Publications by authors named "Michael Levin"

670 Publications

Study protocol for a randomized controlled trial comparing two low-intensity weight loss maintenance interventions based on acceptance and commitment therapy or self-regulation.

Contemp Clin Trials 2021 Feb 22;103:106327. Epub 2021 Feb 22.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University/The Miriam Hospital Weight Control and Diabetes Research Center, Providence, RI, USA.

Background: Weight regain is common following behavioral obesity treatment and attenuates many of the benefits of initial weight loss. This paper describes a randomized controlled trial that will evaluate the efficacy of two low-contact weight loss maintenance interventions based on Acceptance and Commitment Therapy (ACT) and self-regulation (SR). Potential mechanisms of action and moderators of treatment effects will also be evaluated.

Methods: Adults (anticipated N = 480) with overweight or obesity will complete an initial 3-month online weight loss program (Phase 1). Participants who achieve ≥4 kg weight loss (anticipated N = 288) will then be randomized to an ACT or SR weight loss maintenance intervention. Both interventions will entail four 2.5 h, face-to-face, group-based workshop sessions and 6 months of email contact. Assessments will be conducted at phase 1 baseline, phase 1 completion/pre-randomization, and 6, 12, 18, 24, and 30 months post-randomization. The primary outcome will be weight change for the period from randomization to 30 months. Potential process measures including ACT-based constructs (e.g., psychological acceptance, values-consistent behavior), self-weighing frequency, and motivation will be also be assessed, as will potential moderators (e.g., initial weight loss).

Conclusions: This study will compare the efficacy of two intervention approaches (ACT and SR) delivered in a scalable workshop format for long-term weight loss maintenance. Future research could examine efficacy and cost-effectiveness of these approaches in real world settings.
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http://dx.doi.org/10.1016/j.cct.2021.106327DOI Listing
February 2021

Assessment of the Pathogenicity of , , and in a Guinea Pig Model.

Vector Borne Zoonotic Dis 2021 Feb 17. Epub 2021 Feb 17.

Division of Vector Borne Diseases, Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Members of the genus range from nonpathogenic endosymbionts to virulent pathogens such as , the causative agent of Rocky Mountain spotted fever. Many rickettsiae are considered nonpathogenic because they have been isolated from ticks but not vertebrate hosts. We assessed the ability of three presumed endosymbionts: , , and , to infect a guinea pig animal model. These species were chosen because of their high prevalence in respective tick vectors or published reports suggestive of human or animal pathogenicity. Following intraperitoneal (IP) inoculation of cell culture suspensions of , , , or into guinea pigs, animals were monitored for signs of clinical illness for 13 days. Ear biopsies and blood samples were taken at 2- to 3-day intervals for detection of rickettsial DNA by PCR. Animals were necropsied and internal organ samples were also tested using PCR assays. Among the six guinea pigs inoculated with , fever, orchitis, and dermatitis were observed in one, one, and three animals respectively. In -exposed animals, we noted fever in one of six animals, orchitis in one, and dermatitis in two. No PCR-positive tissues were present in either the or exposed groups. In the -exposed group, two of six animals became febrile, two had orchitis, and three developed dermatitis in ears or footpads. DNA was detected in ear skin biopsies collected on multiple days from three animals. Also, a liver specimen from one animal and spleen specimens of two animals were PCR positive. The course and severity of disease in the three experimental groups were significantly milder than that of . This study suggests that the three rickettsiae considered nonpathogenic can cause either subclinical or mild infections in guinea pigs when introduced via IP inoculation.
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http://dx.doi.org/10.1089/vbz.2020.2695DOI Listing
February 2021

Associations between Environmental Dust Composition and Atopic Dermatitis in Urban and Rural Settings.

Pediatr Allergy Immunol 2021 Feb 17. Epub 2021 Feb 17.

Division of Paediatric Allergy, Department of Paediatrics, Faculty of Health Sciences, University of Cape Town, South Africa.

Background: Environmental exposures are involved in the pathogenesis of the allergic phenotype, and in determining which individual triggers a person becomes sensitized to. Atopic dermatitis (AD) may modulate these effects through increased penetration through the skin modifying the immune system and AD may be triggered or intensified by environmental exposures. These exposures and immune-modulating factors may differ in urban and rural environments.

Objectives: To compare house dust composition in urban and rural settings and correlate them with AD outcomes.

Methods: Dust samples were collected from the beds of 156 children aged 6 months to 3 years. 42% of participants had atopic dermatitis. Samples were analysed for bacterial endotoxin, fungal (β-1,3-glucan) levels, and house dust mite, cockroach, dog, cat, mouse and peanut allergen. Exposures were compared in urban and rural environments, and in participants with and without AD.

Results: Endotoxin but not fungal β-glucan exposure is higher in the environment of healthy controls than children with AD in both urban and rural settings. House dust mite allergen exposure is high in urban and rural settings with Dermatophagoides detected in 100% of samples. Cat and dog allergen exposure mirrors pet ownership patterns which differ slightly between groups and environments. Mouse allergen exposure is higher in urban homes.

Conclusion: Environmental endotoxin may be protective against AD in both urban and rural settings. There are marked differences in allergen exposure in urban and rural settings, but these are unlikely to be important protective or risk factors.
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http://dx.doi.org/10.1111/pai.13476DOI Listing
February 2021

Incompetence of the Asian Longhorned Tick (Acari: Ixodidae) in Transmitting the Agent of Human Granulocytic Anaplasmosis in the United States.

J Med Entomol 2021 Feb 16. Epub 2021 Feb 16.

Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.

The Asian longhorned tick, Haemaphysalis longicornis Neumann (Acari: Ixodidae), was recently introduced into the United States and is now established in at least 15 states. Considering its ability for parthenogenetic propagation and propensity for creating high-density populations, there is concern that this tick may become involved in transmission cycles of endemic tick-borne human pathogens. Human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum is one of the more common tick-borne diseases in the United States, especially in the northeastern and midwestern states. There is considerable geographical overlap between HGA cases and the currently known distribution of H. longicornis, which creates a potential for this tick to encounter A. phagocytophilum while feeding on naturally infected vertebrate hosts. Therefore, we evaluated the ability of H. longicornis to acquire and transmit the agent of HGA under laboratory conditions and compared it to the vector competence of I. scapularis. Haemaphysalis longicornis nymphs acquired the pathogen with the bloodmeal while feeding on infected domestic goats, but transstadial transmission was inefficient and PCR-positive adult ticks were unable to transmit the pathogen to naïve goats. Results of this study indicate that the Asian longhorned tick is not likely to play a significant role in the epidemiology of HGA in the United States.
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http://dx.doi.org/10.1093/jme/tjab015DOI Listing
February 2021

House dust microbiota and atopic dermatitis; effect of urbanization.

Pediatr Allergy Immunol 2021 Feb 11. Epub 2021 Feb 11.

Division of Allergy, Department of Paediatrics and Child Health, University of Cape Town, South Africa.

Background: Previous studies have shown that a child's risk of developing atopic disease is impacted by both genetic and environmental factors. Because small children spend the majority of their time in their homes, exposure to microbial factors in their home environment may be protective or risk factors for development of atopic diseases, such as atopic dermatitis.

Methods: Dust samples from the homes of 86 Black South African children 12 to 36 months old were collected for analysis of the bacterial microbiome. This case-control study design included children with and without atopic dermatitis from rural and urban environments.

Results: Significant differences in bacterial composition and diversity were found when comparing children with and without atopic dermatitis. Furthermore, house dust microbiota was significantly different in rural and urban areas. Differences were best accounted for by higher relative abundance of Ruminococcaceae, Lachnospiraceae and Bacteroidaceae families in rural compared to urban houses. Levels of Ruminococcaceae were also found to be significantly depleted in the house dust of rural children with atopic dermatitis as compared to control children.

Conclusions: House dust composition may be an important risk factor for the development of atopic disease, and this association may be driven in part by the gut microbiome. Low levels of the Ruminococcaceae family from Clostridia class in particular may explain the association between urban living and atopy. However, further research is needed to elucidate these links.
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http://dx.doi.org/10.1111/pai.13471DOI Listing
February 2021

Impact of a clinical decision rule on antibiotic prescription for children with suspected lower respiratory tract infections presenting to European emergency departments: a simulation study based on routine data.

J Antimicrob Chemother 2021 Feb 10. Epub 2021 Feb 10.

Department of General Paediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

Background: Discriminating viral from bacterial lower respiratory tract infections (LRTIs) in children is challenging thus commonly resulting in antibiotic overuse. The Feverkidstool, a validated clinical decision rule including clinical symptoms and C-reactive protein, safely reduced antibiotic use in children at low/intermediate risk for bacterial LRTIs in a multicentre trial at emergency departments (EDs) in the Netherlands.

Objectives: Using routine data from an observational study, we simulated the impact of the Feverkidstool on antibiotic prescriptions compared with observed antibiotic prescriptions in children with suspected LRTIs at 12 EDs in eight European countries.

Methods: We selected febrile children aged 1 month to 5 years with respiratory symptoms and excluded upper respiratory tract infections. Using the Feverkidstool, we calculated individual risks for bacterial LRTI retrospectively. We simulated antibiotic prescription rates under different scenarios: (1) applying effect estimates on antibiotic prescription from the trial; and (2) varying both usage (50%-100%) and compliance (70%-100%) with the Feverkidstool's advice to withhold antibiotics in children at low/intermediate risk for bacterial LRTI (≤10%).

Results: Of 4938 children, 4209 (85.2%) were at low/intermediate risk for bacterial LRTI. Applying effect estimates from the trial, the Feverkidstool reduced antibiotic prescription from 33.5% to 24.1% [pooled risk difference: 9.4% (95% CI: 5.7%-13.1%)]. Simulating 50%-100% usage with 90% compliance resulted in risk differences ranging from 8.3% to 15.8%. Our simulations suggest that antibiotic prescriptions would be reduced in EDs with high baseline antibiotic prescription rates or predominantly (>85%) low/intermediate-risk children.

Conclusions: Implementation of the Feverkidstool could reduce antibiotic prescriptions in children with suspected LRTIs in European EDs.
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http://dx.doi.org/10.1093/jac/dkab023DOI Listing
February 2021

COVID-19 vaccine-associated anaphylaxis: A statement of the World Allergy Organization Anaphylaxis Committee.

World Allergy Organ J 2021 Feb 3;14(2):100517. Epub 2021 Feb 3.

Department of Dermatology and Allergology, Charite-Universitätsmedizin, Berlin, Germany.

Vaccines against COVID-19 (and its emerging variants) are an essential global intervention to control the current pandemic situation. Vaccines often cause adverse events; however, the vast majority of adverse events following immunization (AEFI) are a consequence of the vaccine stimulating a protective immune response, and not allergic in etiology. Anaphylaxis as an AEFI is uncommon, occurring at a rate of less than 1 per million doses for most vaccines. However, within the first days of initiating mass vaccination with the Pfizer-BioNTech COVID-19 vaccine BNT162b2, there were reports of anaphylaxis from the United Kingdom and United States. More recent data imply an incidence of anaphylaxis closer to 1:200,000 doses with respect to the Pfizer-BioNTech vaccine. In this position paper, we discuss the background to reactions to the current COVID-19 vaccines and relevant steps to mitigate against the risk of anaphylaxis as an AEFI. We propose a global surveillance strategy led by allergists in order to understand the potential risk and generate data to inform evidence-based guidance, and thus provide reassurance to public health bodies and members of the public.
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http://dx.doi.org/10.1016/j.waojou.2021.100517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857113PMC
February 2021

COVID-19 and Pediatric Lung Disease: A South African Tertiary Center Experience.

Front Pediatr 2020 20;8:614076. Epub 2021 Jan 20.

Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.

The COVID-19 pandemic led to rapid global spread with far-reaching impacts on health-care systems. Whilst pediatric data consistently shown a milder disease course, chronic lung disease has been identified as a risk factor for hospitalization and severe disease. In Africa, comprised predominantly of low middle-income countries (LMIC), the additional burden of HIV, tuberculosis, malnutrition and overcrowding is high and further impacts health risk. This paper reviewed the literature on COVID-19 and chronic lung disease in children and provides our experience from an African pediatric pulmonary center in Cape Town, South Africa. South African epidemiological data confirms a low burden of severe disease with children <18 years comprising 8% of all diagnosed cases and 3% of all COVID-19 admissions. A decrease in hospital admission for other viral lower respiratory tract infections was found. While the pulmonology service manages children with a wide range of chronic respiratory conditions including bronchiectasis, cystic fibrosis, asthma, interstitial lung disease and children with tracheostomies, no significant increase in COVID-19 admissions were noted and in those who developed COVID-19, the disease course was not severe. Current evidence suggests that pre-existing respiratory disease in children does not appear to be a significant risk factor for severe COVID-19. Longitudinal data are still needed to assess risk in children with immunosuppression and interstitial lung diseases. The indirect impacts of the pandemic response on child respiratory health are notable and still likely to be fully realized and quantified. Ensuring children have access to full preventive and care services during this time is priority.
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http://dx.doi.org/10.3389/fped.2020.614076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855972PMC
January 2021

ALLERGY AND CORONAVIRUS DISEASE (COVID-19) INTERNATIONAL SURVEY: REAL-LIFE DATA FROM THE ALLERGY COMMUNITY DURING THE PANDEMIC.

World Allergy Organ J 2021 Jan 31:100515. Epub 2021 Jan 31.

Department of Medicine, Allergy Asthma and Clinical Immunology Section, University Hospital of Verona, Verona Italy.

Background: The COVID-19 outbreak brought an unprecedented challenge to the world. Knowledge in the field has been increasing exponentially and the main allergy societies have produced guidance documents for better management of allergic patients during this period. However, few publications so far have provided real-life data from the allergy community concerning the allergy practice during the COVID-19 outbreak. Therefore, we proposed an international survey on the management of allergic patients during the current pandemic.

Methods: We performed an online survey undertaken to reach out the worldwide allergy community by e-mail and social media. The web-questionnaire contained 24 questions covering demographic data from the participants, clinical practice during this period, and questions related to the new international classification and coding tools addressed for COVID-19. It was circulated for 8 weeks and had anonymous and volunteer context.

Results: Data are presented for 635 participants from 78 countries of all continents. Allergists with long-term professional experience were the main audience. As expected, we received many responses as "I have no data" or "I don't know" to the questions of the survey. However, most with more experience on managing allergic patients during the pandemic agreed that patients suffering from allergic or hypersensitivity conditions have no increased risk of contracting COVID-19 or developing SARS CoV-2. Also, participants mentioned that none of the allergy treatments (inhaled corticosteroids, allergen immunotherapy, biological agents) increased the risk of contracting COVID-19 infection including severe presentations.

Conclusion: The data presented are a starting point to the process of getting a feedback for all the recommendations provided by the allergy societies, it could also be the basis of new strategies to support the health professionals while new COVID-19 specific treatments and vaccines are being explored. The information here presented intends to be helpful to the community but represents a course of action in a highly specific situation due to the state of emergency, and should be helpful to the health systems.
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http://dx.doi.org/10.1016/j.waojou.2021.100515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847410PMC
January 2021

Bistability of somatic pattern memories: stochastic outcomes in bioelectric circuits underlying regeneration.

Philos Trans R Soc Lond B Biol Sci 2021 Mar 8;376(1821):20190765. Epub 2021 Feb 8.

Allen Discovery Center, Tufts University, Medford, MA, USA.

Nervous systems' computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emerging field of developmental bioelectricity, which links the field of basal cognition to state-of-the-art questions in regenerative medicine, synthetic bioengineering and even artificial intelligence. One of the predictions of this view is that regeneration and regulative development can restore correct large-scale anatomies from diverse starting states because, like the brain, they exploit bioelectric encoding of distributed goal states-in this case, pattern memories. We propose a new interpretation of recent stochastic regenerative phenotypes in planaria, by appealing to computational models of memory representation and processing in the brain. Moreover, we discuss novel findings showing that bioelectric changes induced in planaria can be stored in tissue for over a week, thus revealing that somatic bioelectric circuits can implement a long-term, re-writable memory medium. A consideration of the mechanisms, evolution and functionality of basal cognition makes novel predictions and provides an integrative perspective on the evolution, physiology and biomedicine of information processing . This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.
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http://dx.doi.org/10.1098/rstb.2019.0765DOI Listing
March 2021

Uncovering cognitive similarities and differences, conservation and innovation.

Philos Trans R Soc Lond B Biol Sci 2021 Mar 8;376(1821):20200458. Epub 2021 Feb 8.

Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69012 Heidelberg, Germany.

This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.
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http://dx.doi.org/10.1098/rstb.2020.0458DOI Listing
March 2021

Why and when does an enema provoke abdominal pain? Reaction to the article by Peña et al.

J Pediatr Surg 2021 Jan 26. Epub 2021 Jan 26.

Department of Pediatric Radiology of the 1-st State Hospital, Minsk, Belarus. Dorot-Netanya Geriatric Medical Center, Israel. Amnon VeTamar, 1/2, Netanya, 42202, Israel. Electronic address:

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http://dx.doi.org/10.1016/j.jpedsurg.2021.01.029DOI Listing
January 2021

Reframing cognition: getting down to biological basics.

Philos Trans R Soc Lond B Biol Sci 2021 Mar 25;376(1820):20190750. Epub 2021 Jan 25.

Allen Discovery Center at Tufts University, Medford, MA 02155, USA.

The premise of this two-part theme issue is simple: the cognitive sciences should join the rest of the life sciences in how they approach the quarry within their research domain. Specifically, understanding how organisms on the lower branches of the phylogenetic tree become familiar with, value and exploit elements of an ecological niche while avoiding harm can be expected to aid understanding of how organisms that evolved later (including ) do the same or similar things. We call this approach basal cognition. In this introductory essay, we explain what the approach involves. Because no definition of cognition exists that reflects its biological basis, we advance a working definition that can be operationalized; introduce a behaviour-generating toolkit of capacities that comprise the function (e.g. sensing/perception, memory, valence, learning, decision making, communication), each element of which can be studied relatively independently; and identify a (necessarily incomplete) suite of common biophysical mechanisms found throughout the domains of life involved in implementing the toolkit. The articles in this collection illuminate different aspects of basal cognition across different forms of biological organization, from prokaryotes and single-celled eukaryotes-the focus of Part 1-to plants and finally to animals, without and with nervous systems, the focus of Part 2. By showcasing work in diverse, currently disconnected fields, we hope to sketch the outline of a new multidisciplinary approach for comprehending cognition, arguably the most fascinating and hard-to-fathom evolved function on this planet. Doing so has the potential to shed light on problems in a wide variety of research domains, including microbiology, immunology, zoology, biophysics, botany, developmental biology, neurobiology/science, regenerative medicine, computational biology, artificial life and synthetic bioengineering. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.
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http://dx.doi.org/10.1098/rstb.2019.0750DOI Listing
March 2021

Effects of short-term travel on COVID-19 spread: A novel SEIR model and case study in Minnesota.

PLoS One 2021 22;16(1):e0245919. Epub 2021 Jan 22.

Department of Civil, Environmental, and Geo- Engineering, University of Minnesota, Minneapolis, Minnesota, United States of America.

The novel coronavirus responsible for COVID-19 was first identified in Hubei Province, China in December, 2019. Within a matter of months the virus had spread and become a global pandemic. In addition to international air travel, local travel (e.g. by passenger car) contributes to the geographic spread of COVID-19. We modify the common susceptible-exposed-infectious-removed (SEIR) virus spread model and investigate the extent to which short-term travel associated with driving influences the spread of the virus. We consider the case study of the US state of Minnesota, and calibrated the proposed model with travel and viral spread data. Using our modified SEIR model that considers local short-term travel, we are able to better explain the virus spread than using the long-term travel SEIR model. Short-term travel associated with driving is predicted to be a significant contributor to the historical and future spread of COVID-19. The calibrated model also predicts the proportion of infections that were detected. We find that if driving trips remain at current levels, a substantial increase in COVID-19 cases may be observed in Minnesota, while decreasing intrastate travel could help contain the virus spread.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245919PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822539PMC
February 2021

Genetics of Smoking and Risk of Atherosclerotic Cardiovascular Diseases: A Mendelian Randomization Study.

JAMA Netw Open 2021 Jan 4;4(1):e2034461. Epub 2021 Jan 4.

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania.

Importance: Smoking is associated with atherosclerotic cardiovascular disease, but the relative contribution to each subtype (coronary artery disease [CAD], peripheral artery disease [PAD], and large-artery stroke) remains less well understood.

Objective: To determine the association between genetic liability to smoking and risk of CAD, PAD, and large-artery stroke.

Design, Setting, And Participants: Mendelian randomization study using summary statistics from genome-wide associations of smoking (UK Biobank; up to 462 690 individuals), CAD (Coronary Artery Disease Genome Wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics Consortium; up to 60 801 cases, 123 504 controls), PAD (VA Million Veteran Program; up to 24 009 cases, 150 983 controls), and large-artery stroke (MEGASTROKE; up to 4373 cases, 406 111 controls). This study was conducted using summary statistic data from large, previously described cohorts. Review of those publications does not reveal the total recruitment dates for those cohorts. Data analyses were conducted from August 2019 to June 2020.

Exposures: Genetic liability to smoking (as proxied by genetic variants associated with lifetime smoking index).

Main Outcomes And Measures: Risk (odds ratios [ORs]) of CAD, PAD, and large-artery stroke.

Results: Genetic liability to smoking was associated with increased risk of PAD (OR, 2.13; 95% CI, 1.78-2.56; P = 3.6 × 10-16), CAD (OR, 1.48; 95% CI, 1.25-1.75; P = 4.4 × 10-6), and stroke (OR, 1.40; 95% CI, 1.02-1.92; P = .04). Genetic liability to smoking was associated with greater risk of PAD than risk of large-artery stroke (ratio of ORs, 1.52; 95% CI, 1.05-2.19; P = .02) or CAD (ratio of ORs, 1.44; 95% CI, 1.12-1.84; P = .004). The association between genetic liability to smoking and atherosclerotic cardiovascular diseases remained independent from the effects of smoking on traditional cardiovascular risk factors.

Conclusions And Relevance: In this mendelian randomization analysis of data from large studies of atherosclerotic cardiovascular diseases, genetic liability to smoking was a strong risk factor for CAD, PAD, and stroke, although the estimated association was strongest between smoking and PAD. The association between smoking and atherosclerotic cardiovascular disease was independent of traditional cardiovascular risk factors.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.34461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816104PMC
January 2021

Evaluating the effects of guided coaching calls on engagement and outcomes for online acceptance and commitment therapy.

Cogn Behav Ther 2021 Jan 12:1-14. Epub 2021 Jan 12.

Department of Psychology, Utah State University , Logan, UT, USA.

Previous research indicates mixed results for guided support with online interventions. The current secondary analysis evaluated the effects of phone coaching from a dismantling trial of online acceptance and commitment therapy (ACT) in a sample of 136 distressed college students randomized to one of three versions of an ACT website. Participants were randomized to receive email prompts alone (non-coaching condition) or email plus phone coaching (coaching condition). Results indicated no differences between the coaching and non-coaching conditions on program engagement, program satisfaction, mental health outcomes, and almost all psychological flexibility processes. However, participants in the coaching condition reported stronger pre- to posttreatment improvements in psychological inflexibility than the non-coaching condition. This effect was moderated by ACT component condition, with larger pre- to posttreatment effects from coaching on psychological inflexibility in the values/committed action condition and weaker improvements from coaching in the acceptance/defusion condition. Overall, results indicate online self-guided ACT interventions with email prompts are sufficient for addressing college student mental health and that phone coaching provided minimal additional benefit.
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http://dx.doi.org/10.1080/16506073.2020.1846609DOI Listing
January 2021

Variation in hospital admission in febrile children evaluated at the Emergency Department (ED) in Europe: PERFORM, a multicentre prospective observational study.

PLoS One 2021 7;16(1):e0244810. Epub 2021 Jan 7.

Department of General Paediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

Objectives: Hospitalisation is frequently used as a marker of disease severity in observational Emergency Department (ED) studies. The comparison of ED admission rates is complex in potentially being influenced by the characteristics of the region, ED, physician and patient. We aimed to study variation in ED admission rates of febrile children, to assess whether variation could be explained by disease severity and to identify patient groups with large variation, in order to use this to reduce unnecessary health care utilization that is often due to practice variation.

Design: MOFICHE (Management and Outcome of Fever in children in Europe, part of the PERFORM study, www.perform2020.org), is a prospective cohort study using routinely collected data on febrile children regarding patient characteristics (age, referral, vital signs and clinical alarming signs), diagnostic tests, therapy, diagnosis and hospital admission.

Setting And Participants: Data were collected on febrile children aged 0-18 years presenting to 12 European EDs (2017-2018).

Main Outcome Measures: We compared admission rates between EDs by using standardised admission rates after adjusting for patient characteristics and initiated tests at the ED, where standardised rates >1 demonstrate higher admission rates than expected and rates <1 indicate lower rates than expected based on the ED patient population.

Results: We included 38,120 children. Of those, 9.695 (25.4%) were admitted to a general ward (range EDs 5.1-54.5%). Adjusted standardised admission rates ranged between 0.6 and 1.5. The largest variation was seen in short admission rates (0.1-5.0), PICU admission rates (0.2-2.2), upper respiratory tract infections (0.4-1.7) and fever without focus (0.5-2.7). Variation was small in sepsis/meningitis (0.9-1.1).

Conclusions: Large variation exists in admission rates of febrile children evaluated at European EDs, however, this variation is largely reduced after correcting for patient characteristics and therefore overall admission rates seem to adequately reflect disease severity or a potential for a severe disease course. However, for certain patient groups variation remains high even after adjusting for patient characteristics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244810PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790386PMC
January 2021

Why isn't sex optional? Stem-cell competition, loss of regenerative capacity, and cancer in metazoan evolution.

Commun Integr Biol 2020 Dec 10;13(1):170-183. Epub 2020 Dec 10.

Allen Discovery Center at Tufts University, Medford, MA, USA.

Animals that can reproduce vegetatively by fission or budding and also sexually via specialized gametes are found in all five primary animal lineages (Bilateria, Cnidaria, Ctenophora, Placozoa, Porifera). Many bilaterian lineages, including roundworms, insects, and most chordates, have lost the capability of vegetative reproduction and are obligately gametic. We suggest a developmental explanation for this evolutionary phenomenon: obligate gametic reproduction is the result of germline stem cells winning a winner-take-all competition with non-germline stem cells for control of reproduction and hence lineage survival. We develop this suggestion by extending Hamilton's rule, which factors the relatedness between parties into the cost/benefit analysis that underpins cooperative behaviors, to include similarity of cellular state. We show how coercive or deceptive cell-cell signaling can be used to make costly cooperative behaviors appear less costly to the cooperating party. We then show how competition between stem-cell lineages can render an ancestral combination of vegetative reproduction with facultative sex unstable, with one or the other process driven to extinction. The increased susceptibility to cancer observed in obligately-sexual lineages is, we suggest, a side-effect of deceptive signaling that is exacerbated by the loss of whole-body regenerative abilities. We suggest a variety of experimental approaches for testing our predictions.
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http://dx.doi.org/10.1080/19420889.2020.1838809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746248PMC
December 2020

Respiratory Tract Infection Management and Antibiotic Prescription in Children: A Unique Study Comparing Three Levels of Healthcare in The Netherlands.

Pediatr Infect Dis J 2021 Mar;40(3):e100-e105

Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences.

Background: Respiratory tract infections (RTIs) are common in children with febrile illness visiting the general practitioner (GP) or emergency department. We studied the management of children with fever and RTI at 3 different levels of healthcare in The Netherlands, focusing on antibiotic prescription.

Methods: This prospective observational study is part of the Management and Outcome of Febrile children in Europe study. Data were used from face-to-face patient contacts of children with febrile illness in three healthcare settings in Nijmegen, The Netherlands during 2017. These settings were primary (GP), secondary (general hospital) and tertiary care (university hospital).

Results: Of 892 cases with RTI without complex comorbidities, overall antibiotic prescription rates were 29% with no differences between the 3 levels of healthcare, leading to an absolute number of 5031 prescriptions per 100,000 children per year in primary care compared with 146 in secondary and tertiary care combined. The prescription rate in otitis media was similar in all levels: 60%. In cases with lower RTI who received nebulizations prescription rates varied between 19% and 55%.

Conclusions: Antibiotic prescription rates for RTIs in children were comparable between the 3 levels of healthcare, thus leading to a majority of antibiotics being prescribed in primary care. Relatively high prescription rates for all foci of RTIs were found, which was not in agreement with the national guidelines. Antibiotic stewardship needs improvement at all 3 levels of healthcare. Guidelines to prescribe small spectrum antibiotics for RTIs need to be better implemented in hospital care settings.
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http://dx.doi.org/10.1097/INF.0000000000003019DOI Listing
March 2021

Translation of a Host Blood RNA Signature Distinguishing Bacterial From Viral Infection Into a Platform Suitable for Development as a Point-of-Care Test.

JAMA Pediatr 2021 Jan 4. Epub 2021 Jan 4.

Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Imperial College London, London, United Kingdom.

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http://dx.doi.org/10.1001/jamapediatrics.2020.5227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783591PMC
January 2021

Genetically Predicted Blood Pressure and Risk of Atrial Fibrillation.

Hypertension 2021 Feb 4;77(2):376-382. Epub 2021 Jan 4.

Department of Surgery (V.M.W., S.M.D.), University of Pennsylvania Perelman School of Medicine, Philadelphia.

Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. To address this question, this study explored the relationship between genetic predictors of blood pressure and risk of AF. We secondarily explored the relationship between genetically proxied use of antihypertensive drugs and risk of AF. Two-sample Mendelian randomization was performed using an inverse-variance weighted meta-analysis with weighted median Mendelian randomization and Egger intercept tests performed as sensitivity analyses. Summary statistics for systolic blood pressure, diastolic blood pressure, and pulse pressure were obtained from the International Consortium of Blood Pressure and the UK Biobank discovery analysis and AF from the 2018 Atrial Fibrillation Genetics Consortium multiethnic genome-wide association studies. Increases in genetically proxied systolic blood pressure, diastolic blood pressure, or pulse pressure by 10 mm Hg were associated with increased odds of AF (systolic blood pressure: odds ratio [OR], 1.17 [95% CI, 1.11-1.22]; =1×10; diastolic blood pressure: OR, 1.25 [95% CI, 1.16-1.35]; =3×10; pulse pressure: OR, 1.1 [95% CI, 1.0-1.2]; =0.05). Decreases in systolic blood pressure by 10 mm Hg estimated by genetic proxies of antihypertensive medications showed calcium channel blockers (OR, 0.66 [95% CI, 0.57-0.76]; =8×10) and β-blockers (OR, 0.61 [95% CI, 0.46-0.81]; =6×10) decreased the risk of AF. Blood pressure-increasing genetic variants were associated with increased risk of AF, consistent with a causal relationship between blood pressure and AF. These data support the concept that blood pressure reduction with calcium channel blockade or β-blockade could reduce the risk of AF.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803440PMC
February 2021

A proteomics-based method for identifying antigens within immune complexes.

PLoS One 2020 23;15(12):e0244157. Epub 2020 Dec 23.

Department of Infectious Disease, Section of Paediatric Infectious Disease, Imperial College London, London, United Kingdom.

A novel approach to recover and identify immune complexes (ICs) was developed using size exclusion chromatography (SEC) and affinity chromatography on immunoglobulin binding columns (HiTrap Protein G). The purification process was monitored by 1D SDS-PAGE, protein staining, Western blotting and, finally, liquid chromatography tandem mass spectrometry (LC MS/MS) was used to identify the recovered antigens. This approach was applied to serum with artificially created immune complexes (ICs) comprising vaccine antigen (influenza) and antibody, which led to recovery and identification of influenza peptides within the recovered ICs. This approach was compared with the established method for IC detection and recovery, polyethylene glycol (PEG) precipitation, followed by LC MS/MS. Both approaches successfully enabled capture, recovery and characterization of immunoglobulins and influenza antigen(s) in complex with the immunoglobulins. However, PEG precipitation has the advantage of simplicity and is more suited for large scale studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244157PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757895PMC
December 2020

Rewiring Endogenous Bioelectric Circuits in the Xenopus laevis Embryo Model.

Methods Mol Biol 2021 ;2258:93-103

Department of Biology, and Allen Discovery Center, Tufts University, Medford, MA, USA.

Embryogenesis, as well as regeneration, is increasingly recognized to be orchestrated by an interplay of transcriptional and bioelectric networks. Spatiotemporal patterns of resting potentials direct the size, shape, and locations of numerous organ primordia during patterning. These bioelectrical properties are established by the function of ion channels and pumps that set voltage potentials of individual cells, and gap junctions (electrical synapses) that enable physiological states to propagate across tissue networks. Functional experiments to probe the roles of bioelectrical states can be carried out by targeting endogenous ion channels during development. Here, we describe protocols, optimized for the highly tractable Xenopus laevis embryo, for molecular genetic targeting of ion channels and connexins based on CRISPR, and monitoring of resting potential states using voltage-sensing fluorescent dye. Similar strategies can be adapted to other model species.
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http://dx.doi.org/10.1007/978-1-0716-1174-6_7DOI Listing
January 2021

Community effects allow bioelectrical reprogramming of cell membrane potentials in multicellular aggregates: Model simulations.

Phys Rev E 2020 Nov;102(5-1):052412

Departamento Termodinàmica, Universitat de València, E-46100 Burjassot, Spain.

Bioelectrical patterns are established by spatiotemporal correlations of cell membrane potentials at the multicellular level, being crucial to development, regeneration, and tumorigenesis. We have conducted multicellular simulations on bioelectrical community effects and intercellular coupling in multicellular aggregates. The simulations aim at establishing under which conditions a local heterogeneity consisting of a small patch of cells can be stabilized against a large aggregate of surrounding identical cells which are in a different bioelectrical state. In this way, instructive bioelectrical information can be persistently encoded in spatiotemporal patterns of separated domains with different cell polarization states. The multicellular community effects obtained are regulated both at the single-cell and intercellular levels, and emerge from a delicate balance between the degrees of intercellular coupling in: (i) the small patch, (ii) the surrounding bulk, and (iii) the interface that separates these two regions. The model is experimentally motivated and consists of two generic voltage-gated ion channels that attempt to establish the depolarized and polarized cell states together with coupling conductances whose individual and intercellular different states permit a dynamic multicellular connectivity. The simulations suggest that community effects may allow the reprogramming of single-cell bioelectrical states, in agreement with recent experimental data. A better understanding of the resulting electrical regionalization can assist the electroceutical correction of abnormally depolarized regions initiated in the bulk of normal tissues as well as suggest new biophysical mechanisms for the establishment of target patterns in multicellular engineering.
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http://dx.doi.org/10.1103/PhysRevE.102.052412DOI Listing
November 2020

Quantitative multiplex profiling of the complement system to diagnose complement-mediated diseases.

Clin Transl Immunology 2020 9;9(12):e1225. Epub 2020 Dec 9.

Laboratory of Medical Immunology Department of Laboratory Medicine Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands.

Objectives: Complement deficiencies are difficult to diagnose because of the variability of symptoms and the complexity of the diagnostic process. Here, we applied a novel 'complementomics' approach to study the impact of various complement deficiencies on circulating complement levels.

Methods: Using a quantitative multiplex mass spectrometry assay, we analysed 44 peptides to profile 34 complement proteins simultaneously in 40 healthy controls and 83 individuals with a diagnosed deficiency or a potential pathogenic variant in 14 different complement proteins.

Results: Apart from confirming near or total absence of the respective protein in plasma of complement-deficient patients, this mass spectrometry-based profiling method led to the identification of additional deficiencies. In many cases, partial depletion of the pathway up- and/or downstream of the absent protein was measured. This was especially found in patients deficient for complement inhibitors, such as angioedema patients with a C1-inhibitor deficiency. The added value of complementomics was shown in three patients with poorly defined complement deficiencies.

Conclusion: Our study shows the potential clinical utility of profiling circulating complement proteins as a comprehensive read-out of various complement deficiencies. Particularly, our approach provides insight into the intricate interplay between complement proteins due to functional coupling, which contributes to the better understanding of the various disease phenotypes and improvement of care for patients with complement-mediated diseases.
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http://dx.doi.org/10.1002/cti2.1225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724921PMC
December 2020

Paediatric atopic eczema (atopic dermatitis) in South Africa: A practical algorithm for the management of mild-to-moderate disease in daily clinical practice.

S Afr Fam Pract (2004) 2020 Nov 23;62(1):e1-e9. Epub 2020 Nov 23.

Division of Dermatology, Department of Medicine, Faculty of Health Sciences, Stellenbosch University, Cape Town.

Background: Atopic eczema (AE) is a chronic, highly pruritic, inflammatory skin condition with increasing prevalence worldwide. Atopic eczema mostly affects children, impairing quality of life with poor disease control leading to progression of other atopic disorders. As most patients in South Africa have no access to specialist healthcare, a practical approach is needed for the management of mild-to-moderate AE in paediatric patients for daily clinical practice.

Methods: A panel of experts in AE convened to develop a practical algorithm for the management of AE for children and adolescents in South Africa.

Results: Regular moisturising with an oil-based emollient remains the mainstay of AE treatment. Severe AE flares should be managed with topical corticosteroids (TCSs). For mild-to-moderate AE flares in sensitive skin areas, a topical calcineurin inhibitor (TCI) should be applied twice daily from the first signs of AE until complete resolution. Topical corticosteroids may be used when TCIs are unavailable. In non-sensitive skin areas, TCSs should be used for mild-to-moderate AE, but TCIs twice daily may be considered. Proactive maintenance treatment with low-dose TCI or TCS 2-3 times weekly and the liberal use of emollients is recommended for patients with recurrent flares.

Conclusions: This algorithm aims to simplify treatment of paediatric AE, optimising clinical outcomes and reducing disease burden. This approach excludes treatment of patients with severe AE, who should be referred to specialist care. Emphasis has been given to the importance of general skincare, patient education and the topical anti-inflammatory medications available in South Africa (TCSs and TCIs).
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http://dx.doi.org/10.4102/safp.v62i1.5190DOI Listing
November 2020

A randomized controlled trial of online acceptance and commitment therapy to improve diet and physical activity among adults who are overweight/obese.

Transl Behav Med 2020 Dec 8. Epub 2020 Dec 8.

Utah State University, Logan, UT.

Acceptance and commitment therapy (ACT) has shown benefit for improving diet, physical activity, and weight among adults who are overweight and obese. However, research to-date in this area has primarily evaluated ACT delivered through in-person interventions, which has more limited access relative to online formats. The present study evaluated an online guided self-help program that integrated ACT with nutrition education to improve healthy eating and physical activity. A sample of 79 adults who were overweight/obese was randomized to receive the 8-week ACT on Health program plus weekly phone coaching or to a waitlist. Participants completed 5.5 ACT sessions on average (out of 8) and reported moderately high program satisfaction. Participants in the ACT condition improved significantly more than the waitlist at posttreatment on the primary outcome of healthy eating index (HEI; based on 24-hr recall assessments) and almost all secondary outcomes assessing self-reported eating behaviors, weight, mental health, weight self-stigma, and psychological inflexibility. However, no intervention effects were found for self-reported physical activity. At 8-week follow-up, improvements were maintained for most outcomes in the ACT condition, but not for the HEI. Improvements in psychological inflexibility mediated treatment effects on some outcomes, but not HEI or weight. Overall, delivering ACT through online guided self-help combined with nutrition education appears promising for improving healthy eating, weight, and self-stigma, but results for physical activity and long-term behavior change are unclear, possibly due to limitations in the ACT on Health program.
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http://dx.doi.org/10.1093/tbm/ibaa123DOI Listing
December 2020

A Pilot Randomized Controlled Trial of Acceptance and Commitment Therapy Guided Self-Help for Overweight and Obese Adults High in Weight Self-Stigma.

Behav Modif 2020 Nov 30:145445520975112. Epub 2020 Nov 30.

Utah State University, Logan, UT, USA.

Weight self-stigma, in which individuals internalize stigmatizing messages about weight, is a prevalent problem that contributes to poor quality of life and health. This pilot randomized controlled trial evaluated acceptance and commitment therapy (ACT) guided self-help using for 55 overweight/obese adults high in weight self-stigma. Participants were randomized to the ACT self-help book plus phone coaching (GSH-P;  = 17), self-help book plus email prompts only (GSH-E;  = 20), or a waitlist condition ( = 18), with online self-report assessments at baseline and posttreatment (8 weeks later). Participants reported high satisfaction ratings and engagement with the ACT self-help book, with no differences between GSH-P and GSH-E. Both GSH-P and GSH-E improved weight self-stigma relative to waitlist with large effect sizes. There were mixed findings for health outcomes. The GSH-P condition improved more on healthy eating behaviors and general physical activity, but neither ACT condition improved more than waitlist on self-reported body mass index, emotional eating, and a second measure of physical activity. Results suggest an ACT self-help book with email prompts can reduce weight self-stigma and potentially improve some health behavior outcomes. Phone coaching may provide additional benefits for generalizing ACT to diet and physical activity.
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http://dx.doi.org/10.1177/0145445520975112DOI Listing
November 2020

Multisystem Inflammatory Syndrome in Children: An International Survey.

Pediatrics 2021 02 24;147(2). Epub 2020 Nov 24.

Paediatric Cardiology Services, Royal Brompton Hospital, London, United Kingdom;

Objectives: To describe presentation, hospital course, and predictors of bad outcome in multisystem inflammatory syndrome in children (MIS-C).

Methods: Retrospective data review of a case series of children meeting the published definition for MIS-C who were discharged or died between March 1, 2020, and June 15, 2020, from 33 participating European, Asian, and American hospitals. Data were collected through a Web-based survey and included clinical, laboratory, electrocardiographic, and echocardiographic findings and treatment management.

Results: We included 183 patients with MIS-C: male sex, 109 (59.6%); mean age 7.0 ± 4.7 years; Black race, 56 (30.6%); obesity, 48 (26.2%). Overall, 114 of 183 (62.3%) had evidence of severe acute respiratory syndrome coronavirus 2 infection. All presented with fever, 117 of 183 (63.9%) with gastrointestinal symptoms, and 79 of 183 (43.2%) with shock, which was associated with Black race, higher inflammation, and imaging abnormalities. Twenty-seven patients (14.7%) fulfilled criteria for Kawasaki disease. These patients were younger and had no shock and fewer gastrointestinal, cardiorespiratory, and neurologic symptoms. The remaining 77 patients (49.3%) had mainly fever and inflammation. Inotropic support, mechanical ventilation, and extracorporeal membrane oxygenation were indicated in 72 (39.3%), 43 (23.5%), and 4 (2.2%) patients, respectively. A shorter duration of symptoms before admission was found to be associated with poor patient outcome and for extracorporeal membrane oxygenation and/or death, with 72.3% (95% confidence interval: 0.56-0.90; = .006) increased risk per day reduction and 63.3% (95% confidence interval: 0.47-0.82; < .0001) increased risk per day reduction respectively.

Conclusions: In this case series, children with MIS-C presented with a wide clinical spectrum, including Kawasaki disease-like, life-threatening shock and milder forms with mainly fever and inflammation. A shorter duration of symptoms before admission was associated with a worse outcome.
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http://dx.doi.org/10.1542/peds.2020-024554DOI Listing
February 2021

Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine.

Mol Syst Biol 2020 11;16(11):e9888

Department of Paediatrics, University of Oxford, Oxford, UK.

Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations with or without concomitant 4CMenB, to gain insight into the molecular mechanisms underlying post-vaccination reactogenicity and immunogenicity. Infants were randomised to receive control immunisations (PCV13 and DTaP-IPV-Hib) with or without 4CMenB at 2 and 4 months of age. Blood gene expression and plasma proteins were measured prior to, then 4 h, 24 h, 3 days or 7 days post-vaccination. 4CMenB vaccination was associated with increased expression of ENTPD7 and increased concentrations of 4 plasma proteins: CRP, G-CSF, IL-1RA and IL-6. Post-vaccination fever was associated with increased expression of SELL, involved in neutrophil recruitment. A murine model dissecting the vaccine components found the concomitant regimen to be associated with increased gene perturbation compared with 4CMenB vaccine alone with enhancement of pathways such as interleukin-3, -5 and GM-CSF signalling. Finally, we present transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine.
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http://dx.doi.org/10.15252/msb.20209888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674973PMC
November 2020