The moderating effect of cortisol and dehydroepiandrosterone on the relation between sleep and depression or burnout

For poor sleep quality (SQ) as well as major depressive disorder (MDD) and burnout, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been identified. Although poor SQ is often reported as an early symptom of MDD or burnout, it is not clear whether HPA axis-related hormones can influence the association between SQ and MDD or burnout. This manuscript addresses this question by examining HPA axis-related hormones as potential moderators influencing the association between SQ and MDD or burnout. In the fourth annual examination wave of the Dresden Burnout Study, we measured general SQ (including sleep duration and efficiency), depressive and burnout symptoms, and obtained hair samples for quantification of long-term integrated steroid concentrations (cortisol [hC], cortisone [hCn], dehydroepiandrosterone [hDHEA]) from 462 participants (67% female). Data on SQ, depressive and burnout symptoms were available from 342 participants from the preceding examination wave (average time span between examinations 13.2 months). Cross-sectional analyses showed that the negative association between sleep duration and depressive symptoms was buffered by higher levels of hC, and hCn, whereas the negative association between sleep duration and burnout symptoms was buffered by higher levels of hDHEA. The negative association between sleep efficiency and burnout symptoms was intensified by higher levels of hC and hC/hCn ratio and the negative association between general SQ and burnout symptoms was intensified by higher levels of hC/hCn ratio. With regard to longitudinal data, a significant interaction effect between sleep duration and hC/hCn ratio could be detected for burnout symptoms. Our results suggest opposed moderation effects of hair glucocorticoids on the association between SQ and depressive or burnout symptoms. This points toward opposed glucocorticoid receptor functioning in depression and burnout. To fully elucidate the negative consequences of poor SQ on MDD and burnout, the complex underlying mechanisms of action including HPA axis-related hormones need to be investigated in MDD and burnout separately

The contemporary "Trojan Horse"

Pathogens frequently associated with multi-drug resistant (MDR) phenotypes, including extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) and Acinetobacter baumannii isolated from horses admitted to horse clinics, pose a risk for animal patients and personnel in horse clinics. To estimate current rates of colonization, a total of 341 equine patients were screened for carriage of zoonotic indicator pathogens at hospital admission. Horses showing clinical signs associated with colic (n = 233) or open wounds (n = 108) were selected for microbiological examination of nostril swabs, faecal samples and wound swabs taken from the open wound group. The results showed alarming carriage rates of Gram-negative MDR pathogens in equine patients: 10.7% (34 of 318) of validated faecal specimens were positive for ESBL-E (94%: ESBL-producing Escherichia coli), with recorded rates of 10.5% for the colic and 11% for the open wound group. 92.7% of the ESBL-producing E. coli were phenotypically resistant to three or more classes of antimicrobials. A. baumannii was rarely detected (0.9%), and all faecal samples investigated were negative for Salmonella, both directly and after two enrichment steps. Screening results for the equine nostril swabs showed detection rates for ESBL-E of 3.4% among colic patients and 0.9% in the open wound group, with an average rate of 2.6% (9/340) for both indications. For all 41 ESBL-producing E. coli isolated, a broad heterogeneity was revealed using pulsed-field gel electrophoresis (PFGE) patterns and whole genome sequencing (WGS) -analysis. However, a predominance of sequence type complex (STC)10 and STC1250 was observed, including several novel STs. The most common genes associated with ESBL-production were identified as blaCTX-M-1 (31/41; 75.6%) and blaSHV-12 (24.4%). The results of this study reveal a disturbingly large fraction of multi-drug resistant and ESBL-producing E. coli among equine patients, posing a clear threat to established hygiene management systems and work-place safety of veterinary staff in horse clinics

The virtually mature BNP (BNP1-32) is a precursor for the more effective BNP1-30

Background and Purpose: The B‐type natriuretic peptide (BNP1‐32) exerts vasorelaxing and cardioprotective activity. BNP is used as a biomarker for the diagnosis of cardiopathological conditions and recombinant BNP1‐32 as a drug for the treatment of such. BNP1‐32 has a short half‐life time and thus, similar to other vasoactive peptides like angiotensin II and bradykinin, can be enzymatically truncated forming bioactive metabolites. We aimed to investigate the metabolism of BNP1‐32 in mouse lung, to identify potential new BNP metabolites and to disclose their biological activity compared to the BNP1‐32, in vitro and in vivo. Experimental Approach: Using High Performance Liquid Chromatography and Mass‐Spectrometry, we identified a new BNP metabolite, BNP1‐30, in the lung being generated by endothelin‐converting enzyme‐1. Key Results: BNP1‐30 is more efficient in stimulating the guanylyl cyclase receptor A (GC‐A) and, in contrast to BNP1‐32, is also able to profoundly stimulate the GC‐B. In vivo, BNP1‐30 reduced the mean arterial blood pressure of normotensive mice after acute infusion significantly more than BNP1‐32. In a model of severe hypertension, a 3‐day infusion of BNP1‐30 was able to reduce systolic blood pressure by 30 mmHg and to improve markers of heart failure, while BNP1‐32 was without significant effect. Conclusion and Implications: Our results suggest that BNP1‐32 is the precursor for the biologically more active BNP1‐30 leading to a fundamental extension of the natriuretic‐peptide system. Due to expanded activity, BNP1‐30 might be a promising treatment option for cardiovascular diseases. Furthermore, its potency as a new diagnostic marker of specific cardiac diseases should be evaluated

A descriptive study of the surge response and outcomes of ICU patients with COVID-19 during first wave in Nordic countries

Abstract Background We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID-19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden. Methods Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID-19 disease during the first wave of COVID-19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics. Results Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS-CoV-2, the ratio of requiring ICU admission for COVID-19 varied substantially (1.6-6.7%). Apart from age (proportion of patients aged 65 years or over between 29-62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID-19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59-85%) in all countries, the proportion of patients receiving renal replacement therapy (7-26%) and various experimental therapies for COVID-19 disease varied substantially (e.g. use of hydroxychloroquine 0-85%). Crude ICU mortality ranged from 11% to 33%. Conclusion There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID-19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.Peer reviewe

ATRT-02. Neuropsychological function in infant atypical teratoid/rhabdoid tumor versus low-grade glioma survivors reflects tumor malignancy and multimodal treatment [Abstract]

BACKGROUND: Therapy of infants with brain tumors predisposes these patients to increased risks for cognitive sequelae, especially following radiotherapy. Neuropsychological outcome gains importance for those 40-60% of patients with an atypical teratoid/rhabdoid tumor (ATRT) who survive beyond 2 years. Still, reports on cognitive late-effects in children with ATRT are scarce compared to other pediatric brain tumor groups. We analyzed neuropsychological outcome for long-term ATRT-survivors registered in EU-RHAB and infant low-grade glioma (LGG) survivors from the SIOP-LGG 2004-study and LGG-registry. PATIENTS+METHODS: Age at diagnosis of both cohorts was 0-36 months. ATRT-patients (n=13) treated with up to 54Gy radiotherapy (median age 22 months (±7.1)) were evaluated with the “ATRT-Neuropsychology” tool based on SIOPE-BTG QoS-Group recommendations at median 6.8 years (±2.8) after diagnosis. LGG-patients (n=15) treated without radiotherapy (4/15 with chemotherapy) were analyzed with the German “Neuropsychological-Basic-Diagnostic” tool 5.2 years (±0.6) post-diagnosis. RESULTS: The ATRT- vs. LGG-cohorts were comparable for median age at diagnosis, sex-ratio and tumor-localization, though they differed slightly in median age at assessment (9.5/7.2 years (±2.5/1.1)). Results of age-appropriate tests showed increased impairments for ATRT-patients in fluid intelligence (FI) (p=.006, d=1.214) and in visual-spatial processing (VSP) (p<.001, d=2.233) compared to LGG-patients. The median for neuropsychological test results of ATRT-patients spanned from considerably below the normal to the lower normal range (median=65-90), while results of LGG-patients were mostly in the lower normal range (median=83-103). Results for psychomotor speed abilities (PMS) were distinctly below the norm for both patient groups (p=.002-.007). CONCLUSION: Infant ATRT- and LGG-patients develop significant impairments in PMS abilities following multimodal treatment. Long-term survivors of ATRT suffer from additional FI and VSP deficits. Our data suggest that high malignancy requiring multimodal treatment determines the inferior cognitive outcome for the ATRT-cohort. Long-term neuropsychological monitoring (and treatment options) should be implemented as standard of care in ATRT- and LGG-trials

Fluxes and origin of halogenated organic trace gases from Momotombo volcano (Nicaragua)

In order to assess the contribution of quiescent degassing volcanoes to the global halo(hydro)carbon inventory, we have quantified volcanic fluxes of methyl halides (CH3Cl, CH3Br, and CH3I), ethyl halides (C2H5Cl, C2H5Br, and C2H5I), and higher chlorinated methanes (CH2Cl2, CHCl3, and CCl4). About every eight months over a 2-year period (July 2001 to July 2003), gas samples were collected and analyzed from high-temperature fumaroles (472°C–776°C) at the Nicaraguan subduction zone volcano Momotombo. Using a simultaneous record of trace and main compounds in fumarolic gases as well as SO2 fluxes of the plume, we were able to calculate halo(hydro)carbon fluxes for Momotombo and extrapolate our results to estimate halo(hydro)carbon fluxes for the whole Quaternary Nicaraguan volcanic arc and, in addition, for all volcanoes globally. The most abundant halohydrocarbon was CH3Cl with concentrations up to 19 ppmv. Further major halo(hydro)carbons were CH3Br, CH3I, CH2Cl2, CHCl3, CCl4, C2H5Cl, C2H5Br, C2H5I, and C2H3Cl with an average concentration of 0.20 to 720 ppbv. Estimated mean halo(hydro)carbon fluxes from Momotombo were in the range of 630–5000 g/yr for methyl halides, 49–260 g/yr for ethyl halides, and 2.4–24 g/yr for higher chlorinated methanes. When the results for Momotombo are scaled up to SO2 fluxes of the Nicaraguan volcanic transect, fluxes of 1.7 × 105 g/yr CH3Cl and 82 g/yr CCl4 are attained for Nicaragua. Scaled up to the estimated global SO2 flux, this translates to hypothetical global fluxes of 5.6 × 106 g/yr CH3Cl and 2.7 × 103 g/yr CCl4. These volcanic fluxes are negligible compared to global anthropogenic and natural emissions of about 3 × 1012 g/yr CH3Cl and 2 × 1010 g/yr CCl4

Fish Is Food - The FAO’s Fish Price Index

World food prices hit an all-time high in February 2011 and are still almost two and a half times those of 2000. Although three billion people worldwide use seafood as a key source of animal protein, the Food and Agriculture Organization (FAO) of the United Nations–which compiles prices for other major food categories–has not tracked seafood prices. We fill this gap by developing an index of global seafood prices that can help to understand food crises and may assist in averting them. The fish price index (FPI) relies on trade statistics because seafood is heavily traded internationally, exposing non-traded seafood to price competition from imports and exports. Easily updated trade data can thus proxy for domestic seafood prices that are difficult to observe in many regions and costly to update with global coverage. Calculations of the extent of price competition in different countries support the plausibility of reliance on trade data. Overall, the FPI shows less volatility and fewer price spikes than other food price indices including oils, cereals, and dairy. The FPI generally reflects seafood scarcity, but it can also be separated into indices by production technology, fish species, or region. Splitting FPI into capture fisheries and aquaculture suggests increased scarcity of capture fishery resources in recent years, but also growth in aquaculture that is keeping pace with demand. Regionally, seafood price volatility varies, and some prices are negatively correlated. These patterns hint that regional supply shocks are consequential for seafood prices in spite of the high degree of seafood tradability

Prevention and Intervention Studies with Telmisartan, Ramipril and Their Combination in Different Rat Stroke Models

The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats. Normotensive Wistar rats were treated s.c. 5 days prior to middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Groups (n = 10 each): (1) sham, (2) vehicle (V; 0,9% NaCl), (3) T (0,5 mg/kg once daily), (4) R (0,01 mg/kg twice daily), (5) R (0,1 mg/kg twice daily) or (6) T (0,5 mg/kg once daily) plus R (0,01 mg/kg twice daily). Twenty-four and 48 h after MCAO, neurological outcome (NO) was determined. Forty-eight h after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and neurotrophin receptor (TrkB) were analysed.Stroke incidence was reduced, survival was prolonged and neurological outcome was improved in all treated SHR-SP with no differences between treated groups. In the acute intervention study, T and T+R, but not R alone, improved NO, reduced infarct volume, inflammation (TNFα), and induced TrkB receptor and neuronal survival in comparison to V.T, R or T+R had similar beneficial effects on stroke incidence and NO in hypertensive rats, confirming BP reduction as determinant factor in stroke prevention. In contrast, T and T+R provided superior neuroprotection in comparison to R alone in normotensive rats with induced cerebral ischemia