Introducing enteral feeding induces intestinal subclinical inflammation and respective chromatin changes in preterm pigs

Aim: To analyze how enteral food introduction affects intestinal gene regulation and chromatin structure in preterm pigs. Materials &amp; methods: Preterm pigs were fed parenteral nutrition plus/minus slowly increasing volumes of enteral nutrition. Intestinal gene-expression and chromatin structure were analyzed 5 days after birth. Results: Enteral feeding led to differential upregulation of inflammatory and pattern recognition receptor genes, including IL8 (median: 5.8, 95% CI: 3.9–7.8 for formula; median: 2.2, 95% CI: 1.3–3.3 for colostrum) and TLR4 (median: 3.7, 95% CI: 2.6–4.8 for formula; no significant differences for colostrum) with corresponding decondensed chromatin configurations. On histology this correlated with mild mucosal lesions, particularly in formula-fed pigs. In CaCo-2 cells, histone hyperacetylation led to a marked increase in TLR4 mRNA and increased IL8 expression upon stimulation with lipopolysaccharide (median: 7.0; interquartile range: 5.63–8.85) compared with naive cells (median 4.2; interquartile range: 2.45–6.33; p = 0.03). Conclusion: Enteral feeding, particular with formula, induces subclinical inflammation in the premature intestine and more open chromatin structure in key inflammatory genes. This may increase the susceptibility for necrotizing enterocolitis. </jats:p

“Luck of the draw really”: a qualitative exploration of Australian trainee doctors’ experiences of mandatory research

BACKGROUND: Many medical trainees, prior to achieving specialist status, are required to complete a mandatory research project, the usefulness of which has been debated. The aim of this study was to gain an in-depth understanding of trainees' experiences and satisfaction of conducting such research projects in Australia.METHODS: A qualitative descriptive approach was used. Semi-structured interviews with trainees were undertaken between May 2021 and June 2022. Australian medical trainees who had completed a research project as part of specialty training within the past five years were invited to participate. The purposive sample was drawn from participants in a survey on the same topic who had indicated interest in participating in an interview. Interviews explored trainees' overall experience of and satisfaction with conducting research projects, as well as their perceptions of research training, support, barriers, enablers, and perceived benefits. Interviews were transcribed verbatim and thematically analysed.RESULTS: Sixteen medical doctors from seven medical colleges were interviewed. Trainee experience and satisfaction was highly variable between participants and was shaped by four factors: 1) trainees entered their specialty training with their own perspectives on the value and purpose of the research project, informed by their previous experiences with research and perceived importance of research in their planned career path; 2) in conducting the project, enablers including protected time, supervisor support and institutional structures, were vital to shaping their experience; 3) trainees' access to these enablers was variable, mediated by a combination of luck, and the trainees' own drive and research skill; and 4) project outcomes, in terms of research merit, learning, career benefits and impacts on patient care.CONCLUSIONS: Trainee experiences of doing research were mixed, with positive experiences often attributed to chance rather than an intentionally structured learning experience. We believe alternatives to mandatory trainee research projects must be explored, including recognising other forms of research learning activities, and directing scarce resources to supporting the few trainees who plan to pursue clinician researcher careers.</p

Examination of Fully Automated Mammographic Density Measures Using Libra and Breast Cancer Risk in a Cohort of 21,000 Non-Hispanic White Women

BACKGROUND: Breast density is strongly associated with breast cancer risk. Fully automated quantitative density assessment methods have recently been developed that could facilitate large-scale studies, although data on associations with long-term breast cancer risk are limited. We examined LIBRA assessments and breast cancer risk and compared results to prior assessments using Cumulus, an established computer-assisted method requiring manual thresholding. METHODS: We conducted a cohort study among 21,150 non-Hispanic white female participants of the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California who were 40-74 years at enrollment, followed for up to 10 years, and had archived processed screening mammograms acquired on Hologic or General Electric full-field digital mammography (FFDM) machines and prior Cumulus density assessments available for analysis. Dense area (DA), non-dense area (NDA), and percent density (PD) were assessed using LIBRA software. Cox regression was used to estimate hazard ratios (HRs) for breast cancer associated with DA, NDA and PD modeled continuously in standard deviation (SD) increments, adjusting for age, mammogram year, body mass index, parity, first-degree family history of breast cancer, and menopausal hormone use. We also examined differences by machine type and breast view. RESULTS: The adjusted HRs for breast cancer associated with each SD increment of DA, NDA and PD were 1.36 (95% confidence interval, 1.18-1.57), 0.85 (0.77-0.93) and 1.44 (1.26-1.66) for LIBRA and 1.44 (1.33-1.55), 0.81 (0.74-0.89) and 1.54 (1.34-1.77) for Cumulus, respectively. LIBRA results were generally similar by machine type and breast view, although associations were strongest for Hologic machines and mediolateral oblique views. Results were also similar during the first 2 years, 2-5 years and 5-10 years after the baseline mammogram. CONCLUSION: Associations with breast cancer risk were generally similar for LIBRA and Cumulus density measures and were sustained for up to 10 years. These findings support the suitability of fully automated LIBRA assessments on processed FFDM images for large-scale research on breast density and cancer risk

WISDOM project XX. - Strong shear tearing molecular clouds apart in NGC 524

Early-type galaxies (ETGs) are known to harbour dense spheroids of stars but scarce star formation (SF). Approximately a quarter of these galaxies have rich molecular gas reservoirs yet do not form stars efficiently. We study here the ETG NGC 524, with strong shear suspected to result in a smooth molecular gas disc and low star-formation efficiency (SFE). We present new spatially resolved observations of the 12CO(2-1)-emitting cold molecular gas from the Atacama Large Millimeter/sub-millimeter Array (ALMA) and of the warm ionized-gas emission lines from SITELLE at the Canada–France–Hawaii Telescope. Although constrained by the resolution of the ALMA observations (≈37 pc), we identify only 52 GMCs with radii ranging from 30 to 140 pc, a low mean molecular gas mass surface density 〈Σgas〉 ≈ 125 M⊙ pc−2 and a high mean virial parameter 〈αobs, vir〉 ≈ 5.3. We measure spatially resolved molecular gas depletion times (τdep ≡ 1/SFE) with a spatial resolution of ≈100 pc within a galactocentric distance of 1.5 kpc. The global depletion time is ≈2.0 Gyr but τdep increases towards the galaxy centre, with a maximum τdep, max ≈ 5.2 Gyr. However, no pure H II region is identified in NGC 524 using ionized-gas emission-line ratio diagnostics, so the τdep inferred are in fact lower limits. Measuring the GMC properties and dynamical states, we conclude that shear is the dominant mechanism shaping the molecular gas properties and regulating SF in NGC 524. This is supported by analogous analyses of the GMCs in a simulated ETG similar to NGC 524

The effectiveness of a low-intensity problem-solving intervention for common adolescent mental health problems in New Delhi, India: protocol for a school-based, individually randomized controlled trial with an embedded stepped-wedge, cluster randomized controlled recruitment trial

BackgroundConduct, anxiety, and depressive disorders account for over 75% of the adolescent mental health burden globally. The current protocol will test a low-intensity problem-solving intervention for school-going adolescents with common mental health problems in India. The protocol also tests the effects of a classroom-based sensitization intervention on the demand for counselling services in an embedded recruitment trial.Methods/designWe will conduct a two-arm, individually randomized controlled trial in six Government-run secondary schools in New Delhi. The targeted sample is 240 adolescents in grades 9-12 with persistent, elevated mental health symptoms and associated distress/impairment. Participants will receive either a brief problem-solving intervention delivered over 3 weeks by lay counsellors (intervention) or enhanced usual care comprised of problem-solving booklets (control). Self-reported adolescent mental health symptoms and idiographic problems will be assessed at 6 weeks (co-primary outcomes) and again at 12 weeks post-randomization. In addition, adolescent-reported distress/impairment, perceived stress, mental wellbeing, and clinical remission, as well as parent-reported adolescent mental health symptoms and impact scores, will be assessed at 6 and 12 weeks post-randomization. We will also complete a parallel process evaluation, including estimations of the costs of delivering the interventions. An embedded recruitment trial will apply a stepped-wedge, cluster (class)-randomized controlled design in 70 classes across the six schools. This will evaluate the added effect of a classroom-based sensitization intervention over&nbsp;and above school-level sensitization activities on the primary outcome of referral rate into the host trial. Other outcomes will be the proportion of referrals eligible to participate in the host trial, proportion of self-generated referrals, and severity and pattern of symptoms among referred adolescents in each condition. Power calculations were undertaken separately for each trial. A detailed statistical analysis plan will be developed separately for each trial prior to unblinding.DiscussionBoth trials were initiated on 20 August 2018. A single research protocol for both trials offers a resource-efficient methodology for testing the effectiveness of linked procedures to enhance uptake and outcomes of a school-based psychological intervention for common adolescent mental health problems.Trial registrationBoth trials are registered prospectively with the National Institute of Health registry ( www.clinicaltrials.gov ), registration numbers NCT03633916 and NCT03630471 , registered on 16th August, 2018 and 14th August, 2018 respectively)

Plexus 2025: Momentum

UC Irvine School of MedicineWelcome to the 26th issue of PLEXUS, UC Irvine School of Medicine’s Journal of Medical Humanities &amp; Arts. PLEXUS is an annual, medical-student-organized publication that proudly showcases the vast talents, diverse perspectives, and nuanced experiences of the greater UCI Health community through art. It is our mission to spark introspection, catalyze meaningful discussions, and ultimately apply the tenets of medical humanities to foster a cohort of compassionate healers.This year, we present to you MOMENTUM. Whether it is the persistence of a heartbeat, the individual steps that accumulate into seismic shifts, or the tidal surge of collective efforts, momentum surrounds us. It is the wave of progress, the rush of breakthroughs, and the everyday moments that coalesce into transformative change— the flows, eddies, and vectors that define our lives and serve as the undercurrents to our stories. We sought to explore the momentum that shapes our journeys in healthcare, as students, physicians, and patients. We sought to define the very moments that push and pull us forward, past the swirling tides of uncertainty.We sincerely thank our advisors Dr. Juliet McMullin, Dr. Tan Nguyen, and Leonora Naser-Saravia for their guidance, and the UCISOM Medical Humanities &amp; Arts Program and Department of Family Medicine for their steadfast support. We hope the following pages offer you a sense of solace, inspiration, and fulfillment.Christopher Sahagian, Editor-in-ChiefKathleen Powers, Editor-in-ChiefHuan Nguyen, Creative ReviewCaroline Gee, Creative ReviewSana Shah, Creative ReviewRhea Gandhi, Creative ReviewBritney Weng, DesignNicole Parker, DesignBohan Zhang, DesignKaveri Curlin, InitiativesJustin Yang, InitiativesSara Araghi, Initiative

Investigating Instructor Talk in Novel Contexts: Widespread Use, Unexpected Categories, and an Emergent Sampling Strategy.

Instructor Talk-noncontent language used by instructors in classrooms-is a recently defined and promising variable for better understanding classroom dynamics. Having previously characterized the Instructor Talk framework within the context of a single course, we present here our results surrounding the applicability of the Instructor Talk framework to noncontent language used by instructors in novel course contexts. We analyzed Instructor Talk in eight additional biology courses in their entirety and in 61 biology courses using an emergent sampling strategy. We observed widespread use of Instructor Talk with variation in the amount and category type used. The vast majority of Instructor Talk could be characterized using the originally published Instructor Talk framework, suggesting the robustness of this framework. Additionally, a new form of Instructor Talk-Negatively Phrased Instructor Talk, language that may discourage students or distract from the learning process-was detected in these novel course contexts. Finally, the emergent sampling strategy described here may allow investigation of Instructor Talk in even larger numbers of courses across institutions and disciplines. Given its widespread use, potential influence on students in learning environments, and ability to be sampled, Instructor Talk may be a key variable to consider in future research on teaching and learning in higher education

Implementation and effectiveness of a nurse-enabled, shared-care follow-up model for early breast cancer survivors (The IBIS-Survivorship Study): Protocol for a stepped-wedge cluster randomised trial

Introduction Breast cancer is the most commonly diagnosed cancer among women worldwide. Survivors often experience physical and psychological effects arising from breast cancer and its treatment, which can last months and years, adversely impacting quality of life. As the number of early breast cancer survivors increases, models of specialist-led follow-up care in hospital settings are not sustainable and evidence suggests that they may not meet survivors’ needs. Nurse-enabled, shared-care, follow-up models between cancer specialist and primary care teams have potential to address this need. Methods and analysis The proposed research is a multicentre, prospective, pragmatic, stepped-wedge cluster-randomised trial designed to test the effectiveness and implementation of IBIS-Survivorship, a follow-up care model for patients with early breast cancer who have completed primary treatment. The IBIS-Survivorship intervention involves a nurse-led consultation, development of a Survivorship Care Plan and case-conferencing between a breast care nurse and the patient’s primary care provider. This study seeks to recruit 1079 breast cancer survivors across six cancer centres (clusters) in Australia. Health-related quality of life at 12 months assessed by the Functional Assessment of Cancer Therapy - Breast Cancer questionnaire will be the primary endpoint, along with a range of patient-reported outcomes, safety indicators and cost-effectiveness measures as secondary endpoints. General and generalised linear mixed models will be used to assess the effectiveness of the intervention versus usual care. Implementation and process outcomes will be assessed using the Reach Effectiveness Adoption Implementation Maintenance framework. Ethics and dissemination Ethical approval was provided by the Metro South Hospital and Health Service Human Research Ethics Committee (HREC/2020/QMS/59892) and reciprocally across the other five trial sites under National Mutual Acceptance arrangements. Results will be disseminated through peer-reviewed academic journal publications and presentations at national and international conferences

Identification of 31 loci for mammographic density phenotypes and their associations with breast cancer risk

Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Abstract: Mammographic density (MD) phenotypes are strongly associated with breast cancer risk and highly heritable. In this GWAS meta-analysis of 24,192 women, we identify 31 MD loci at P < 5 × 10−8, tripling the number known to 46. Seventeen identified MD loci also are associated with breast cancer risk in an independent meta-analysis (P < 0.05). Mendelian randomization analyses show that genetic estimates of dense area (DA), nondense area (NDA), and percent density (PD) are all significantly associated with breast cancer risk (P < 0.05). Pathway analyses reveal distinct biological processes involving DA, NDA and PD loci. These findings provide additional insights into the genetic basis of MD phenotypes and their associations with breast cancer risk

Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries

Background: The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs. Methods: First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score. Findings: In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45·6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84·5 (95% CI 84·1–84·9), which varied between HIC (88·5 [89·0–88·0]), MIC (81·8 [82·5–81·1]), and LIC (66·8 [64·9–68·7]) settings. In the third phase, 1217 (74·6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51·4%) were from HIC, 538 (44·2%) from MIC, and 54 (4·4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3·6% (95% CI 3·0–4·1; p<0·0001) increase in SVR. This was consistent in HIC (4·8% [4·1–5·5]; p<0·0001), MIC (2·8 [2·0–3·7]; p<0·0001), and LIC (3·8 [1·3–6·7%]; p<0·0001) settings. InterpBackground The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs. Methods: First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score. Findings: In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45·6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84·5 (95% CI 84·1–84·9), which varied between HIC (88·5 [89·0–88·0]), MIC (81·8 [82·5–81·1]), and LIC (66·8 [64·9–68·7]) settings. In the third phase, 1217 (74·6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51·4%) were from HIC, 538 (44·2%) from MIC, and 54 (4·4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3·6% (95% CI 3·0–4·1; p<0·0001) increase in SVR. This was consistent in HIC (4·8% [4·1–5·5]; p<0·0001), MIC (2·8 [2·0–3·7]; p<0·0001), and LIC (3·8 [1·3–6·7%]; p<0·0001) settings. Interpretation: The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs.retation The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs