Engaging Long-Term Care Workers in Research: Recruitment Approaches and Participant Characteristics From a Randomized Controlled Trial to Improve COVID-19 Vaccine Confidence.

OBJECTIVE: To describe and compare the recruitment methods employed in a randomized controlled trial targeting long-term care workers, and resulting participant baseline characteristics. DESIGN: We used a multifaceted recruitment process to enroll long-term care workers in our 3-arm randomized controlled trial comparing 2 interventions to enhanced usual practice, for improving COVID-19 vaccine confidence and other outcomes. SETTING AND PARTICIPANTS: Adult long-term care workers living in the United States employed within the last 2 years were invited to join the study. Participants also had to meet specific screening criteria related to their degree of worry about the vaccine and/or their vaccination status. METHODS: We used a participatory approach to engage our long-term care stakeholders in codesigning and executing a combination of recruitment methods, including targeted e-recruitment, paid e-recruitment, and in-person recruitment. Participants were screened, consented, and enrolled online. We implemented a participant verification process to ensure the integrity of our study data, and used a tailored participant management platform to manage enrollment. RESULTS: We enrolled 1930 long-term care workers between May 2022 and January 2023. We met our enrollment target, despite each recruitment method having limitations. Total variable costs of approximately $102,700 were incurred and differed on a per-enrolled participant basis across methods: $25.72 for targeted e-recruitment, $57.12 for paid e-recruitment, and $64.92 for in-person methods. Our sample differed from the national population in age, gender, race/ethnicity, education, and role in long-term care. Differences were also observed between online and in-person recruitment methods. CONCLUSIONS AND IMPLICATIONS: Our results support the feasibility of enrolling a large number of long-term care workers in a randomized controlled trial to increase COVID-19 vaccine confidence. Findings build upon the evidence base for engaging this important population in research, a critical step to improving long-term care resident health and well-being. Results from our trial are anticipated in 2024.

AICAR confers prophylactic cardioprotection in doxorubicin-induced heart failure in rats.

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects, leading to heart failure (HF). Impaired mitochondrial function is thought to be key factor driving progression into HF. We have previously shown in a rat model of DOX-HF that heart failure with reduced ejection fraction correlates with mitochondrial loss and dysfunction. Adenosine monophosphate-dependent kinase (AMPK) is a cellular energy sensor, regulating mitochondrial biogenesis and energy metabolism, including fatty acid oxidation. We hypothesised that AMPK activation could restore mitochondrial function and therefore be a novel cardioprotective strategy for the prevention of DOX-HF. Consequently, we set out to assess whether 5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR), an activator of AMPK, could prevent cardiac functional decline in this chronic intravenous rat model of DOX-HF. In line with our hypothesis, AICAR improved cardiac systolic function. AICAR furthermore improved cardiac mitochondrial fatty acid oxidation, independent of mitochondrial number, and in the absence of observable AMPK-activation. In addition, we found that AICAR prevented loss of myocardial mass. RNAseq analysis showed that this may be driven by normalisation of pathways associated with ribosome function and protein synthesis, which are impaired in DOX-treated rat hearts. AICAR furthermore prevented dyslipidemia and excessive body-weight loss in DOX-treated rats, which may contribute to preservation of myocardial mass. Though it is unclear whether AICAR exerted its cardioprotective effect through cardiac or extra-cardiac AMPK-activation or via an AMPK-independent effect, these results show promise for the use of AICAR as a cardioprotective agent in DOX-HF to both preserve cardiac function and mass.

White matter hyperintensities and the surrounding normal appearing white matter are associated with water channel disruption in the oldest old.

INTRODUCTION: Age-related magnetic resonance imaging (MRI) T2 white matter hyperintensities (WMHs) are common and associated with neurological decline. We investigated the histopathological underpinnings of MRI WMH and surrounding normal appearing white matter (NAWM), with a focus on astroglial phenotypes. METHODS: Brain samples from 51 oldest old Oregon Alzheimer's Disease Research Center participants who came to autopsy underwent post mortem (PM) 7 tesla MRI with targeted histopathological sampling of WMHs and NAWM. Stained slides were digitized and quantified. Mixed-effects models determined differences in molecular characteristics between WMHs and the NAWM and across NAWM. RESULTS: PM MRI-targeted WMHs are characterized by demyelination, microglial activation, and prominent astrocytic alterations, including disrupted aquaporin (AQP) expression. Similar changes occur within the surrounding NAWM in a pattern of decreasing severity with increased distance from WMHs. DISCUSSION: Decreased AQP expression within WMH and proximal NAWM suggest an overwhelmed system wherein water homeostasis is no longer maintained, contributing to WM damage in older individuals. HIGHLIGHTS: Post mortem magnetic resonance imaging (MRI) was used to characterize the pathology of white matter hyperintensities (WMHs) and surrounding normal appearing white matter (NAWM). Stained immunohistochemical (IHC) slides from targeted WMH and NAWM samples were digitized and quantified. WMHs and NAWM were associated with inflammation, demyelination, and gliosis. WMHs and NAWM astrocytic changes included decreased AQP1 and AQP4 expression. Abnormal NAWM pathology diminished in severity with increasing distance from WMH.

Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolaemia: An expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Vital Signs: Mammography Use and Association with Social Determinants of Health and Health-Related Social Needs Among Women - United States, 2022.

Introduction: Approximately 40,000 U.S. women die from breast cancer each year. Mammography is recommended to screen for breast cancer and reduce breast cancer mortality. Adverse social determinants of heath (SDOH) and health-related social needs (HRSNs) (e.g., lack of transportation and social isolation) can be barriers to getting mammograms. Methods: Data from the 2022 Behavioral Risk Factor Surveillance System were analyzed to estimate the prevalence of mammography use within the previous 2 years among women aged 40-74 years by jurisdiction, age group, and sociodemographic factors. The association between mammography use and measures of SDOH and HRSNs was assessed for jurisdictions that administered the Social Determinants and Health Equity module. Results: Among women aged 50-74 years, state-level mammography use ranged from 64.0% to 85.5%. Having health insurance and a personal health care provider were associated with having had a mammogram within the previous 2 years. Among women aged 50-74 years, mammography prevalence was 83.2% for those with no adverse SDOH and HRSNs and 65.7% for those with three or more adverse SDOH and HRSNs. Life dissatisfaction, feeling socially isolated, experiencing lost or reduced hours of employment, receiving food stamps, lacking reliable transportation, and reporting cost as a barrier for access to care were all strongly associated with not having had a mammogram within the previous 2 years. Conclusions and Implications for Public Health Practice: Identifying specific adverse SDOH and HRSNs that women experience and coordinating activities among health care providers, social services, community organizations, and public health programs to provide services that help address these needs might increase mammography use and ultimately decrease breast cancer deaths.

Mortality burden of pre-treatment weight loss in patients with non-small-cell lung cancer: A systematic literature review and meta-analysis.

Cachexia, with weight loss (WL) as a major component, is highly prevalent in patients with cancer and indicates a poor prognosis. The primary objective of this study was to conduct a meta-analysis to estimate the risk of mortality associated with cachexia (using established WL criteria prior to treatment initiation) in patients with non-small-cell lung cancer (NSCLC) in studies identified through a systematic literature review. The review was conducted according to PRISMA guidelines. Embase® and PubMed were searched to identify articles on survival outcomes in adult patients with NSCLC (any stage) and cachexia published in English between 1 January 2016 and 10 October 2021. Two independent reviewers screened titles, abstracts and full texts of identified records against predefined inclusion/exclusion criteria. Following a feasibility assessment, a meta-analysis evaluating the impact of cachexia, defined per the international consensus criteria (ICC), or of pre-treatment WL ≥ 5% without a specified time interval, on overall survival in patients with NSCLC was conducted using a random-effects model that included the identified studies as the base case. The impact of heterogeneity was evaluated through sensitivity and subgroup analyses. The standard measures of statistical heterogeneity were calculated. Of the 40 NSCLC publications identified in the review, 20 studies that used the ICC for cachexia or reported WL ≥ 5% and that performed multivariate analyses with hazard ratios (HRs) or Kaplan-Meier curves were included in the feasibility assessment. Of these, 16 studies (80%; n = 6225 patients; published 2016-2021) met the criteria for inclusion in the meta-analysis: 11 studies (69%) used the ICC and 5 studies (31%) used WL ≥ 5%. Combined criteria (ICC plus WL ≥ 5%) were associated with an 82% higher mortality risk versus no cachexia or WL < 5% (pooled HR [95% confidence interval, CI]: 1.82 [1.47, 2.25]). Although statistical heterogeneity was high (I2 = 88%), individual study HRs were directionally aligned with the pooled estimate, and there was considerable overlap in CIs across included studies. A subgroup analysis of studies using the ICC (HR [95% CI]: 2.26 [1.80, 2.83]) or WL ≥ 5% (HR [95% CI]: 1.28 [1.12, 1.46]) showed consistent findings. Assessments of methodological, clinical and statistical heterogeneity indicated that the meta-analysis was robust. Overall, this analysis found that ICC-defined cachexia or WL ≥ 5% was associated with inferior survival in patients with NSCLC. Routine assessment of both weight and weight changes in the oncology clinic may help identify patients with NSCLC at risk for worse survival, better inform clinical decision-making and assess eligibility for cachexia clinical trials.

Artificial Intelligence and the National Violent Death Reporting System: A Rapid Review.

As the awareness on violent deaths from guns, drugs, and suicides emerges as a public health crisis in the United States, attempts to prevent injury and mortality through nursing research are critical. The National Violent Death Reporting System provides public health surveillance of US violent deaths; however, understanding the National Violent Death Reporting System's research utility is limited. The purpose of our rapid review of the 2019-2023 literature was to understand to what extent artificial intelligence methods are being used with the National Violent Death Reporting System. We identified 16 National Violent Death Reporting System artificial intelligence studies, with more than half published after 2020. The text-rich content of National Violent Death Reporting System enabled researchers to center their artificial intelligence approaches mostly on natural language processing (50%) or natural language processing and machine learning (37%). Significant heterogeneity in approaches, techniques, and processes was noted across the studies, with critical methods information often lacking. The aims and focus of National Violent Death Reporting System studies were homogeneous and mostly examined suicide among nurses and older adults. Our findings suggested that artificial intelligence is a promising approach to the National Violent Death Reporting System data with significant untapped potential in its use. Artificial intelligence may prove to be a powerful tool enabling nursing scholars and practitioners to reduce the number of preventable, violent deaths.

Enlarged perivascular spaces are associated with white matter injury, cognition and inflammation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Enlarged perivascular spaces have been previously reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, but their significance and pathophysiology remains unclear. We investigated associations of white matter enlarged perivascular spaces with classical imaging measures, cognitive measures and plasma proteins to better understand what enlarged perivascular spaces represent in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and whether radiographic measures of enlarged perivascular spaces would be of value in future therapeutic discovery studies for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Twenty-four individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and 24 age- and sex-matched controls were included. Disease status was determined based on the presence of NOTCH3 mutation. Brain imaging measures of white matter hyperintensity, brain parenchymal fraction, white matter enlarged perivascular space volumes, clinical and cognitive measures as well as plasma proteomics were used in models. White matter enlarged perivascular space volumes were calculated via a novel, semiautomated pipeline, and levels of 7363 proteins were quantified in plasma using the SomaScan assay. The relationship of enlarged perivascular spaces with global burden of white matter hyperintensity, brain atrophy, functional status, neurocognitive measures and plasma proteins was modelled with linear regression models. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and control groups did not exhibit differences in mean enlarged perivascular space volumes. However, increased enlarged perivascular space volumes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy were associated with increased white matter hyperintensity volume (ß = 0.57, P = 0.05), Clinical Dementia Rating Sum-of-Boxes score (ß = 0.49, P = 0.04) and marginally with decreased brain parenchymal fraction (ß = -0.03, P = 0.10). In interaction term models, the interaction term between cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy disease status and enlarged perivascular space volume was associated with increased white matter hyperintensity volume (ß = 0.57, P = 0.02), Clinical Dementia Rating Sum-of-Boxes score (ß = 0.52, P = 0.02), Mini-Mental State Examination score (ß = -1.49, P = 0.03) and marginally with decreased brain parenchymal fraction (ß = -0.03, P = 0.07). Proteins positively associated with enlarged perivascular space volumes were found to be related to leukocyte migration and inflammation, while negatively associated proteins were related to lipid metabolism. Two central hub proteins were identified in protein networks associated with enlarged perivascular space volumes: CXC motif chemokine ligand 8/interleukin-8 and C-C motif chemokine ligand 2/monocyte chemoattractant protein 1. The levels of CXC motif chemokine ligand 8/interleukin-8 were also associated with increased white matter hyperintensity volume (ß = 42.86, P = 0.03), and levels of C-C motif chemokine ligand 2/monocyte chemoattractant protein 1 were further associated with decreased brain parenchymal fraction (ß = -0.0007, P < 0.01) and Mini-Mental State Examination score (ß = -0.02, P < 0.01) and increased Trail Making Test B completion time (ß = 0.76, P < 0.01). No proteins were associated with all three studied imaging measures of pathology (brain parenchymal fraction, enlarged perivascular spaces, white matter hyperintensity). Based on associations uncovered between enlarged perivascular space volumes and cognitive functions, imaging and plasma proteins, we conclude that white matter enlarged perivascular space volumes may capture pathologies contributing to chronic brain dysfunction and degeneration in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

The diversity of well-being indicators: a latent profile analysis.

Introduction: Research on the dimensional structure of subjective well-being (SWB) suggests a five-dimensional solution, consisting of the three established dimensions of life satisfaction, positive affect, and negative affect, and two additional empirically supported dimensions: domain satisfaction and happiness. While these dimensions can be aggregated into a superordinate SWB construct, little research has explored how these dimensions differ in their variation across subpopulations of individuals. Methods: The present study addresses this gap via secondary analysis of a sample of 1,487 partnered individuals, using the five dimensions of SWB as indicators for latent profile analysis. Results: Analyses returned five profiles, which we labeled Satisfied, Ambivalent, Indifferent, Dissatisfied, and Very Dissatisfied. In the Ambivalent and Indifferent profiles, the dimensions of negative affect and happiness exhibit discrepant behavior, resulting in shape differences. The five profiles are organized with reference to the external criterion of couple satisfaction. At the theoretical level, the results of the present study have the potential to inform current debates about the structure of well-being. Discussion: These findings suggest that, while SWB can usually be measured as a unidimensional construct, there is still merit to using multidimensional approaches and alternative forms of measurement-such as LPA-that capture complexities normally absent from unidimensional treatments. At the practical level, the results of the current study have the potential to inform well-being interventions (both clinical and otherwise), suggesting that those dealing with well-being in real life situations should pause before concluding that the absence of negativity implies the presence of positivity, or vice versa.

Treatment of femoral bone loss in revision total hip arthroplasty: a clinical practice review.

Patient and implant selection is essential to optimize outcome. Femoral bone loss classifications such as the American Academy of Orthopaedic Surgeons, Gross, and Paprosky classifications permit surgeons to systematically manage bone stock deficiencies and guide implant selection. Here we provide a comprehensive report on the pitfalls and management of this reconstructive challenge. Preoperative planning remains vital to the treatment of femoral bone loss in revision hip arthroplasty and the authors believe it is essential and should include the entire femur. This commonly includes imaging for bone loss such as Judet views or computed tomography scan and must include the entire femur though additional radiographs such as Judet views apply more for acetabular bone loss as opposed to femoral bone loss. All patients should have pre-operative work up to exclude infection. If any of these results area elevated, an aspirate and sampling is required to guide microbiological management. Classically with regards femoral revision surgery, uncemented fixation has proven to give the best outcomes but surgeons must remain flexible and use cemented fixation when necessary. Adequate proximal bone stock permits the use of implants used in primary joint surgery. Implants with proximal modularity can be used in cases where bone stock allows for superb proximal bone support. The vast majority of femoral revisions have inadequate proximal bone stock, thus distally fixed stems should be used and have been shown to provide both axial and rotational stability provided there is an intact isthmus. Taper fluted stems can provide good outcomes even in cases of major bone loss. However, with severe bony loss, impaction grating or the use of a megaprotsthesis is sometimes necessary and is down to surgeon choice and preference. This article has been written as a guide for management and summarises the best evidence available.

Optimizing Triage Practice in Pediatric Trauma: Lessons From Under-triage and Over-triage Rates and Risk Factors.

BACKGROUND: Triage accuracy is essential for delivering effective trauma care, especially in the pediatric population where unique challenges exist. The purpose of this study was to investigate risk factors contributing to under-triage and over-triage in an urban pediatric trauma center. METHODS: This retrospective cohort study included all trauma activations at an urban level 1 trauma center between January 1, 2021, and July 31, 2023 (patients <18 years old.) Patients who were under- or over-triaged were identified based on the level of trauma activation and injury severity score. RESULTS: There were 1094 trauma activations included in this study. The rate of under-triage was 3.8% (n = 42) and over-triage was 13.6% (n = 149). Infants aged 0-1 years had the highest rate of under-triage (10.9%, n = 19, P < .001), while those aged 11-17 had the highest rate of over-triage (17.0%, n = 82, P = .003). Non-accidental trauma was the strongest risk factor for under-triage (OR 30.2 [6.4-142.8] P < .001). Penetrating mechanism was the strongest risk factor for over-triage (OR 12.2 [5.6-26.2] P < .001). DISCUSSION: This study reveals the complexity of trauma triage in the pediatric population. We identified key predictive factors, such as age, comorbidities, and mechanism of injury, that can be used to refine triage practices and improve the care of pediatric trauma patients.

Artificial intelligence and machine learning in axial spondyloarthritis.

PURPOSE OF REVIEW: To evaluate the current applications and prospects of artificial intelligence and machine learning in diagnosing and managing axial spondyloarthritis (axSpA), focusing on their role in medical imaging, predictive modelling, and patient monitoring. RECENT FINDINGS: Artificial intelligence, particularly deep learning, is showing promise in diagnosing axSpA assisting with X-ray, computed tomography (CT) and MRI analyses, with some models matching or outperforming radiologists in detecting sacroiliitis and markers. Moreover, it is increasingly being used in predictive modelling of disease progression and personalized treatment, and could aid risk assessment, treatment response and clinical subtype identification. Variable study designs, sample sizes and the predominance of retrospective, single-centre studies still limit the generalizability of results. SUMMARY: Artificial intelligence technologies have significant potential to advance the diagnosis and treatment of axSpA, providing more accurate, efficient and personalized healthcare solutions. However, their integration into clinical practice requires rigorous validation, ethical and legal considerations, and comprehensive training for healthcare professionals. Future advances in artificial intelligence could complement clinical expertise and improve patient care through improved diagnostic accuracy and tailored therapeutic strategies, but the challenge remains to ensure that these technologies are validated in prospective multicentre trials and ethically integrated into patient care.

Intensive Glycemic Management Is Associated With Reduced Retinal Structure Abnormalities on Ocular Coherence Tomography in the DCCT/EDIC Study.

OBJECTIVE: To investigate quantitative and qualitative changes in retinal structure using optical coherence tomography (OCT) and their associations with systemic or other risk factors in individuals with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In the Epidemiology of Diabetes Interventions and Complications (EDIC) study, OCT images were obtained during study years 25-28 (2019-2022) in 937 participants; 54% and 46% were from the original intensive (INT) and conventional (CONV) glycemic management treatment groups, respectively. RESULTS: Average age for participants was 61 years old, diabetes duration 39 years, and HbA1c 7.6%. Participants originally in the CONV group were more likely to have disorganization of retinal inner layers (DRIL) (CONV 27.3% vs. INT 18.7%; P = 0.0003), intraretinal fluid (CONV 24.4% vs. INT 19.2%; P = 0.0222), and intraretinal cysts (CONV 20.8% vs. INT 16.6%; P = 0.0471). In multivariable models, sex, age, smoking, mean updated systolic blood pressure, and history of "clinically significant" macular edema (CSME) and of anti-VEGF treatment were independently associated with changes in central subfield thickness, while HbA1c, BMI, and history of CSME and of ocular surgery were associated with DRIL. Visual acuity (VA) decline was associated with significant thinning of all retinal subfields except for the central and inner nasal subfields. CONCLUSIONS: Early intensive glycemic management in T1D is associated with a decreased risk of DRIL. This important morphological abnormality was associated with a history of macular edema, a history of ocular surgery, and worse VA. This study reveals benefits of intensive glycemic management on the retina beyond features detected by fundus photographs and ophthalmoscopy.

Five million years of Antarctic Circumpolar Current strength variability.

The Antarctic Circumpolar Current (ACC) represents the world's largest ocean-current system and affects global ocean circulation, climate and Antarctic ice-sheet stability1-3. Today, ACC dynamics are controlled by atmospheric forcing, oceanic density gradients and eddy activity4. Whereas palaeoceanographic reconstructions exhibit regional heterogeneity in ACC position and strength over Pleistocene glacial-interglacial cycles5-8, the long-term evolution of the ACC is poorly known. Here we document changes in ACC strength from sediment cores in the Pacific Southern Ocean. We find no linear long-term trend in ACC flow since 5.3 million years ago (Ma), in contrast to global cooling9 and increasing global ice volume10. Instead, we observe a reversal on a million-year timescale, from increasing ACC strength during Pliocene global cooling to a subsequent decrease with further Early Pleistocene cooling. This shift in the ACC regime coincided with a Southern Ocean reconfiguration that altered the sensitivity of the ACC to atmospheric and oceanic forcings11-13. We find ACC strength changes to be closely linked to 400,000-year eccentricity cycles, probably originating from modulation of precessional changes in the South Pacific jet stream linked to tropical Pacific temperature variability14. A persistent link between weaker ACC flow, equatorward-shifted opal deposition and reduced atmospheric CO2 during glacial periods first emerged during the Mid-Pleistocene Transition (MPT). The strongest ACC flow occurred during warmer-than-present intervals of the Plio-Pleistocene, providing evidence of potentially increasing ACC flow with future climate warming.

Expanding the Public Health Pipeline Through the Public Health Influencers Summer Institute.

The need for a robust public health system in the United States is critical for safeguarding population health. However, current data suggest an insufficient number of individuals entering or staying in the governmental public health workforce. Expanding the public health pipeline requires creative thinking about recruitment and training activities. To attract students to public health and other health-related fields, including medicine, one institution in the Southeast recently initiated the Public Health Influencers Summer Institute (PHISI), a program that addresses the beginning of the career development continuum: recruitment of high school students. For this investigation, we reviewed evaluation data of the PHISI and provided descriptive analyses and selected quotes to reflect student learning. Participants reported increased familiarity with all public health topics after participating in the program, with the greatest increases in public health policy and social determinants of health. In addition, all participants reported increased or significantly increased understanding of public health after participating in the program. While interest in the field of public health increased due to the COVID-19 pandemic, there are not enough individuals entering or staying in the public health workforce, leaving a critical shortfall. Introducing high school students to the field of public health may increase their interest in entering the public health workforce in the future, thereby strengthening the overall public health infrastructure. We propose that the PHISI may be an innovative strategy for increasing both the number and diversity of students interested in pursuing a career in public health.

Dynamic changes in perivascular space morphology predict signs of spaceflight-associated neuro-ocular syndrome in bed rest.

During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Transitions from child and adolescent to adult mental health services for eating disorders: an in-depth systematic review and development of a transition framework.

BACKGROUND: Eating disorders (EDs) peak in mid-to-late adolescence and often persist into adulthood. Given their early onset and chronicity, many patients transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS) for ongoing, speciality ED care. This transition typically occurs at 18 years of age, when important biological, psychosocial, and vocational changes take place. Thus, smooth and effective transitions are paramount for ensuring service continuity, as well as reducing the risk of ED relapse and premature death. Here, we synthesized evidence on transitions from CAMHS to AMHS for young people with EDs, aiming to inform future research, clinical practice, and healthcare policy. METHODS: A systematic review of the literature was conducted. This adhered to PRISMA guidelines. PubMed, Embase, and Scopus electronic databases were queried from inception to December 3, 2023. Leveraging the PICOS framework, study eligibility was evaluated in the qualitative synthesis. Data regarding methodology, analytic approach, and associated outcomes were then extracted. The quality of evidence was examined using critical appraisal tools. Finally, concept mapping was applied to organize findings into a transition framework. RESULTS: The search returned 76 articles. Of these, 14 were included in the final review. Articles were grouped into 'qualitative' (n = 10), 'cross-sectional' (n = 2), and 'longitudinal cohort' (n = 2) studies based on research design. Overall, ED transitions were complex, multifaceted, and challenging for patients, caregivers, and providers alike. This resulted from an interplay of temporal- (e.g., timing of ED onset and transition), stakeholder- (e.g., patient ambivalence towards recovery) and systemic- (e.g., differences between services) related factors. Most studies were of moderate-to-high quality. Findings informed the development of five transition strategies designed to facilitate effective transfers across ED care: Timely talks, Readiness, Inclusion, Preparation, and Synergy (TRIPS). CONCLUSIONS: Transitions from CAMHS to AMHS appear problematic for young people with EDs and other involved stakeholders. The field stands to benefit from TRIPS, an actionable, evidence-based framework that aims to alleviate challenges of transitioning and subsequently improve ED trajectories. As a logical next step, future work should empirically test the TRIPS framework, exploring its predictive utility and clinical value.

Eating disorders often develop in youth and persist into adulthood. Given this, many young people transition from pediatric to adult care for ongoing treatment. This usually occurs at 18 years of age, when important life changes take place, such as leaving home or pursuing higher education. Hence, smooth and effective transitions are critical for mental health. The present review summarized studies investigating transitions from pediatric to adult care for young people with eating disorders, and subsequently developed an evidence-informed transition framework (TRIPS). Based on the 14 studies included in the review, transitions from pediatric to adult care are challenging for young people with eating disorders, as well as for caregivers and providers. This is due to several factors related to the timing of transitions, the types of stakeholders involved, and the differences between care. Looking ahead, the field may benefit from the TRIPS framework that aims to improve transitions and clinical outcomes.

Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus.

Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.

Dietary carbohydrates regulate intestinal colonization and dissemination of Klebsiella pneumoniae.

Bacterial translocation from the gut microbiota is a source of sepsis in susceptible patients. Previous work suggests that overgrowth of gut pathobionts, including Klebsiella pneumoniae, increases the risk of disseminated infection. Our data from a human dietary intervention study found that in the absence of fiber, K. pneumoniae bloomed during microbiota recovery from antibiotic treatment. We thus hypothesized that dietary nutrients directly support or suppress colonization of this gut pathobiont in the microbiota. Consistent with our human subject study, complex carbohydrates in dietary fiber suppressed colonization of K. pneumoniae and allowed for recovery of competing commensals in mouse modeling. In contrast, through ex-vivo and in vivo modeling, we identify simple carbohydrates as a limiting resource for K. pneumoniae in the gut. As proof of principle, supplementation with lactulose, a non-absorbed simple carbohydrate and an FDA approved therapy, increased colonization of K. pneumoniae. Disruption of the intestinal epithelium led to dissemination of K. pneumoniae into the bloodstream and liver, which was prevented by dietary fiber. Our results show that dietary simple and complex carbohydrates are critical not only in the regulation of pathobiont colonization but also disseminated infection, suggesting that targeted dietary interventions may offer a preventative strategy in high-risk patients.