Prefrontal gamma oscillations reflect ongoing pain intensity in chronic back pain patients

Chronic pain is a major health care issue characterized by ongoing pain and a variety of sensory, cognitive, and affective abnormalities. The neural basis of chronic pain is still not completely understood. Previous work has implicated prefrontal brain areas in chronic pain. Furthermore, prefrontal neuronal oscillations at gamma frequencies (60–90 Hz) have been shown to reflect the perceived intensity of longer lasting experimental pain in healthy human participants. In contrast, noxious stimulus intensity has been related to alpha (8–13 Hz) and beta (14–29 Hz) oscillations in sensorimotor areas. However, it is not fully understood how the intensity of ongoing pain as the key symptom of chronic pain is represented in the human brain. Here, we asked 31 chronic back pain patients to continuously rate their ongoing pain while simultaneously recording electroencephalography (EEG). Time–frequency analyses revealed a positive association between ongoing pain intensity and prefrontal beta and gamma oscillations. No association was found between pain and alpha or beta oscillations in sensorimotor areas. These findings indicate that ongoing pain as the key symptom of chronic pain is reflected by neuronal oscillations implicated in the subjective perception of longer lasting pain rather than by neuronal oscillations related to the processing of objective nociceptive input. The findings, thus, support a dissociation of pain intensity from nociceptive processing in chronic back pain patients. Furthermore, although possible confounds by muscle activity have to be taken into account, they might be useful for defining a neurophysiological marker of ongoing pain in the human brain

Readiness for and Response to Coronavirus Disease 2019 Among Pediatric Healthcare Providers: The Role of Simulation for Pandemics and Other Disasters

Objectives: Early preparation for the training and education of healthcare providers, as well as the continuation or modification of routine medical education programs, is of great importance in times of the coronavirus disease 2019 pandemic or other public health emergencies. The goal of this study was to characterize these self-reported efforts by the pediatric simulation community. Design: This was a global, multicenter survey developed via a Delphi process. Setting: International survey study. SUBJECTS: The survey was sent to 555 individual members of the three largest international pediatric simulation societies (The International Pediatric Simulation Society, International Network for Simulation-based Pediatric Innovation, Research & Education, and Netzwerk Kindersimulation e.V.) between April 27, 2020, and May 18, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Description of coronavirus disease 2019 pandemic simulation-based preparation activities of pediatric acute and critical care healthcare providers. The Delphi process included 20 content experts and required three rounds to reach consensus. The survey was completed by 234 participants (42.2%) from 19 countries. Preparation differed significantly between the geographic regions, with 79.3% of Anglo-American/Anglo-Saxon, 82.6% of Indian, and 47.1% of European participants initiating specifically coronavirus disease 2019-related simulation activities. Frequent modifications to existing simulation programs included the use of telesimulation and virtual reality training. Forty-nine percent of institutions discontinued noncoronavirus disease 2019-related simulation training. Conclusions: The swift incorporation of disease-specific sessions and the transition of standard education to virtual or hybrid simulation training modes occurred frequently. The approach used, however, depended heavily on local requirements, limitations, and circumstances. In particular, the use of telesimulation allowed education to continue while maintaining social distancing requirements

National preparedness survey of pediatric intensive care units with simulation centers during the coronavirus pandemic

Background: The coronavirus disease pandemic caught many pediatric hospitals unprepared and has forced pediatric healthcare systems to scramble as they examine and plan for the optimal allocation of medical resources for the highest priority patients. There is limited data describing pediatric intensive care unit (PICU) preparedness and their health worker protections. Aim: To describe the current coronavirus disease 2019 (COVID-19) preparedness efforts among a set of PICUs within a simulation-based network nationwide. Methods: A cross-sectional multi-center national survey of PICU medical director(s) from children's hospitals across the United States. The questionnaire was developed and reviewed by physicians with expertise in pediatric critical care, disaster readiness, human factors, and survey development. Thirty-five children's hospitals were identified for recruitment through a long-established national research network. The questions focused on six themes: (1) PICU and medical director demographics; (2) Pediatric patient flow during the pandemic; (3) Changes to the staffing models related to the pandemic; (4) Use of personal protective equipment (PPE); (5) Changes in clinical practice and innovations; and (6) Current modalities of training including simulation. Results: We report on survey responses from 22 of 35 PICUs (63%). The majority of PICUs were located within children's hospitals (87%). All PICUs cared for pediatric patients with COVID-19 at the time of the survey. The majority of PICUs (83.4%) witnessed decreases in non-COVID-19 patients, 43% had COVID-19 dedicated units, and 74.6% pivoted to accept adult COVID-19 patients. All PICUs implemented changes to their staffing models with the most common changes being changes in COVID-19 patient room assignment in 50% of surveyed PICUs and introducing remote patient monitoring in 36% of the PICU units. Ninety-five percent of PICUs conducted training for donning and doffing of enhanced PPE. Even 6 months into the pandemic, one-third of PICUs across the United States reported shortages in PPE. The most common training formats for PPE were hands-on training (73%) and video-based content (82%). The most common concerns related to COVID-19 practice were changes in clinical protocols and guidelines (50%). The majority of PICUs implemented significant changes in their airway management (82%) and cardiac arrest management protocols in COVID-19 patients (68%). Simulation-based training was the most commonly utilized training modality (82%), whereas team training (73%) and team dynamics (77%) were the most common training objectives. Conclusions: A substantial proportion of surveyed PICUs reported on large changes in their preparedness and training efforts before and during the pandemic. PICUs implemented broad strategies including modifications to staffing, PPE usage, workflow, and clinical practice, while using simulation as the preferred training modality. Further research is needed to advance the level of preparedness, support staff assuredness, and support deep learning about which preparedness actions were effective and what lessons are needed to improve PICU care and staff protection for the next COVID-19 patient waves

A review of reporting of participant recruitment and retention in RCTs in six major journals

<p>Abstract</p> <p>Background</p> <p>Poor recruitment and retention of participants in randomised controlled trials (RCTs) is problematic but common. Clear and detailed reporting of participant flow is essential to assess the generalisability and comparability of RCTs. Despite improved reporting since the implementation of the CONSORT statement, important problems remain. This paper aims: (i) to update and extend previous reviews evaluating reporting of participant recruitment and retention in RCTs; (ii) to quantify the level of participation throughout RCTs.</p> <p>Methods</p> <p>We reviewed all reports of RCTs of health care interventions and/or processes with individual randomisation, published July–December 2004 in six major journals. Short, secondary or interim reports, and Phase I/II trials were excluded. Data recorded were: general RCT details; inclusion of flow diagram; participant flow throughout trial; reasons for non-participation/withdrawal; target sample sizes.</p> <p>Results</p> <p>133 reports were reviewed. Overall, 79% included a flow diagram, but over a third were incomplete. The majority reported the flow of participants at each stage of the trial after randomisation. However, 40% failed to report the numbers assessed for eligibility. Percentages of participants retained at each stage were high: for example, 90% of eligible individuals were randomised, and 93% of those randomised were outcome assessed. On average, trials met their sample size targets. However, there were some substantial shortfalls: for example 21% of trials reporting a sample size calculation failed to achieve adequate numbers at randomisation, and 48% at outcome assessment. Reporting of losses to follow up was variable and difficult to interpret.</p> <p>Conclusion</p> <p>The majority of RCTs reported the flow of participants well after randomisation, although only two-thirds included a complete flow chart and there was great variability over the definition of "lost to follow up". Reporting of participant eligibility was poor, making assessments of recruitment practice and external validity difficult. Reporting of participant flow throughout RCTs could be improved by small changes to the CONSORT chart.</p

In vivo screening characterizes chromatin factor functions during normal and malignant hematopoiesis

Bulk ex vivo and single-cell in vivo CRISPR knockout screens are used to characterize 680 chromatin factors during mouse hematopoiesis, highlighting lineage-specific and normal and leukemia-specific functions. Cellular differentiation requires extensive alterations in chromatin structure and function, which is elicited by the coordinated action of chromatin and transcription factors. By contrast with transcription factors, the roles of chromatin factors in differentiation have not been systematically characterized. Here, we combine bulk ex vivo and single-cell in vivo CRISPR screens to characterize the role of chromatin factor families in hematopoiesis. We uncover marked lineage specificities for 142 chromatin factors, revealing functional diversity among related chromatin factors (i.e. barrier-to-autointegration factor subcomplexes) as well as shared roles for unrelated repressive complexes that restrain excessive myeloid differentiation. Using epigenetic profiling, we identify functional interactions between lineage-determining transcription factors and several chromatin factors that explain their lineage dependencies. Studying chromatin factor functions in leukemia, we show that leukemia cells engage homeostatic chromatin factor functions to block differentiation, generating specific chromatin factor-transcription factor interactions that might be therapeutically targeted. Together, our work elucidates the lineage-determining properties of chromatin factors across normal and malignant hematopoiesis

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly