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Background: Improving survival from pediatric cardiac arrest requires a well-functioning system of care with appropriately trained healthcare providers and designated cardiac arrest teams. This study aimed to describe the current organization and training for pediatric cardiac arrest in Denmark. Methods: We performed a nationwide cross-sectional study. A questionnaire was distributed to all hospitals in Denmark with a pediatric department. The survey included questions about receiving patients with out-of-hospital cardiac arrest, protocols for extracorporeal life support, cardiac arrest team compositions, and training. Results: We obtained responses from 17 of 19 hospitals with a pediatric department. In total, 76% of hospitals received patients with pediatric out-of-hospital cardiac arrest and 35% of hospitals had a protocol for extracorporeal life support. None of the hospitals had identical cardiac arrest team member compositions. The total number of team members ranged from 4-10, with a median of 8 members (IQR 7;9). In 84% of hospitals a specialized course in pediatric resuscitation was implemented and in 5% of hospitals, the specialized course was for the entire cardiac arrest team. Only few hospitals had training in laryngeal mask (6%) and intubation (29%) for pediatric cardiac arrest and none of them were trained in extracorporeal life support. Conclusion: We found high variability in the composition of the pediatric cardiac arrest teams and training across the surveyed Danish hospitals. Many hospitals lack training in important pediatric resuscitation skills. Although many hospitals receive pediatric patients after out-of-hospital cardiac arrest, only few have protocols for transfer for extracorporeal life support.

Introduction: Prior research identified four neurochemical cerebrospinal fluid (CSF) biomarkers, Aβ1-42, Aβ1-40, tTau, and pTau(181), as core diagnostic markers for Alzheimer's disease (AD). Determination of AD biomarkers using immunoassays can support differential diagnosis of AD vs. several neuropsychiatric disorders, which is important because the respective treatment regimens differ. Results of biomarker determination can be classified according to the Amyloid/Tau/Neurodegeneration (ATN) system into profiles. Less is known about the clinical performance of chemiluminescence immunoassays (ChLIA) measuring specific biomarkers in CSF samples from patients suffering from neuropsychiatric impairments with various underlying causes., Methods: Chemiluminescence immunoassays (ChLIAs, EUROIMMUN) were used to determine Beta-Amyloid (1-40), Beta-Amyloid (1-42), Total-Tau, and pTau(181) concentrations in precharacterized cerebrospinal fluid (CSF) samples from 219 AD patients, 74 patients with mild cognitive impairment (MCI), and 220 disease control (DC) patients., Results: 83.0% of AD patients had ATN profiles consistent with AD, whereas 85.5% of DC patients and 77.0% of MCI patients had profiles inconsistent with AD. AD patients showed significantly lower amyloid ratio Aβ1-42/Aβ1-40 (mean: 0.07) and significantly higher concentrations of tTau (mean: 901.6 pg/ml) and pTau(181) (mean: 129 pg/ml) compared to DC and MCI patients (all p values < 0.0071)., Discussion: The ChLIAs effectively determined specific biomarkers and can support differential diagnostics of AD. Their quality was demonstrated in samples from 513 patients with cognitive impairments, representing a realistic mix of underlying causes for seeking treatment at a memory clinic., Competing Interests: VB-L, KR, BB, and PA are employees of EUROIMMUN Medizinische Labordiagnostika AG, Luebeck, Germany, a company that manufactures diagnostic tests and instruments. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Arendt, Römpler, Brix, Borchardt-Lohölter, Busse and Busse.)

Introduction: Robust immunoassays for quantification of Alzheimer's disease (AD)-specific biomarkers are required for routine diagnostics. We report analytical performance characteristics of four new chemiluminescence immunoassays (ChLIA, EUROIMMUN) running on closed, fully automated random-access instruments for quantification of Aβ 1-40 , Aβ 1-42 , tTau, and pTau(181) in human cerebrospinal fluid (CSF)., Methods: ChLIAs were validated according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Optimal cut-offs for biomarkers and biomarker ratios were determined using samples from 219 AD patients and 220 patients with AD-related symptoms. For performance comparison, biomarker concentrations were measured in 110 diagnostic leftover samples using the ChLIAs and established Lumipulse G assays (Fujirebio)., Results: All ChLIAs met CLSI criteria. Overall agreement between assays was 89.0%-97.3 % with highly correlating results (Pearson's correlation coefficients: 0.82-0.99). Passing-Bablok regression analysis revealed systematic differences., Discussion: EUROIMMUN ChLIAs showed good analytical performances and represent new valuable tools for diagnostics of AD., Competing Interests: KR, PA, BB, VBL, and AS are or have been employees of EUROIMMUN Medizinische Labordiagnostika AG, Luebeck, Germany, a company that manufactures diagnostic tests and instruments. None of the authors benefits from any potential or actual financial or non-financial gain as a result of the work., (© 2024 The Authors.)

Introduction: Isolation and confinement are significant stressors during space travel that can impact crewmembers' physical and mental health. Space travel has been shown to accelerate vascular aging and increase the risk of cardiovascular and cerebrovascular disorders. However, the effect of prolonged isolation and confinement on microvascular function has not yet been thoroughly investigated., Methods: Retinal vascular imaging was conducted on four crewmembers during- and post-8-month SIRIUS-21 space analog mission. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and arteriovenous ratio (AVR) were measured. Pulse wave velocity (PWV), an indicator of arterial stiffness, was also measured., Results: Data from 4 participants was analyzed. These participants had a mean age of 34.75 ± 5.44 years, height of 170.00 ± 2.00 cm, weight of 74.50 ± 12.53 kg, and average BMI of 25.47 ± 3.94 kg/m 2 . During- and post-isolation, average CRVE showed an upward trend (Pearson's r 0.784, R-square 0.62), suggesting a dilation of retinal venules, while AVR showed a downward trend (Pearson's r -0.238, R-square 0.057), which is suggestive of a higher risk of cardiovascular and cerebrovascular dysfunctions. But neither of these trends were statistically significant. Additionally, the average PWV showed an upward trend during- and after-isolation across all crew members., Conclusion: Isolation and confinement appear to contribute towards retinal vascular damage and arterial stiffness. This cautiously suggests an increased risk of cardiovascular and cerebrovascular disorders due to the contribution of the isolation in space flight. Further studies are needed to confirm and expand on these results as we prepare for future manned missions to the Moon and Mars., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elmoselhi, Shankhwar, Qaisar, Hamoudi, Brix, Salon and Goswami.)

Scope: LTP-syndrome is characterized by sensitization (IgE) to multiple non-specific lipid transfer proteins (nsLTPs) with a variable clinical outcome. The treatment is primarily based on offending food avoidance. However, the determination of Pru p 3-specific IgE is currently the main diagnostic tool to assess sensitization to nsLTPs. Herein, the study evaluates improvement of LTP-syndrome diagnosis and clinical management using a new IgE multiplex-immunoblot assay with a high diversity of food nsLTPs., Methods and Results: An EUROLINE-LTP strip with 28 recombinant nsLTPs from 18 allergenic sources is designed. In total the study investigates 38 patients with LTP-syndrome and compares results from the nsLTPs (LTP-strip) with the respective food extracts of Prick-by-prick (PbP) testing. The agreement exceeds 70% for most nsLTPs, e.g., Pru p 3 (100%), Mal d 3 (97%), Pru av 3 (89%), Pha v 3 isoforms (87%/84%), Ara h 9 (82%), Cor a 8 (82%), and Jug r 3 (82%). The functionality and allergenic relevance of nine recombinant nsLTPs are proven by Basophil activation testing (BAT)., Conclusions: The new IgE multiplex-immunoblot nsLTP assay shows a good diagnostic performance allowing culprit food assessment. Negative results from LTP-strip may indicate potentially tolerable foods, improving diet intervention and patients' quality of life., (© 2023 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Cerebral blood flow autoregulation protects brain tissue from blood pressure variations and maintains cerebral perfusion pressure by changes in vascular resistance. High salt (HS) diet impairs endothelium-dependent vasodilation in many vascular beds, including cerebral microcirculation, and may affect vascular resistance. The aim of present study was to determine if 7-day HS diet affected the reactivity of middle cerebral artery (MCA) to orthostatic challenge in healthy human individuals, and if autoregulatory mechanisms and sympathetic neural regulation were involved in this phenomenon.Twenty-seven persons participated in study (F:21, M:6, age range 19-24). Participants consumed 7-day low-salt (LS) diet (< 2.3 g kitchen salt/day) and afterwards 7-day HS diet (> 11.2 g kitchen salt/day). Blood and urine analysis and anthropometric measurements were performed after each diet. Arterial blood pressure, heart rate and heart rate variability, and cerebral and systemic hemodynamic parameters were recorded simultaneously with transcranial Doppler ultrasound and The Task Force® Monitor in response to orthostatic test.Participants remained normotensive during HS diet. Following both, the LS and HS dietary protocols, mean cerebral blood flow (CBF), as well as the velocity time integral and diastolic blood pressure decreased, and cerebral pulsatility index increased after rising up. Importantly, cerebrovascular resistance significantly increased in response to orthostasis only after HS diet. Urine concentration of noradrenaline and vanillylmandelic acid, baroreflex sensitivity (BRS), and sympathetic neural control was significantly decreased in HS diet.Results suggest that CBF in response to orthostatic test was preserved in HS condition due to altered vascular reactivity of MCA, with increased cerebrovascular resistance and blunted BRS and sympathetic activity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The phenylpropanoid cinnamic acid (CA) is a plant metabolite that can occur under a trans - or cis -form. In contrast to the proven bioactivity of the cis -form ( c -CA), the activity of trans -CA ( t -CA) is still a matter of debate. We tested both compounds using a submerged rice coleoptile assay and demonstrated that they have opposite effects on cell elongation. Notably, in the tip of rice coleoptile t -CA showed an inhibiting and c -CA a stimulating activity. By combining transcriptomics and (untargeted) metabolomics with activity assays and genetic and pharmacological experiments, we aimed to explain the underlying mechanistic processes. We propose a model in which c -CA treatment activates proton pumps and stimulates acidification of the apoplast, which in turn leads to the loosening of the cell wall, necessary for elongation. We hypothesize that c -CA also inactivates auxin efflux transporters, which might cause a local auxin accumulation in the tip of the coleoptile. For t -CA, the phenotype can partially be explained by a stimulation of cell wall polysaccharide feruloylation, leading to a more rigid cell wall. Metabolite profiling also demonstrated that salicylic acid (SA) derivatives are increased upon t -CA treatment. As SA is a known antagonist of auxin, the shift in SA homeostasis provides an additional explanation of the observed t -CA-mediated restriction on cell growth., Competing Interests: The authors declare that there are no conflicts of interest., (© 2022 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Ionophores are small molecules or peptides that transport metal ions across biological membranes. Their transport capabilities are typically characterized in vitro using vesicles and single ion species. It is difficult to infer from these data which effects ionophores have on living cells in a complex environment (e.g., culture medium), since net ion movement is influenced by many factors including ion composition of the medium, concentration gradients, pH gradient, and protein-mediated transport processes across the membrane. To gain insights into the antibacterial mechanism of action of the semisynthetic polyether ionophore 4-Br-A23187, known to efficiently transport zinc and manganese in vitro, we investigated its effects on the gram-positive model organism Bacillus subtilis. In addition to monitoring cellular ion concentrations, the physiological impact of treatment was assessed on the proteome level. 4-Br-A23187 treatment resulted in an increase in intracellular copper levels, the extent of which depended on the copper concentration of the medium. Effects of copper accumulation mirrored by the proteomic response included oxidative stress, disturbance of proteostasis, metal and sulfur homeostasis. The antibiotic effect of 4-Br-A23187 is further aggravated by a decrease in intracellular manganese and magnesium. A liposome model confirmed that 4-Br-A23187 acts as copper ionophore in vitro., (© 2022 The Authors. Proteomics published by Wiley-VCH GmbH.)

Electrical activity is considered a key driver for the neurochemical and morphological maturation of neurons and the formation of neuronal networks. Designer receptors exclusively activated by designer drugs (DREADDs) are tools for controlling neuronal activity at the single cell level by triggering specific G protein signaling. Our objective was to investigate if prolonged silencing of differentiating cortical neurons can influence dendritic and axonal maturation. The DREADD hM4Di couples to G i/o signaling and evokes hyperpolarization via GIRK channels. HM4Di was biolistically transfected into neurons in organotypic slice cultures of rat visual cortex, and activated by clozapine-N-oxide (CNO) dissolved in H 2 O; controls expressed hM4Di, but were mock-stimulated with H 2 O. Neurons were analyzed after treatment for two postnatal time periods, DIV 5-10 and 10-20. We found that CNO treatment delays the maturation of apical dendrites of L2/3 pyramidal cells. Further, the number of collaterals arising from the main axon was significantly lower, as was the number of bouton terminaux along pyramidal cell and basket cell axons. The dendritic maturation of L5/6 pyramidal cells and of multipolar interneurons (basket cells and bitufted cells) was not altered by CNO treatment. Returning CNO-treated cultures to CNO-free medium for 7 days was sufficient to recover dendritic and axonal complexity. Our findings add to the view that activity is a key driver in particular of postnatal L2/3 pyramidal cell maturation. Our results further suggest that inhibitory G protein signaling may represent a factor balancing the strong driving force of neurotrophic factors, electrical activity and calcium signaling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gasterstädt, Schröder, Cronin, Kusch, Rennau, Mücher, Herlitze, Jack and Wahle.)

Background: Overweight/obesity in children and adolescents, largely arising due to increased food intake and reduced physical activity, is a major health concern. Physical activity (PA) integrated into learning has been shown to not only lead to improved health outcomes and wellbeing but also positively affect academic performance. The Health and Academic Performance with Happy Children (HAPHC) project aims at enhancing health and academic performance in elementary school children via implementation of a daily unit of Physical Activity Across the Curriculum (PAAC), which is carried out within the school setting. In this project, PA as an integrated part of learning will be evaluated and the learning material adapted for a large scale implementation across several European countries., Methods: In three European countries (Austria, Slovenia, and Belgium), 12 primary schools in total will be recruited to act as either intervention or control school in a large intervention study, which applies the PAAC pedagogy during lectures. It is estimated that, at least 3,000+ children across the three countries will be recruited in this study. All teachers of intervention schools will receive training and materials/teaching equipment that will allow them to integrate a daily PA unit of 45 min over 3 years across the curriculum. In response to the daily PA intervention, the following primary outcomes will be assessed: changes in health related physiological factors, academic achievement, psycho-social aspects and wellbeing., Impact of Project: The HAPHC project aims at promoting public health by increasing PA at an early age within the school setting and therewith preventing the increasing risk of non-communicable diseases across Europe. HAPHC project aims to develop knowledge and materials, which will ensure that the PAAC can be scalable to other European countries., Trial Registration Number: ClinicalTrials.gov, identifier: NCT04956003., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Goswami, Hansen, Gumze, Brix, Schmid-Zalaudek and Fredriksen.)

Absence seizures (ASs) are characterized by pathological electrographic oscillations in the cerebral cortex and thalamus, which are called spike-and-wave discharges (SWDs). Subcortical structures, such as the cerebellum, may well contribute to the emergence of ASs, but the cellular and molecular underpinnings remain poorly understood. Here we show that the genetic ablation of P/Q-type calcium channels in cerebellar granule cells (quirky) or Purkinje cells (purky) leads to recurrent SWDs with the purky model showing the more severe phenotype. The quirky mouse model showed irregular action potential firing of their cerebellar nuclei (CN) neurons as well as rhythmic firing during the wave of their SWDs. The purky model also showed irregular CN firing, in addition to a reduced firing rate and rhythmicity during the spike of the SWDs. In both models, the incidence of SWDs could be decreased by increasing CN activity via activation of the G q -coupled designer receptor exclusively activated by designer drugs (DREADDs) or via that of the G q -coupled metabotropic glutamate receptor 1. In contrast, the incidence of SWDs was increased by decreasing CN activity via activation of the inhibitory G i/o -coupled DREADD. Finally, disrupting CN rhythmic firing with a closed-loop channelrhodopsin-2 stimulation protocol confirmed that ongoing SWDs can be ceased by activating CN neurons. Together, our data highlight that P/Q-type calcium channels in cerebellar granule cells and Purkinje cells can be relevant for epileptogenesis, that G q -coupled activation of CN neurons can exert anti-epileptic effects and that precisely timed activation of the CN can be used to stop ongoing SWDs., (© 2022. The Author(s).)

Aims: Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transporter SPECT (DaTscan). Methods: We retrospectively identified 47 patients (17 Alzheimer's dementia, 10 idiopathic Parkinson's disease, 7 Lewy body dementia, 13 progressive supranuclear palsy or corticobasal degeneration) who received a DaTscan and a lumbar puncture. DaTscan imaging was performed according to current guidelines, and z-scores indicating the decrease in uptake were software based calculated for the nucleus caudatus and putamen. The CSF biomarkers progranulin, total-tau, alpha-synuclein, NfL, and pNfH were correlated with the z-scores. Results: DaTscan results in AD patients did not correlate with any biomarker. Subsuming every movement disorder with nigrostriatal neurodegeneration resulted in a strong correlation between putamen/nucleus caudatus and NfL (nucleus caudatus right p < 0.01, putamen right p < 0.05, left p < 0.05) and between pNfH and putamen (right p < 0.05; left p < 0.042). Subdividing in disease cohorts did not reveal significant correlations. Progranulin, alpha-synuclein, and total-tau did not correlate with DaTscan results. Conclusion: We show a strong correlation of NfL and pNfH with pathological changes in presynaptic dopamine transporter density in the putamen concomitant to nigrostriatal degeneration. This correlation might explain the reported correlation of impaired motor functions in PD and NfL as seen before, despite the pathological heterogeneity of these diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Diekämper, Brix, Stöcker, Vielhaber, Galazky, Kreissl, Genseke, Düzel and Körtvelyessy.)

Elevated hair cortisol concentrations in children have been linked to several stress-related conditions, including school-related demands. However, little is known about changes in hair testosterone in children. The present study investigated changes in hair cortisol and hair testosterone concentrations in the time course of four months - from summer holidays until mid of autumn of the following school year - in 60, 10-12-year-old (11.31 ± 0.63) school children (29 girls). Children's mental health was assessed by the strengths and difficulties questionnaire (SDQ) and related to hair cortisol and hair testosterone levels. Body mass index, waist-to-height ratio, and parental education were evaluated as potential confounders. In girls, the expected increase of hair cortisol concentrations was observed during school as compared to summer holidays, partly accounted for by peer- and emotional problems and the increase of HTC. In boys, hair cortisol and testosterone concentrations were significantly higher. Hair cortisol increased only slightly, while hair testosterone decreased significantly during school. The findings suggest a reciprocal influence of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axis, differentially affecting girls' and boys' hormone production in response to environmental changes.

Frailty and falls are a major public health problem in older adults. Muscle weakness of the lower and upper extremities are risk factors for any, as well as recurrent falls including injuries and fractures. While the Timed Up-and-Go (TUG) test is often used to identify frail members and fallers, tensiomyography (TMG) can be used as a non-invasive tool to assess the function of skeletal muscles. In a clinical study, we evaluated the correlation between the TMG parameters of the skeletal muscle contraction of 23 elderly participants (22 f, age 86.74 ± 7.88) and distance-based TUG test subtask times. TUG tests were recorded with an ultrasonic-based device. The sit-up and walking phases were significantly correlated to the contraction and delay time of the muscle vastus medialis ( ρ = 0.55-0.80, p < 0.01). In addition, the delay time of the muscles vastus medialis ( ρ = 0.45, p = 0.03) and gastrocnemius medialis ( ρ = -0.44, p = 0.04) correlated to the sit-down phase. The maximal radial displacements of the biceps femoris showed significant correlations with the walk-forward times ( ρ = -0.47, p = 0.021) and back ( ρ = -0.43, p = 0.04). The association of TUG subtasks to muscle contractile parameters, therefore, could be utilized as a measure to improve the monitoring of elderly people's physical ability in general and during rehabilitation after a fall in particular. TUG test subtask measurements may be used as a proxy to monitor muscle properties in rehabilitation after long hospital stays and injuries or for fall prevention.

Background: The etiology of autoimmune rheumatic diseases is unknown. Endothelial dysfunction and premature atherosclerosis are commonly seen in these patients. Atherosclerosis is considered one of the main causes of cardiovascular diseases. Hypertension is considered the most important traditional cardiovascular risk. This case-control study aimed to investigate the relationship between autoimmune diseases and cardiovascular risk., Methods: This study was carried out in patients with rheumatoid arthritis, RA ( n = 10), primary Sjögren syndrome, PSS ( n = 10), and healthy controls ( n = 10). Mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse wave velocity (PWV, an indicator of arterial stiffness) were assessed via a Vicorder device. Asymmetric dimethylarginine (ADMA) was measured via ELISA. Retinal photos were taken via a CR-2 retinal camera, and retinal microvasculature analysis was carried out. T-tests were conducted to compare the disease and control groups. ANOVA and ANOVA-ANCOVA were also used for the correction of covariates., Results: A high prevalence of hypertension was seen in RA (80% of cases) and PSS (40% of cases) compared to controls (only 20% of cases). Significant changes were seen in MBP (RA 101 ± 11 mmHg; PSS 93 ± 10 mm Hg vs. controls 88 ± 7 mmHg, p = 0.010), SBP (148 ± 16 mmHg in RA vs. 135 ± 16 mmHg in PSS vs. 128 ± 11 mmHg in control group; p = 0.007), DBP (77 ± 8 mmHg in RA, 72 ± 8 mmHg in PSS vs. 67 ± 6 mmHg in control; p = 0.010 in RA compared to the controls). Patients with PSS showed no significant difference as compared to controls (MBP: p = 0.240, SBP: p = 0.340, DBP: p = 0.190). Increased plasma ADMA was seen in RA (0.45 ± 0.069 ng/mL) and PSS (0.43 ± 0.060 ng/mL) patients as compared to controls (0.38 ± 0.059 ng/mL). ADMA in RA vs. control was statistically significant ( p = 0.022). However, no differences were seen in ADMA in PSS vs. controls. PWV and retinal microvasculature did not differ across the three groups., Conclusions: The prevalence of hypertension in our cohort was very high. Similarly, signs of endothelial dysfunction were seen in autoimmune rheumatic diseases. As hypertension and endothelial dysfunction are important contributing risk factors for cardiovascular diseases, the association of hypertension and endothelial dysfunction should be monitored closely in autoimmune diseases.

Multicomponent cardiac rehabilitation (CR) is a secondary prevention strategy for cardiac patients to tackle stress and psychosocial wellbeing. However, there is a lack of data on its psychoneuroimmunological effects and of biomarkers to determine individual risk and to develop treatment strategies. We conducted a pilot randomized controlled trial (RCT) to investigate the feasibility of deriving psychophysiological stress markers in patients with cardiovascular diseases. Thirty individuals with cardiovascular disease (mean age 58.8 years; 23.3% female) were enrolled and randomized into three treatment groups: standard rehabilitation, yoga, or transcendental meditation (TM). Depression, anxiety, sleep, stress perception, personality functioning, hair cortisol, serum tryptophan, kynurenine and neopterin concentrations were estimated at baseline and after a four-week intervention. Hair cortisol levels decreased significantly after rehabilitation in all groups (F = 15.98, p < 0.001). In addition, personality functioning improved in all patients over time. Participants with impairments in personality functioning showed a positive correlation with baseline neopterin that did not remain significant after Bonferroni correction. Concentrations of serum tryptophan and its metabolite kynurenine did not change significantly. This pilot RCT provides preliminary evidence of multicomponent CR leading to stabilization of hair cortisol levels and improved psychophysiological wellbeing and personality functioning. Impairments in personality functioning were correlated with neopterin levels, which may impact the symptomatology and outcome.

The core cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers amyloid beta (Aβ42 and Aβ40), total tau, and phosphorylated tau, have been extensively clinically validated, with very high diagnostic performance for AD, including the early phases of the disease. However, between-center differences in pre-analytical procedures may contribute to variability in measurements across laboratories. To resolve this issue, a workgroup was led by the Alzheimer's Association with experts from both academia and industry. The aim of the group was to develop a simplified and standardized pre-analytical protocol for CSF collection and handling before analysis for routine clinical use, and ultimately to ensure high diagnostic performance and minimize patient misclassification rates. Widespread application of the protocol would help minimize variability in measurements, which would facilitate the implementation of unified cut-off levels across laboratories, and foster the use of CSF biomarkers in AD diagnostics for the benefit of the patients., (© 2021 Alzheimer's Association. Alzheimer's & Dementia published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: COVID-19 has affected almost every country in the world, especially in terms of health system capacity and economic burden. People from sub-Saharan Africa (SSA) often face interaction between human immunodeficiency virus (HIV) infection and non-communicable diseases such as cardiovascular disease. Role of HIV infection and anti-retroviral treatment (ART) in altered cardiovascular risk is questionable and there is still need to further carry out research in this field. However, thus far it is unclear, what impact the COVID-19 co-infection in people living with HIV (PLHIV), with or without therapy will have. The ENDOCOVID project aims to investigate whether and how HIV-infection in COVID-19 patients modulates the time course of the disease, alters cardiovascular risk, and changes vascular endothelial function and coagulation parameters/ thrombosis risk., Methods: A total of 1026 patients will be included into this study. Cardiovascular research PLHIV with (n = 114 in each of the three recruiting centers) - or without - ART (n = 114 in each of the three recruiting centers) with COVID-19 and HIV-negative with COVID-19 (n = 114 in each of the three recruiting centers) will be carried out via clinical and biochemical measurements for cardiovascular risk factors and biomarkers of cardiovascular disease (CVD). Vascular and endothelial function will be measured by brachial artery flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) assessments, and retinal blood vessel analyses, along with vascular endothelial biomarkers and cogualation markers. The correlation between HIV-infection in COVID-19 PLHIV with or without ART and its role in enhancement of cardiovascular risk and endothelial dysfunction will be assessed at admission, weekly, at discharge and, 4 weeks post-discharge (if possible)., Impact of Project: The ENDOCOVID project aims to evaluate in the long-term the cardiovascular risk and vascular endothelial function in PLHIV thus revealing an important transitional cardiovascular phenotype in COVID-19. The study was registered under clinicaltrials.gov (NCT04709302)., (© 2021. The Author(s).)

Opn7b is a non-visual G protein-coupled receptor expressed in zebrafish. Here we find that Opn7b expressed in HEK cells constitutively activates the G i/o pathway and illumination with blue/green light inactivates G protein-coupled inwardly rectifying potassium channels. This suggests that light acts as an inverse agonist for Opn7b and can be used as an optogenetic tool to inhibit neuronal networks in the dark and interrupt constitutive inhibition in the light. Consistent with this prediction, illumination of recombinant expressed Opn7b in cortical pyramidal cells results in increased neuronal activity. In awake mice, light stimulation of Opn7b expressed in pyramidal cells of somatosensory cortex reliably induces generalized epileptiform activity within a short (<10 s) delay after onset of stimulation. Our study demonstrates a reversed mechanism for G protein-coupled receptor control and Opn7b as a tool for controlling neural circuit properties., (© 2021. The Author(s).)

Background: Lymphedema arises due to a malfunction of the lymphatic system, leading to extensive tissue swelling. Complete decongestive therapy (CDT), which is a physical therapy lasting for 3 weeks and includes manual lymphatic drainages (MLD), leads to fluid mobilization and increases in plasma volume. Here, we investigated hemodynamic responses induced by these fluid shifts due to CDT and MLD., Methods: Hemodynamic parameters were assessed continuously during a sit-to-stand test (5 min baseline, 5 min of standing, and 5 min of recovery). This intervention was repeated on days 1, 2, 7, 14, and 21 of CDT, before and after MLD. Volume regulatory hormones were assessed in plasma samples., Results: A total number of 13 patients took part in this investigation. Resting diastolic blood pressure significantly decreased over three weeks of CDT ( p = 0.048). No changes in baseline values were shown due to MLD. However, MLD led to a significant decrease in heart rate during orthostatic loading over all epochs on therapy day 14, as well as day 21. Volume regulatory hormones did not show changes over lymphedema therapy., Conclusion: We did not observe any signs of orthostatic hypotension at rest, as well as during to CDT, indicating that lymphedema patients do not display an elevated risk of orthostatic intolerance. Although baseline hemodynamics were not affected, MLD has shown to have potential beneficial effects on hemodynamic responses to a sit-to-stand test in patients undergoing lymphedema therapy.

Objectives: Tensiomyography (TMG) derived contraction time (Tc) and amplitude (Dm) are related to muscle fibre composition and to muscle atrophy/tone, respectively. However, the link between mobility and TMG-derived skeletal muscle contractile properties in older persons is unknown. The aim of the study was to correlate lower limb skeletal muscle contractile properties with balance and mobility measures in senior female residents of retirement homes in Austria., Methods: Twenty-eight female participants (aged from 67-99 years) were included in measurements of contractile properties (TMG) of four skeletal muscles: vastus lateralis, vastus medialis, biceps femoris and gastrocnemius medialis. Their balance and mobility performance was measured using a timed up and go test (TUG)., Results: Time needed to complete TUG is negatively correlated to biceps femoris (r= -0.490; p= 0.008), vastus lateralis (r= -0.414; p=0.028) and vastus medialis (r= -0.353; p=0.066) Dm and positively correlated to vastus lateralis Tc (r=0.456; p=0.015). Overall, vastus lateralis Tc and vastus medialis Dm explained 37% of TUG time variance., Conclusions: Our study demonstrates that TMG-derived quadriceps muscle contractile parameters are correlated with the balance and mobility function in female nursing home residents., Competing Interests: The authors have no conflict of interest.

Monitoring of children at heightened risk of cardio-metabolic diseases raises the need for accurate assessment of obesity. A standardized approach for measuring subcutaneous adipose tissue (SAT) by bright-mode ultrasound was evaluated in relation to body indices and anthropometry in a cross-sectional sample of 76 South African children (7-10 years) and 86 adolescents (13-17 years) to assess cardio-metabolic risk. SAT was higher in girls as compared to boys (children: 50.0 ± 21.7 mm > 34.42 ± 15.8 mm, adolescents: 140.9 ± 59.4 mm > 79.5 ± 75.6 mm, p < 0.001) and up to four times higher in adolescents than in children. In children, measures of relative body weight showed only a poor correlation to SAT (BMI: r = 0.607, p < 0.001), while in adolescents, BMI correlated high with SAT (r = 0.906, p < 0.001) based on high rates of overweight and obesity (41.8%). Children with identical BMIs may have large differences (>2-3-fold) in their amount of SAT. The moderate association to systolic (r = 0.534, r = 0.550, p < 0.001) and diastolic blood pressure (r = 0.402, r = 0.262, p < 0.001) further substantiates that SAT measured by ultrasound provides an accurate, safe and easy applicable approach for monitoring in children and adolescents at cardio-metabolic risk.

A novel coronavirus-Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2)-outbreak correlated with the global coronavirus disease 2019 (COVID-19) pandemic was declared by the WHO in March 2020, resulting in numerous counted cases attributed to SARS-CoV-2 worldwide. Herein, we discuss current knowledge on the available therapy options for patients diagnosed with COVID-19. Based on available scientific data, we present an overview of solutions in COVID-19 management by use of drugs, vaccines and antibodies. Many questions with non-conclusive answers on the measures for the management of the COVID-19 pandemic and its impact on health still exist-i.e., the actual infection percentage of the population, updated precise mortality data, variability in response to infection by the population, the nature of immunity and its duration, vaccine development issues, a fear that science might end up with excessive promises in response to COVID-19-and were raised among scientists. Indeed, science may or may not deliver results in real time. In the presented paper we discuss some consequences of disease, its detection and serological tests, some solutions to disease prevention and management, pitfalls and obstacles, including vaccination. The presented ideas and data herein are meant to contribute to the ongoing debate on COVID-19 without pre-selection of available information.

Lymphatic flow is necessary for maintenance of vital physiological functions in humans and animals. To carry out optimal lymphatic flow, adequate contractile activity of the lymphatic collectors is necessary. Like in all body systems, aging has also an effect on the lymphatic system. However, limited knowledge is available on how aging directly affects the lymphatic system anatomy, physiology and function. We investigated how senescence leads to alterations in morphology and function of the lymphatic vessels. We used the strategy of a review to summarize the scientific literature of studies that have been published in the area of lymphatic senescence. Searches were carried out on PubMed and Web of Science using predefined search queries. We obtained an initial set of 1060 publications. They were filtered to 114 publications based on strict inclusion and exclusion criteria. Finally, the most appropriate 57 studies that specifically addressed lymphatic senescence have been selected for the preparation of this review. Analysis of the literature showed that lymphatic senescence is associated with alterations in lymphatic muscles and nerve fibers, lymphatic glycocalyx function of lymphatic endothelial cells, effects of chronic ultraviolet light exposure and oxidative stress as well as changes in lymphatic pump, acute inflammation responses and immune function. The current review underscores the relevance of the understudied area of lymphatic senescence. Continued research on the impact of aging on the structure and function of the lymphatic vasculature is needed to provide further insights to develop innovative clinical diagnostic-and treatment-modalities as well as to reduce the morbidity associated with diseases related to the lymphatic system.