Effects of Yohimbine and Tolazoline on Isoproterenol and Angiotensin 2-Induced Water Intake in Rats

Subcutaneous administration of the alpha(sub 2)-adrenoreceptor antagonists, yohimbine and tolazoline, at doses up to 1000 micro-g/kg, had no effect on water intake of female rats. However, when these compounds were administered SC in combination with either the beta-adrenoreceptor agonist, isoproterenol (10 to 25 micro-g/kg, SC), or with angiotensin 2 (200 micro-g/kg, SC). water intake was enhanced. In contrast, intraventricular administration of either tolazoline (10 and 20 micro-g/kg) or yohimbine (300 micro-g/kg) failed to augment the dipsogenic response to angiotensin 2 (150 micro-g/kg, SC). Thus, the enhancing effect of these alpha(sub 2)-adrenoreceptor antagonists on isoproterenol- and angiotensin 2-induced water intakes appears to be manifested peripherally, rather than centrally. In view of the fact that clonidine, an alpha(sub 2)-adrenoreceptor agonist, has been shown to inhibit water intake induced by both isoproterenol and angiotensin 2, the results suggest that the alpha(sub 2)-adrenoreceptor may play a role in modulating water intake induced by these two dipsogenic agents

MR diffusion changes in the perimeter of the lateral ventricles demonstrate periventricular injury in post-hemorrhagic hydrocephalus of prematurity

OBJECTIVES: Injury to the preterm lateral ventricular perimeter (LVP), which contains the neural stem cells responsible for brain development, may contribute to the neurological sequelae of intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus of prematurity (PHH). This study utilizes diffusion MRI (dMRI) to characterize the microstructural effects of IVH/PHH on the LVP and segmented frontal-occipital horn perimeters (FOHP). STUDY DESIGN: Prospective study of 56 full-term infants, 72 very preterm infants without brain injury (VPT), 17 VPT infants with high-grade IVH without hydrocephalus (HG-IVH), and 13 VPT infants with PHH who underwent dMRI at term equivalent. LVP and FOHP dMRI measures and ventricular size-dMRI correlations were assessed. RESULTS: In the LVP, PHH had consistently lower FA and higher MD and RD than FT and VPT (p\u3c.050). However, while PHH FA was lower, and PHH RD was higher than their respective HG-IVH measures (p\u3c.050), the MD and AD values did not differ. In the FOHP, PHH infants had lower FA and higher RD than FT and VPT (p\u3c.010), and a lower FA than the HG-IVH group (p\u3c.001). While the magnitude of AD in both the LVP and FOHP were consistently less in the PHH group on pairwise comparisons to the other groups, the differences were not significant (p\u3e.050). Ventricular size correlated negatively with FA, and positively with MD and RD (p\u3c.001) in both the LVP and FOHP. In the PHH group, FA was lower in the FOHP than in the LVP, which was contrary to the observed findings in the healthy infants (p\u3c.001). Nevertheless, there were no regional differences in AD, MD, and RD in the PHH group. CONCLUSION: HG-IVH and PHH results in aberrant LVP/FOHP microstructure, with prominent abnormalities among the PHH group, most notably in the FOHP. Larger ventricular size was associated with greater magnitude of abnormality. LVP/FOHP dMRI measures may provide valuable biomarkers for future studies directed at improving the management and neurological outcomes of IVH/PHH

FLNC Gene Splice Mutations Cause Dilated\ua0Cardiomyopathy

OBJECTIVE: To identify novel dilated cardiomyopathy (DCM) causing genes, and to elucidate the pathological mechanism leading to DCM by utilizing zebrafish as a model organism. BACKGROUND: DCM, a major cause of heart failure, is frequently familial and caused by a genetic defect. However, only 50% of DCM cases can be attributed to a known DCM gene variant, motivating the ongoing search for novel disease genes. METHODS: We performed whole exome sequencing (WES) in two multigenerational Italian families and one US family with arrhythmogenic DCM without skeletal muscle defects, in whom prior genetic testing had been unrevealing. Pathogenic variants were sought by a combination of bioinformatic filtering and cosegregation testing among affected individuals within the families. We performed function assays and generated a zebrafish morpholino knockdown model. RESULTS: A novel filamin C gene splicing variant (FLNC c.7251+1 G>A) was identified by WES in all affected family members in the two Italian families. A separate novel splicing mutation (FLNC c.5669-1delG) was identified in the US family. Western blot analysis of cardiac heart tissue from an affected individual showed decreased FLNC protein, supporting a haploinsufficiency model of pathogenesis. To further analyze this model, a morpholino knockdown of the ortholog filamin Cb in zebrafish was created which resulted in abnormal cardiac function and ultrastructure. CONCLUSIONS: Using WES, we identified two novel FLNC splicing variants as the likely cause of DCM in three families. We provided protein expression and in vivo zebrafish data supporting haploinsufficiency as the pathogenic mechanism leading to DCM

Managing talent across advanced and emerging economies: HR issues and challenges in a Sino-German strategic collaboration

The human resource (HR) practices involved in global talent management continue to advance and evolve. A majority of talent management commentary is from multinational corporation (MNC) perspectives. However, the less commented small-to-medium-sized enterprise (SME) also confronts challenges grounded in economic (i.e. resources, finance), organisational (i.e. size, scope and structure) and consequent behavioural rationales (i.e. mindsets and stances). This paper establishes and examines a number of propositions which consider how these factors impact on an advanced economy SME’s talent management in emerging economy collaborations. An interpretive qualitative methodology is employed using interviews conducted within two cases – SME and an MNC comparator case. The SME case is used as the driving force of the paper and its theoretical focus and findings. The MNC is used to develop issues as a comparator case. The findings show SME economic and organisational drivers producing behavioural dynamics in relation to mimesis of planned actions yet informal serendipitous responses in reality; a predilection for the proximate and familiar; design configurations of short-term expatriate visits and inpatriates; cumulating in ongoing inpatriate acculturisation and re-acculturation oscillation. Consequently, the implication is that the SME needs a HR practices encompassing resignation to the situation, flexibility and resilience in order to survive and progress

Representing the function and sensitivity of coastal interfaces in earth system models

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Ward, N. D., Megonigal, J. P., Bond-Lamberty, B., Bailey, V. L., Butman, D., Canuel, E. A., Diefenderfer, H., Ganju, N. K., Goni, M. A., Graham, E. B., Hopkinson, C. S., Khangaonkar, T., Langley, J. A., McDowell, N. G., Myers-Pigg, A. N., Neumann, R. B., Osburn, C. L., Price, R. M., Rowland, J., Sengupta, A., Simard, M., Thornton, P. E., Tzortziou, M., Vargas, R., Weisenhorn, P. B., & Windham-Myers, L. Representing the function and sensitivity of coastal interfaces in earth system models. Nature Communications, 11(1), (2020): 2458, doi:10.1038/s41467-020-16236-2.Between the land and ocean, diverse coastal ecosystems transform, store, and transport material. Across these interfaces, the dynamic exchange of energy and matter is driven by hydrological and hydrodynamic processes such as river and groundwater discharge, tides, waves, and storms. These dynamics regulate ecosystem functions and Earth’s climate, yet global models lack representation of coastal processes and related feedbacks, impeding their predictions of coastal and global responses to change. Here, we assess existing coastal monitoring networks and regional models, existing challenges in these efforts, and recommend a path towards development of global models that more robustly reflect the coastal interface.Funding for this work was provided by Pacific Northwest National Laboratory (PNNL) Laboratory Directed Research & Development (LDRD) as part of the Predicting Ecosystem Resilience through Multiscale Integrative Science (PREMIS) Initiative. PNNL is operated by Battelle for the U.S. Department of Energy under Contract DE-AC05-76RL01830. Additional support to J.P.M. was provided by the NSF-LTREB program (DEB-0950080, DEB-1457100, DEB-1557009), DOE-TES Program (DE-SC0008339), and the Smithsonian Institution. This manuscript was motivated by discussions held by co-authors during a three-day workshop at PNNL in Richland, WA: The System for Terrestrial Aquatic Research (STAR) Workshop: Terrestrial-Aquatic Research in Coastal Systems. The authors thank PNNL artist Nathan Johnson for preparing the figures in this manuscript and Terry Clark, Dr. Charlette Geffen, and Dr. Nancy Hess for their aid in organizing the STAR workshop. The authors thank all workshop participants not listed as authors for their valuable insight: Lihini Aluwihare (contributed to biogeochemistry discussions and development of concept for Fig. 3), Gautam Bisht (contributed to modeling discussion), Emmett Duffy (contributed to observational network discussions), Yilin Fang (contributed to modeling discussion), Jeremy Jones (contributed to biogeochemistry discussions), Roser Matamala (contributed to biogeochemistry discussions), James Morris (contributed to biogeochemistry discussions), Robert Twilley (contributed to biogeochemistry discussions), and Jesse Vance (contributed to observational network discussions). A full report on the workshop discussions can be found at https://www.pnnl.gov/publications/star-workshop-terrestrial-aquatic-research-coastal-systems

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK:a prospective multicentre cohort study

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council

A function-based typology for Earth’s ecosystems

As the United Nations develops a post-2020 global biodiversity framework for the Convention on Biological Diversity, attention is focusing on how new goals and targets for ecosystem conservation might serve its vision of ‘living in harmony with nature’(1,2). Advancing dual imperatives to conserve biodiversity and sustain ecosystem services requires reliable and resilient generalizations and predictions about ecosystem responses to environmental change and management(3). Ecosystems vary in their biota(4), service provision(5) and relative exposure to risks(6), yet there is no globally consistent classification of ecosystems that reflects functional responses to change and management. This hampers progress on developing conservation targets and sustainability goals. Here we present the International Union for Conservation of Nature (IUCN) Global Ecosystem Typology, a conceptually robust, scalable, spatially explicit approach for generalizations and predictions about functions, biota, risks and management remedies across the entire biosphere. The outcome of a major cross-disciplinary collaboration, this novel framework places all of Earth’s ecosystems into a unifying theoretical context to guide the transformation of ecosystem policy and management from global to local scales. This new information infrastructure will support knowledge transfer for ecosystem-specific management and restoration, globally standardized ecosystem risk assessments, natural capital accounting and progress on the post-2020 global biodiversity framework

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council