Serum Alpha and Beta-CGRP Levels in Chronic Migraine Patients Before and After Monoclonal Antibodies Against CGRP or its Receptor.

OBJECTIVE: The objective of this study was to analyze the evolution of alpha and beta-CGRP circulating levels throughout CGRP monoclonal antibodies (mAbs) treatment in patients with chronic migraine (CM). METHODS: We recruited patients with CM beginning mAbs along with sex and age paired healthy controls (HCs). Blood was extracted before, 2 weeks (M0.5) and 3 months (M3) after the first dose of mAbs, always in free-migraine periods, and once for HCs. Alpha and beta-CGRP serum levels were measured using enzyme-linked immunosorbent assays (ELISAs) specific for each isoform. RESULTS: Baseline alpha-CGRP levels were significantly elevated in 103 patients with CM (median = 50.3, 95% confidence interval [CI] = 40.5-57.0 pg/ml) compared to 78 HCs (median = 37.5, 95% CI = 33.9-45.0 pg/ml; 95% CI of differences = 2.85-17.08 pg/ml) and significantly decreased (n = 96) over the course of mAb treatment (M0.5: median = 40.4, 95% CI = 35.6-48.2 pg/ml; and M3: median = 40.9, 95% CI = 36.3-45.9 pg/ml). Absolute decrease of alpha-CGRP throughout the treatment positively correlated with the decrease in MMDs. Negative modulation of alpha-CGRP significantly associated with positive scores at the Patient Global Impression of Change scale and with analgesic overuse reversal. Beta-CGRP did not differ at baseline between patients with CM (median = 4.2, 95% CI = 3.0-4.8 pg/ml) and HCs (median = 4.4, 95% CI = 3.4-5.6 pg/ml; -1.09 to 0.60) nor was modulated by mAb treatment (n = 96; M0.5: median = 4.5, 95% CI = 3.5-5.2 pg/ml; and M3: median = 4.6, 95% CI = 3.7-5.2 pg/ml). INTERPRETATION: Treatment with mAbs, regardless of its target, is able to progressively normalize basally increased alpha-CGRP levels in CM and this effect correlates with efficacy measures, which supports a role of this neuropeptide as the first CM biomarker. ANN NEUROL 2023;94:285-294.

Effectiveness of nurse-home visiting in improving child and maternal outcomes prenatally to age two years: a randomised controlled trial (British Columbia Healthy Connections Project).

BACKGROUND: We investigated the effectiveness of Nurse-Family Partnership (NFP), a prenatal-to-age-two-years home-visiting programme, in British Columbia (BC), Canada. METHODS: For this randomised controlled trial, we recruited participants from 26 public health settings who were: <25 years, nulliparous, <28 weeks gestation and experiencing socioeconomic disadvantage. We randomly allocated participants (one-to-one; computer-generated) to intervention (NFP plus existing services) or comparison (existing services) groups. Prespecified outcomes were prenatal substance exposure (reported previously); child injuries (primary), language, cognition and mental health (problem behaviour) by age two years; and subsequent pregnancies by 24 months postpartum. Research interviewers were masked. We used intention-to-treat analyses. (ClinicalTrials.gov, NCT01672060.) RESULTS: From 2013 to 2016 we enrolled 739 participants (368 NFP, 371 comparison) who had 737 children. Counts for child injury healthcare encounters [rate per 1,000 person-years or RPY] were similar for NFP (223 [RPY 316.17]) and comparison (223 [RPY 305.43]; rate difference 10.74, 95% CI -46.96, 68.44; rate ratio 1.03, 95% CI 0.78, 1.38). Maternal-reported language scores (mean, M [SD]) were statistically significantly higher for NFP (313.46 [195.96]) than comparison (282.77 [188.15]; mean difference [MD] 31.33, 95% CI 0.96, 61.71). Maternal-reported problem-behaviour scores (M [SD]) were statistically significantly lower for NFP (52.18 [9.19]) than comparison (54.42 [9.02]; MD -2.19, 95% CI -3.62, -0.75). Subsequent pregnancy counts were similar (NFP 115 [RPY 230.69] and comparison 117 [RPY 227.29]; rate difference 3.40, 95% CI -55.54, 62.34; hazard ratio 1.01, 95% CI 0.79, 1.29). We observed no unanticipated adverse events. CONCLUSIONS: NFP did not reduce child injuries or subsequent maternal pregnancies but did improve maternal-reported child language and mental health (problem behaviour) at age two years. Follow-up of long-term outcomes is warranted given that further benefits may emerge across childhood and adolescence.

Outcomes for clinical trials involving adults with chronic kidney disease: a multinational Delphi survey involving patients, caregivers, and health professionals.

BACKGROUND: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in CKD, which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices. METHODS: Online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals, who could read English, Spanish, or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a best-worst scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically. RESULTS: In total, 1 399 participants from 73 countries completed Round 1 of the Delphi survey including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization, and cardiovascular disease (mean difference > 0.3). Consensus was based upon the two groups yielding median scores of ≥ 7 and mean scores > 7, and the proportions of both groups rating the outcome as 'critically important' being greater than 50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences. CONCLUSION: Across trials in CKD, the outcomes of highest priority to patients, caregivers, and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death.

Hidden variable models reveal the effects of infection from changes in host survival.

The impacts of disease on host vital rates can be demonstrated using longitudinal studies, but these studies can be expensive and logistically challenging. We examined the utility of hidden variable models to infer the individual effects of infectious disease from population-level measurements of survival when longitudinal studies are not possible. Our approach seeks to explain temporal deviations in population-level survival after introducing a disease causative agent when disease prevalence cannot be directly measured by coupling survival and epidemiological models. We tested this approach using an experimental host system (Drosophila melanogaster) with multiple distinct pathogens to validate the ability of the hidden variable model to infer per-capita disease rates. We then applied the approach to a disease outbreak in harbor seals (Phoca vituline) that had data on observed strandings but no epidemiological data. We found that our hidden variable modeling approach could successfully detect the per-capita effects of disease from monitored survival rates in both the experimental and wild populations. Our approach may prove useful for detecting epidemics from public health data in regions where standard surveillance techniques are not available and in the study of epidemics in wildlife populations, where longitudinal studies can be especially difficult to implement.

Left ventricular shape index and eccentricity index with ECG-gated Nitrogen-13 ammonia PET/CT in patients with myocardial infarction, ischemia, and normal perfusion.

BACKGROUND: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. METHODS AND RESULTS: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). CONCLUSIONS: Shape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.

Paraproteinaemic keratopathy simulating a crystalline keratopathy.

BACKGROUND: Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy. CASE PRESENTATION: a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity. CONCLUSIONS: Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease.

Validation of the inventory: lockdown and its impact on the university Community.

BACKGROUND: Significant consequences of COVID-19 within academic/professional life are, at the psychological level, related to worry, tension, stress; coping strategies and lifestyle changes. This study describes the process of design and validation of an inventory (QPIC), which aims to assess the psychological impact that a situation of confinement can produce among university students and teachers. METHODS: Design of the instrument and psychometric tests. A sample of 862 students and 229 professors affiliated to Spanish and Colombian universities was used. Data were collected in April 2020 with the request of the favourable Bioethics Committee IR/2020. RESULTS: Six experts carried out the content validation. A confirmatory factor analysis of the theoretical dimensions proposed for the scales was performed and the internal consistency of each of the three initial scales was confirmed (0.866, 0.813 and 0.834). CONCLUSION: A rigorous and reliable instrument is achieved, consisting of two final scales: (a) Worry, tension and stress scale (b) Coping scale, which helps to measure individual psychological effects in housebound situations. It is an instrument designed, constructed ad hoc to assess the impact of confinement and subjected to validation. The factor structure and reliability of the instrument are examined and good psychometric properties are obtained. The application of this inventory will make it possible to assess the impact on people's mental health during a period of confinement.

Effects of Two Early Parenting Programmes on Child Aggression and Risk for Violence in Brazil: a Randomised Controlled Trial.

Violence is a major public health problem globally, with the highest rates in low- and middle-income countries (LMICs) in the Americas and southern Africa. Parenting programmes in high-income countries can diminish risk for violence, by reducing risk factors such as child aggression and harsh parenting, and increasing protective factors such as child cognitive development and school readiness. However, there is critical need to identify low-cost programmes with replicable benefits that work in real-world LMICs contexts. A three-arm, randomised, single-blind trial evaluated effects of two low-cost, group-based parenting programmes recommended for LMICs (ACT: Raising Safe Kids; DBS: dialogic book-sharing) on child aggression (primary outcome), child development, parenting, maltreatment, and stress. Participants were 369 children with medium-high levels of aggression (mean age 3.1 years at baseline) in poor households. Interventions were implemented in city health and education services in southern Brazil. Maternal reports, filmed observations, child tasks, and hair cortisol were assessed at baseline, 1-month post-intervention, and 8-month follow-up. Intention-to-treat analyses compared each of ACT and DBS with a control group. Three hundred sixty-eight (99.7%) participants completed follow-up assessments 8 months after the interventions. There was no effect of ACT (standardised mean difference, SMD 0.11, 95% CI - 0.05, 0.27) or DBS (SMD 0.05, 95% CI - 0.11, 0.21) on the primary outcome of child aggression. ACT reduced harsh parenting behaviour post-intervention (SMD - 0.23; 95% CI - 0.46, - 0.01), but not at follow-up. DBS improved book-sharing practices at both time points (e.g., maternal sensitivity at follow-up SMD 0.33; 95% CI 0.08, 0.57). There were no benefits of either programme for other parenting, child development, or stress outcomes. Two parenting programmes in Brazil had small effects on parenting practices but did not reduce child aggression or several other important risk/protective factors for violence. Effective early interventions that reduce violence in real-world LMIC settings are highly desirable but may be challenging to achieve.

A longitudinal study examining the associations between prenatal and postnatal maternal distress and toddler socioemotional developmental during the COVID-19 pandemic.

Elevated psychological distress, experienced by pregnant women and parents, has been well-documented during the COVID-19 pandemic. Most research focuses on the first 6-months postpartum, with single or limited repeated measures of perinatal distress. The present longitudinal study examined how perinatal distress, experienced over nearly 2 years of the COVID-19 pandemic, impacted toddler socioemotional development. A sample of 304 participants participated during pregnancy, 6-weeks, 6-months, and 15-months postpartum. Mothers reported their depressive, anxiety, and stress symptoms, at each timepoint. Mother-reported toddler socioemotional functioning (using the Brief Infant-Toddler Social and Emotional Assessment) was measured at 15-months. Results of structural equation mediation models indicated that (1) higher prenatal distress was associated with elevated postpartum distress, from 6-weeks to 15-months postpartum; (2) associations between prenatal distress and toddler socioemotional problems became nonsignificant after accounting for postpartum distress; and (3) higher prenatal distress was indirectly associated with greater socioemotional problems, and specifically elevated externalizing problems, through higher maternal distress at 6 weeks and 15 months postpartum. Findings suggest that the continued experience of distress during the postpartum period plays an important role in child socioemotional development during the COVID-19 pandemic.

Social support buffers the impact of pregnancy stress on perceptions of parent-infant closeness during the COVID-19 pandemic.

Pregnant individuals and parents have experienced elevated mental health problems and stress during COVID-19. Stress during pregnancy can be harmful to the fetus and detrimental to the parent-child relationship. However, social support is known to act as a protective factor, buffering against the adverse effects of stress. The present study examined whether (1) prenatal stress during COVID-19 was associated with parent-infant closeness at 6 months postpartum, and (2) social support moderated the effect of prenatal stress on the parent-infant relationship. In total, 181 participants completed questionnaires during pregnancy and at 6 months postpartum. A hierarchical linear regression analysis was conducted to assess whether social support moderated the effect of stress during pregnancy on parent-infant closeness at 6 months postpartum. Results indicated a significant interaction between prenatal stress and social support on parents' perceptions of closeness with their infants at 6 months postpartum (ß = .805, p = .029); parents who experienced high prenatal stress with high social support reported greater parent-infant closeness, compared to those who reported high levels of stress and low social support. Findings underscore the importance of social support in protecting the parent-infant relationship, particularly in times of high stress, such as during the COVID-19 pandemic.

Individuos y progenitores en estado de embarazo experimentan elevados problemas de salud mental y estrés durante el COVID­19. El estrés durante el embarazo puede ser dañino para el feto y perjudicial para la relación progenitor­niño. Sin embargo, es sabido que el apoyo social actúa como un factor de protección, sirviendo como agente amortiguador contra los adversos efectos del estrés. El presente estudio longitudinal examinó si 1) el estrés prenatal durante el COVID­19 se asociaba con la cercanía madre­infante a los seis meses después del parto, y 2) el apoyo social moderaba el efecto del estrés prenatal en la relación madre­infante. Un total de 181 participantes completaron cuestionarios durante el embarazo y a los seis meses después del parto. Un análisis de regresión lineal jerárquico se llevó a cabo para evaluar si el apoyo social moderaba el efecto del estrés durante el embarazo en cuanto a la cercanía progenitor­infante a los seis meses después del parto. Los resultados indicaron una interacción significativa entre el estrés prenatal y el apoyo social sobre las percepciones que los progenitores tenían de la cercanía con sus infantes a los seis meses después del parto (ß = .805, p = .029); los progenitores que experimentaron un alto estrés prenatal con un alto apoyo social reportaron una mayor cercanía progenitor­infante, comparados con aquellos que reportaron altos niveles de estrés y bajo apoyo social. Los resultados subrayan la importancia del apoyo social para proteger la relación progenitor­infante, particularmente en épocas de alto estés, tal como durante la pandemia del COVID­19.

Les personnes enceintes et les parents font l'expérience de plus grands problèmes de santé mentale et de plus de stress durant la crise du COVID­19. Le stress durant la grossesse peut être néfaste pour le foetus et vient au détriment de la relation parent­enfant. Cependant l'on sait que le soutien social est un facteur de protection, faisant tampon face aux effets adverses du stress. Cette étude longitudinale a examiné si 1) le stress prénatal durant le COVID­19 était lié à la proximité mère­nourrisson à six mois postpartum, et 2) le soutien social a modéré l'effet du stress prénatale sur la relation mère­nourrisson. En tout 181 participants ont rempli des questionnaires durant la grossesse et à sic mois postpartum. Une analyse de régression linéaire hiérarchique a été faite pour évaluer si le soutien social a modéré l'effet du stress durant la grossesse sur la proximité parent­nourrisson à six mois postpartum. Les résultats ont indiqué une interaction importante entre le stress prénatal et le soutien social sur les perceptions des parents de la proximité avec leurs nourrissons à six mois postpartum (ß = ,805, p = ,029); les parents qui ont fait l'expérience d'un stress prénatal élevé avec un soutien social élevé ont signalé une plus grande proximité parent­nourrisson, comparé à ceux ayant signalé des niveaux de stress élevés et un faible soutien social. Les résultats soulignent l'importance du soutien social dans la protection de la relation parent­nourrisson, particulièrement en temps de stress élevé, comme durant la pandémie de COVID­19.

Relation and effect of resilience on burnout in nurses: A literature review and meta-analysis.

AIM: To study the relation between burnout and resilience and to identify the profile of nurses presenting this quality. BACKGROUND AND INTRODUCTION: Healthcare professionals are subject to high rates of burnout. Resilience could be an important factor in preventing or alleviating this condition. METHODS: The PubMed, ProQuest, Scopus and ScienceDirect databases were consulted in February 2022 using the equation 'burnout AND resilience AND nurs*'. The inclusion criteria applied were that the texts should describe quantitative studies, be published in English or Spanish, in any year, and be directly related to the question considered. The meta-analysis was performed using StatsDirect statistical software. RESULTS: Analysis of the 29 studies shows that among the dimensions of burnout, nurses are especially prone to emotional exhaustion, and are less affected by depersonalisation and low personal accomplishment. Those who score highly for resilience tend to have longer service experience, acceptable salaries and less work overload. Meta-analysis reveals an inverse correlation between resilience and burnout (r = -0.41; n = 2750), exhaustion (r = -0.27; n = 6966) and depersonalisation (r = -0.23; n = 6115). CONCLUSION: Many nurses present low levels of resilience and suffer from burnout syndrome. The application of programmes to enhance their resilience would help prevent burnout and optimise the potential to provide quality health care. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Resilience is inversely correlated with burnout, depersonalisation and emotional exhaustion. Accordingly, healthcare organisations should develop and implement evidence-based programmes to foster nurses' resilience and thus reduce their susceptibility to burnout.

Obesity and adverse childhood experiences in relation to stress during the COVID-19 pandemic: an analysis of the Canadian Longitudinal Study on Aging.

BACKGROUND: People with obesity are at increased risk of chronic stress, and this may have been exacerbated during the COVID-19 pandemic. Adverse childhood experiences (ACE) are also associated with both obesity and stress, and may modify risk of stress among people with obesity. The objectives of this study were to evaluate the associations between obesity, ACEs, and stress during the pandemic, and to determine if the association between obesity and stress was modified by ACEs. METHODS: A longitudinal study was conducted among adults aged 50-96 years (n = 23,972) from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Study. Obesity and ACEs were collected pre-pandemic (2015-2018), and stress was measured at COVID-19 Exit Survey (Sept-Dec 2020). We used logistic, Poisson, and negative binomial regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the associations between obesity, ACEs, and stress outcomes during the pandemic. Interaction by ACEs was evaluated on the additive and multiplicative scales. RESULTS: People with obesity were more likely to experience an increase in overall stressors (class III obesity vs. healthy weight RR = 1.19; 95% CI: 1.12-1.27) as well as increased health related stressors (class III obesity vs. healthy weight RR: 1.25; 95% CI: 1.12-1.39) but did not perceive the consequences of the pandemic as negative. ACEs were also associated an increase in overall stressors (4-8 ACEs vs. none RR = 1.38; 95% CI: 1.33-1.44) and being more likely to perceive the pandemic as negative (4-8 ACEs vs. none RR = 1.32; 95% CI: 1.19-1.47). The association between obesity and stress was not modified by ACEs. CONCLUSIONS: Increased stress during the first year of the COVID-19 pandemic was observed among people with obesity or ACEs. The long-term outcomes of stress during the pandemic need to be determined.

Social engagement and allostatic load mediate between adverse childhood experiences and multimorbidity in mid to late adulthood: the Canadian Longitudinal Study on Aging.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with multimorbidity in adulthood. This link may be mediated by psychosocial and biological factors, but evidence is lacking. The current study evaluates this mediation model. METHOD: We analyzed data from the Canadian Longitudinal Study of Aging (N = 27 170 community participants). Participants were 45-85 years at recruitment, when allostatic load and social engagement data were collected, and 3 years older at follow-up, when ACEs and multimorbidity data were collected. Structural equation modeling was used to test for mediation in the overall sample, and in sex- and age-stratified subsamples, all analyses adjusted for concurrent lifestyle confounds. RESULTS: In the overall sample, ACEs were associated with multimorbidity, directly, ß = 0.12 (95% confidence interval 0.11-0.13) and indirectly. Regarding indirect associations, ACEs were related to social engagement, ß = -0.14 (-0.16 to -0.12) and social engagement was related to multimorbidity, ß = -0.10 (-0.12 to -0.08). ACEs were related to allostatic load, ß = 0.04 (0.03-0.05) and allostatic load was related to multimorbidity, ß = 0.16 (0.15-0.17). The model was significant for males and females and across age cohorts, with qualifications in the oldest stratum (age 75-85). CONCLUSIONS: ACEs are related to multimorbidity, directly and via social engagement and allostatic load. This is the first study to show mediated pathways between early adversity and multimorbidity in adulthood. It provides a platform for understanding multimorbidity as a lifespan dynamic informing the co-occurrence of the varied disease processes represented in multimorbidity.

Automated Breast Density Assessment in MRI Using Deep Learning and Radiomics: Strategies for Reducing Inter-Observer Variability.

BACKGROUND: Accurate breast density evaluation allows for more precise risk estimation but suffers from high inter-observer variability. PURPOSE: To evaluate the feasibility of reducing inter-observer variability of breast density assessment through artificial intelligence (AI) assisted interpretation. STUDY TYPE: Retrospective. POPULATION: Six hundred and twenty-one patients without breast prosthesis or reconstructions were randomly divided into training (N = 377), validation (N = 98), and independent test (N = 146) datasets. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T; T1-weighted spectral attenuated inversion recovery. ASSESSMENT: Five radiologists independently assessed each scan in the independent test set to establish the inter-observer variability baseline and to reach a reference standard. Deep learning and three radiomics models were developed for three classification tasks: (i) four Breast Imaging-Reporting and Data System (BI-RADS) breast composition categories (A-D), (ii) dense (categories C, D) vs. non-dense (categories A, B), and (iii) extremely dense (category D) vs. moderately dense (categories A-C). The models were tested against the reference standard on the independent test set. AI-assisted interpretation was performed by majority voting between the models and each radiologist's assessment. STATISTICAL TESTS: Inter-observer variability was assessed using linear-weighted kappa (κ) statistics. Kappa statistics, accuracy, and area under the receiver operating characteristic curve (AUC) were used to assess models against reference standard. RESULTS: In the independent test set, five readers showed an overall substantial agreement on tasks (i) and (ii), but moderate agreement for task (iii). The best-performing model showed substantial agreement with reference standard for tasks (i) and (ii), but moderate agreement for task (iii). With the assistance of the AI models, almost perfect inter-observer variability was obtained for tasks (i) (mean κ = 0.86), (ii) (mean κ = 0.94), and (iii) (mean κ = 0.94). DATA CONCLUSION: Deep learning and radiomics models have the potential to help reduce inter-observer variability of breast density assessment. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Providers' perspectives of the neonatal intensive care unit context and care provision for adolescent parents: an interpretive description.

BACKGROUND: The neonatal intensive care unit (NICU) is a complex care environment, with the NICU patient population among the most vulnerable in a hospital setting. Adolescent parents are a unique group within the broader NICU parent population and admission of their infant to the NICU contributes to an already complex situation as adolescent pregnancy and parenting is often associated with a range of psychosocial challenges. How the NICU care context influences care provision for adolescent parents is a significant gap in the NICU parenting and support discourse. Therefore, this study aimed to explore health and social care providers' perspectives of the NICU care context and how providers perceive the context as influencing the experiences of adolescent parents in the NICU. METHODS: This was a qualitative, interpretive description study design. In-depth interviews were conducted with providers, including nurses and social workers, caring for adolescent parents in the NICU. Data was collected between December 2019 and November 2020. Data were analyzed concurrently with data collection. Constant comparison, analytic memos, and iterative diagramming techniques were used to challenge developing analytic patterns. RESULTS: Providers (n = 23) described how the unit context influenced care provision as well as experiences for adolescent parents. We learned that having a baby in the NICU was perceived by providers as a traumatic experience for parents - impacting attachment, parenting confidence and competence, and mental health. Environmental factors - such as privacy and time - and perceptions that adolescent parents are treated differently in the NICU were also seen as influencing this overall experience. CONCLUSIONS: Providers involved in the care of adolescent parents in the neonatal intensive care unit described the distinctiveness of this group within the broader parent population and how quality of care may be impacted by contextual factors as well as experiences of age-related stigma. Further understanding of NICU experiences from the parents' perspectives are warranted. Findings highlight opportunities for strengthened interprofessional collaboration and trauma- and violence-informed care strategies within the neonatal intensive care environment to mitigate the potential negative influence of this experience and improve care for adolescent parents.

Upregulation of CCL5/RANTES Gene Expression in the Diaphragm of Mice with Cholestatic Liver Disease.

Chronic liver diseases are a group of pathologies affecting the liver with high prevalence worldwide. Among them, cholestatic chronic liver diseases (CCLD) are characterized by alterations in liver function and increased plasma bile acids. Secondary to liver disease, under cholestasis, is developed sarcopenia, a skeletal muscle dysfunction with decreased muscle mass, strength, and physical function. CCL5/RANTES is a chemokine involved in the immune and inflammatory response. Indeed, CCL5 is a myokine because it is produced by skeletal muscle. Several studies show that bile acids induce CCL5/RANTES expression in liver cells. However, it is unknown if the expression of CCL5/RANTES is changed in the skeletal muscle of mice with cholestatic liver disease. We used a murine model of cholestasis-induced sarcopenia by intake of hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC diet), in which we detected the mRNA levels for ccl5. We determined that mice fed the DDC diet presented high levels of serum bile acids and developed typical features of sarcopenia. Under these conditions, we detected the ccl5 gene expression in diaphragm muscle showing elevated mRNA levels compared to mice fed with a standard diet (chow diet). Our results collectively suggest an increased ccl5 gene expression in the diaphragm muscle concomitantly with elevated serum bile acids and the development of sarcopenia.

Physical Activity, Burnout, and Engagement in Latin American Students of Higher Education During the COVID-19 Pandemic.

The coronavirus-disease-2019 (COVID-19) pandemic has had a devastating physical and psychological impact on society, especially on students. In this study, we describe the levels of physical activity (Physical-Activity-Questionnaire-Short-Form (IPAQ-SF)), Burnout (School-Burnout-Inventory for students (SBI-U)) and engagement (Utrecht-Work-Engagement-Scale-9 items (UWES-9S)) in a cohort of Latin American higher education students during the COVID-19 pandemic in 2020. We also determined whether physical activity, Burnout, and engagement are related according to gender and area of study. Self-reported data from 571 Latin American students (64.79% women, 34.15% men; average age 25.24 ± 5.52 years) were collected via an online survey questionnaire. Spearman correlation analyses evaluated the associations between physical activity, Burnout, and engagement. Comparative analyses by gender and field of study were also performed. The results showed no correlation or association in the linear regression between the IPAQ-SF and SBI-U scores or between the IPAQ-SF and the UWES-9S scores. By gender, men had higher IPAQ-SF scores (p < 0.05) and reported higher intensity physical activity than women, but women had higher SBI-U scores (p < 0.05). No difference was found between men and women according to the UWES-9S scores (p = 0.28). There was also no difference in IPAQ-SF scores (p = 0.29) regarding the field of study. Our results suggest that women perform less physical activity than men, which is consistent with higher Burnout. However, physical activity was not associated with Burnout or engagement overall, which indicates that it was insufficient to prevent emotional stress in Latin American higher education students during a pandemic.

Leveraging Dynamic Norms to Reduce College Student Alcohol Use: A Test of Four Mediators.

Social norms are common in persuasive messaging. For norms trending in a positive direction, it may be beneficial to emphasize change (i.e. dynamic norm) rather than the status quo (i.e. static norm). To test this proposition, we examined college students' responses to social norm messages encouraging moderate alcohol use. Undergraduates (N = 842) were randomly assigned to view a dynamic norm ("More college students drinking in moderation"), a static descriptive norm ("Most college students drink in moderation"), or a no message control. Four mechanisms were examined as potential mediators, three of which have been examined in previous work (preconformity, perceived importance, self-efficacy) and one of which was novel (psychological reactance). Results revealed that exposure to either social norm message (dynamic or static descriptive) was associated with more favorable attitude relative to a no message control. Attitude did not differ between the dynamic norm and static descriptive norm conditions. Only psychological reactance mediated the relationship between message condition (dynamic vs. static descriptive norm) and favorable attitude. Implications and future directions are discussed.

Exploring the effect of prenatal maternal stress on the microbiomes of mothers and infants: A systematic review.

Prenatal maternal stress (PNMS)-characterized by exposure to stress, anxiety, depression, or intimate partner violence-has been linked to biological alterations in infants, including disruptions to their intestinal microbiota, which have long-term implications for children's developmental outcomes. Significant research has been done examining the effects of PNMS on the microbiome in animals, but less is known about these effects in human research. The current systematic review aimed to synthesize current findings on the association between PNMS and mother and infant microbiomes. Medline, Embase, PsycInfo, Web of Science, and Eric databases were searched through to February 2022. A total of eight studies (n = 2219 infants, 2202 mothers) were included in the qualitative synthesis. Findings provided promising evidence of the role that PNMS plays in altering the microbial composition, diversity, and gut immunity in mothers and infants. Notably, majority of included studies found that higher PNMS was linked to increases in genera from the phylum Proteobacteria. The factors influencing these effects are explored including nutrition, birth mode, and parenting behaviors. Potential interventions to mitigate the adverse effects of PNMS are discussed, along with recommendations for future studies with longitudinal designs to better understand the appropriate type and timing of interventions needed to promote "healthy" maternal and infant microbial functioning.

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss the preclinical evidence that suggests that EP300 inhibition can attenuate fibrosis-related molecular processes, including extracellular matrix deposition, inflammation, and epithelial-to-mesenchymal transition. We also highlight the contributions of small molecule inhibitors and gene therapy approaches targeting EP300 as novel therapies against fibrosis.