Heart rate vARiability and physical activity in inpatient treatMent of burnOut and DepressIon (HARMODI): protocol of a cross-sectional study with up to 8-week follow up.

INTRODUCTION: Chronic stress can cause an imbalance within the autonomic nervous system, thereby affecting cardiovascular and mental health. Physical activity (PA) may have a positive effect on the autonomic nervous system and stress-related disorders, such as depression and burnout. Heart rate variability (HRV) is a non-invasive marker of the autonomic nervous system. However, limited and inconsistent data exist on the exact relationship between HRV, PA and depression and burnout symptoms. The HARMODI study aims to explore whether HRV is a feasible marker of depression and burnout symptoms and aims to evaluate the role of PA in the treatment of stress-related disorders. METHODS AND ANALYSES: This is an observational study with a cross-sectional up to 8 week follow-up study design. A total of 153 patients, undergoing psychiatric inpatient treatment with burnout syndrome (Z73) and depressive episode (F32 or F33) or adjustment disorder (F43.2), will be recruited. Data on depression and burnout symptoms, HRV recordings (24-hour, supine, standing and exercise stress test), cognitive function, cardiorespiratory fitness, cardiovascular health, balance and strength will be collected at baseline (T1) and after up to 8 weeks (T2). Continuous data on PA and Ecological Momentary Assessments of exhaustion, mood and tension will be monitored daily throughout inpatient treatment. Multiple regression models, adjusted for potential confounders, will assess the association between HRV as the primary outcome, PA and depression and burnout severity score. ETHICS AND DISSEMINATION: The protocol has been approved by Swiss Ethics Committee, Cantonal Ethics Committee Zürich. Results of HARMODI will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05874856.

Experimental and Model-Based Analysis to Optimize Microalgal Biomass Productivity in a Pilot-Scale Tubular Photobioreactor.

A dynamic coarse-grained model of microalgal growth considering light availability and temperature under discontinuous bioprocess operation was parameterized using experimental data from 15 batch cultivations of Nannochloropsis granulata in a pilot-scale tubular photobioreactor. The methodology applied consists of a consecutive two-step model parameter estimation using pooled, clustered and reorganized data to obtain initial estimates and multi-experiment fitting to obtain the final estimates, which are: maximum specific growth rate µmax = 1.56 d-1, specific photon half-saturation constant K S,ph = 1.89 mol ph g X - 1 d - 1 , specific photon maintenance coefficient m ph = 0.346 mol ph g X - 1 d - 1 and the cardinal temperatures T min = 2.3°C, T opt = 27.93°C and T max = 32.59°C. Biomass productivity prediction proved highly accurate, expressed by the mean absolute percent error MAPE = 7.2%. Model-based numerical optimization of biomass productivity for repeated discontinuous operation with respect to the process parameters cultivation cycle time, inoculation biomass concentration and temperature yielded productivity gains of up to 35%. This optimization points to best performance under continuous operation. The approach successfully applied here to small pilot-scale confirms an earlier one to lab-scale, indicating its transferability to larger scale tubular photobioreactors.

Midterm Results after Implant-Free Patellar Fixation Technique for Medial Patellofemoral Ligament Reconstruction.

Problems and complications concerning the patellar fixation in medial patellofemoral ligament reconstruction (MPFLR) have been reported. The purpose of this retrospective study was to systematically analyze the surgical technique for MPFLR with a V: -shaped patellar bonetunnel for implant-free fixation of an autologous gracilis tendon, allowing early functional rehabilitation, regarding restoration of the patellofemoral stability, patient satisfaction, return to sports, and technique-specific complications. In 2010, 128 cases of consecutive isolated MPFLR were performed. All these cases were included. After a minimum follow-up of 3 years, 104 cases were retrospectively analyzed (follow-up: 81.3%) with regard to redislocation, subjective functional outcome (Tegner's score and sports level compared with preoperative level), patient satisfaction, revision surgery, and technique-specific complications. After a follow-up of 45.7 ± 3.2 months, 101 of 104 cases (97.1%) showed no redislocation. Mean Tegner's score was 5.1 ± 1.8 (range, 2-9). A total of 61.5% patients reported about a higher sports level compared with their preoperative level. The patient satisfaction was high with 94.2%. In two cases (1.9%), technique-specific problems occurred as the bone bridge of the V: -shaped tunnel was insufficient due to a malpositioning of the aiming device. No further technique-specific problems occurred and no revision surgery was necessary during the observational period. The presented surgical technique is safe and it reliably restores the patellofemoral stability, with a low rate of redislocations, an excellent subjective functional outcome, and a high-patient-reported satisfaction. No major technique-specific complications occurred.

How fast can raptors see?

Birds, and especially raptors, are highly visual animals. Some of them have the highest spatial resolving power known in the animal kingdom, allowing prey detection at distance. While many raptors visually track fast-moving and manoeuvrable prey, requiring high temporal resolution, this aspect of their visual system has never been studied before. In this study, we estimated how fast raptors can see, by measuring the flicker fusion frequency of three species with different lifestyles. We found that flicker fusion frequency differed among species, being at least 129 Hz in the peregrine falcon, Falco peregrinus, 102 Hz in the saker falcon, Falco cherrug, and 81 Hz in the Harris's hawk, Parabuteo unicinctus We suggest a potential link between fast vision and hunting strategy, with high temporal resolution in the fast-flying falcons that chase fast-moving, manoeuvrable prey and a lower resolution in the Harris's hawk, which flies more slowly and targets slower prey.

Optimality in the zonation of ammonia detoxification in rodent liver.

The rodent liver eliminates toxic ammonia. In mammals, three enzymes (or enzyme systems) are involved in this process: glutaminase, glutamine synthetase and the urea cycle enzymes, represented by carbamoyl phosphate synthetase. The distribution of these enzymes for optimal ammonia detoxification was determined by numerical optimization. This in silico approach predicted that the enzymes have to be zonated in order to achieve maximal removal of toxic ammonia and minimal changes in glutamine concentration. Using 13 compartments, representing hepatocytes, the following predictions were generated: glutamine synthetase is active only within a narrow pericentral zone. Glutaminase and carbamoyl phosphate synthetase are located in the periportal zone in a non-homogeneous distribution. This correlates well with the paradoxical observation that in a first step glutamine-bound ammonia is released (by glutaminase) although one of the functions of the liver is detoxification by ammonia fixation. The in silico approach correctly predicted the in vivo enzyme distributions also for non-physiological conditions (e.g. starvation) and during regeneration after tetrachloromethane (CCl4) intoxication. Metabolite concentrations of glutamine, ammonia and urea in each compartment, representing individual hepatocytes, were predicted. Finally, a sensitivity analysis showed a striking robustness of the results. These bioinformatics predictions were validated experimentally by immunohistochemistry and are supported by the literature. In summary, optimization approaches like the one applied can provide valuable explanations and high-quality predictions for in vivo enzyme and metabolite distributions in tissues and can reveal unknown metabolic functions.

Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation.

INTRODUCTION: Discrimination of rheumatoid arthritis (RA) patients from patients with other inflammatory or degenerative joint diseases or healthy individuals purely on the basis of genes differentially expressed in high-throughput data has proven very difficult. Thus, the present study sought to achieve such discrimination by employing a novel unbiased approach using rule-based classifiers. METHODS: Three multi-center genome-wide transcriptomic data sets (Affymetrix HG-U133 A/B) from a total of 79 individuals, including 20 healthy controls (control group - CG), as well as 26 osteoarthritis (OA) and 33 RA patients, were used to infer rule-based classifiers to discriminate the disease groups. The rules were ranked with respect to Kiendl's statistical relevance index, and the resulting rule set was optimized by pruning. The rule sets were inferred separately from data of one of three centers and applied to the two remaining centers for validation. All rules from the optimized rule sets of all centers were used to analyze their biological relevance applying the software Pathway Studio. RESULTS: The optimized rule sets for the three centers contained a total of 29, 20, and 8 rules (including 10, 8, and 4 rules for 'RA'), respectively. The mean sensitivity for the prediction of RA based on six center-to-center tests was 96% (range 90% to 100%), that for OA 86% (range 40% to 100%). The mean specificity for RA prediction was 94% (range 80% to 100%), that for OA 96% (range 83.3% to 100%). The average overall accuracy of the three different rule-based classifiers was 91% (range 80% to 100%). Unbiased analyses by Pathway Studio of the gene sets obtained by discrimination of RA from OA and CG with rule-based classifiers resulted in the identification of the pathogenetically and/or therapeutically relevant interferon-gamma and GM-CSF pathways. CONCLUSION: First-time application of rule-based classifiers for the discrimination of RA resulted in high performance, with means for all assessment parameters close to or higher than 90%. In addition, this unbiased, new approach resulted in the identification not only of pathways known to be critical to RA, but also of novel molecules such as serine/threonine kinase 10.

Integrated metabolic spatial-temporal model for the prediction of ammonia detoxification during liver damage and regeneration.

UNLABELLED: The impairment of hepatic metabolism due to liver injury has high systemic relevance. However, it is difficult to calculate the impairment of metabolic capacity from a specific pattern of liver damage with conventional techniques. We established an integrated metabolic spatial-temporal model (IM) using hepatic ammonia detoxification as a paradigm. First, a metabolic model (MM) based on mass balancing and mouse liver perfusion data was established to describe ammonia detoxification and its zonation. Next, the MM was combined with a spatial-temporal model simulating liver tissue damage and regeneration after CCl4 intoxication. The resulting IM simulated and visualized whether, where, and to what extent liver damage compromised ammonia detoxification. It allowed us to enter the extent and spatial patterns of liver damage and then calculate the outflow concentrations of ammonia, glutamine, and urea in the hepatic vein. The model was validated through comparisons with (1) published data for isolated, perfused livers with and without CCl4 intoxication and (2) a set of in vivo experiments. Using the experimentally determined portal concentrations of ammonia, the model adequately predicted metabolite concentrations over time in the hepatic vein during toxin-induced liver damage and regeneration in rodents. Further simulations, especially in combination with a simplified model of blood circulation with three ammonia-detoxifying compartments, indicated a yet unidentified process of ammonia consumption during liver regeneration and revealed unexpected concomitant changes in amino acid metabolism in the liver and at extrahepatic sites. CONCLUSION: The IM of hepatic ammonia detoxification considerably improves our understanding of the metabolic impact of liver disease and highlights the importance of integrated modeling approaches on the way toward virtual organisms.

Initial immune reaction and angiogenesis in bone healing.

During hematoma formation following injury, an inflammatory reaction ensues as an initial step in the healing process. As granulation tissue matures, revascularization is a prerequisite for successful healing. The hypothesis of this study was that scarless tissue reconstitution in the regenerative bone healing process is dependent on a balanced immune reaction that initiates revasculatory steps. To test this hypothesis, cellular composition and expression profiles of a bone hematoma (regenerative, scarless) was compared with a muscle soft tissue hematoma (healing with a scar) in a sheep model. Upregulation of regulatory T helper cells and anti-inflammatory cytokine expression (IL-10) coincided with an upregulation of angiogenic factors (HIF1α and HIF1α regulated genes) in the regenerative bone hematoma but not in the soft tissue hematoma. These results indicate that the timely termination of inflammation and early onset of revascularization are interdependent and essential for a regenerative healing process. Prolonged pro-inflammatory signaling occurring in a delayed bone-healing model supports the finding that timely termination of inflammation furthers the regenerative process. Differing cellular compositions are due to different cell sources invading the hematoma, determining the ensuing cytokine expression profile and thus paving the path for regenerative healing in bone or the formation of scar tissue in muscle injury.

[Electroconvulsive therapy as a "last resort" in the treatment of depression?]. / Elektrokonvulsionstherapie als Ultima Ratio in der Behandlung der Depression?

OBJECTIVE: The use of electroconvulsive therapy (ECT) in treatment-resistant depressed patients is supported by numerous international guidelines. This study aims to describe what type of patients are actually referred to treatment with ECT. METHODS: We included all patients referred to two main ECT-treatment centers in Switzerland during the period of August 2008 to February 2011. We collected data on the diagnosis, severity of illness, and the history of treatment. RESULTS: Most of the patients (n = 104) were referred after an average of 124 weeks of an index episode of unipolar depression. The patients were severely and chronically ill and had been treated on average for more than a decade. Eighty-three percent of the patients were referred for ECT treatment for the first time. CONCLUSIONS: The surveyed practice of referral does not concur with evidence-based guidelines for the use of ECT in the treatment of depression.

Flexible responses to visual and olfactory stimuli by foraging Manduca sexta: larval nutrition affects adult behaviour.

Here, we show that the consequences of deficient micronutrient (beta-carotene) intake during larval stages of Manduca sexta are carried across metamorphosis, affecting adult behaviour. Our manipulation of larval diet allowed us to examine how developmental plasticity impacts the interplay between visual and olfactory inputs on adult foraging behaviour. Larvae of M. sexta were reared on natural (Nicotiana tabacum) and artificial laboratory diets containing different concentrations of beta-carotene (standard diet, low beta-carotene, high beta-carotene and cornmeal). This vitamin-A precursor has been shown to be crucial for photoreception sensitivity in the retina of M. sexta. After completing development, post-metamorphosis, starved adults were presented with artificial feeders that could be either scented or unscented. Regardless of their larval diet, adult moths fed with relatively high probabilities on scented feeders. When feeders were unscented, moths reared on tobacco were more responsive than moths reared on beta-carotene-deficient artificial diets. Strikingly, moths reared on artificial diets supplemented with increasing amounts of beta-carotene (low beta and high beta) showed increasing probabilities of response to scentless feeders. We discuss these results in relationship to the use of complex, multi-modal sensory information by foraging animals.

Cellular composition of the initial fracture hematoma compared to a muscle hematoma: a study in sheep.

Bone fracture leads to a cycle of inflammation, cellular migration, and proliferation to restore tissue integrity. Immune cells at the site of injury are involved especially in the early phase of the healing process, but little is known about the cells present in the initial fracture hematoma. The hypothesis of this study was that the cellular composition in a fracture hematoma differs from that found in a muscle hematoma and that these divergences get more pronounced over time. By using a reproducible osteotomy model and muscle trauma in sheep the distributions of the immune cell subpopulations were evaluated 1 and 4 h after surgery. The cell amount within the first 4 h increased in both hematoma. The number of dead cells was higher in the muscle hematoma. One hour postoperatively the initial fracture hematoma revealed a lower granulocyte percentage compared to the muscle hematoma. The ratio of T helper to cytotoxic T cells was higher in the fracture hematoma compared to the muscle hematoma at both investigated time points. B cell percentage increased in the fracture but not in the muscle hematoma from 1 to 4 h. This is the first study that compares the immune cell subpopulations of a fracture and muscle hematoma.

[Schizophrenia and religiousness--a comparative study at the time of the two German states]. / Schizophrenie und Religiosität--Eine Vergleichsstudie zur Zeit der innerdeutschen Teilung.

OBJECTIVE: Religious delusions are prevalent symptoms in schizophrenia. It is unclear, however, whether religious delusions reflect illness- or culture-related factors. METHODS: Cross-cultural retrospective comparison of the prevalence of religious delusions in 132 patients treated for paranoid schizophrenia in East Berlin (former GDR) from 1980 to 1985, and 151 patients from Regensburg (FRG) who were treated as in-patients from 1980 to 1983. RESULTS: Prior to the German re-unification, religious delusions were significantly less frequent in East Berlin compared to Regensburg (11.6% as opposed to 28.6 %, chi2 = 8.029; p = 0.0046). CONCLUSIONS: The prevalence of religious delusions in schizophrenia is, above all, associated with cultural factors. Religious delusions are therefore secondary phenomena in schizophrenia, and not inherent to the illness process.

Why do Manduca sexta feed from white flowers? Innate and learnt colour preferences in a hawkmoth.

Flower colour is an important signal used by flowering plants to attract pollinators. Many anthophilous insects have an innate colour preference that is displayed during their first foraging bouts and which could help them locate their first nectar reward. Nevertheless, learning capabilities allow insects to switch their colour preferences with experience and thus, to track variation in floral nectar availability. Manduca sexta, a crepuscular hawkmoth widely studied as a model system for sensory physiology and behaviour, visits mostly white, night-blooming flowers lacking UV reflectance throughout its range in the Americas. Nevertheless, the spectral sensitivity of the feeding behaviour of naïve moths shows a narrow peak around 450 nm wavelengths, suggesting an innate preference for the colour blue. Under more natural conditions (i.e. broader wavelength reflectance) than in previous studies, we used dual choice experiments with blue- and white-coloured feeders to investigate the innate preference of naïve moths and trained different groups to each colour to evaluate their learning capabilities. We confirmed the innate preference of M. sexta for blue and found that these moths were able to switch colour preferences after training experience. These results unequivocally demonstrate that M. sexta moths innately prefer blue when presented against white flower models and offer novel experimental evidence supporting the hypothesis that learning capabilities could be involved in their foraging preferences, including their widely observed attraction to white flowers in nature.