Clinical Outcome Assessments in Encephalitis

Background and ObjectivesMost patients with encephalitis experience persisting neurocognitive and neuropsychiatric sequelae in the years following this acute illness. Reported outcomes are often based on generic clinical outcome assessments that rarely capture the patient perspective. This may result in an underestimation of disease-specific sequelae. Disease-specific clinical outcome assessments can improve clinical relevance of reported outcomes and increase the power of research and trials. There are no patient-reported outcome measures (PROMs) developed or validated specifically for patients with encephalitis. The primary objective of this systematic literature review was to identify PROMs that have been developed for or validated in patients with encephalitis. MethodsWe performed a systematic review of the literature published from inception until May 2023 in 3 large international databases (MEDLINE, EMBASE and Cochrane libraries). Eligible studies should have developed or validated a PROM in patients with encephalitis or encephalopathy. Methodologic quality was evaluated using the Consensus-based Standards for the selection of health status Measurement Instruments study design checklist for PROMs. ResultsWe identified no disease-specific PROMs developed or validated for patients with encephalitis. We identified one study on the development and validation of a disease-specific PROM for hepatic encephalopathy, although this disease course is substantially different to that of patients with encephalitis. The methodologic quality of the included study was generally rated as "doubtful." We identified 30 PROMs that have been applied in 46 studies on encephalitis or encephalopathy, although not validated in these populations. The most commonly applied PROMs for measuring Health-Related Quality of Life were the Medical Outcomes Study Short Form-36 and the Sickness Impact Profile. Emotional well-being was often assessed with the Beck Depression Inventory (BDI-II). Sporadically, PROMs were applied to address other aspects of outcome including daily functioning and sleep quality. DiscussionThis systematic review confirms a critical gap in clinical outcome assessments in patients with encephalitis, failing to identify a validated measuring tool for detecting neurocognitive, functional, and health status. It is therefore essential to develop and/or validate disease-specific PROMs for the population with encephalitis to capture relevant information for patient management and clinical trials about the effects of disease that are at risk of being overlooked.</p

The interaction of fluorescent nanodiamond probes with cellular media

Fluorescent nanodiamonds (FNDs) are promising tools to image cells, bioanalytes and physical quantities such as temperature, pressure, and electric or magnetic fields with nanometer resolution. To exploit their potential for intracellular applications, the FNDs have to be brought into contact with cell culture media. The interactions between the medium and the diamonds crucially influence sensitivity as well as the ability to enter cells. The authors demonstrate that certain proteins and salts spontaneously adhere to the FNDs and may cause aggregation. This is a first investigation on the fundamental questions on how (a) FNDs interact with the medium, and (b) which proteins and salts are being attracted. A differentiation between strongly binding and weakly binding proteins is made. Not all proteins participate in the formation of FND aggregates. Surprisingly, some main components in the medium seem to play no role in aggregation. Simple strategies to prevent aggregation are discussed. These include adding the proteins, which are naturally present in the cell culture to the diamonds first and then inserting them in the full medium. Graphical abstractSchematic of the interaction of nanodiamonds with cell culture medium. Certain proteins and salts adhere to the diamond surface and lead to aggregation or to formation of a protein corona

Blue space in urban and peri-urban areas and mental health: which blue space types and characteristics are most beneficial?

There is an increasing awareness that besides green spaces, blue spaces can also positively influence mental as well as physical health (see for example, Völker & Kistemann, 2011; Gascon et al., 2017). Blue spaces are: “outdoor environments – either natural or manmade – that prominently feature water and are accessible to humans either proximally (being in, on or near water) or distally/virtually (being able to see, hear or otherwise sense water)” (Grellier et al., 2017, p. 3). Examples include coasts, lakes, ponds and pond systems, wadis systems, artificial buffer basins and water courses. Together with green spaces they form the green-blue infrastructure. Therefore, a second systematic review focused on effects of blue spaces on mental health

Green space in urban and peri-urban areas and mental health: which green space types and characteristics are most beneficial?

Urban green space plays an important role in the mental and physical health of urbanites, as well as of people working in or visiting urban areas (WHO Regional Office for Europe, 2016). But green space can be very diverse in its typology, including for instance urban forests, parks, playgrounds, allotments and urban farming locations. These green space types can also differ greatly in their defining characteristics; for instance, parks can differ in scenic beauty, vegetative composition or openness. Globally, continuing urbanization, as well as climate change, is increasingly putting pressure on the existence of green spaces within urban areas (e.g. Dallimer et al., 2011; Richards & Belcher, 2020). The scarcity of urban green space and the desire to create liveable cities requires in-depth knowledge on how different green space types and characteristics influence mental health, to facilitate well-informed design and planning choices

Multi-Ancestry Sleep-by-SNP Interaction Analysis in 126,926 Individuals Reveals Lipid Loci Stratified by Sleep Duration

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles

Green space in urban and peri-urban areas and mental health: which green space types and characteristics are most beneficial?

Urban green space plays an important role in the mental and physical health of urbanites, as well as of people working in or visiting urban areas (WHO Regional Office for Europe, 2016). But green space can be very diverse in its typology, including for instance urban forests, parks, playgrounds, allotments and urban farming locations. These green space types can also differ greatly in their defining characteristics; for instance, parks can differ in scenic beauty, vegetative composition or openness. Globally, continuing urbanization, as well as climate change, is increasingly putting pressure on the existence of green spaces within urban areas (e.g. Dallimer et al., 2011; Richards & Belcher, 2020). The scarcity of urban green space and the desire to create liveable cities requires in-depth knowledge on how different green space types and characteristics influence mental health, to facilitate well-informed design and planning choices

Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier

BACKGROUND: The sphingosine 1-phosphate (S1P) receptor modulator FTY720P (Gilenya®) potently reduces relapse rate and lesion activity in the neuroinflammatory disorder multiple sclerosis. Although most of its efficacy has been shown to be related to immunosuppression through the induction of lymphopenia, it has been suggested that a number of its beneficial effects are related to altered endothelial and blood–brain barrier (BBB) functionality. However, to date it remains unknown whether brain endothelial S1P receptors are involved in the maintenance of the function of the BBB thereby mediating immune quiescence of the brain. Here we demonstrate that the brain endothelial receptor S1P(5) largely contributes to the maintenance of brain endothelial barrier function. METHODS: We analyzed the expression of S1P(5) in human post-mortem tissues using immunohistochemistry. The function of S1P(5) at the BBB was assessed in cultured human brain endothelial cells (ECs) using agonists and lentivirus-mediated knockdown of S1P(5). Subsequent analyses of different aspects of the brain EC barrier included the formation of a tight barrier, the expression of BBB proteins and markers of inflammation and monocyte transmigration. RESULTS: We show that activation of S1P(5) on cultured human brain ECs by a selective agonist elicits enhanced barrier integrity and reduced transendothelial migration of monocytes in vitro. These results were corroborated by genetically silencing S1P(5) in brain ECs. Interestingly, functional studies with these cells revealed that S1P(5) strongly contributes to brain EC barrier function and underlies the expression of specific BBB endothelial characteristics such as tight junctions and permeability. In addition, S1P(5) maintains the immunoquiescent state of brain ECs with low expression levels of leukocyte adhesion molecules and inflammatory chemokines and cytokines through lowering the activation of the transcription factor NFκB. CONCLUSION: Our findings demonstrate that S1P(5) in brain ECs contributes to optimal barrier formation and maintenance of immune quiescence of the barrier endothelium

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels