Cortisol rapidly increases baroreflex sensitivity of heart rate control, but does not affect cardiac modulation of startle

Cortisol, the final product of human HPA axis activation, rapidly modulates the cortical processing of afferent signals originating from the cardiovascular system. While peripheral effects have been excluded, it remains unclear whether this effect is mediated by cortical or subcortical (e.g. brainstem) CNS mechanisms. Cardiac modulation of startle (CMS) has been proposed as a method to reflect cardio-afferent signals at subcortical (potentially brainstem-) level. Using a single blind, randomized controlled design, the cortisol group (n = 16 volunteers) received 1 mg cortisol intravenously, while the control group (n = 16) received a placebo substance. The CMS procedure involved the assessment of eye blink responses to acoustic startle stimuli elicited at six different latencies to ECG-recorded R-waves (R + 0, 100, 200, 300, 400 and 500 ms). CMS was assessed at four measurement points: baseline, -16 min, +0 min, and +16 min relative to substance application. Baroreflex sensitivity (BRS) of heart rate (HR) control was measured non-invasively based on spontaneous beat-to-beat HR and systolic blood pressure changes. In the cortisol group, salivary cortisol concentration increased after IV cortisol administration, indicating effective distribution of the substance throughout the body. Furthermore, BRS increased in the cortisol group after cortisol infusion. There was no effect of cortisol on the CMS effect, however. These results suggest that low doses of cortisol do not affect baro-afferent signals, but central or efferent components of the arterial baroreflex circuit presumably via rapid, non-genomic mechanisms

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Glucose as an adjuvant of fear exposure psychotherapy in anxiety disorders

Improving the treatment of mental disorders ranks among the central health challenges. Anxiety disorders (ADs) are the most frequent group of mental disorders, and significantly contribute to the burden of disease. Exposure therapy is commonly considered the central therapeutic component in their treatment. Still, not all patients profit and the relapse rate is considerable. Classical conditioning models represent a valuable tool to study the mechanisms of ADs. Fear extinction constitutes a valuable laboratory analogue process to exposure therapy, and predicts the success of exposure therapy. There is a raised interest in cognitive enhancers as possible adjuvants of fear extinction processes and consequently fear exposure therapy. The substances studied have however considerable secondary effects, limiting the number of patients that can benefit from them. Therefore, there is a need for efficient therapy enhancers, easy to apply and with little to none secondary effects. It has been shown that glucose can enhance human memory but to date there are no studies on its effects on fear extinction processes. In a preliminary study, we confirmed that also glucose administration enhances fear extinction. Contrary to other cognitive enhancers, glucose is not a pharmaceutical substance, is easy to apply and has no significant side effects. The aim of the proposed project is to further investigate the use of glucose as potential adjuvant treatment in exposure therapy. We plan two independent studies assessing fear reactions through affective ratings and physiological measures

Learning to see the threat: temporal dynamics of ERPs of motivated attention in fear conditioning

Social threat detection is important in everyday life. Studies of cortical activity have shown that event-related potentials (ERPs) of motivated attention are modulated during fear conditioning. The time course of motivated attention in learning and extinction of fear is however still largely unknown. We aimed to study temporal dynamics of learning processes in classical fear conditioning to social cues (neutral faces) by selecting an experimental setup that produces large effects on well-studied ERP components (early posterior negativity, EPN; late positive potential, LPP; stimulus preceding negativity, SPN), and then exploring small consecutive groups of trials. EPN, LPP, and SPN markedly and quickly increased during the acquisition phase in response to the CS+ but not the CS-. These changes were visible even at high temporal resolution and vanished completely during extinction. Moreover, some evidence was found for component differences in extinction learning, with differences between CS+ and CS- extinguishing faster for late as compared to early ERP components. Results demonstrate that fear learning to social cues is a very fast and highly plastic process and conceptually different ERPs of motivated attention are sensitive to these changes at high temporal resolution, pointing to specific neurocognitive and affective processes of social fear learning

Kurzzeitige Nahrungsdeprivation erhöht Herzschlag-evozierte Potenziale (HEPs) als Indikatoren für kortikale Verarbeitung kardial-interozeptiver Prozesse

Interozeption – die Wahrnehmung von Körpervorgängen – spielt bei der Regulation des Essverhaltens möglicherweise eine entscheidende Rolle. Nahrungsdeprivation hat eine Reihe von metabolischen und endokrinologischen Konsequenzen. Bei kurzzeitiger Nahrungsdeprivation zeigt sich eine Erhöhung des sympathischen Tonus, welche dafür verantwortlich sein könnte, dass sich die Interozeptionsgenauigkeit gegenüber kardialer Stimuli gleichzeitig erhöht. Die physiologischen Grundlagen von Interozeption sind die Übermittlung von viszeral-afferenten neuronalen Signalen, während die Wahrnehmung dieser Signale die Lenkung der Aufmerksamkeit auf diese Signale erfordert. Bisherige Ergebnisse gehen auf Leistungen in Herzschlagdetektionsaufgaben zurück. Obwohl diese Methoden mehrfach validiert wurden, sind sie wahrscheinlich ungeeignet dazu, die viszeral-afferente Signalübermittlung und Aufmerksamkeitslenkung auf diese Signale voneinander zu trennen. Daher hatte die vorliegende Studienreihe zum Ziel, den Einfluss von kurzzeitiger Nahrungsdeprivation auf Herzschlag-evozierte Potenziale (HEPs) in Ruhebedingung zu untersuchen. Die HEPs gelten als psychophysiologischer Indikator für die kortikale Verarbeitung kardial-interozeptiver Prozesse. Bislang ist unbekannt, ob metabolische und endokrinologische Prozesse HEPs modulieren können. In einer ersten Studie wurden 16 gesunden Männern (Alter: 23,8 [2,1] Jahre) intravenös sowohl das Stresshormon Cortisol, als auch eine Placebo-Substanz verabreicht. Es zeigte sich, dass Cortisol bei offenen Augen kurzfristig zu einer höheren HEP-Amplitude führte, als bei geschlossenen Augen (p = .03). Daraus kann man ableiten, dass endokrinologische Prozesse das Potenzial haben, die HEP-Amplitude zu modulieren. In der folgenden Studie wurden 16 gesunde Frauen (Alter: 22,6 [1,9] Jahre) sowohl nach standardisierter Nahrungsaufnahme, als auch nach 18-stündiger Nahrungsdeprivation getestet. Es zeigte sich eine Erhöhung der HEP-Amplitude nach Nahrungsdeprivation (p = .02). Gleichzeitig konnten keine Veränderungen der Herzrate, noch der Herzratenvariabilität beobachtet werden. Unsere Ergebnisse legen nahe, dass Nahrungsdeprivation die kortikale Verarbeitung afferenter Signale aus dem kardiovaskulären System intensiviert, was nicht durch eine höhere sympathische Aktivität erklärt werden kann. Mögliche physiologische Signalwege und Implikationen für die Ätiologie von Essstörungen werden diskutiert

Cortisol rapidly increases baroreflex sensitivity of heart rate control, but does not affect cardiac modulation of startle

Cortisol, the final product of human HPA axis activation, rapidly modulates the cortical processing of afferent signals originating from the cardiovascular system. While peripheral effects have been excluded, it remains unclear whether this effect is mediated by cortical or subcortical (e.g. brainstem) CNS mechanisms. Cardiac modulation of startle (CMS) has been proposed as a method to reflect cardio-afferent signals at subcortical (potentially brainstem-) level. Using a single blind, randomized controlled design, the cortisol group (n = 16 volunteers) received 1 mg cortisol intravenously, while the control group (n = 16) received a placebo substance. The CMS procedure involved the assessment of eye blink responses to acoustic startle stimuli elicited at six different latencies to ECG-recorded R-waves (R + 0, 100, 200, 300, 400 and 500 ms). CMS was assessed at four measurement points: baseline, -16 min, +0 min, and +16 min relative to substance application. Baroreflex sensitivity (BRS) of heart rate (HR) control was measured non-invasively based on spontaneous beat-to-beat HR and systolic blood pressure changes. In the cortisol group, salivary cortisol concentration increased after IV cortisol administration, indicating effective distribution of the substance throughout the body. Furthermore, BRS increased in the cortisol group after cortisol infusion. There was no effect of cortisol on the CMS effect, however. These results suggest that low doses of cortisol do not affect baro-afferent signals, but central or efferent components of the arterial baroreflex circuit presumably via rapid, non-genomic mechanisms