The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay.

Gene duplication is a major evolutionary force driving adaptation and speciation, as it allows for the acquisition of new functions and can augment or diversify existing functions. Here, we report a gene duplication event that yielded another outcome--the generation of antagonistic functions. One product of this duplication event--UPF3B--is critical for the nonsense-mediated RNA decay (NMD) pathway, while its autosomal counterpart--UPF3A--encodes an enigmatic protein previously shown to have trace NMD activity. Using loss-of-function approaches in vitro and in vivo, we discovered that UPF3A acts primarily as a potent NMD inhibitor that stabilizes hundreds of transcripts. Evidence suggests that UPF3A acquired repressor activity through simple impairment of a critical domain, a rapid mechanism that may have been widely used in evolution. Mice conditionally lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and gametogenesis. Our results support a model in which UPF3A serves as a molecular rheostat that directs developmental events.

Improved Cardiac Function in Postischemic Rats Using an Optimized Cardiac Reprogramming Cocktail Delivered in a Single Novel Adeno-Associated Virus.

BACKGROUND: Cardiac reprogramming is a technique to directly convert nonmyocytes into myocardial cells using genes or small molecules. This intervention provides functional benefit to the rodent heart when delivered at the time of myocardial infarction or activated transgenically up to 4 weeks after myocardial infarction. Yet, several hurdles have prevented the advancement of cardiac reprogramming for clinical use. METHODS: Through a combination of screening and rational design, we identified a cardiac reprogramming cocktail that can be encoded in a single adeno-associated virus. We also created a novel adeno-associated virus capsid that can transduce cardiac fibroblasts more efficiently than available parental serotypes by mutating posttranslationally modified capsid residues. Because a constitutive promoter was needed to drive high expression of these cell fate-altering reprogramming factors, we included binding sites to a cardiomyocyte-restricted microRNA within the 3' untranslated region of the expression cassette that limits expression to nonmyocytes. After optimizing this expression cassette to reprogram human cardiac fibroblasts into induced cardiomyocyte-like cells in vitro, we also tested the ability of this capsid/cassette combination to confer functional benefit in acute mouse myocardial infarction and chronic rat myocardial infarction models. RESULTS: We demonstrated sustained, dose-dependent improvement in cardiac function when treating a rat model 2 weeks after myocardial infarction, showing that cardiac reprogramming, when delivered in a single, clinically relevant adeno-associated virus vector, can support functional improvement in the postremodeled heart. This benefit was not observed with GFP (green fluorescent protein) or a hepatocyte reprogramming cocktail and was achieved even in the presence of immunosuppression, supporting myocyte formation as the underlying mechanism. CONCLUSIONS: Collectively, these results advance the application of cardiac reprogramming gene therapy as a viable therapeutic approach to treat chronic heart failure resulting from ischemic injury.

Multiscale deep learning framework captures systemic immune features in lymph nodes predictive of triple negative breast cancer outcome in large-scale studies.

The suggestion that the systemic immune response in lymph nodes (LNs) conveys prognostic value for triple-negative breast cancer (TNBC) patients has not previously been investigated in large cohorts. We used a deep learning (DL) framework to quantify morphological features in haematoxylin and eosin-stained LNs on digitised whole slide images. From 345 breast cancer patients, 5,228 axillary LNs, cancer-free and involved, were assessed. Generalisable multiscale DL frameworks were developed to capture and quantify germinal centres (GCs) and sinuses. Cox regression proportional hazard models tested the association between smuLymphNet-captured GC and sinus quantifications and distant metastasis-free survival (DMFS). smuLymphNet achieved a Dice coefficient of 0.86 and 0.74 for capturing GCs and sinuses, respectively, and was comparable to an interpathologist Dice coefficient of 0.66 (GC) and 0.60 (sinus). smuLymphNet-captured sinuses were increased in LNs harbouring GCs (p < 0.001). smuLymphNet-captured GCs retained clinical relevance in LN-positive TNBC patients whose cancer-free LNs had on average ≥2 GCs, had longer DMFS (hazard ratio [HR] = 0.28, p = 0.02) and extended GCs' prognostic value to LN-negative TNBC patients (HR = 0.14, p = 0.002). Enlarged smuLymphNet-captured sinuses in involved LNs were associated with superior DMFS in LN-positive TNBC patients in a cohort from Guy's Hospital (multivariate HR = 0.39, p = 0.039) and with distant recurrence-free survival in 95 LN-positive TNBC patients of the Dutch-N4plus trial (HR = 0.44, p = 0.024). Heuristic scoring of subcapsular sinuses in LNs of LN-positive Tianjin TNBC patients (n = 85) cross-validated the association of enlarged sinuses with shorter DMFS (involved LNs: HR = 0.33, p = 0.029 and cancer-free LNs: HR = 0.21 p = 0.01). Morphological LN features reflective of cancer-associated responses are robustly quantifiable by smuLymphNet. Our findings further strengthen the value of assessment of LN properties beyond the detection of metastatic deposits for prognostication of TNBC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Functional Outcomes and Satisfaction Rates in Patients Aged 80 Years or Older are Not Clinically Different From Their Younger (65 to 75 Years) Counterparts Following Total Hip Arthroplasty.

BACKGROUND: As the population ages, the proportion of elderly patients requiring total hip arthroplasty (THA) increases, but it is not clear whether older age independently influences outcome. The aim was to assess function, quality of life, and satisfaction after THA in patients ≥ 80 years compared with those aged between 65 and 75 years when adjusting for confounding factors. METHODS: A single-center retrospective cohort study was performed between 2010 and 2019. A total 2,367 THAs were performed on patients ≥ 80 years and 5,113 on patients aged 65 to 75 years. The demographic data and length of stay (LOS) were recorded. Preoperative and 2-year postoperative Oxford Hip Scores (OHS), EuroQol (EQ-5D), and satisfaction scores were collected. Clinically meaningful difference was defined as 5 points in OHS and utility of 0.085 in EQ-5D. Regression analyses were performed to adjust for confounding factors. RESULTS: Patients in ≥ 80-years group were more likely women (P < .001), have higher American Society of Anesthesiolgists grade (P < .001), worse preoperative OHS (mean difference [MD] 2.3, P < .001), and EQ-5D (MD 0.087, P < .001). Both age groups achieved clinically meaningful and statistically significant (P < .001) improvement in OHS and EQ-5D utility at 2 years. When adjusting for confounding variables, the ≥ 80-year-old group had significantly (P < .001) lower improvement in OHS (MD -1.9 points) and EQ-5D (MD -0.055 utility), but these differences were not clinically meaningful. There was no difference (P = .813) in satisfaction between the groups. When adjusting for confounding variables, ≥ 80-year-old group had increased risk of longer LOS (odds ratio 1.27, P < .001). CONCLUSIONS: There were no clinically meaningful differences in hip-specific outcome or health-related quality of life according to age group, and both were equally satisfied with their outcome. The older age group did, however, have longer LOS. LEVEL OF EVIDENCE: Level III retrospective cohort study.

Intracerebroventricular dosing of N-sulfoglucosamine sulfohydrolase in mucopolysaccharidosis IIIA mice reduces markers of brain lysosomal dysfunction.

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by N-sulfoglucosamine sulfohydrolase (SGSH) deficiency. SGSH removes the sulfate from N-sulfoglucosamine residues on the nonreducing end of heparan sulfate (HS-NRE) within lysosomes. Enzyme deficiency results in accumulation of partially degraded HS within lysosomes throughout the body, leading to a progressive severe neurological disease. Enzyme replacement therapy has been proposed, but further evaluation of the treatment strategy is needed. Here, we used Chinese hamster ovary cells to produce a highly soluble and fully active recombinant human sulfamidase (rhSGSH). We discovered that rhSGSH utilizes both the CI-MPR and LRP1 receptors for uptake into patient fibroblasts. A single intracerebroventricular (ICV) injection of rhSGSH in MPS IIIA mice resulted in a tissue half-life of 9 days and widespread distribution throughout the brain. Following a single ICV dose, both total HS and the MPS IIIA disease-specific HS-NRE were dramatically reduced, reaching a nadir 2 weeks post dose. The durability of effect for reduction of both substrate and protein markers of lysosomal dysfunction and a neuroimmune response lasted through the 56 days tested. Furthermore, seven weekly 148 µg doses ICV reduced those markers to near normal and produced a 99.5% reduction in HS-NRE levels. A pilot study utilizing every other week dosing in two animals supports further evaluation of less frequent dosing. Finally, our dose-response study also suggests lower doses may be efficacious. Our findings show that rhSGSH can normalize lysosomal HS storage and markers of a neuroimmune response when delivered ICV.

Exploring the intersectionality of race/ethnicity with rurality on breast cancer outcomes: SEER analysis, 2000-2016.

PURPOSE: Disparities in breast cancer survival have been observed within marginalized racial/ethnic groups and within the rural-urban continuum for decades. We examined whether there were differences among the intersectionality of race/ethnicity and rural residence on breast cancer outcomes. METHODS: We performed a retrospective analysis among 739,448 breast cancer patients using Surveillance Epidemiology and End Results (SEER) 18 registries years 2000 through 2016. We conducted multilevel logistic-regression and Cox proportional hazards models to estimate adjusted odds ratios (AORs) and hazard ratios (AHRs), respectively, for breast cancer outcomes including surgical treatment, radiation therapy, chemotherapy, late-stage disease, and risk of breast cancer death. Rural was defined as 2013 Rural-Urban Continuum Codes (RUCC) of 4 or greater. RESULTS: Compared with non-Hispanic white-urban (NH-white-U) women, NH-black-U, NH-black-rural (R), Hispanic-U, and Hispanic-R women, respectively, were at increased odds of no receipt of surgical treatment (NH-black-U, AOR = 1.98, 95% CI 1.91-2.05; NH-black-R, AOR = 1.72, 95% CI 1.52-1.94; Hispanic-U, AOR = 1.58, 95% CI 1.52-1.65; and Hispanic-R, AOR = 1.40, 95% CI 1.18-1.67), late-stage diagnosis (NH-black-U, AOR = 1.32, 95% CI 1.29-1.34; NH-black-R, AOR = 1.29, 95% CI 1.22-1.36; Hispanic-U, AOR = 1.25, 95% CI 1.23-1.27; and Hispanic-R, AOR = 1.17, 95% CI 1.08-1.27), and increased risks for breast cancer death (NH-black-U, AHR = 1.46, 95% CI 1.43-1.50; NH-black-R, AHR = 1.42, 95% CI 1.32-1.53; and Hispanic-U, AHR = 1.10, 95% CI 1.07-1.13). CONCLUSION: Regardless of rurality, NH-black and Hispanic women had significantly increased odds of late-stage diagnosis, no receipt of treatment, and risk of breast cancer death.

Investigating the association between educational attainment and allostatic load with risk of cancer mortality among African American women.

BACKGROUND: African American (AA) women navigate the world with multiple intersecting marginalized identities. Accordingly, AA women have higher cumulative stress burden or allostatic load (AL) compared to other women. Studies suggest that AA women with a college degree or higher have lower AL than AA women with less than a high school diploma. We examined the joint effect of educational attainment and AL status with long-term risk of cancer mortality, and whether education moderated the association between AL and cancer mortality. METHODS: We performed a retrospective analysis among 4,677 AA women within the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2010 with follow-up data through December 31, 2019. We fit weighted Cox proportional hazards models to estimate adjusted hazard ratios (aHRs) of cancer death between educational attainment/AL (adjusted for age, income, and smoking status). RESULTS: AA women with less than a high school diploma living with high AL had nearly a 3-fold increased risk (unadjusted HR: 2.98; 95%C CI: 1.24-7.15) of cancer death compared to AA college graduates living with low AL. However, after adjusting for age, this effect attenuated (age-adjusted HR: 1.11; 95% CI: 0.45-2.74). AA women with high AL had 2.3-fold increased risk of cancer death (fully adjusted HR: 2.26; 95% CI: 1.10-4.57) when compared to AA with low AL, specifically among women with high school diploma or equivalent and without history of cancer. CONCLUSIONS: Our findings suggest that high allostatic load is associated with a higher risk of cancer mortality among AA women with lower educational attainment, while no such association was observed among AA women with higher educational attainment. Thus, educational attainment plays a modifying role in the relationship between allostatic load and the risk of cancer death for AA women. Higher education can bring several benefits, including improved access to medical care and enhanced medical literacy, which in turn may help mitigate the adverse impact of AL and the heightened risk of cancer mortality among AA women.

Development and validation of the MAnchester Needs Tool for Injured Children (MANTIC).

OBJECTIVE: To develop a measure of the needs injured children and their families' needs throughout recovery; The MAnchester Needs Tool for Injured Children (MANTIC). DESIGN: Tool development, psychometric testing. SETTING: Five children's major trauma centres in England. PARTICIPANTS: Children aged 2 to 16 years with any type of moderate/severe injury(ies) treated in a major trauma centre within 12 months of injury, plus their parents. METHODS: Stage 1a (Item generation): Interviews with injured children and their parents to generate draft items. Stage 1b (Co-production): Feedback about item clarity, relevance and appropriate response options was provided by parents and the patient and public involvement group. Stage 2 (Psychometric development): Completion of the prototype MANTIC by injured children and their parents with restructuring (as necessary) to establish construct validity. Concurrent validity was assessed by correlation with quality of life (EQ-5D-Y). MANTICs were repeated 2 weeks later to assess test-retest reliability. RESULTS: Stages 1a,b: Interviews (13 injured children, 19 parents) generated 64 items with semantic differential four-point response scale (strongly disagree, disagree, agree, strongly agree). Stage 2: One hundred and forty-four participants completed MANTIC questionnaires (mean age 9.8 years, SD 3.8; 68.1% male). Item responses were strong requiring only minor changes to establish construct validity. Concurrent validity with quality of life was moderate (r = 0.55, P < 0.01) as was test-retest reliability (ICC = 0.46 and 0.59, P < 0.001). Uni-dimensionality was strong (Cronbach's α > 0.7). CONCLUSION: The MANTIC is a feasible, acceptable, valid self-report measure of the needs of injured children and their families, freely available for clinical or research purposes.

How Attributes of Place Threaten Community Trust in the American South: Opportunities for Improving Pandemic-Related Communication.

Trust and mistrust influence the utilization of health services, the quality of overall healthcare, and the prevalence of health disparities. Trust has significant bearing on how communities, and the individuals within them, perceive health information and recommendations. The People and Places Framework is utilized to answer what attributes of place threaten community trust in public health and medical recommendations.Augusta-Richmond County is ranked among the least healthy counties in Georgia despite being home to the best healthcare-to-residence ratios and a vast array of healthcare services. Semi-structured interviews were conducted with 31 neighborhood residents. Data were analyzed using the Sort & Sift, Think & Shift method. Threats to community trust were identified within four local-level attributes of place: availability of products and services, social structures, physical structures, and cultural and media messages. We found a broader web of services, policies, and institutions, beyond interactions with health care, that influence the trust placed in health officials and institutions. Participants spoke to both a potential lack of trust (e.g. needs not being met, as through lack of access to services) and mistrust (e.g. negative motives, such as profit seeking or experimentation). Across the four attributes of place, residents expressed opportunities to build trust. Our findings highlight the importance of examining trust at the community level, providing insight into an array of factors that impact trust at a local level, and extend the work on trust and its related constructs (e.g. mistrust). Implications for improving pandemic-related communication through community relationship building are presented.

Penalized Logistic Regression Analysis for Genetic Association Studies of Binary Phenotypes.

INTRODUCTION: Increasingly, logistic regression methods for genetic association studies of binary phenotypes must be able to accommodate data sparsity, which arises from unbalanced case-control ratios and/or rare genetic variants. Sparseness leads to maximum likelihood estimators (MLEs) of log-OR parameters that are biased away from their null value of zero and tests with inflated type 1 errors. Different penalized-likelihood methods have been developed to mitigate sparse-data bias. We study penalized logistic regression using a class of log-F priors indexed by a shrinkage parameter m to shrink the biased MLE towards zero. For a given m, log-F-penalized logistic regression may be easily implemented using data augmentation and standard software. METHOD: We propose a two-step approach to the analysis of a genetic association study: first, a set of variants that show evidence of association with the trait is used to estimate m; and second, the estimated m is used for log-F-penalized logistic regression analyses of all variants using data augmentation with standard software. Our estimate of m is the maximizer of a marginal likelihood obtained by integrating the latent log-ORs out of the joint distribution of the parameters and observed data. We consider two approximate approaches to maximizing the marginal likelihood: (i) a Monte Carlo EM algorithm (MCEM) and (ii) a Laplace approximation (LA) to each integral, followed by derivative-free optimization of the approximation. RESULTS: We evaluate the statistical properties of our proposed two-step method and compared its performance to other shrinkage methods by a simulation study. Our simulation studies suggest that the proposed log-F-penalized approach has lower bias and mean squared error than other methods considered. We also illustrate the approach on data from a study of genetic associations with "super senior" cases and middle aged controls. DISCUSSION/CONCLUSION: We have proposed a method for single rare variant analysis with binary phenotypes by logistic regression penalized by log-F priors. Our method has the advantage of being easily extended to correct for confounding due to population structure and genetic relatedness through a data augmentation approach.

Perceived discrimination and Latina college students' depressive symptoms: The roles of dyadic coping with sisters and familism values.

Latinx young adults' experiences of discrimination are associated with high levels of depressive symptoms and examining protective factors that buffer the negative consequences of discrimination is important. In a sample of 195 Latina college students, predominately of Mexican origin, we examined associations between perceived discrimination and depressive symptoms, and how sisters' dyadic coping behaviors and familism values moderated this association. We conducted hierarchical regression analyses to test our study hypotheses. We found that Latina college students who were older sisters reported more conflictual and antagonistic sibling relationships, or who perceived higher levels of discrimination also reported the most depressive symptoms, which supports prior research. Importantly, Latina college students who strongly endorsed supportive, obligatory, and referent familism values reported fewer depressive symptoms. Supportive familism values weakened the association between perceived discrimination and Latina college students' depressive symptoms but strengthened associations between sisters' negative dyadic coping behaviors and depressive symptoms. Furthermore, sisters' negative dyadic coping behaviors strengthened the positive association between perceived discrimination and depressive symptoms. Our findings highlight the importance of familism values for Latinx young adults' well-being, as well as the harmful effects of perceived discrimination, particularly in the context of sisters' negative dyadic coping behaviors.

Home-based rehabilitation following anterior cruciate ligament reconstruction in the Kurdistan region of Iraq: epidemiology and outcomes.

PURPOSE: This study, set in in the Kurdistan region of Iraq, describes the epidemiology and outcomes of anterior cruciate ligament reconstruction (ACLR) followed by home-based rehabilitation alone. METHODS: A cohort observational study of patients aged ≥ 16 years with an ACL rupture who underwent an ACLR under a single surgeon. Followed by a home-based rehabilitation programme of appropriate simplicity for completion in the home setting; consisting of stretching, range of motion and strengthening exercises. Demographics, mechanism of injury, operative findings, and outcome data (Lysholm, Tegner Activity Scale (TAS), and revision rates) were collected from 2016 to 2021. Data were analysed using descriptive statistics. RESULTS: The cohort consisted of 545 patients (547 knees), 99.6% were male with a mean age of 27.8 years (SD 6.18 years). The mean time from diagnosis to surgery was 40.6 months (SD 40.3). Despite data attrition Lysholm scores improved over the 15-month follow-up period, matched data showed the most improvement occurred within the first 2 months post-operatively. Post-operative TAS results showed an improvement in level of function, but did not reach pre-injury levels by final follow-up. At final follow-up, six (1.1%) patients required an ACLR revision. CONCLUSION: Patients who completed a home-based rehabilitation programme in Kurdistan had low revision rates and improved Lysholm scores 15 months post-operatively. To optimise resources, further research should investigate the efficacy of home-based rehabilitation for trauma and elective surgery in low- to middle-income countries and the developed world.

Embedding post-doctoral clinical academic careers in practice: The St Bartholomew's Hospital model.

AIMS AND OBJECTIVES: In order to retain and develop pre-doctoral and doctoral staff, we sought to establish and implement a model for supporting postdoctoral clinical academic careers at our hospital. BACKGROUND: Doctorally-prepared nurses can raise clinical practice standards, but there is a deficit of career opportunities and post-doctoral positions. This will inevitably impact delivering the evidence for improving patient outcomes and service delivery. It is therefore imperative that post-doctoral nursing and allied professional post-doctoral clinical academic career opportunities are developed and embedded in practice. DESIGN: We describe the development and implementation of a model to provide and embed post-doctoral clinical academic roles at our hospital. METHODS: A multidisciplinary group devised the model which was approved by the Hospital Executive Board. RESULTS: The model includes having a bespoke plan for each individual, planning the post-doctoral role at time of PhD planning, providing 1 day a week protected research time for a minimum of 12 months after PhD completion, having an appropriate honorary academic contract at a partner University, and providing integrated clinical and academic supervision throughout. Other key components include senior clinical and Executive Board support and an existing vibrant research culture at our organisation. CONCLUSIONS: The St Bartholomew's Hospital model, focusing on individualised posts integrating clinical and academic roles to address service needs, offers a novel approach to supporting post-doctoral clinical academic careers in a clinical setting. RELEVANCE TO CLINICAL PRACTICE: Since doctorally-prepared nurses can raise clinical practice standards we developed a sustainable infrastructure to increase our postdoctoral nursing and allied professional workforce. This model could provide a framework for other hospitals to embed postdoctoral clinical academic careers in practice.

Appraising strategic adaptive management as a process of organizational learning.

Adaptive management is a systematic approach for linking learning with implementation to facilitate ongoing improvement in natural resource management. The idea of learning from experience and adapting subsequent policies, strategies and actions, is intuitively appealing. However, application of adaptive management has been hindered by several obstacles, including a paucity of documented lessons from existing adaptive management practices and inadequate attention to the complex social aspects of learning. Here we address these two impediments through (i) a case study of an established version of adaptive management and its application in the context of protected area management plans, and (ii) its critical comparison and conceptual integration with the seminal theory of organizational knowledge creation (TOKC), which emphasizes the social aspects of learning. As case study, we focus on Strategic Adaptive Management (SAM), which has been iteratively developed and implemented by South African National Parks for more than 20 years. We used TOKC as a conceptual sounding board to reflect on and appraise the learning that takes place through SAM. A comparison of the main steps of the SAM cycle with corresponding stages outlined by TOKC revealed remarkable complementarity between these two approaches, but also important differences. The conceptual comparison deepened our understanding of SAM's learning performance as well as potential, revealing strengths, weaknesses and opportunities for improvement. Key insights include that valuable and different forms of learning takes place during each step of the SAM cycle. This learning can be enhanced through careful attention to approaches for creating, sharing and making explicit the tacit knowledge of individuals. Furthermore, dialogue and co-learning with stakeholders should be maintained beyond the visioning and objectives setting step of SAM. Based on insights gained, we developed a new and complementary conceptualization of SAM, as a spiraling process of organizational learning enabled by the interplay between tacit and explicit forms of knowledge, which in turn is mediated by different types of social interactions, media and engagement with practice. We believe that this conceptualization can help to better acknowledge and enable learning as one of the most fundamental purposes and outcomes of SAM, and adaptive management more generally.

A microRNA cluster in the Fragile-X region expressed during spermatogenesis targets FMR1.

Testis-expressed X-linked genes typically evolve rapidly. Here, we report on a testis-expressed X-linked microRNA (miRNA) cluster that despite rapid alterations in sequence has retained its position in the Fragile-X region of the X chromosome in placental mammals. Surprisingly, the miRNAs encoded by this cluster (Fx-mir) have a predilection for targeting the immediately adjacent gene, Fmr1, an unexpected finding given that miRNAs usually act in trans, not in cis Robust repression of Fmr1 is conferred by combinations of Fx-mir miRNAs induced in Sertoli cells (SCs) during postnatal development when they terminate proliferation. Physiological significance is suggested by the finding that FMRP, the protein product of Fmr1, is downregulated when Fx-mir miRNAs are induced, and that FMRP loss causes SC hyperproliferation and spermatogenic defects. Fx-mir miRNAs not only regulate the expression of FMRP, but also regulate the expression of eIF4E and CYFIP1, which together with FMRP form a translational regulatory complex. Our results support a model in which Fx-mir family members act cooperatively to regulate the translation of batteries of mRNAs in a developmentally regulated manner in SCs.

The impact of injury: The experiences of children and families after a child's traumatic injury.

OBJECTIVE: To explore the experiences of children and families after a child's traumatic injury (Injury Severity Score >8). DESIGN: Qualitative interview study. SETTING: Two children's major trauma centres in England. PARTICIPANTS: 32 participants: 13 children with traumatic injuries, their parents/guardians (n = 14) and five parents whose injured child did not participate. METHODS: Semi-structured interviews exploring the emotional, social, practical and physical impacts of children's injuries, analysed by thematic analysis. RESULTS: Interviews were conducted a median of 8.5 months (IQR 9.3) post-injury. Injuries affected the head, chest, abdomen, spine, limbs or multiple body parts. Injured children struggled with changes to their appearance, physical activity restrictions and late onset physical symptoms, which developed after hospital discharge when activity levels increased. Social participation was affected by activity restrictions, concerns about their appearance and interruptions to friendships. Psychological impacts, particularly post-traumatic stress type symptoms often affected both children and parents. Parents' responsibilities suddenly increased, which affected family relationships and roles, their ability to work and carry out daily tasks. Rapid hospital discharge was wanted, but participants often felt vulnerable on return home. They valued continued contact with a healthcare professional and practical supports from family and friends, which enabled resumption of their usual lives. CONCLUSIONS: Injured children experience changes to their appearance, friendships, physical activity levels and develop new physical and mental health symptoms after hospital discharge. Such challenges can be addressed by the provision of advice about potential symptoms, alternative activities during recovery, strategies to build resilience and how to access services after hospital discharge.

Perceived Experiences of Discrimination and Latino/a Young Adults' Personal and Relational Well-being.

US Latino/as experience high rates of discrimination, resulting in personal and relational distress. A sample of 238 Latino/a young adults (Mage = 25.37 years; 57.6% men; 54.4% Mexican) was used to investigate how perceived discrimination was associated with romantic relationship instability via young adults' depressive symptoms. The moderating roles of ethnic identity and romantic relationship maintenance on these associations were examined. Greater relationship maintenance and ethnic identity affirmation were associated with less depression and relationship instability. Under conditions of high ethnic identity exploration and resolution, the association between discrimination and depressive symptoms was stronger, leading to greater relationship instability. The findings reveal that the protective roles of cultural and relational factors may depend on the stressor and outcomes examined.

A scoping review of the needs of children and other family members after a child's traumatic injury.

OBJECTIVE: To review children's and their families' needs after a child's traumatic injury and assessment tools to measure needs. DATA SOURCES: Medline, Embase, CINAHL and PsycINFO databases (2005-September 2017) were searched and screened for papers (of any design) investigating children's and families' needs after a child's traumatic physical injury. REVIEW METHODS: Data regarding children's and families' needs were extracted by two independent raters. Methodological quality of the identified papers was not assessed. Thematic content analysis drew out the key needs. RESULTS: A total of 12 studies were identified, involving 932 participants including 105 injured adolescents and 827 family members or professionals. The needs of children under 12 years were identified indirectly from families or professionals. Most studies focussed on traumatic brain injuries. Two groups of needs were identified: person-related and service-related. Person-related needs were categorized into adolescent-specific needs, need for support with cognitive, emotional, social and physical problems and help with practical problems. Service-related needs were categorized into the need for information, educational needs and support during care transitions (specifically access to community-based services). These needs were largely unmet, particularly regarding information, emotional support and care transitions, which were compounded by professionals' limited understanding of the children's difficulties. We found no published measurement tools to assess children's and families' needs after a child's traumatic injury. CONCLUSION: The evidence about children's and families' needs following a child's traumatic injury was limited, but needs for information, emotional support and access to community-based services were consistently unmet.

Dietary Whole Egg Consumption Attenuates Body Weight Gain and Is More Effective than Supplemental Cholecalciferol in Maintaining Vitamin D Balance in Type 2 Diabetic Rats.

Background: Type 2 diabetes (T2D) is characterized by vitamin D insufficiency owing to excessive urinary loss of 25-hydroxycholecalciferol [25(OH)D]. We previously reported that a diet containing dried whole egg, a rich source of vitamin D, was effective at maintaining circulating 25(OH)D concentrations in rats with T2D. Furthermore, whole egg consumption reduced body weight gain in rats with T2D.Objective: This study was conducted to compare whole egg consumption with supplemental cholecalciferol with respect to vitamin D balance, weight gain, and body composition in rats with T2D.Methods: Male Zucker diabetic fatty (ZDF) rats (n = 24) and their lean controls (n = 24) were obtained at 5 wk of age and randomly assigned to 3 treatment groups: a casein-based diet (CAS), a dried whole egg-based diet (WE), or a casein-based diet containing supplemental cholecalciferol (CAS+D) at the same amount of cholecalciferol provided by WE (37.6 µg/kg diet). Rats were fed their respective diets for 8 wk. Weight gain and food intake were measured daily, circulating 25(OH)D concentrations were measured by ELISA, and body composition was analyzed by dual X-ray absorptiometry.Results: Weight gain and percentage of body fat were reduced by ∼20% and 11%, respectively, in ZDF rats fed WE compared with ZDF rats fed CAS or CAS+D. ZDF rats fed CAS had 21% lower serum 25(OH)D concentrations than lean rats fed CAS. In ZDF rats, WE consumption increased serum 25(OH)D concentrations 130% compared with CAS, whereas consumption of CAS+D increased serum 25(OH)D concentrations 35% compared with CAS.Conclusions: Our data suggest that dietary consumption of whole eggs is more effective than supplemental cholecalciferol in maintaining circulating 25(OH)D concentrations in rats with T2D. Moreover, whole egg consumption attenuated weight gain and reduced percentage of body fat in ZDF rats. These data may support new dietary recommendations targeting the prevention of vitamin D insufficiency in T2D.