15 research outputs found
Inbred Mouse Populations Exhibit Intergenerational Changes in Intestinal Microbiota Composition and Function Following Introduction to a Facility
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Inbred mice are used to investigate many aspects of human physiology, including susceptibility to disease and response to therapies. Despite increasing evidence that the composition and function of the murine intestinal microbiota can substantially influence a broad range of experimental outcomes, relatively little is known about microbiome dynamics within experimental mouse populations. We investigated changes in the intestinal microbiome between C57BL/6J mice spanning six generations (assessed at generations 1, 2, 3, and 6), following their introduction to a stringently controlled facility. Fecal microbiota composition and function were assessed by 16S rRNA gene amplicon sequencing and liquid chromatography mass spectrometry, respectively. Significant divergence of the intestinal microbiota between founder and second generation mice, as well as continuing inter-generational variance, was observed. Bacterial taxa whose relative abundance changed significantly through time included Akkermansia, Turicibacter, and Bifidobacterium (p < 0.05), all of which are recognized as having the potential to substantially influence host physiology. Shifts in microbiota composition were mirrored by corresponding differences in the fecal metabolome (r = 0.57, p = 0.0001), with notable differences in levels of tryptophan pathway metabolites and amino acids, including glutamine, glutamate and aspartate. We related the magnitude of changes in the intestinal microbiota and metabolome characteristics during acclimation to those observed between populations housed in separate facilities, which differed in regards to husbandry, barrier conditions and dietary intake. The microbiome variance reported here has implications for experimental reproducibility, and as a consequence, experimental design and the interpretation of research outcomes across wide range of contexts
Nitrogen but not phosphorus addition affects symbiotic N2 fixation by legumes in natural and semiânatural grasslands located on four continents
The amount of nitrogen (N) derived from symbiotic N2 fixation by legumes in grasslands might be affected by anthropogenic N and
phosphorus (P) inputs, but the underlying mechanisms are not known. Methods We evaluated symbiotic N2 fixation in 17
natural and semi-natural grasslands on four continents that are subjected to the same full-factorial N and P addition experiment, using the 15N natural abundance method. Results N as well as combined N and P (NP) addition reduced aboveground legume biomass by 65% and 45%, respectively, compared to the control, whereas P addition had no significant impact. Addition of N and/or P had no significant effect on the symbiotic N2 fixation per unit legume biomass. In consequence, the amount of N fixed annually per grassland area was less than half in the N addition treatments compared to control and P addition, irrespective of whether the dominant legumes were annuals or perennials. Conclusion Our results reveal that N addition mainly impacts symbiotic N2 fixation via reduced
biomass of legumes rather than changes in N2 fixation per unit legume biomass. The results show that soil N enrichment by anthropogenic activities significantly reduces N 2 fixation in grasslands, and these effects cannot be reversed by additional P amendment.EEA Santa CruzFil: VĂĄzquez, Eduardo. University of Bayreuth. Department of Soil Ecology. Bayreuth Center of Ecology and Environmental Research (BayCEER); AlemaniaFil: VĂĄzquez, Eduardo. Swedish University of Agricultural Sciences. Department of Soil and Environment; SueciaFil: Schleuss, PerâMarten. University of Bayreuth. Department of Soil Ecology. Bayreuth Center of Ecology and Environmental Research (BayCEER); AlemaniaFil: Borer, Elizabeth T. University of Minnesota. Department of Ecology, Evolution, and Behavior; Estados UnidosFil: Bugalho, Miguel N. University of Lisbon. Centre for Applied Ecology âProf. Baeta Nevesâ (CEABN-InBIO). School of Agriculture; Portugal.Fil: Caldeira, Maria. C. University of Lisbon. Forest Research Centre. School of Agriculture; Portugal.Fil: Eisenhauer, Nico. German Centre for Integrative Biodiversity Research; AlemaniaFil: Eisenhauer, Nico. Leipzig University. Institute of Biology; AlemaniaFil: Eskelinen, Anu. German Centre for Integrative Biodiversity Research; AlemaniaFil: Eskelinen, Anu. Physiological Diversity, Helmholtz Centrefor Environmental Research; AlemaniaFil: Eskelinen, Anu. University of Oulu. Ecology & Genetics; FinlandiaFil: Fay, Philip A. Grassland Soil and Water Research Laboratory (USDA-ARS); Estados UnidosFil: Haider, Sylvia. German Centre for Integrative Biodiversity Research; AlemaniaFil: Haider, Sylvia. Martin Luther University. Institute of Biology. Geobotany and Botanical Garden; AlemaniaFil: Jentsch, Anke. University of Bayreuth. Department of Soil Ecology. Bayreuth Center of Ecology and Environmental Research (BayCEER); AlemaniaFil: Kirkman, Kevin P. University of KwaZulu-Natal. School of Life Sciences; SudĂĄfricaFil: McCulley, Rebecca L. University of Kentucky. Department of Plant and Soil Sciences; Estados UnidosFil: Peri, Pablo Luis. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Price, Jodi. Charles Sturt University. Institute for Land, Water and Society; Australia.Fil: Richards, Anna E. CSIRO Land and Water. Northern Territory; Australia.Fil: Risch, Anita C. Swiss Federal Institute for Forest, Snow and Landscape Research WSL; SuizaFil: Roscher, Christiane. German Centre for Integrative Biodiversity Research; AlemaniaFil: Roscher, Christiane. Physiological Diversity, Helmholtz Centre for Environmental Research; AlemaniaFil: SchĂŒtz, Martin. Swiss Federal Institute for Forest, Snow and Landscape Research WSL; SuizaFil: Seabloom, Eric William. University of Minnesota. Dept. of Ecology, Evolution, and Behavior; Estados UnidosFil: Standish, Rachel J. Murdoch University. Harry Butler Institute; Australia.Fil: Stevens, Carly J. Lancaster University. Lancaster Environment Centre; Reino UnidoFil: Tedder, Michelle J. University of KwaZulu-Natal. School of Life Sciences; SudĂĄfricaFil: Virtanen, Risto. University of Oulu. Ecology & Genetics; Finlandia.Fil: Spohn, Marie. University of Bayreuth. Department of Soil Ecology. Bayreuth Center of Ecology and Environmental Research (BayCEER); AlemaniaFil: Spohn, Marie. Swedish University of Agricultural Sciences. Department of Soil and Environment; Sueci
Nitrogen but not phosphorus addition affects symbiotic N-2 fixation by legumes in natural and semi-natural grasslands located on four continents
Background and aims: The amount of nitrogen (N) derived from symbiotic N-2 fixation by legumes in grasslands might be affected by anthropogenic N and phosphorus (P) inputs, but the underlying mechanisms are not known.Methods: We evaluated symbiotic N-2 fixation in 17 natural and semi-natural grasslands on four continents that are subjected to the same full-factorial N and P addition experiment, using the N-15 natural abundance method.Results: N as well as combined N and P (NP) addition reduced aboveground legume biomass by 65% and 45%, respectively, compared to the control, whereas P addition had no significant impact. Addition of N and/or P had no significant effect on the symbiotic N-2 fixation per unit legume biomass. In consequence, the amount of N fixed annually per grassland area was less than half in the N addition treatments compared to control and P addition, irrespective of whether the dominant legumes were annuals or perennials.Conclusion: Our results reveal that N addition mainly impacts symbiotic N-2 fixation via reduced biomass of legumes rather than changes in N-2 fixation per unit legume biomass. The results show that soil N enrichment by anthropogenic activities significantly reduces N-2 fixation in grasslands, and these effects cannot be reversed by additional P amendment
Young people's data governance preferences for their mental health data: MindKind Study findings from India, South Africa, and the United Kingdom
Mobile devices offer a scalable opportunity to collect longitudinal data that facilitate advances in mental health treatment to address the burden of mental health conditions in young people. Sharing these data with the research community is critical to gaining maximal value from rich data of this nature. However, the highly personal nature of the data necessitates understanding the conditions under which young people are willing to share them. To answer this question, we developed the MindKind Study, a multinational, mixed methods study that solicits young people's preferences for how their data are governed and quantifies potential participants' willingness to join under different conditions. We employed a community-based participatory approach, involving young people as stakeholders and co-researchers. At sites in India, South Africa, and the UK, we enrolled 3575 participants ages 16-24 in the mobile app-mediated quantitative study and 143 participants in the public deliberation-based qualitative study. We found that while youth participants have strong preferences for data governance, these preferences did not translate into (un)willingness to join the smartphone-based study. Participants grappled with the risks and benefits of participation as well as their desire that the "right people" access their data. Throughout the study, we recognized young people's commitment to finding solutions and co-producing research architectures to allow for more open sharing of mental health data to accelerate and derive maximal benefit from research
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 nonâcritically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ supportâfree days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Tackling Health Inequities: A Unique, Asynchronous Course Designed Through Peer-to-Peer Methods
OBJECTIVES This study investigates the efficacy and feasibility of an asynchronous, peer-to-peer health disparities enrichment course on postbaccalaureate prehealth studentsâ knowledge, behaviors, and reaction to course materials. INTRODUCTION Growing awareness of social inequities has prompted educators of prehealth and medical students to explore student education by addressing systemic healthcare issues. This cross-sectional study assessed reactions, learning, and self-reported behavior changes in students after taking the course âSocial Determinants, Disparities, and Preparing for the Future of Healthcareâ (SDDH). METHODS The curriculum was designed by prehealth postbaccalaureate students for their peers. Course goals were to educate participants on social determinants of health and to build cultural and structural competence in their roles as future healthcare professionals. SDDH is an asynchronous, noncredit-bearing, 5-h online course with 10 modules covering various topics. The Kirkpatrick Model was used to assess the effectiveness of the curriculum, alongside qualitative and quantitative analyses of student performance. RESULTS Out of the 102 active students in the prehealth program that accepted the invitation to join, 29 students successfully completed the course (rate of completionâ=â28%). On average, students expressed positive reactions and attitudes toward the course and experienced an observable increase in knowledge assessment scores upon curriculum completion ( P -valueâ=â.0002). Studentsâ self-reported observations demonstrated sustained behavioral change 3 months after course completion. CONCLUSION It is critical to educate prehealth students on health disparities, structural, and cultural competence. A course such as SDDH may help prehealth students build effective communication skills for advocacy and develop an empathetic, patient-centered approach earlier on in their career pursuit. Some barriers to students completing the entire course include its length, uncredited status, and voluntary self-enrollment
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An Application of EvidenceâBased Approaches to Engage Young People in the Design of a Global Mental Health Databank
Publication status: PublishedFunder: This study was funded by the Wellcome Trust.; doi: http://dx.doi.org/10.13039/100004440ABSTRACTIntroductionEngaging youth in mental health research and intervention design has the potential to improve their relevance and effectiveness. Frameworks like Roger Hart's ladder of participation, Shier's pathways to participation and Lundy's voice and influence model aim to balance power between youth and adults. Hart's Ladder, specifically, is underutilized in global mental health research, presenting new opportunities to examine power dynamics across various contexts. Drawing on Hart's ladder, our study examined youth engagement in mental health research across highâ and middleâincome countries using Internetâbased technologies, evaluating youth involvement in decisionâmaking and presenting research stages that illustrate these engagements.MethodsWe conducted a directed content analysis of youth engagement in the study using primary data from project documents, weekly AirTable updates and discussions and interviews with youth and the research consortium. Using Hart's Ladder as a framework, we describe youth engagement along rungs throughout different research stages: crossâcutting research process, onboarding, formative research and quantitative and qualitative study designs.ResultsYouth engagement in the MindKind study fluctuated between Rung 4 (âAssign, but informedâ) and Rung 7 (âYouth initiated and directedâ) on Hart's Ladder. Engagement was minimal in the early project stages as project structures and goals were defined, with some youth feeling that their experiences were underutilized and many decisions being adultâled. Communication challenges and structural constraints, like tight timelines and limited budget, hindered youth engagement in highest ladder rungs. Despite these obstacles, youth engagement increased, particularly in developing recruitment strategies and in shaping data governance models and the qualitative study design. Youth helped refine research tools and protocols, resulting in moderate to substantial engagement in the later research stages.ConclusionOur findings emphasize the value of youthâadult partnerships, which offer promise in amplifying voices and nurturing skills, leadership and inclusiveness of young people. Youth engagement in project decisionâmaking progressed from lower to higher rungs on Hart's Ladder over time; however, this was not linear. Effective youth engagement requires dynamic strategies, transparent communication and mutual respect, shaping outcomes that authentically reflect diverse perspectives and mental health experiences.Patient or Public ContributionThere was substantial patient and public involvement in this study. This paper reports findings on youth engagement conducted with 35 young people from India, South Africa and the United Kingdom, all of whom had lived experience of mental health challenges. Youth engagement in the MindKind study was coordinated and led by three professional youth advisors (PYAs) in these contexts, who were also young people with lived experience of mental health challenges. Each of the three study sites embedded a fullâtime, communityâbased PYA within their study team to inform all aspects of the research project, including the development of informational materials and the facilitation of Young People's Advisory Group (YPAG) sessions referenced in this paper. Each PYA also consulted with a siteâspecific YPAG that met biâmonthly throughout the project, shaping the formation of study materials and serving as a test group in both the quantitative and qualitative studies. Youth participants in this study also contributed extensively, engaging in data collection and manuscript writing. The following youth advisory panels members (J.B., L.B., D.O.J., M.V.) and all PYAs (E.B., S.R., R.S.) in the MindKind study contributed to the writing of this manuscript and are acknowledged as coâauthors.</jats:sec
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Young peopleâs data governance preferences for their mental health data: MindKind Study findings from India, South Africa, and the United Kingdom
Funder: Wellcome Trust; funder-id: http://dx.doi.org/10.13039/100010269Mobile devices offer a scalable opportunity to collect longitudinal data that facilitate advances in mental health treatment to address the burden of mental health conditions in young people. Sharing these data with the research community is critical to gaining maximal value from rich data of this nature. However, the highly personal nature of the data necessitates understanding the conditions under which young people are willing to share them. To answer this question, we developed the MindKind Study, a multinational, mixed methods study that solicits young peopleâs preferences for how their data are governed and quantifies potential participantsâ willingness to join under different conditions. We employed a community-based participatory approach, involving young people as stakeholders and co-researchers. At sites in India, South Africa, and the UK, we enrolled 3575 participants ages 16â24 in the mobile app-mediated quantitative study and 143 participants in the public deliberation-based qualitative study. We found that while youth participants have strong preferences for data governance, these preferences did not translate into (un)willingness to join the smartphone-based study. Participants grappled with the risks and benefits of participation as well as their desire that the âright peopleâ access their data. Throughout the study, we recognized young peopleâs commitment to finding solutions and co-producing research architectures to allow for more open sharing of mental health data to accelerate and derive maximal benefit from research
Young peopleâs data governance preferences for their mental health data: MindKind Study findings from India, South Africa, and the United Kingdom
Mobile devices offer a scalable opportunity to collect longitudinal data that facilitate advances in mental health treatment to address the burden of mental health conditions in young people. Sharing these data with the research community is critical to gaining maximal value from rich data of this nature. However, the highly personal nature of the data necessitates understanding the conditions under which young people are willing to share them. To answer this question, we developed the MindKind Study, a multinational, mixed methods study that solicits young peopleâs preferences for how their data are governed and quantifies potential participantsâ willingness to join under different conditions. We employed a community-based participatory approach, involving young people as stakeholders and co-researchers. At sites in India, South Africa, and the UK, we enrolled 3575 participants ages 16â24 in the mobile app-mediated quantitative study and 143 participants in the public deliberation-based qualitative study. We found that while youth participants have strong preferences for data governance, these preferences did not translate into (un)willingness to join the smartphone-based study. Participants grappled with the risks and benefits of participation as well as their desire that the âright peopleâ access their data. Throughout the study, we recognized young peopleâs commitment to finding solutions and co-producing research architectures to allow for more open sharing of mental health data to accelerate and derive maximal benefit from research
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Young people's data governance preferences for their mental health data: MindKind Study findings from India, South Africa, and the United Kingdom.
Funder: Wellcome TrustMobile devices offer a scalable opportunity to collect longitudinal data that facilitate advances in mental health treatment to address the burden of mental health conditions in young people. Sharing these data with the research community is critical to gaining maximal value from rich data of this nature. However, the highly personal nature of the data necessitates understanding the conditions under which young people are willing to share them. To answer this question, we developed the MindKind Study, a multinational, mixed methods study that solicits young people's preferences for how their data are governed and quantifies potential participants' willingness to join under different conditions. We employed a community-based participatory approach, involving young people as stakeholders and co-researchers. At sites in India, South Africa, and the UK, we enrolled 3575 participants ages 16-24 in the mobile app-mediated quantitative study and 143 participants in the public deliberation-based qualitative study. We found that while youth participants have strong preferences for data governance, these preferences did not translate into (un)willingness to join the smartphone-based study. Participants grappled with the risks and benefits of participation as well as their desire that the "right people" access their data. Throughout the study, we recognized young people's commitment to finding solutions and co-producing research architectures to allow for more open sharing of mental health data to accelerate and derive maximal benefit from research