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

QOL-31. Neuropsychological functioning and quality of life in infant AT/RT survivors: focus on fluid intelligence and visual processing [Abstract]

BACKGROUND Understanding the long-term cognitive sequelae in infant brain tumor survivors remains incomplete, particularly regarding the impact of tumor type, multimodal treatment, and other patient-related factors. This retrospective analysis explores neuropsychological and quality of survival (QoS) outcomes in survivors of atypical teratoid/rhabdoid tumors (AT/RT) and extracranial malignant rhabdoid tumors of soft tissues (eMRT) and kidneys (RTK), all treated within the same framework. Neuropsychological data from children with AT/RT were compared to data from children with non-irradiated low-grade glioma (LGG). METHODS Patients (0 - 36 months at diagnosis) underwent various treatments, including radio-chemotherapy for AT/RT (n = 13) and eMRT/RTK (n = 7), chemotherapy only for LGG (n = 4) and eMRT/RTK (n = 1), or observation for LGG (n = 11). Neuropsychological evaluations were conducted at a median of 6.8 years (AT/RT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post-diagnosis. RESULTS Impairments were observed for all tumour types. Patients with AT/RT exhibited impairments in fluid intelligence (p =.041; d = 1.11) and visual processing (p =.001; d = 2.09) when compared to LGG-patients. Both groups demonstrated deficits in psychomotor speed and attention abilities (p <.001–.019; d = 0.79–1.90). Diagnosis significantly predicted cognitive outcomes, whereas gender and age-related variables did not. QoS outcomes for all rhabdoid patients indicated lower scores in psychosocial functioning (p =.023; d = 0.78) and quality of life (p =.006; d = 0.79) compared to healthy controls. CONCLUSIONS Infant rhabdoid tumor survivors experience cognitive and quality-of-life sequelae. Patients with AT/RT are especially vulnerable to impairments in fluid intelligence and visual processing, while infant LGG-patients without radiotherapy demonstrated comparable deficits in psychomotor and attention abilities. Close monitoring of neuropsychological and quality of life outcomes is crucial for early onset and multimodal treatment

Survivors of infant atypical teratoid/rhabdoid tumors present with severely impaired cognitive functions especially for fluid intelligence and visual processing: data from the German brain tumor studies

Background The contribution of tumor type, multimodal treatment, and other patient-related factors upon long-term cognitive sequelae in infant brain tumor survivors remains undefined. We add our retrospective analysis of neuropsychological and quality of survival (QoS) outcome data of survivors of atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors of the soft tissues (eMRT) and kidneys (RTK) treated within the same framework. Neuropsychological data from children with ATRT were compared to data from children with non-irradiated low-grade glioma (LGG). Patients and methods Following surgery, patients (0–36 months at diagnosis) had received radio-chemotherapy (up to 54 Gy; ATRT: n = 13; eMRT/RTK: n = 7), chemotherapy only (LGG: n = 4; eMRT/RTK: n = 1) or had been observed (LGG: n = 11). Neuropsychological evaluation employing comparable tests was performed at median 6.8 years (ATRT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post diagnosis. Results We detected sequelae in various domains for all tumor types. Group comparison showed impairments, specifically in fluid intelligence (p = .041; d = 1.11) and visual processing (p = .001; d = 2.09) in ATRT patients when compared to LGG patients. Results for psychomotor speed and attention abilities were significantly below the norm for both groups (p < .001–.019; d = 0.79–1.90). Diagnosis predicted impairments of cognitive outcome, while sex- and age-related variables did not. QoS outcome for all rhabdoid patients displayed impairments mainly in social (p = .008; d = 0.74) and school functioning (p = .048; d = 0.67), as well as lower overall scores in psychosocial functioning (p = .023; d = 0.78) and quality of life (p = .006; d = 0.79) compared to healthy controls. Conclusion Survivors of infant ATRT experience various late effects in cognition and QoS following multimodal treatment, while infant LGG patients without radiotherapy demonstrated comparable impairments in psychomotor and attention abilities. Early onset and multimodal treatment of rhabdoid tumors require close monitoring of neuropsychological and QoS sequelae

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