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Background: The advance directive and lasting power of attorney are instruments to strengthen patients' autonomy. A hospital-based palliative care consultation service can advise patients and family members about these instruments. This study investigates the need for such consultation among patients with life-limiting illness., Methods: This prospective observational study on intensive and non-intensive care units includes patients with a request for palliative care consultation. Patient-related factors were evaluated for their possible association with the presence or absence of advance directives or power of attorney. In addition, focus group interviews with members of the palliative care consultation team were carried out to identify barriers which prevent patients from drawing up such documents., Results: A total of 241 oncological and 53 non-oncological patients were included with a median age of 67 years; 69 (23%) patients were treated in the intensive care unit (ICU). Overall, 98 (33%) patients had advance directives, and 133 (45%) had determined a legal health care proxy in advance. A total of 52 patients died in hospital (17.7%). Only age and relationship status were associated with directives. In interviews, the following barriers were identified: information deficit, concern regarding discontinuation of treatment, loss of autonomy and wish to avoid a burden for the family., Conclusion: The majority in this severely ill patient population lack advance directives. In order to remove barriers, more effective information and counseling is required about such directives. In particular, guidance should include potential clinical situations in which such directives are potentially beneficial., (© 2024. The Author(s).)

Background: Inflammaging represents an accepted concept where the immune system shifts to a low-grade chronic pro-inflammatory state without overt infection upon aging. In the CNS, inflammaging is mainly driven by glia cells and associated with neurodegenerative processes. White matter degeneration (WMD), a well-known process in the aging brain, manifests in myelin loss finally resulting in motor, sensory and cognitive impairments. Oligodendrocytes (OL) are responsible for homeostasis and maintenance of the myelin sheaths, which is a complex and highly energy demanding process sensitizing these cells to metabolic, oxidative and other forms of stress. Yet, the immediate impact of chronic inflammatory stress like inflammaging on OL homeostasis, myelin maintenance and WMD remains open., Methods: To functionally analyze the role of IKK/NF-κB signaling in the regulation of myelin homeostasis and maintenance in the adult CNS, we established a conditional mouse model allowing NF-κB activation in mature myelinating oligodendrocytes. IKK2-CA PLP-CreERT2 mice were characterized by biochemical, immunohistochemical, ultrastructural and behavioral analyses. Transcriptome data from isolated, primary OLs and microglia cells were explored by in silico pathway analysis and validated by complementary molecular approaches., Results: Chronic NF-κB activation in mature OLs leads to aggravated neuroinflammatory conditions phenocopying brain inflammaging. As a consequence, IKK2-CA PLP-CreERT2 mice showed specific neurological deficits and impaired motoric learning. Upon aging, persistent NF-κB signaling promotes WMD in these mice as ultrastructural analysis revealed myelination deficits in the corpus callosum accompanied by impaired myelin protein expression. RNA-Seq analysis of primary oligodendrocytes and microglia cells uncovers gene expression signatures associated with activated stress responses and increased post mitotic cellular senescence (PoMiCS) which was confirmed by elevated senescence-associated β-galactosidase activity and SASP gene expression profile. We identified an elevated integrated stress response (ISR) characterized by phosphorylation of eIF2α as a relevant molecular mechanism which is able to affect translation of myelin proteins., Conclusions: Our findings demonstrate an essential role of IKK/NF-κB signaling in mature, post-mitotic OLs in regulating stress-induced senescence in these cells. Moreover, our study identifies PoMICS as an important driving force of age-dependent WMD as well as of traumatic brain injury induced myelin defects., (© 2023. The Author(s).)

Because drowsiness is a major cause in vehicle accidents, its automated detection is critical. Scale-free temporal dynamics is known to be typical of physiological and body rhythms. The present work quantifies the benefits of applying a recent and original multivariate selfsimilarity analysis to several modalities of polysomnographic measurements (heart rate, blood pressure, electroencephalogram and respiration), from the MIT-BIH Polysomnographic Database, to better classify drowsiness-related sleep stages. Clinical relevance- This study shows that probing jointly temporal dynamics amongst polysomnographic measurements, with a proposed original multivariate multiscale approach, yields a gain of above 5% in the Area-under-Curve quanti-fying drowsiness-related sleep stage classification performance compared to univariate analysis.

In March 2020, the COVID-19 virus turned into a pandemic that hit organizations globally. This pandemic qualifies as an exogenous shock. Based on the threat-rigidity hypothesis, we hypothesize that this shock led to an increase in directive leadership behavior. We also argue that this relationship depends on the magnitude of the crisis and on well-learned responses of managers. In our empirical analysis we employ a differences-in-differences design with treatment intensity and focus on the period of the first lockdown, March until June 2020. Using a dataset covering monthly data for almost 27,000 managers across 48 countries and 32 sectors for January 2019 to December 2020, we find support for the threat-rigidity hypothesis. During the first lockdown, directive leadership increased significantly. We also find that this relationship is moderated by COVID-19 deaths per country, the sectoral working from home potential, and the organizational level of management. Our findings provide new evidence how large exogenous shocks like COVID-19 can impact leadership behavior., (© 2022 Elsevier Inc. All rights reserved.)

In quorum sensing, bacteria secrete or release small molecules into the environment that, once they reach a certain threshold, trigger a behavioural change in the population. As the concentration of these so-called autoinducers is supposed to reflect population density, they were originally assumed to be continuously produced by all cells in a population. However, here we show that in the α-proteobacterium Sinorhizobium meliloti expression of the autoinducer synthase gene is realized in asynchronous stochastic pulses that result from scarcity and, presumably, low binding affinity of the key activator. Physiological cues modulate pulse frequency, and pulse frequency in turn modulates the velocity with which autoinducer levels in the environment reach the threshold to trigger the quorum sensing response. We therefore propose that frequency-modulated pulsing in S. meliloti represents the molecular mechanism for a collective decision-making process in which each cell's physiological state and need for behavioural adaptation is encoded in the pulse frequency with which it expresses the autoinducer synthase gene; the pulse frequencies of all members of the population are then integrated in the common pool of autoinducers, and only once this vote crosses the threshold, the response behaviour is initiated., (© 2022. The Author(s).)

Background: In early stages, individuals with Primary Progressive Aphasia (PPA) report language symptoms while scoring within norm in formal language tests. Early intervention is important due to the progressive nature of the disease., Method: We report a single case study of an individual with logopenic variant PPA (lvPPA). We tested whether letter fluency, used as a therapy task, can improve lexical retrieval when combined with tDCS to either the left inferior-frontal gyrus (IFG) or the left inferior parietal lobe (IPL), administered in two separate therapy phases separated by a wash-out period of three months., Outcomes and Results: We observed increases in number of words retrieved during a letter fluency task in trained and untrained letters, when letter fluency therapy (LeFT) was administered with anodal tDCS. When LeFT was combined with left IFG stimulation, words produced in a letter fluency task were lower frequency and higher age of acquisition after treatment, compared to before treatment and there was also an increase in accuracy and response times in an untrained picture-naming task., Conclusions: The results indicate that letter fluency therapy combined anodal tDCS is effective in improving lexical retrieval, particularly when left IFG stimulation was used. Effects generalize beyond the trained task, albeit slowing down of responses in picture naming. This task may provide a useful clinical intervention strategy for patients with mild anomia, who are not challenged enough by traditional naming therapies., Competing Interests: DISCLOSURE OF INTEREST The authors report no conflict of interest.