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Recently, novel dietary oils with modified fatty acid profiles have been manufactured to improve fatty acid intakes and reduce CVD risk. Our objective was to evaluate the efficacy of novel high-oleic rapeseed (canola) oil (HOCO), alone or blended with flaxseed oil (FXCO), on circulating lipids and inflammatory biomarkers v. a typical Western diet (WD). Using a randomised, controlled, crossover trial, thirty-six hypercholesterolaemic subjects consumed three isoenergetic diets for 28 d each containing approximately 36 % energy from fat, of which 70 % was provided by HOCO, FXCO or WD. Dietary fat content of SFA, MUFA, PUFA n-6 and n-3 was 6, 23, 5, 1 % energy for HOCO; 6, 16, 5, 7·5 % energy for FXCO; 11·5, 16, 6, 0·5 % energy for WD. After 28 d, compared with WD, LDL-cholesterol was reduced 15·1 % (P < 0·001) with FXCO and 7·4 % (P < 0·001) with HOCO. Total cholesterol (TC) was reduced 11 % (P < 0·001) with FXCO and 3·5 % (P = 0·002) with HOCO compared with WD. Endpoint TC differed between FXCO and HOCO (P < 0·05). FXCO consumption reduced HDL-cholesterol by 8·5 % (P < 0·001) and LDL:HDL ratio by 7·5 % (P = 0·008) v. WD. FXCO significantly decreased E-selectin concentration compared with WD (P = 0·02). No differences were observed in inflammatory markers after the consumption of HOCO compared with WD. In conclusion, consumption of novel HOCO alone or when blended with flaxseed oil is cardioprotective through lipid-lowering effects. The incorporation of flaxseed oil may also target inflammation by reducing plasma E-selectin.

Recent analyses indicate that global fruit and vegetable (F&V) production will need to increase by 50%–150% by 2050 in order to achieve sustainable and healthy diets for 10 billion people. Although global production of F&V has grown by 50% during the last two decades alone, simply scaling up current systems of F&V production, supply chains, and consumption will inevitably worsen environmental and socioeconomic tradeoffs. This article examines three examples of important F&V—avocados, leafy greens, and tomatoes—to assess the global challenge of meeting dietary recommendations at affordable prices to consumers while sustaining producer livelihoods and minimizing environmental damage. These three cases highlight key characteristics of F&V systems that make the challenge of sustainable expansion especially difficult: knowledge-, input-, and labor-intensive production, high rates of food loss and waste, and low affordability to consumers relative to less nutrient-dense food groups. Our analysis shows that only by investing in innovations that increase diversity, integrate technology, and improve equity will truly sustainable expansion of F&V systems be possible.

BackgroundEstimation of the risk of malignancy in pulmonary nodules detected by CT is central in clinical management. The use of artificial intelligence (AI) offers an opportunity to improve risk prediction. Here we compare the performance of an AI algorithm, the lung cancer prediction convolutional neural network (LCP-CNN), with that of the Brock University model, recommended in UK guidelines.MethodsA dataset of incidentally detected pulmonary nodules measuring 5–15 mm was collected retrospectively from three UK hospitals for use in a validation study. Ground truth diagnosis for each nodule was based on histology (required for any cancer), resolution, stability or (for pulmonary lymph nodes only) expert opinion. There were 1397 nodules in 1187 patients, of which 234 nodules in 229 (19.3%) patients were cancer. Model discrimination and performance statistics at predefined score thresholds were compared between the Brock model and the LCP-CNN.ResultsThe area under the curve for LCP-CNN was 89.6% (95% CI 87.6 to 91.5), compared with 86.8% (95% CI 84.3 to 89.1) for the Brock model (p≤0.005). Using the LCP-CNN, we found that 24.5% of nodules scored below the lowest cancer nodule score, compared with 10.9% using the Brock score. Using the predefined thresholds, we found that the LCP-CNN gave one false negative (0.4% of cancers), whereas the Brock model gave six (2.5%), while specificity statistics were similar between the two models.ConclusionThe LCP-CNN score has better discrimination and allows a larger proportion of benign nodules to be identified without missing cancers than the Brock model. This has the potential to substantially reduce the proportion of surveillance CT scans required and thus save significant resources.

Background Triple-negative breast cancer (TNBC) remains an aggressive breast cancer subtype with limited treatment options. ENMD-2076 is a small-molecule inhibitor of Aurora and angiogenic kinases with proapoptotic and antiproliferative activity in preclinical models of TNBC. Methods This dual-institution, single-arm, two-stage, phase II clinical trial enrolled patients with locally advanced or metastatic TNBC previously treated with one to three prior lines of chemotherapy in the advanced setting. Patients were treated with ENMD-2076 250 mg orally once daily with continuous dosing in 4-week cycles until disease progression or unacceptable toxicity occurred. The primary endpoint was 6-month clinical benefit rate (CBR), and secondary endpoints included progression-free survival, pharmacokinetic profile, safety, and biologic correlates in archival and fresh serial tumor biopsies in a subset of patients. Results Forty-one patients were enrolled. The 6-month CBR was 16.7% (95% CI, 6–32.8%) and included two partial responses. The 4-month CBR was 27.8% (95% CI, 14–45.2%), and the average duration of benefit was 6.5 cycles. Common adverse events included hypertension, fatigue, diarrhea, and nausea. Treatment with ENMD-2076 resulted in a decrease in cellular proliferation and microvessel density and an increase in p53 and p73 expression, consistent with preclinical observations. Conclusions Single-agent ENMD-2076 treatment resulted in partial response or clinical benefit lasting more than 6 months in 16.7% of patients with pretreated, advanced, or metastatic TNBC. These results support the development of predictive biomarkers using archival and fresh tumor tissue, as well as consideration of mechanism-based combination strategies. Trial registration ClinicalTrials.gov, NCT01639248 . Registered on July 12, 2012.

Blood is the most commonly used body fluid for extracellular vesicle (EV) research. The composition of a blood sample and its derivatives (i.e., plasma and serum) are not only donor‐dependent but also influenced by collection and preparation protocols. Since there are hundreds of pre‐analytical protocols and over forty variables, the development of standard operating procedures for EV research is very challenging. To improve the reproducibility of blood EV research, the International Society for Extracellular Vesicles (ISEV) Blood EV Task Force proposes standardized reporting of (i) the applied blood collection and preparation protocol and (ii) the quality of the prepared plasma and serum samples. Gathering detailed information will provide insight into the performance of the protocols and more effectively identify potential confounders in the prepared plasma and serum samples. To collect this information, the ISEV Blood EV Task Force created the Minimal Information for Blood EV research (MIBlood‐EV), a tool to record and report information about pre‐analytical protocols used for plasma and serum preparation as well as assays used to assess the quality of these preparations. This tool does not require modifications of established local pre‐analytical protocols and can be easily implemented to enhance existing databases thereby enabling evidence‐based optimization of pre‐analytical protocols through meta‐analysis. Taken together, insight into the quality of prepared plasma and serum samples will (i) improve the quality of biobanks for EV research, (ii) guide the exchange of plasma and serum samples between biobanks and laboratories, (iii) facilitate inter‐laboratory comparative EV studies, and (iv) improve the peer review process.

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise \"state-of-the-science\" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

The white spotting locus (S) in dogs is colocalized with the MITF (microphtalmia-associated transcription factor) gene. The phenotypic effects of the four S alleles range from solid colour (S) to extreme white spotting (s(w)). We have investigated four candidate mutations associated with the s(w) allele, a SINE insertion, a SNP at a conserved site and a simple repeat polymorphism all associated with the MITF-M promoter as well as a 12 base pair deletion in exon 1B. The variants associated with white spotting at all four loci were also found among wolves and we conclude that none of these could be a sole causal mutation, at least not for extreme white spotting. We propose that the three canine white spotting alleles are not caused by three independent mutations but represent haplotype effects due to different combinations of causal polymorphisms. The simple repeat polymorphism showed extensive diversity both in dogs and wolves, and allele-sharing was common between wolves and white spotted dogs but was non-existent between solid and spotted dogs as well as between wolves and solid dogs. This finding was unexpected as Solid is assumed to be the wild-type allele. The data indicate that the simple repeat polymorphism has been a target for selection during dog domestication and breed formation. We also evaluated the significance of the three MITF-M associated polymorphisms with a Luciferase assay, and found conclusive evidence that the simple repeat polymorphism affects promoter activity. Three alleles associated with white spotting gave consistently lower promoter activity compared with the allele associated with solid colour. We propose that the simple repeat polymorphism affects cooperativity between transcription factors binding on either flanking sides of the repeat. Thus, both genetic and functional evidence show that the simple repeat polymorphism is a key regulator of white spotting in dogs.

In 2021, the American Academy of Pediatrics released a policy statement spotlighting the health-promoting and stress-buffering effects of early relational health (ERH) and calling for universal ERH promotion in pediatric primary care. However, little educational content for the observation and promotion of ERH is available, highlighting the need for scalable ERH training modules. This study aims to investigate the acceptability, feasibility, and impact of the \"Lens of Emotional Connection,\" a self-paced, asynchronous, ~45-minute ERH training module codeveloped by Reach Out and Read and the Center for Early Relational Health at Columbia University. The module introduces practitioners to emotional connection, an observable component of ERH, through written and video didactic content and experiential rating of emotional connection in videos of parent-child dyads interacting face-to-face. The evaluation was conducted by the Carolinas Collaborative. Pediatric providers across 8 clinical sites were invited to participate and responded to embedded pre-post surveys. Focus groups conducted with participants further examined the educational experience. Of 653 invited clinicians, 207 (31.7%) participated in the module. Individual survey responses were available for 44-75 participants, depending on the question. Of responders, 64 out of 69 (93%) reported the module was a good way to learn about emotional connection, and 63 out of 69 (91%) felt the module provided valuable knowledge. Overall, 60 out of 69 respondents (87%) reported satisfaction with the module length, and 36 out of 44 respondents (82%) reported they would recommend this training to other clinicians. Focus groups echoed these findings. Comparison of pre-post data showed the greatest changes were in familiarity with emotional connection (n=75, pre mean 54.20, SD 18.59; post mean 73.99, SD 14.73; Cohen d=1.14; P<.001) and confidence in observing the quality of the parent- or caregiver-infant relationship during well-child visits (n=75, pre mean 55.36, SD 18.49; post mean 74.20, SD 14.07; Cohen d=1.28; P<.001). Suggested areas for improvement included more thorough explanations of specific components of emotional connection identified in parent-child interaction videos, a desire for synchronous live training, and additional content addressing what to do if low emotional connection is identified. In this evaluation of a training module designed to introduce pediatric practitioners to ERH and emotional connection, acceptability among participants was found to be high, with most responders reporting it as valuable and reporting they would recommend it. Statistically significant impact was noted in both perceptions of the importance of information about emotional connection and perceived knowledge acquisition. Feasibility of widespread implementation with voluntary participation, as here, was relatively low, with only a minority completing the module. Critically, Reach Out and Read's commitment to iterative creation, validation, and eventual delivery of ERH training creates a scalable avenue for wide-scale implementation, given the organization's presence in >6500 clinics across the 50 states.

Background Hospitalizations involving opioid use disorder (OUD) are increasing. Medications for opioid use disorder (MOUD) reduce mortality and acute care utilization. Hospitalization is a reachable moment for initiating MOUD and arranging for ongoing MOUD engagement following hospital discharge. Despite existing quality metrics for MOUD initiation and engagement, few hospitals provide hospital based opioid treatment (HBOT). This protocol describes a cluster-randomized hybrid type-2 implementation study comparing low-intensity and high-intensity implementation support strategies to help community hospitals implement HBOT. Methods Four state implementation hubs with expertise in initiating HBOT programs will provide implementation support to 24 community hospitals (6 hospitals/hub) interested in starting HBOT. Community hospitals will be randomized to 24-months of either a low-intensity intervention (distribution of an HBOT best-practice manual, a lecture series based on the manual, referral to publicly available resources, and on-demand technical assistance) or a high-intensity intervention (the low-intensity intervention plus funding for a hospital HBOT champion and regular practice facilitation sessions with an expert hub). The primary efficacy outcome, adapted from the National Committee on Quality Assurance, is the proportion of patients engaged in MOUD 34-days following hospital discharge. Secondary and exploratory outcomes include acute care utilization, non-fatal overdose, death, MOUD engagement at various time points, hospital length of stay, and discharges against medical advice. Primary, secondary, and exploratory outcomes will be derived from state Medicaid data. Implementation outcomes, barriers, and facilitators are assessed via longitudinal surveys, qualitative interviews, practice facilitation contact logs, and HBOT sustainability metrics. We hypothesize that the proportion of patients receiving care at hospitals randomized to the high-intensity arm will have greater MOUD engagement following hospital discharge. Discussion Initiation of MOUD during hospitalization improves MOUD engagement post hospitalization. Few studies, however, have tested different implementation strategies on HBOT uptake, outcome, and sustainability and only one to date has tested implementation of a specific type of HBOT (addiction consultation services). This cluster-randomized study comparing different intensities of HBOT implementation support will inform hospitals and policymakers in identifying effective strategies for promoting HBOT dissemination and adoption in community hospitals. Trial registration NCT04921787.

COVID-19 exposed issues in our mental health system, prompting an emergency advisory from the Surgeon General on youth mental health. This Comment offers two lessons drawn from empirically supported aspects of a public health model to guide a transformation of youth mental health services: (1) the importance of recruiting local community members (peer support specialists [PSSs]) with lived experiences to promote engagement in services and (2) the necessity of expanding services to natural settings to enhance access and uptake. Examples of service models applying these lessons and illustrating how they are interrelated are provided. These initiatives are overdue in response to persistent disparities and the need to provide services across the prevention to intervention continuum.