Effects of oxidized LDL versus IL-1ß/TNF-ɑ/INFÉ£ on human gingival mesenchymal stem cells properties.

AIMS: Oxidized low-density lipoprotein (oxLDL) is an important player in the course of metabolic inflammatory diseases. oxLDL was identified in the gingival crevicular fluid, denoting possible associations between oxLDL-induced inflammation and periodontal disease. The current investigation compared for the first-time direct effects of oxLDL to a cytokine cocktail of IL-1ß/TNF-ɑ/INF-γ on gingival mesenchymal stem cells' (G-MSCs) attributes. METHODS: Human third passage G-MSCs, isolated from connective tissue biopsies (n = 5) and characterized, were stimulated in three groups over 7 days: control group, cytokine group (IL-1ß[1 ng/mL], TNF-α[10 ng/mL], IFN-γ[100 ng/mL]), or oxLDL group (oxLDL [50 µg/mL]). Next Generation Sequencing and KEGG pathway enrichment analysis, stemness gene expression (NANOG/SOX2/OCT4A), cellular proliferation, colony-formation, multilinear potential, and altered intracellular pathways were investigated via histochemistry, next-generation sequencing, and RT-qPCR. RESULTS: G-MSCs exhibited all mesenchymal stem cells' characteristics. oxLDL group and cytokine group displayed no disparities in their stemness markers (p > .05). Next-generation-sequencing revealed altered expression of the TXNIP gene in response to oxLDL treatment compared with controls (p = .04). Following an initial boosting for up to 5 days by inflammatory stimuli, over 14 day, cellular counts [median count ×10-5 (Q25/Q75)] were utmost in control - [2.6607 (2.0804/4.5357)], followed by cytokine - [0.0433 (0.0026/1.4215)] and significantly lowered in the oxLDL group [0.0274 (0.0023/0.7290); p = .0047]. Osteogenic differentiation [median relative Ca2+ content(Q25/Q75)] was significantly lower in cytokine - [0.0066 (0.0052/0.0105)] compared to oxLDL - [0.0144 (0.0108/0.0216)] (p = .0133), with no differences notable for chondrogenic and adipogenic differentiation (p > .05). CONCLUSIONS: Within the current investigation's limitations, in contrast to cytokine-mediated inflammation, G-MSCs appear to be minimally responsive to oxLDL-mediated metabolic inflammation, with little negative effect on their differentiation attributes and significantly reduced cellular proliferation.

Dispersal and connectivity in increasingly extreme climatic conditions.

While climate change has been shown to impact several life-history traits of wild-living animal populations, little is known about its effects on dispersal and connectivity. Here, we capitalize on the highly variable flooding regime of the Okavango Delta to investigate the impacts of changing environmental conditions on the dispersal and connectivity of the endangered African wild dog (Lycaon pictus). Based on remote sensed flood extents observed over 20 years, we derive two extreme flood scenarios: a minimum and a maximum flood extent, representative of very dry and very wet environmental periods. These conditions are akin to those anticipated under increased climatic variability, as it is expected under climate change. Using a movement model parameterized with GPS data from dispersing individuals, we simulate 12,000 individual dispersal trajectories across the ecosystem under both scenarios and investigate patterns of connectivity. Across the entire ecosystem, surface water coverage during maximum flood extent reduces dispersal success (i.e., the propensity of individuals to disperse between adjacent subpopulations) by 12% and increases dispersal durations by 17%. Locally, however, dispersal success diminishes by as much as 78%. Depending on the flood extent, alternative dispersal corridors emerge, some of which in the immediate vicinity of human-dominated landscapes. Notably, under maximum flood extent, the number of dispersing trajectories moving into human-dominated landscapes decreases by 41% at the Okavango Delta's inflow, but increases by 126% at the Delta's distal end. This may drive the amplification of human-wildlife conflict. While predicting the impacts of climate change on environmental conditions on the ground remains challenging, our results highlight that environmental change may have significant consequences for dispersal patterns and connectivity, and ultimately, population viability. Acknowledging and anticipating such impacts will be key to effective conservation strategies and to preserve vital dispersal corridors in light of climate change and other human-related landscape alterations.

Electroencephalographic guided propofol-remifentanil TCI anesthesia with and without dexmedetomidine in a geriatric population: electroencephalographic signatures and clinical evaluation.

Elderly and multimorbid patients are at high risk for developing unfavorable postoperative neurocognitive outcomes; however, well-adjusted and EEG-guided anesthesia may help titrate anesthesia and improve postoperative outcomes. Over the last decade, dexmedetomidine has been increasingly used as an adjunct in the perioperative setting. Its synergistic effect with propofol decreases the dose of propofol needed to induce and maintain general anesthesia. In this pilot study, we evaluate two highly standardized anesthetic regimens for their potential to prevent burst suppression and postoperative neurocognitive dysfunction in a high-risk population. Prospective, randomized clinical trial with non-blinded intervention. Operating room and post anesthesia care unit at Hospital Base San José, Osorno/Universidad Austral, Valdivia, Chile. 23 patients with scheduled non-neurologic, non-cardiac surgeries with age > 69 years and a planned intervention time > 60 min. Patients were randomly assigned to receive either a propofol-remifentanil based anesthesia or an anesthetic regimen with dexmedetomidine-propofol-remifentanil. All patients underwent a slow titrated induction, followed by a target controlled infusion (TCI) of propofol and remifentanil (n = 10) or propofol, remifentanil and continuous dexmedetomidine infusion (n = 13). We compared the perioperative EEG signatures, drug-induced changes, and neurocognitive outcomes between two anesthetic regimens in geriatric patients. We conducted a pre- and postoperative Montreal Cognitive Assessment (MoCa) test and measured the level of alertness postoperatively using a sedation agitation scale to assess neurocognitive status. During slow induction, maintenance, and emergence, burst suppression was not observed in either group; however, EEG signatures differed significantly between the two groups. In general, EEG activity in the propofol group was dominated by faster rhythms than in the dexmedetomidine group. Time to responsiveness was not significantly different between the two groups (p = 0.352). Finally, no significant differences were found in postoperative cognitive outcomes evaluated by the MoCa test nor sedation agitation scale up to one hour after extubation. This pilot study demonstrates that the two proposed anesthetic regimens can be safely used to slowly induce anesthesia and avoid EEG burst suppression patterns. Despite the patients being elderly and at high risk, we did not observe postoperative neurocognitive deficits. The reduced alpha power in the dexmedetomidine-treated group was not associated with adverse neurocognitive outcomes.

Assessment of the Prescribing Pharmacist's Role in Supporting Access to Prescription-Only Medicines-Metadata Analysis in Poland.

In 2020, pharmacists in Poland received additional authority to prescribe drugs. In this study, we analyzed prescribing after the implementation of this new responsibility. We assessed how the new regulation works in practice and what it means for the healthcare system in the area of access to prescription-only medicines. Data analysis included information on the prescriptions written, the type of substance according to the ATC classification, and data on the prescribing pharmacists. The study used over 2.994 million e-prescriptions written by pharmacists in Poland, which were made available by the e-Health Center. The largest group of drugs prescribed were drugs used in the treatment of cardiovascular diseases, accounting for 25% of all prescribed medications during the time of the analysis. The next prescription groups were for drugs used in gastrointestinal diseases and metabolic disorders, and those acting on the central nervous system, the respiratory system, and the musculoskeletal system. Among pharmaceutical prescriptions, 73% were pharmaceutical prescriptions issued in pharmacies at full price to the patient. The results indicate that pharmacists are eager to use their permission to prescribe drugs in authority situations. Almost three million records showed improved patient access to medicines in the healthcare system (approximately 5% of repeat prescriptions for all patients during the study period). These data confirm the possibility of cooperation between physicians and pharmacists in strengthening the efficiency of the patient healthcare system. An important conclusion from this work is the need to create the possibility for the pharmacist to access the information resources of the implemented Internet Patient Account system, including therapeutic indications for the drugs used.

Higher Mortality Is Not a Universal Cost of Dispersal: A Case Study in African Wild Dogs.

AbstractMortality is considered one of the main costs of dispersal. A reliable evaluation of mortality, however, is often hindered by a lack of information about the fate of individuals that disappear under unexplained circumstances (i.e., missing individuals). Here, we addressed this uncertainty by applying a Bayesian mortality analysis that inferred the fate of missing individuals according to information from individuals with known fate. Specifically, we tested the hypothesis that mortality during dispersal is higher than mortality among nondispersers using 32 years of mark-resighting data from a free-ranging population of the endangered African wild dog (Lycaon pictus) in northern Botswana. Contrary to expectations, we found that mortality during dispersal was lower than mortality among nondispersers, indicating that higher mortality is not a universal cost of dispersal. Our findings suggest that group living can incur costs for certain age classes, such as limited access to resources as group density increases, that exceed the mortality costs associated with dispersal. By challenging the accepted expectation of higher mortality during dispersal, we urge for further investigations of this key life history trait and propose a robust statistical approach to reduce bias in mortality estimates.

Phase-Driving Hole Spin Qubits.

The spin-orbit interaction in spin qubits enables spin-flip transitions, resulting in Rabi oscillations when an external microwave field is resonant with the qubit frequency. Here, we introduce an alternative driving mechanism mediated by the strong spin-orbit interactions in hole spin qubits, where a far-detuned oscillating field couples to the qubit phase. Phase-driving at radio frequencies, orders of magnitude slower than the microwave qubit frequency, induces highly nontrivial spin dynamics, violating the Rabi resonance condition. By using a qubit integrated in a silicon fin field-effect transistor, we demonstrate a controllable suppression of resonant Rabi oscillations and their revivals at tunable sidebands. These sidebands enable alternative qubit control schemes using global fields and local far-detuned pulses, facilitating the design of dense large-scale qubit architectures with local qubit addressability. Phase-driving also decouples Rabi oscillations from noise, an effect due to a gapped Floquet spectrum and can enable Floquet engineering high-fidelity gates in future quantum processors.

Effect of Hyperbaric Oxygen and Inflammation on Human Gingival Mesenchymal Stem/Progenitor Cells.

The present study explores for the first time the effect of hyperbaric oxygen (HBO) on gingival mesenchymal stem cells' (G-MSCs) gene expression profile, intracellular pathway activation, pluripotency, and differentiation potential under an experimental inflammatory setup. G-MSCs were isolated from five healthy individuals (n = 5) and characterized. Single (24 h) or double (72 h) HBO stimulation (100% O2, 3 bar, 90 min) was performed under experimental inflammatory [IL-1ß (1 ng/mL)/TNF-α (10 ng/mL)/IFN-γ (100 ng/mL)] and non-inflammatory micro-environment. Next Generation Sequencing and KEGG pathway enrichment analysis, G-MSCs' pluripotency gene expression, Wnt-/ß-catenin pathway activation, proliferation, colony formation, and differentiation were investigated. G-MSCs demonstrated all mesenchymal stem/progenitor cells' characteristics. The beneficial effect of a single HBO stimulation was evident, with anti-inflammatory effects and induction of differentiation (TLL1, ID3, BHLHE40), proliferation/cell survival (BMF, ID3, TXNIP, PDK4, ABL2), migration (ABL2) and osteogenic differentiation (p < 0.05). A second HBO stimulation at 72 h had a detrimental effect, significantly increasing the inflammation-induced cellular stress and ROS accumulation through HMOX1, BHLHE40, and ARL4C amplification and pathway enrichment (p < 0.05). Results outline a positive short-term single HBO anti-inflammatory, regenerative, and differentiation stimulatory effect on G-MSCs. A second (72 h) stimulation is detrimental to the same properties. The current results could open new perspectives in the clinical application of short-termed HBO induction in G-MSCs-mediated periodontal reparative/regenerative mechanisms.

Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.

BACKGROUND: People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic. OBJECTIVE: To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic. METHODS: Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP. FINDINGS: In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic. CONCLUSIONS: People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use. CLINICAL IMPLICATIONS: Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.

Kinetics of UV Radiation-Induced Fast Collapse and Recovery in Thermally Cycled and Rehydrated Light- and Thermo- Double-Responsive Copolymer Films Probed by In Situ Neutron Reflectivity.

The kinetics of UV radiation-induced fast collapse and recovery in thermally cycled and rehydrated light- and thermo- double-responsive copolymer films of poly(oligo(ethylene glycol) methyl ether methacrylate-co-6-(4-phenylazophenoxy)hexyl acrylate), abbreviated as P(OEGMA300-co-PAHA), are probed by in situ neutron reflectivity (NR). The copolymer film is exposed to a thermal treatment starting at a temperature of 60 °C, which is well above its transition temperature (TT = 53 °C) before the temperature is rapidly decreased from 60 to 23 °C. Based on the applied protocol, the initially collapsed P(OEGMA300-co-PAHA) film is rehydrated due to the switching of polymer chains from a more hydrophobic to a more hydrophilic state when the temperature falls below its TT. The whole rehydration process can be divided into 3 stages: D2O absorption, chain rearrangement, and film reswelling. After rehydration, the thermally cycled P(OEGMA300-co-PAHA) film is switched by UV irradiation via setting the UV radiation on and off. Considering the UV-induced collapse and recovery, both processes are slower than those observed in freshly hydrated films without any thermal stimulus history. Therefore, the experienced thermal history of the film should be considered in the design of sensors and detectors based on double-responsive copolymer films.

SNF1-RELATED KINASE 1 and TARGET OF RAPAMYCIN control light-responsive splicing events and developmental characteristics in etiolated Arabidopsis seedlings.

The kinases SNF1-RELATED KINASE 1 (SnRK1) and TARGET OF RAPAMYCIN (TOR) are central sensors of the energy status, linking this information via diverse regulatory mechanisms to plant development and stress responses. Despite the well-studied functions of SnRK1 and TOR under conditions of limited or ample energy availability, respectively, little is known about the extent to which the 2 sensor systems function and how they are integrated in the same molecular process or physiological context. Here, we demonstrate that both SnRK1 and TOR are required for proper skotomorphogenesis in etiolated Arabidopsis (Arabidopsis thaliana) seedlings, light-induced cotyledon opening, and regular development in light. Furthermore, we identify SnRK1 and TOR as signaling components acting upstream of light- and sugar-regulated alternative splicing events, expanding the known action spectra for these 2 key players in energy signaling. Our findings imply that concurring SnRK1 and TOR activities are required throughout various phases of plant development. Based on the current knowledge and our findings, we hypothesize that turning points in the activities of these sensor kinases, as expected to occur upon illumination of etiolated seedlings, instead of signaling thresholds reflecting the nutritional status may modulate developmental programs in response to altered energy availability.

Effects of lifestyle and associated diseases on serum CC16 suggest complex interactions among metabolism, heart and lungs.

INTRODUCTION: Clara cell 16-kDa protein (CC16) is an anti-inflammatory, immunomodulatory secreted pulmonary protein with reduced serum concentrations in obesity according to recent data. OBJECTIVE: Studies focused solely on bodyweight, which does not properly reflect obesity-associated implications of the metabolic and reno-cardio-vascular system. The purpose of this study was therefore to examine CC16 in a broad physiological context considering cardio-metabolic comorbidities of primary pulmonary diseases. METHODS: CC16 was quantified in serum samples in a subset of the FoCus (N = 497) and two weight loss intervention cohorts (N = 99) using ELISA. Correlation and general linear regression analyses were applied to assess CC16 effects of lifestyle, gut microbiota, disease occurrence and treatment strategies. Importance and intercorrelation of determinants were validated using random forest algorithms. RESULTS: CC16 A38G gene mutation, smoking and low microbial diversity significantly decreased CC16. Pre-menopausal female displayed lower CC16 compared to post-menopausal female and male participants. Biological age and uricosuric medications increased CC16 (all p < 0.01). Adjusted linear regression revealed CC16 lowering effects of high waist-to-hip ratio (est. -11.19 [-19.4; -2.97], p = 7.99 × 10-3), severe obesity (est. -2.58 [-4.33; -0.82], p = 4.14 × 10-3) and hypertension (est. -4.31 [-7.5; -1.12], p = 8.48 × 10-3). ACEi/ARB medication (p = 2.5 × 10-2) and chronic heart failure (est. 4.69 [1.37; 8.02], p = 5.91 × 10-3) presented increasing effects on CC16. Mild associations of CC16 were observed with blood pressure, HOMA-IR and NT-proBNP, but not manifest hyperlipidemia, type 2 diabetes, diet quality and dietary weight loss intervention. CONCLUSION: A role of metabolic and cardiovascular abnormalities in the regulation of CC16 and its modifiability by behavioral and pharmacological interventions is indicated. Alterations by ACEi/ARB and uricosurics could point towards regulatory axes comprising the renin-angiotensin-aldosterone system and purine metabolism. Findings altogether strengthen the importance of interactions among metabolism, heart and lungs.

Behavioral responses of terrestrial mammals to COVID-19 lockdowns.

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.

Overconfidence at the time of COVID-19:Does it lead to laxer attitudes?

BACKGROUND: Health education campaigns often aim to create awareness by increasing objective knowledge about pathogens, such as COVID-19. However, the present paper proposes that confidence in one's knowledge more than knowledge is a significant factor that leads to a laxer attitude toward COVID-19 and hence lower support for protective measures and reduced intention to comply with preemptive behaviors. METHODS: We tested two hypotheses in three studies conducted between 2020 and 2022. In Study 1, we assessed participants' level of knowledge and confidence, as well as attitudes toward COVID-19. In Study 2, we tested the relation between fear of COVID-19 and protective behaviors. In Study 3, we used an experimental approach to show the causal effect of overconfidence on fear of COVID-19. In addition to manipulating overconfidence and measuring fear of COVID-19, we also measured prophylactic behaviors. RESULTS: In Study 1, more overconfident participants had a laxer attitude toward COVID-19. While knowledge had an increasing effect on worry, confidence in said knowledge significantly decreased worry about COVID-19. In Study 2, participants who were more worried about COVID-19 were more likely to engage in protective behaviors (e.g., wearing masks). In Study 3, we show that when overconfidence was experimentally diminished, fear of COVID-19 increased. The results support our claim that the effect of overconfidence on attitudes toward COVID-19 is causal in nature. Moreover, the results show that people with higher fear of COVID-19 are more likely to wear masks, use hand sanitizers, avoid crowded places or social gatherings, and get vaccinated. CONCLUSIONS: Managing adherence to public health measures is critical when it comes to highly infectious diseases. Our findings suggest that efficient information campaigns to increase adherence to public health measures should focus on calibrating people's confidence in their knowledge about COVID-19 to prevent the spread of the virus.

Relapsing Syndrome of Inappropriate Antidiuretic Hormone Production Responding to Tolvaptan Treatment in a Patient With a Micronodular Formation of the Posterior Pituitary Gland.

The syndrome of inappropriate ADH-secretion (SIADH) is a common cause of low sodium levels with diverse aetiology. Here, we report a case of a 41 years old male patient diagnosed with SIADH and a good response to Tolvaptan therapy. Of interest, as a potential unique cause, magnetic resonance imaging revealed a micronodular structure in the posterior pituitary, while no other common cause of SIADH could be identified. Hence, to the best of our knowledge, this is the first case of a Tolvaptan-responsive SIADH associated with a pituitary micronodular structure.

Integration of optic flow into the sky compass network in the brain of the desert locust.

Flexible orientation through any environment requires a sense of current relative heading that is updated based on self-motion. Global external cues originating from the sky or the earth's magnetic field and local cues provide a reference frame for the sense of direction. Locally, optic flow may inform about turning maneuvers, travel speed and covered distance. The central complex in the insect brain is associated with orientation behavior and largely acts as a navigation center. Visual information from global celestial cues and local landmarks are integrated in the central complex to form an internal representation of current heading. However, it is less clear how optic flow is integrated into the central-complex network. We recorded intracellularly from neurons in the locust central complex while presenting lateral grating patterns that simulated translational and rotational motion to identify these sites of integration. Certain types of central-complex neurons were sensitive to optic-flow stimulation independent of the type and direction of simulated motion. Columnar neurons innervating the noduli, paired central-complex substructures, were tuned to the direction of simulated horizontal turns. Modeling the connectivity of these neurons with a system of proposed compass neurons can account for rotation-direction specific shifts in the activity profile in the central complex corresponding to turn direction. Our model is similar but not identical to the mechanisms proposed for angular velocity integration in the navigation compass of the fly Drosophila.

A three-step approach for assessing landscape connectivity via simulated dispersal: African wild dog case study.

Context: Dispersal of individuals contributes to long-term population persistence, yet requires a sufficient degree of landscape connectivity. To date, connectivity has mainly been investigated using least-cost analysis and circuit theory, two methods that make assumptions that are hardly applicable to dispersal. While these assumptions can be relaxed by explicitly simulating dispersal trajectories across the landscape, a unified approach for such simulations is lacking. Objectives: Here, we propose and apply a simple three-step approach to simulate dispersal and to assess connectivity using empirical GPS movement data and a set of habitat covariates. Methods: In step one of the proposed approach, we use integrated step-selection functions to fit a mechanistic movement model describing habitat and movement preferences of dispersing individuals. In step two, we apply the parameterized model to simulate dispersal across the study area. In step three, we derive three complementary connectivity maps; a heatmap highlighting frequently traversed areas, a betweenness map pinpointing dispersal corridors, and a map of inter-patch connectivity indicating the presence and intensity of functional links between habitat patches. We demonstrate the applicability of the proposed three-step approach in a case study in which we use GPS data collected on dispersing African wild dogs (Lycaon pictus) inhabiting northern Botswana. Results: Using step-selection functions we successfully parametrized a detailed dispersal model that described dispersing individuals' habitat and movement preferences, as well as potential interactions among the two. The model substantially outperformed a model that omitted such interactions and enabled us to simulate 80,000 dispersal trajectories across the study area. Conclusion: By explicitly simulating dispersal trajectories, our approach not only requires fewer unrealistic assumptions about dispersal, but also permits the calculation of multiple connectivity metrics that together provide a comprehensive view of landscape connectivity. In our case study, the three derived connectivity maps revealed several wild dog dispersal hotspots and corridors across the extent of our study area. Each map highlighted a different aspect of landscape connectivity, thus emphasizing their complementary nature. Overall, our case study demonstrates that a simulation-based approach offers a simple yet powerful alternative to traditional connectivity modeling techniques. It is therefore useful for a variety of applications in ecological, evolutionary, and conservation research. Supplementary Information: The online version contains supplementary material available at 10.1007/s10980-023-01602-4.

A Prospective Analysis of the Metyrapone Short Test Using Targeted and Untargeted Metabolomics.

INTRODUCTION: The present study aimed to prove the metyrapone short test in a day clinic to be suitable for examining the integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with suspected secondary and tertiary adrenal insufficiency and to identify novel effector molecules in acute stress response. METHODS: 44 patients were prospectively enrolled. Based on stimulated 11-deoxycortisol levels, patients were divided into a physiological (11-deoxycortisol ≥70 µg/L) and a pathological (11-deoxycortisol <70 µg/L) response group. Clinical follow-up examination was performed for validation. Ultraperformance liquid chromatography tandem mass spectrometry and a Fourier-transform-ion-cyclotron-resonance-mass-spectrometry were used for targeted and untargeted steroid metabolomics. RESULTS: At baseline, lower levels of cortisone (42 vs. 50 nmol/L, p = 0.048) and 17-OH-progesterone (0.6 vs. 1.2 nmol/L, p = 0.041) were noted in the pathological response group. After metyrapone administration, the pathological response group exhibited significantly lower 11-deoxycortisol (39.0 vs. 94.2 µg/L, p < 0.001) and ACTH (49 vs. 113 pg/mL, p < 0.001) concentrations as well as altered upstream metabolites. Untargeted metabolomics identified a total of 76 metabolites to be significantly up- or downregulated by metyrapone. A significant increase of the bile acid glycochenodeoxycholic acid (GCDC, p < 0.01) was detected in both groups with an even stronger increase in the physiological response group. After a mean follow-up of 17.2 months, an 11-deoxycortisol cut-off of 70 µg/L showed a high diagnostic performance (sensitivity 100%, specificity 96%). CONCLUSION: The metyrapone short test is safe and feasible in a day clinic setting. The alterations of the bile acid GCDC indicate that the liver might be involved in the acute stress response of the HPA axis.

Resting Energy Expenditure in the Critically Ill and Healthy Elderly-A Retrospective Matched Cohort Study.

The use of indirect calorimetry to measure resting energy expenditure (mREE) is widely recommended as opposed to calculating REE (cREE) by predictive equations (PE). The aim of this study was to compare mREE with cREE in critically ill, mechanically ventilated patients aged ≥ 75 years and a healthy control group matched by age, gender and body mass index. The primary outcome was the PE accuracy rate of mREE/cREE, derived using Bland Altman plots. Secondary analyses included linear regression analyses for determinants of intraindividual mREE/cREE differences in the critically ill and interindividual mREE differences in the matched healthy cohort. In this retrospective study, 90 critically ill patients (median age 80 years) and 58 matched healthy persons were included. Median mREE was significantly higher in the critically ill (1457 kcal/d) versus the healthy cohort (1351 kcal/d), with low PE accuracy rates (21% to 49%). Independent predictors of mREE/cREE differences in the critically ill were body temperature, heart rate, FiO2, hematocrit, serum sodium and urea. Body temperature, respiratory rate, and FiO2 were independent predictors of interindividual mREE differences (critically ill versus healthy control). In conclusion, the commonly used PE in the elderly critically ill are inaccurate. Respiratory, metabolic and energy homeostasis variables may explain intraindividual mREE/cREE as well as interindividual mREE differences.

Cohort profile: the Food Chain Plus (FoCus) cohort.

The Food Chain Plus (FoCus) cohort was launched in 2011 for population-based research related to metabolic inflammation. To characterize this novel pathology in a comprehensive manner, data collection included multiple omics layers such as phenomics, microbiomics, metabolomics, genomics, and metagenomics as well as nutrition profiling, taste perception phenotyping and social network analysis. The cohort was set-up to represent a Northern German population of the Kiel region. Two-step recruitment included the randomised enrolment of participants via residents' registration offices and via the Obesity Outpatient Centre of the University Medical Center Schleswig-Holstein (UKSH). Hence, both a population- and metabolic inflammation- based cohort was created. In total, 1795 individuals were analysed at baseline. Baseline data collection took place between 2011 and 2014, including 63% females and 37% males with an age range of 18-83 years. The median age of all participants was 52.0 years [IQR: 42.5; 63.0 years] and the median baseline BMI in the study population was 27.7 kg/m2 [IQR: 23.7; 35.9 kg/m2]. In the baseline cohort, 14.1% of participants had type 2 diabetes mellitus, which was more prevalent in the subjects of the metabolic inflammation group (MIG; 31.8%). Follow-up for the assessment of disease progression, as well as the onset of new diseases with changes in subject's phenotype, diet or lifestyle factors is planned every 5 years. The first follow-up period was finished in 2020 and included 820 subjects.