activation of corticosteroid receptors alters ion conductances and neurotransmitter responses within 1-2 hours (6). In particular, the membrane hyperpolarization mediated by serotonin-...

BackgroundThe hormone somatostatin inhibits growth hormone release from the pituitary gland and is theoretically linked to diabetes and diabetes related complications. This study aimed to investigate the relationship between levels of the stable somatostatin precursor, N-terminal prosomatostatin (NT-proSST), with mortality in type 2 diabetes (T2DM) patients.MethodsIn 1,326 T2DM outpatients, participating in this ZODIAC prospective cohort study, Cox proportional hazards models were used to investigate the independent relationship between plasma NT-proSST concentrations with all-cause and cardiovascular mortality.ResultsMedian concentration of NT-proSST was 592 [IQR 450–783] pmol/L. During follow-up for 6 [3–10] years, 413 (31%) patients died, of which 176 deaths (43%) were attributable to cardiovascular causes. The age and sex adjusted hazard ratios (HRs) for all-cause and cardiovascular mortality were 1.48 (95%CI 1.14 - 1.93) and 2.21 (95%CI 1.49 - 3.28). However, after further adjustment for cardiovascular risk factors there was no independent association of log NT-proSST with mortality, which was almost entirely attributable to adjustment for serum creatinine. There were no significant differences in Harrell’s C statistics to predict mortality for the models with and without NT-proSST: both 0.79 (95%CI 0.77 – 0.82) and 0.81 (95%CI 0.77 – 0.84).ConclusionsNT-proSST is unsuitable as a biomarker for cardiovascular and all-cause mortality in stable outpatients with T2DM.

Background POCUS (point-of-care ultrasound) is an important diagnostic tool for several medical specialties. To provide safe patient care, the quality of this exam should be as high as possible. This includes solid documentation with a written report and the availability of images for review. However, international guidelines or publications about this quality assessment and its application in clinical practice are scarce. Methods We designed a criteria-checklist to evaluate the quality of POCUS examinations. This checklist was made based on international guidelines and protocols and was validated by a Dutch expert group using the nominal group technique (NGT). All POCUS exams in general internal medicine patients documented between August 2019 and November 2020 in our ED were evaluated using this checklist. Results A total of 169 exams were included. In general, the compliance for most important criteria was high, but not optimal. A clinical question or indication for the POCUS exam was stated in 75.7% of cases. The completeness of all standard views differed per indication, but was lower when more than one standard view was required. Labels were provided in 83.5% of the saved images, while 90.8% of all examinations showed a written conclusion. Conclusions Our research showed that the overall quality of documentation varies with regard to several important criteria. Suboptimal compliance of documentation may have adverse effects on patient safety. We have developed a checklist which can be used to improve POCUS documentation.