Objectives
Updated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using ...higher‐level ecological evidence.
Methods
The study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries. Variables analyzed included (1) ED inpatient care opportunities, (2) unique number of ED inpatients and (3) mean length of ED‐related inpatient stays in age groups 15–19 and 20–88+, across 1998–2020.
Results
Mean length of inpatient stays was inversely correlated to relapse to ED‐related inpatient care within the same year (p < 0.001, R‐squaredadj = 0.5216 and p < 0.00001, R‐squaredadj = 0.5090, in the 15–19 and 20–88+ age groups, respectively), independent of number of ED inpatients treated within a year in both age groups. Extending mean adolescent inpatient duration from 35 to 45 days was associated with a ∼30% reduction in the year‐wise relapse rate.
Conclusions
Mean length of ED‐related inpatient treatment stays was associated with reduced relapses to inpatient care within the same year, which could be interpreted as support for recommendations to include a stabilization phase in inpatient ED treatment.
The mammalian circadian clock underlies both diurnal and seasonal changes in physiology, and its function is thought to be disturbed in both seasonal and non-seasonal depression. In humans, molecular ...imaging studies have reported seasonal changes in the serotonin system. Despite the role of the circadian clock in generating seasonal physiological changes, however, diurnal variation of serotonin receptors and transporters has never been directly studied in humans. We used positron emission tomography to examine diurnal and seasonal changes in the serotonin 5-HT1A receptor and serotonin transporter in two large cohorts of healthy male subjects, employing a cross-sectional design. In 56 subjects measured with (11)CWAY-100635, we observed diurnal increases in the availability of 5-HT1A receptors in the cortex. In 40 subjects measured with (11)CMADAM, a decrease in 5-HTT was observed in the midbrain across the day. We also found seasonal changes in the 5-HT1A receptor in serotonin projection regions, with higher availability on days with a longer duration of daylight. Our observation that serotonin receptor and transporter levels may change across the day in humans is corroborated by experimental research in rodents. These findings have important implications for understanding the relationship between the circadian and serotonin systems in both the healthy brain and in affective disorders, as well as for the design of future molecular imaging studies.
The objective of the study was to investigate the safety profile of high-risk micro-endomyocardial biopsy (micro-EMB) compared to conventional EMB in a large animal model. Twenty pigs were subjected ...to a maximum of 30 consecutive biopsies, including sampling from the free ventricular wall, with either micro-EMB (
n
= 10) or conventional EMB (
n
= 10). There were no major complications in the micro-EMB group (0/10), compared to six major complications in the EMB group (6/10;
p
= 0.003). Survival analysis further highlighted these differences (
p
= 0.004). There were significantly higher volumes of pericardial effusion in the EMB group (
p
= 0.01). The study shows a safety advantage of micro-EMB compared to standard EMB in the experimental high-risk circumstances investigated in this animal study. These results indicate enhanced possibilities to collect samples from sensitive areas by using the micro-EMB technique instead of standard EMB.
Background
Evidence demonstrates that brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B) have a pivotal role in the pathogenesis of major depressive disorder (MDD) ...and they are proposed as predictors of antidepressant response. Ketamine produces rapid antidepressant effects in MDD and pre-clinical studies suggest the necessity of increased BDNF levels for the antidepressant action of ketamine. However, studies observing the change of blood BDNF levels after ketamine intervention are inconsistent and studies about the role of plasma S100B in ketamine administration in MDD patients are lacking.
Method
We evaluated mature BDNF (mBDNF), S100B levels in plasma and their associations with depression severity in 30 Selective Serotonin Reuptake Inhibitor (SSRI)-resistant MDD patients enrolled in a randomized controlled trial of ketamine compared (
n
= 20) to a placebo (
n
= 10) control (saline). Severity of depression was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS).
Results
Plasma mBDNF and S100B were not significantly changed after 1–2 days of single ketamine compared to placebo. Plasma mBDNF and S100B levels did not significantly differ in responders compared to non-responders of ketamine treatment. The change of plasma mBDNF levels was positively correlated with the improvement of MADRS score after 1–2 weeks of open-label ketamine treatment (rho = 0.495,
p
= 0.031), though this change did not survive correction for multiple comparisons.
Conclusion
These findings do not support the hypothesis that ketamine treatment increases BDNF plasma levels in MDD patients. No effect of ketamine treatment on S100B plasma levels was seen.
Micro-endomyocardial biopsy (micro-EMB) is a novel catheter-based biopsy technique, aiming to increase flexibility and safety compared to conventional EMB. The technique was developed and evaluated ...in healthy swine. Therefore, the ability to detect disease related tissue changes could not be evaluated. The aim of the present pilot study was to investigate the ability to detect disease related gene expression changes using micro-EMB. Myocardial infarction was induced in three swine by coronary artery balloon occlusion. Micro-EMB samples (n = 164) were collected before, during, and after occlusion. RNA-sequencing was performed on 85 samples, and 53 of these were selected for bioinformatic analysis. A large number of responding genes was detected from the infarcted area (n = 1911). The early responding genes (n = 1268) were mostly related to apoptosis and inflammation. There were fewer responding genes two days after infarction (n = 6), which were related to extra-cellular matrix changes, and none after 14 days. In contrast to the infarcted area, samples harvested from a non-infarcted myocardial region showed considerably fewer regulated genes (n = 33). Deconvolution analysis, to estimate the proportion of different cell types, revealed a higher proportion of fibroblasts and a reduced proportion of cardiomyocytes two days after occlusion compared to baseline (p < 0.02 and p < 0.01, respectively. S5 File). In conclusion, this pilot study demonstrates the capabilities of micro-EMB to detect local gene expression responses at an early stage after ischemia, but not at later timepoints.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cell therapy is an integral modality of regenerative medicine. Macrophages are known for their sensitivity to activation stimuli and capability to recruit other immune cells to the sites of injury ...and healing. In addition, the route of administration can impact engraftment and efficacy of cell therapy, and modern neuro-interventional techniques provide the possibility for selective intra-arterial (IA) delivery to the central nervous system (CNS) with very low risk. The effects of radiolabelling and catheter transport on differentially activated macrophages were evaluated. Furthermore, the safety of selective IA administration of these macrophages to the rabbit brain was assessed by single-photon emission computed tomography/computed tomography (SPECT/CT) and ultra-high-field (9.4 T) magnetic resonance imaging (MRI). Cells were successfully labeled with (
In)In-(oxinate)
and passed through a microcatheter with preserved phenotype. No cells were retained in the healthy rabbit brain after IA administration, and no adverse events could be observed either 1 h (
= 6) or 24 h (
= 2) after cell administration. The procedure affected both lipopolysaccharide/gamma interferon (LPS/IFNγ) activated cells and interleukin 4 (IL4), interleukin 10 (IL10)/transforming growth factor beta 1 (TGFβ1) activated cells to some degree. The LPS/IFNγ activated cells had a significant increase in their phagocytotic function. Overall, the major impact on the cell phenotypes was due to the radiolabeling and not passage through the catheter. Unstimulated cells were substantially affected by both radiolabeling and catheter administration and are hence not suited for this procedure, while both activated macrophages retained their initial phenotypes. In conclusion, activated macrophages are suitable candidates for targeted IA administration without adverse effects on normal, healthy brain parenchyma.
Women and men differ in serotonin associated psychiatric conditions, such as depression, anxiety and suicide. Despite this, very few studies focus on sex differences in the serotonin system. Of the ...biomarkers in the serotonin system, serotonin1A (5-HT1A) receptor is implicated in depression, and anxiety and serotonin transporter (5-HTT) is a target for selective serotonin reuptake inhibitors, psychotropic drugs used in the treatment of these disorders. The objective of the present study was to study sex related differences in the 5-HT1A receptor and 5-HTT binding potentials (BPNDs) in healthy humans, in vivo. Positron emission tomography and selective radioligands 11CWAY100635 and 11CMADAM were used to evaluate binding potentials for 5-HT1A receptors (14 women and 14 men) and 5-HTT (8 women and 10 men). The binding potentials were estimated both on the level of anatomical regions and voxel wise, derived by the simplified reference tissue model and wavelet/Logan plot parametric image techniques respectively.
Compared to men, women had significantly higher 5-HT1A receptor and lower 5-HTT binding potentials in a wide array of cortical and subcortical brain regions. In women, there was a positive correlation between 5-HT1A receptor and 5-HTT binding potentials for the region of hippocampus. Sex differences in 5-HT1A receptor and 5-HTT BPND may reflect biological distinctions in the serotonin system contributing to sex differences in the prevalence of psychiatric disorders such as depression and anxiety. The result of the present study may help in understanding sex differences in drug treatment responses to drugs affecting the serotonin system.
In a recent COVID-19 case series, ANGII levels were markedly elevated and linearly associated with viral load and lung injury 4. ...in a prepublished report currently under journal review, infusion ...of ANGII in a porcine model rapidly (within hours) induced a clinical syndrome closely reflecting the one seen in COVID-19 patients, including histological changes in the lungs with severe thickening of the alveolar walls, possible hyaline membranes, and clotting of vessels, as previously reported in the human COVID-19 phenotype 5. ...hypothetical interactions, however, remain unmeasured. ...it is not a surprise that angiotensin II levels are higher in patients with greater viral load and illness severity. ...the infusion of angiotensin II in the porcine model cited by the correspondents is clearly irrelevant to angiotensin therapy in humans as described in our report 1. At such toxic doses which were 10 to 30 times those administered to our patients, it is no surprise that toxic, even lethal side effects developed. ...more relevant experiments are performed or clear evidence emerges that angiotensin II infusion is injurious in COVID-19 patients, the data are strong that angiotensin II is a safe and effective vasopressor agent 8 especially in patients with high renin levels 9.
...Dr. Backes proposes that our findings of low or non-existing dopamine D2/3-receptor (D2/3R) occupancy of quetiapine in extrastriatal regions could be explained by a putative presence of specific ...11Craclopride binding in cerebellar grey matter, i.e. the reference region in our analysis. A more suitable cross-validation would be in the setting of a within subject design. ...as we show in our article, even for a region with “medium binding” such as thalamus, a large sample size (N = 350) would be needed for an appropriately powered examination of a 10% between-group difference in 11Craclopride BPND. ...we stay with our overall conclusion that caution must be exercised when interpreting results from reference tissue based quantification of 11Craclopride binding outside of the striatum.
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