Immune gene co-expression signatures implicated in occurence and persistence of cognitive dysfunction in depression.

Cognitive dysfunction contributes significantly to the burden caused by Major Depressive Disorder (MDD). Yet, while compelling evidence suggests that different biological processes play a part in both MDD aetiology and the development of cognitive decline more generally, we only begin to understand the molecular underpinnings of depression-related cognitive impairment. Developments in psychometric assessments, molecular high-throughput methods and systems biology derived analysis strategies advance this endeavour. Here, we aim to identify gene expression signatures associated with cognitive dysfunction and cognitive improvement following therapy using RNA sequencing to analyze the whole blood-derived transcriptome of altogether 101 MDD patients who enrolled in the CERT-D study. The mRNA(Nova)Seq based transcriptome was analyzed from whole blood taken at baseline assessment, and patients' cognitive performance was measured twice at baseline and following eight weeks of therapy by means of the THINC integrated tool. Thirty-six patients showed comparatively low cognitive performance at baseline assessment, and 32 patients showed comparatively strong cognitive improvement following therapy. Differential gene expression analysis was performed using limma to a significance threshold of 0.05 and a logFC cutoff of |1.2|. Although we observed some indications for expression differences related to low cognitive performance and cognitive therapy response, signals did not withstand adjustment for multiple testing. Applying WGCNA, we retrieved altogether 25 modules of co-expressed genes and we used a combination of correlational and linear analyses to identify modules related to baseline cognitive performance and cognitive improvement following therapy. Three immune modules reflected distinct but interrelated immune processes (the yellow module: neutrophil-mediated immunity, the darkorange module: interferon signaling, the tan module: platelet activation), and higher expression of the yellow (r = -0.21, p < .05), the dark orange (r = 0.2, p < .05), and the tan (r = -0.23, p < .05) module correlated significantly negatively with patients' cognitive baseline performance. Patients' cognitive baseline performance was a significant predictor of the darkorange module (b = -0.039, p < .05) and the tan module's expression (b = 0.02, p < .05) and was close to becoming a significant predictor of the yellow module's expression (b = -0.02, p = .05). Furthermore, patients characterized by comparatively low cognitive performance at baseline showed significantly higher expression of the tan module when compared to all other patients F(1,97) = 4.32, p < .05, η= 0.04. Following eight weeks of treatment, we observed altogether significant improvement in patients' cognitive performance (b = 0.30, p < .001), and patients with comparatively high cognitive gain showed noticeably lower, but not significantly lower F(1,98) = 3.76, p = .058, expression of a dark turquoise module, which reflects complement and B-cell-associated immune processes. Noteworthy, the relation between cognitive performance and module expression remained observable after controlling for symptom severity and BMI, which partly accounted for variance in module expression. As such, our findings provide further evidence for the involvement of immune processes in MDD related cognitive dysfunction and they suggest that different immune processes contribute to the development and long-term persistence of cognitive dysfunction in the context of depression.

Magnesium Anode Protection by an Organic Artificial Solid Electrolyte Interphase for Magnesium-Sulfur Batteries.

In the search for post-lithium battery systems, magnesium-sulfur batteries have attracted research attention in recent years due to their high potential energy density, raw material abundance, and low cost. Despite significant progress, the system still lacks cycling stability mainly associated with the ongoing parasitic reduction of sulfur at the anode surface, resulting in the loss of active materials and passivating surface layer formation on the anode. In addition to sulfur retention approaches on the cathode side, the protection of the reductive anode surface by an artificial solid electrolyte interphase (SEI) represents a promising approach, which contrarily does not impede the sulfur cathode kinetics. In this study, an organic coating approach based on ionomers and polymers is pursued to combine the desired properties of mechanical flexibility and high ionic conductivity while enabling a facile and energy-efficient preparation. Despite exhibiting higher polarization overpotentials in Mg-Mg cells, the charge overpotential in Mg-S cells was decreased by the coated anodes with the initial Coulombic efficiency being significantly increased. Consequently, the discharge capacity after 300 cycles applying an Aquivion/PVDF-coated Mg anode was twice that of a pristine Mg anode, indicating effective polysulfide repulsion from the Mg surface by the artificial SEI. This was backed by operando imaging during long-term OCV revealing a non-colored separator, i.e. mitigated self-discharge. While SEM, AFM, IR and XPS were applied to gain further insights into the surface morphology and composition, scalable coating techniques were investigated in addition to ensure practical relevance. Remarkably therein, the Mg anode preparation and all surface coatings were prepared under ambient conditions, which facilitates future electrode and cell assembly. Overall, this study highlights the important role of Mg anode coatings to improve the electrochemical performance of magnesium-sulfur batteries.

Patient Safety in a Box: Implementation and Evaluation of the Emergency Box in Geriatric and Parkinson Patients.

In an industrial society, the proportion of geriatric people increases with rising age. These people are likely to use polypharmacy and experience medical emergencies. However, their emergency care can be complicated by unclear comorbidities and medication. The aim of this prospective interventional study was to assess the demand for a drug safety tool in clinical practice and to analyze whether the emergency box can improve acute care in a geriatric cohort. Therefore, emergency room (ER) doctors in a German tertiary hospital recorded the number of geriatric patients lacking medical information and its impact on diagnostics/treatment. Furthermore, the emergency box was distributed to patients on the neurological ward and their current drug safety concepts were assessed. After 6 months, we evaluated in a follow-up whether the tool was helpful in emergency cases. Our study revealed that 27.4% (n = 28) of the patients came to the ER without their medical information, which caused a relevant delay or possible severe complications in 11.8% (n = 12). The emergency box was perceived as easily manageable and 87.9% (n = 109) of the participants wanted to keep it after the study. Subjectively, participants benefitted in emergencies. In conclusion, the emergency box is a cheap tool that is easy to use. It can save valuable time in emergencies and increases the safety of geriatric patients.

Using migrating cells as probes to illuminate features in live embryonic tissues.

The biophysical and biochemical properties of live tissues are important in the context of development and disease. Methods for evaluating these properties typically involve destroying the tissue or require specialized technology and complicated analyses. Here, we present a novel, noninvasive methodology for determining the spatial distribution of tissue features within embryos, making use of nondirectionally migrating cells and software we termed "Landscape," which performs automatized high-throughput three-dimensional image registration. Using the live migrating cells as bioprobes, we identified structures within the zebrafish embryo that affect the distribution of the cells and studied one such structure constituting a physical barrier, which, in turn, influences amoeboid cell polarity. Overall, this work provides a unique approach for detecting tissue properties without interfering with animal's development. In addition, Landscape allows for integrating data from multiple samples, providing detailed and reliable quantitative evaluation of variable biological phenotypes in different organisms.

The effect of educational information about treatments for schizophrenia on stigmatizing perceptions.

BACKGROUND: A promising strategy for reducing stigmatizing perceptions towards people with schizophrenia is education about treatment and recovery. The effects of different kinds of treatment information on stigmatizing perceptions, however, have yet to be compared directly. This study compared three different educational interventions focusing on medication, CBT, and psychodynamic psychotherapy in their potential to reduce stigmatizing perceptions towards people with schizophrenia. METHODS: In an online experiment 178 participants received one of three psychoeducation texts that focused on medication, CBT or psychodynamic therapy. The effects on stereotypical beliefs about psychosis (dangerousness, unpredictability, blame, prognostic pessimism) and emotional responses towards people with schizophrenia (anxiety, anger, sympathy) were tested. RESULTS: Perceptions of dangerousness, unpredictability, and anxiety towards people with schizophrenia were reduced in all conditions. Prognostic pessimism was reduced only after reading the CBT information. LIMITATIONS: No neutral control group was included. The sample was not representative with respect to level of education or gender. CONCLUSIONS: Stigmatizing perceptions may be reduced by receiving information about any type of treatment for psychosis and without producing negative side-effects, although this needs to be replicated in a controlled study. However, information on CBT seems most suitable to reduce stigma, since it was able to reduce prognostic pessimism.