The state of the science on the health benefits of blueberries: a perspective.

Mounting evidence indicates that blueberry consumption is associated with a variety of health benefits. It has been suggested that regular consumption of blueberries can support and/or protect against cardiovascular disease and function, pre-diabetes and type 2 diabetes, and brain and cognitive function in individuals with health conditions and age-related decline. Further, mechanistic investigations highlight the role of blueberry anthocyanins in mediating these health benefits, in part through interactions with gut microbiota. Also, nutritional interventions with blueberries have demonstrated the ability to improve recovery following exercise-induced muscle damage, attributable to anti-inflammatory effects. Despite these advancements in blueberry health research, research gaps persist which affects the generalizability of findings from clinical trials. To evaluate the current state of knowledge and research gaps, a blueberry health roundtable with scientific experts convened in Washington, DC (December 6-7, 2022). Discussions centered around five research domains: cardiovascular health, pre-diabetes and diabetes, brain health and cognitive function, gut health, and exercise recovery. This article synthesizes the outcomes of a blueberry research roundtable discussion among researchers in these domains, offering insights into the health benefits of blueberries and delineating research gaps and future research directions.

Relationship between serum ß-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation that can progress to inflammation (nonalcoholic steatohepatitis, NASH), and fibrosis. Serum ß-hydroxybutyrate (ß-HB), a product of the ketogenic pathway, is commonly used as a surrogate marker for hepatic fatty acid oxidation (FAO). However, it remains uncertain whether this relationship holds true in the context of NAFLD in humans. We compared fasting serum ß-HB levels with direct measurement of liver mitochondrial palmitate oxidation in humans stratified based on NAFLD severity (n = 142). Patients were stratified based on NAFLD activity score (NAS): NAS = 0 (no disease), NAS = 1-2 (mild), NAS = 3-4 (moderate), and NAS ≥ 5 (advanced). Moderate and advanced NAFLD is associated with reductions in liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), serum ß-HB, but not 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) mRNA, relative to no disease. Worsening liver mitochondrial complete palmitate oxidation corresponded with lower HMGCS2 mRNA but not total (complete + incomplete) palmitate oxidation. Interestingly, we found that liver HMGCS2 mRNA and serum ß-HB correlated with liver mitochondrial ß-hydroxyacyl-CoA dehydrogenase (ß-HAD) activity and CPT1A mRNA. Also, lower mitochondrial mass and markers of mitochondrial turnover positively correlated with lower HMGCS2 in the liver. These data suggest that liver ketogenesis and FAO occur at comparable rates in individuals with NAFLD. Our findings support the utility of serum ß-HB to serve as a marker of liver injury and hepatic FAO in the context of NAFLD.NEW & NOTEWORTHY Serum ß-hydroxybutyrate (ß-HB) is frequently utilized as a surrogate marker for hepatic fatty acid oxidation; however, few studies have investigated this relationship during states of liver disease. We found that the progression of nonalcoholic fatty liver disease (NAFLD) is associated with reductions in circulating ß-HB and liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). As well, decreased rates of hepatic fatty acid oxidation correlated with liver HMGCS2 mRNA and serum ß-HB. Our work supports serum ß-HB as a potential marker for hepatic fatty acid oxidation and liver injury during NAFLD.

Protective effects of blueberries on vascular function: A narrative review of preclinical and clinical evidence.

Blueberries are rich in nutrients and (poly)phenols, popular with consumers, and a major agricultural crop with year-round availability supporting their use in food-based strategies to promote human health. Accumulating evidence indicates blueberry consumption has protective effects on cardiovascular health including vascular dysfunction (i.e., endothelial dysfunction and arterial stiffening). This narrative review synthesizes evidence on blueberries and vascular function and provides insight into underlying mechanisms with a focus on oxidative stress, inflammation, and gut microbiota. Evidence from animal studies supports beneficial impacts on vascular function. Human studies indicate acute and chronic blueberry consumption can improve endothelial function in healthy and at-risk populations and may modulate arterial stiffness, but that evidence is less certain. Results from cell, animal, and human studies suggest blueberry consumption improves vascular function through improving nitric oxide bioavailability, oxidative stress, and inflammation. Limited data in animals suggest the gut microbiome mediates beneficial effects of blueberries on vascular function; however, there is a paucity of studies evaluating the gut microbiome in humans. Translational evidence indicates anthocyanin metabolites mediate effects of blueberries on endothelial function, though this does not exclude potential synergistic and/or additive effects of other blueberry components. Further research is needed to establish the clinical efficacy of blueberries to improve vascular function in diverse human populations in a manner that provides mechanistic information. Translation of clinical research to the community/public should consider feasibility, social determinants of health, culture, community needs, assets, and desires, barriers, and drivers to consumption, among other factors to establish real-world impacts of blueberry consumption.

Saturated Fat Intake and the Prevention and Management of Cardiovascular Disease in Adults: An Academy of Nutrition and Dietetics Evidence-Based Nutrition Practice Guideline.

Cardiovascular disease (CVD) is the leading cause of death in the United States and globally and is largely attributable to atherosclerosis. Evidence indicates that multiple dietary components contribute to the complex causes of CVD and associated events and mortality. Public health authorities and scientific organizations have recommended reduced saturated fatty acid (SFA) intake for decades to promote cardiovascular health, which is linked to favorable impacts on established and emerging atherosclerotic CVD risk factors. Recently, a debate has emerged about whether SFA intake should be reduced for CVD prevention, which has contributed to confusion among health care professionals, including registered dietitian nutritionists (RDNs), and the general public, and necessitates the critical evaluation of the evidence. The objective of this evidence-based nutrition practice guideline is to provide health care and public health professionals, particularly RDNs, with evidence-based recommendations on how to address SFA intake in adults within an individualized healthy dietary pattern. Moderate evidence supports the reduction of SFA intake for CVD event reduction, low- to moderate-certainty evidence supports prioritization of replacement of SFAs with polyunsaturated fatty acids, and low-certainty evidence supports focusing on reducing the total amount of SFA rather than specific food sources of SFA. Guideline implementation should include consideration of individual preferences; principles of inclusion, diversity, equity, and access; and potential nutritional deficiencies that may occur with reduced SFA intake. Future research is needed to address gaps that were identified and provide high-quality evidence to support stronger future recommendations based on the relationship between SFA and CVD.

Cabergoline for Lactation Inhibition After Second-Trimester Abortion or Pregnancy Loss: A Randomized Controlled Trial.

OBJECTIVE: To assess cabergoline's efficacy at decreasing breast symptoms after second-trimester abortion or pregnancy loss. METHODS: This was a double-blinded, block-randomized superiority trial comparing cabergoline 1 mg once to placebo for preventing bothersome breast engorgement after second-trimester uterine evacuation. We enrolled pregnant people at 18-28 weeks of gestation who were English- or Spanish-speaking and without contraindication to the study drug. Participants completed a validated, piloted, electronic survey at baseline and at multiple timepoints through 2 weeks postprocedure to assess breast symptoms, side effects, and bother. Our primary outcome was any breast symptoms (a composite of engorgement, milk leakage, tenderness, and need for pain relief) on day 4; we planned to enroll 80 patients to show a 30% difference in breast symptoms (80% power, α=0.049). A subgroup of participants returned for serum prolactin levels. RESULTS: After screening 150 patients from April 2021 to June 2022, we enrolled 73 participants. Baseline demographics were balanced between groups: median gestational age was 21 weeks (range 18-26 weeks), 56.2% of participants were nulliparous, 34.2% self-identified as Hispanic, and 37.0% had public insurance. At baseline, reported breast symptoms were similar between groups. Among 69 participants who returned surveys on day 4, significantly fewer participants receiving cabergoline reported any breast symptoms compared with placebo (27.8% vs 97.0%, P<.001) (primary outcome) and fewer reported significant bother (2.8% vs 33.3%, P=.001) (secondary outcome). These differences persisted through day 14. Reported incidence and severity of bother from side effects were similar between groups: most common were constipation, fatigue, and headache. Serum prolactin levels were similar at baseline. On day 4, mean serum prolactin level was 6.5 ng/mL (SD 2.2) for those who received cabergoline and 18.0 ng/mL (SD 5.9) for placebo (P=.049). CONCLUSION: Cabergoline is an effective and well-tolerated strategy to prevent breast symptoms after second-trimester abortion or pregnancy loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04701333.

Daily mindfulness, negative affect, and eating behaviors in adolescents at risk for excess weight gain.

OBJECTIVE: Loss-of-control and overeating are common in adolescents with high body mass index (BMI). Mindfulness may affect negative affect, and both may relate to loss-of-control and overeating. Yet, there is limited understanding of these associations in adolescents' daily lives. METHODS: Forty-five adolescents (77% female; Mage = 14.4 years, SDage = 1.7 years) with high weight (92% with BMI [kg/m2 ] ≥85th percentile for age/sex) provided daily, repeated measurements of mindfulness, negative affect, loss-of-control, and overeating for ~7 days (M = 5.6 days; range = 1-13). Multilevel mixed modeling was conducted to test within-person (intraindividual) and between-person (interindividual) associations for the same-day (concurrent) and next-day (time-ordered/prospective). RESULTS: There were within-person and between-person associations of higher mindfulness with lower negative affect on the same-day and next-day. Greater between-person mindfulness related to lower odds of adolescents' loss-of-control occurrence (same-day) and conversely, more perceived control over eating (same-day and next-day). Greater within-person mindfulness related to less odds of next-day overeating. DISCUSSION: Dynamic relations exist among mindfulness, negative affect, and eating in adolescents at-risk for excess weight gain. Mindfulness may be an important element to consider in loss-of-control and overeating. Future work using momentary-data within an experimental design would help disentangle the intraindividual effects of increasing mindfulness/decreasing negative affect on disordered eating. PUBLIC SIGNIFICANCE: Loss-of-control and overeating are common in teenagers with high weight. Greater mindfulness-present-moment, non-judgmental attention-and less negative emotions may relate to healthier eating, but we do not know how these processes play out in teenagers' daily lives. Addressing this knowledge gap, the current findings showed that greater daily mindfulness, but not negative affect, related to less loss-of-control/overeating, suggesting the importance of mindfulness for eating patterns in teenagers' daily lives.

Daily blueberry consumption for 12 weeks improves endothelial function in postmenopausal women with above-normal blood pressure through reductions in oxidative stress: a randomized controlled trial.

Estrogen-deficient postmenopausal women have oxidative stress-mediated suppression of endothelial function that is exacerbated by high blood pressure. Previous research suggests blueberries may improve endothelial function through reductions in oxidative stress, while also exerting other cardiovascular benefits. The objective of this study was to examine the efficacy of blueberries to improve endothelial function and blood pressure in postmenopausal women with above-normal blood pressure, and to identify potential mechanisms for improvements in endothelial function. A randomized, double-blind, placebo-controlled, parallel-arm clinical trial was performed, where postmenopausal women aged 45-65 years with elevated blood pressure or stage 1-hypertension (total n = 43, endothelial function n = 32) consumed 22 g day-1 of freeze-dried highbush blueberry powder or placebo powder for 12 weeks. Endothelial function was assessed at baseline and 12 weeks through ultrasound measurement of brachial artery flow-mediated dilation (FMD) normalized to shear rate area under the curve (FMD/SRAUC) before and after intravenous infusion of a supraphysiologic dose of ascorbic acid to evaluate whether FMD improvements were mediated by reduced oxidative stress. Hemodynamics, arterial stiffness, cardiometabolic blood biomarkers, and plasma (poly)phenol metabolites were assessed at baseline and 4, 8, and 12 weeks, and venous endothelial cell protein expression was assessed at baseline and 12 weeks. Absolute FMD/SRAUC was 96% higher following blueberry consumption compared to baseline (p < 0.05) but unchanged in the placebo group (p > 0.05), and changes from baseline to 12 weeks were greater in the blueberry group than placebo (+1.09 × 10-4 ± 4.12 × 10-5vs. +3.82 × 10-6 ± 1.59 × 10-5, p < 0.03, respectively). The FMD/SRAUC response to ascorbic acid infusion was lower (p < 0.05) at 12 weeks compared to baseline in the blueberry group with no change in the placebo group (p > 0.05). The sum of plasma (poly)phenol metabolites increased at 4, 8, and 12 weeks in the blueberry group compared to baseline, and were higher than the placebo group (all p < 0.05). Increases in several plasma flavonoid and microbial metabolites were also noted. No major differences were found for blood pressure, arterial stiffness, blood biomarkers, or endothelial cell protein expression following blueberry consumption. These findings suggest daily consumption of freeze-dried blueberry powder for 12 weeks improves endothelial function through reduced oxidative stress in postmenopausal women with above-normal blood pressure. The clinical trial registry number is NCT03370991 (https://clinicaltrials.gov).

Ribosomal DNA replication time coordinates completion of genome replication and anaphase in yeast.

Timely completion of genome replication is a prerequisite for mitosis, genome integrity, and cell survival. A challenge to this timely completion comes from the need to replicate the hundreds of untranscribed copies of rDNA that organisms maintain in addition to the copies required for ribosome biogenesis. Replication of these rDNA arrays is relegated to late S phase despite their large size, repetitive nature, and essentiality. Here, we show that, in Saccharomyces cerevisiae, reducing the number of rDNA repeats leads to early rDNA replication, which results in delaying replication elsewhere in the genome. Moreover, cells with early-replicating rDNA arrays and delayed genome-wide replication aberrantly release the mitotic phosphatase Cdc14 from the nucleolus and enter anaphase prematurely. We propose that rDNA copy number determines the replication time of the rDNA locus and that the release of Cdc14 upon completion of rDNA replication is a signal for cell cycle progression.

Positive impact of postfire environment on bumble bees not explained by habitat variables in a remote forested ecosystem.

Bumble bees are important pollinators in temperate forested regions where fire is a driving force for habitat change, and thus understanding how these insects respond to fire is critical. Previous work has shown bees are often positively affected by the postfire environment, with burned sites supporting greater bee abundance and diversity, and increased floral resources. The extent to which fire impacts variation in bumblebee site occupancy is not well-understood, especially in higher latitude regions with dense, primarily coniferous forests. Occupancy models are powerful tools for biodiversity analyses, as they separately estimate occupancy probability (likelihood that a species is present at a particular location) and detection probability (likelihood of observing a species when it is present). Using these models, we tested whether bumblebee site occupancy is higher in burned locations as a result of the increase in canopy openness, floral species richness, and floral abundance. We quantified the impact of fire, and associated habitat changes, on bumblebee species' occupancy in an area with high wildfire frequency in British Columbia, Canada. The burn status of a site was the only significant predictor for determining bumblebee occurrence (with burned sites having higher occupancy); floral resource availability and canopy openness only impacted detection probability (roughly, sample bias). These findings highlight the importance of controlling for the influence of habitat on species detection in pollinator studies and suggest that fire in this system changes the habitat for bumble bees in positive ways that extend beyond our measurements of differences in floral resources and canopy cover.

Observations of parent-adolescent interactions relate to food parenting practices and adolescent disordered eating in adolescents at risk for adult obesity.

Adolescent disordered eating and obesity are interrelated and adversely relate to mental and metabolic health. Parental feeding practices have been associated with adolescent disordered eating and obesity. Yet, observable interactions related to food parenting have not been well characterized. To address this gap, N = 30 adolescents (M ± SD 14 ± 2 year) at risk for adult obesity due to above-average body mass index (BMI ≥70th percentile) or parental obesity (BMI ≥30 kg/m2 ) participated in a video-recorded parent-adolescent task to discuss a food/eating-related disagreement. Interactions were coded for individual/dyadic affect/content using the Interactional Dimensions Coding System. We examined associations of interaction qualities with parent-reported food practices, adolescent disordered eating behaviors/attitudes, and insulin resistance. Reported parenting practices were correlated with multiple interaction qualities (p-values <0.05), with the most consistent correspondence between parent-reported pressure to eat (e.g., pressure to eat more healthy foods) and negative aspects of parent-adolescent interactions. Also, after accounting for adolescent age, sex, and BMI-standard score, parent-adolescent interaction qualities were associated with adolescents' disordered eating and insulin resistance. Specifically, greater adolescent problem-solving related to less adolescent global disordered eating, shape, and weight concern (p-values <0.05); adolescent autonomy related to less weight concern (p = 0.03). Better parent communication skills were associated with less adolescent eating concern (p = 0.04), and observed dyadic mutuality related to adolescents' lower insulin resistance (p = 0.03). Parent-adolescent interaction qualities during food/eating-related disagreements show associations with parent-reported food practices and adolescent disordered eating. This method may offer a tool for measuring the qualities of parent-adolescent food/eating-related interactions. A nuanced understanding of conversations about food/eating may inform family-based intervention in youth at-risk for adult obesity.

Physicochemical Characterization of Interactions between Blueberry Polyphenols and Food Proteins from Dairy and Plant Sources.

Polyphenols are widely known for their benefits to human health; however, dietary intake of this class of compounds is low in the United States due to low intake of fruits and vegetables. Dairy foods (i.e., milk, yogurt) have been shown to increase polyphenol bioavailability via protein-polyphenol interactions, which may have important implications for human health. Increasing consumer interest in sustainability and health has led to the introduction of a variety of novel plant-based proteins and related food products as dairy alternatives. This study compared whey, a popular dairy-based food protein, to pea and hemp proteins for their abilities to form complexes with polyphenols from blueberries, which are a widely consumed fruit in the US with demonstrated health effects. Physical and chemical characteristics of each protein extract in the presence and absence of blueberry polyphenols were investigated using a variety of spectroscopic methods. The influence of polyphenol complexation on protein digestion was also assessed in vitro. While all proteins formed complexes with blueberry polyphenols, the hemp and pea proteins demonstrated greater polyphenol binding affinities than whey, which may be due to observed differences in protein secondary structure. Polyphenol addition did not affect the digestion of any protein studied. Solution pH appeared to play a role in protein-polyphenol complex formation, which suggests that the effects observed in this model food system may differ from food systems designed to mimic other food products, such as plant-based yogurts. This study provides a foundation for exploring the effects of plant-based proteins on phytochemical functionality in complex, "whole food" matrices, and supports the development of plant-based dairy analogs aimed at increasing polyphenol stability and bioavailability.

Mental health and health behaviors among college student mentors in a randomized controlled trial interrupted by COVID-19.

Objective: The benefits of mindfulness-training and mentoring for college students have yet to be investigated. We aimed to provide an exploratory and descriptive account of their potential benefits during the COVID-19 pandemic. Participants: In February 2020, 49 undergraduates (M = 20.51 years-old; 94% female) participated in a randomized trial of 12-week mentoring + mindfulness or mentoring-as-usual. After five weekly mentoring-sessions, programs were interrupted by COVID-19; mentoring continued online. Methods: Undergraduates completed questionnaires about mental health, behaviors, and regulatory processes in February and July 2020, with additional COVID-19-related questions at follow-up. Results: Participants reported moderate COVID-19-related perceived stress, but mental health, health behaviors, and regulatory processes did not diminish over time, with no condition differences. Undergraduates described using contemplative practices and social support to cope with COVID-19-stress. Conclusions: Undergraduates showed stable mental health/health behaviors despite moderate COVID-19-related-stress. Future research on mentoring with a mindfulness component among a larger and more heterogeneous sample will be necessary.

Climate change winners and losers among North American bumblebees.

Mounting evidence suggests that climate change, agricultural intensification and disease are impacting bumblebee health and contributing to species' declines. Identifying how these factors impact insect communities at large spatial and temporal scales is difficult, partly because species may respond in different ways. Further, the necessary data must span large spatial and temporal scales, which usually means they comprise aggregated, presence-only records collected using numerous methods (e.g. diversity surveys, educational collections, citizen-science projects, standardized ecological surveys). Here, we use occupancy models, which explicitly correct for biases in the species observation process, to quantify the effect of changes in temperature, precipitation and floral resources on bumblebee site occupancy over the past 12 decades in North America. We find no evidence of genus-wide declines in site occupancy, but do find that occupancy is strongly related to temperature, and is only weakly related to precipitation or floral resources. We also find that more species are likely to be climate change 'losers' than 'winners' and that this effect is primarily associated with changing temperature. Importantly, all trends were highly species-specific, highlighting that genus or community-wide measures may not reflect diverse species-specific patterns that are critical in guiding allocation of conservation resources.

Incidence of Expired Blood Product Use in the US Central Command Theater of Operations.

OBJECTIVE: Introduction: During multi-domain combat operations, logistical constraints may compel forward medical personnel to decide whether to use expired blood products. The incidence of expired blood product usage in recent conflicts is unknown. METHODS: We queried the Armed Services Blood Program (ASBP) database of all blood administered in theater from 2002-2019. We categorized any administration of blood product with a transfusion date of 1-30 days after the expiration date for this analysis. We excluded any documented transfusions more than 30 days after the expiration date as likely represents clerical error based on study team experience. RESULTS: There were 1,491 (0.4% of the total transfusion dataset) units that met inclusion for this analysis. Of the 1,491, 86% (n=1,278 transfusions) will occur within 1-3 days post-expiration. These 1,491 units were transfused into 741 patients. The majority of expired blood product recipients were male (87%). Afghans were most frequent (46%), followed by US forces (22%) with most occurring during Operation Enduring Freedom (64%). Trauma was the most common mechanism of injury for these patients (70%). The most common blood type transfused to recipients was O positive (28%). The most frequently transfused expired unit was red blood cells (n=899), followed by platelets (n=299), followed by whole blood (n=152). CONCLUSIONS: Expired red blood cell and platelet use suggests a need for better methods for extending the lifespan of whole blood and further development of longer stability cold-stored platelets to meet the needs of our end-users. Our data arises from mature theaters during counterinsurgency operations. The incidence of transfusion of expired blood products may increase in future multi-domain operations where medical personnel are likely to operate under more resource constrained settings.

A Scoping Review of Promising Alternative Blood Products for Prolonged Field Care.

Hemorrhage is the leading cause of potentially preventable death on the battlefield. Blood transfusions are used as treatment to restore circulating volume until the hemorrhage can be surgically controlled. Research has shown earlier transfusion of blood products has better casualty outcomes, so blood products have been pushed forward to the point of injury. Currently, there is a mixed use of blood components and whole blood in the prehospital setting-both of which have challenging supply chain requirements. Alternative blood products offer several potential advantages, as they are easier to mass produce, obviating the need for donor recruitment. They also have improved shelf-life stability, potentially remove cold-chain storage, and even cross-matching requirements. In this limited review, we sought to provide a narrative review of current promising developments including hemoglobin-based oxygen carriers, polyhemoglobin, platelet like cells, dried plasma, liquid plasma, fibrinogen concentrates, enzyme concentrates, nanoparticles, and perfluorocarbon-based artificial oxygen carriers.

Injuries and Interventions on Transported Military Working Dogs Within the US Central Command.

BACKGROUND: Limited veterinary care is available in the far forward environment, leading to human medical personnel being responsible, in part, for treatment of military working dogs (MWD). Though guidelines for MWD care exist, there is little research on the care and treatment of MWDs by human medical personnel. There is a lot of research on the care and treatment of MWDs. METHODS: This is a secondary analysis of a dataset from the Transportation Command (TRANSCOM) Regulating Command & Control and Evacuation System (TRAC2ES) database within the US Central Command (CENTCOM) from 2008 to 2018. Within this dataset specific to regulated transport from locations within CENTCOM, we abstracted all entries involving MWDs and analyzed causes of injury, type of injury, and interventions performed on traumatically and non-traumatically injured MWDs. RESULTS: Within our dataset, there were 84 MWD cases for analysis. Of those, 36 (43%) were transported for traumatic injuries, and the remaining 48 (57%) were transported for other medical ailments. The most common cause of trauma was gunshot wound (31%), followed by explosion (22%). The majority of trauma MWDs had injuries to the extremities (67%), and hemorrhage requiring intervention occurred in 25%. The most common interventions performed on traumas were analgesia (67%), antibiotics (31%), IV fluids (28%), and surgery (31%). The most common indications that occurred in MWDs treated for nontraumatic medical indications were gastrointestinal diseases (33%), followed by nontraumatic orthopedic injuries (21%). CONCLUSIONS: Of the MWDs in our dataset, most were transported for nontraumatic medical events. The most frequent intervention performed was medication administration for both traumatic and medical ailments. Our dataset adds to the limited body of MWD data from theater.