Effects of Supplementation with Microalgae Extract from Phaeodactylum tricornutum (Mi136) to Support Benefits from a Weight Management Intervention in Overweight Women.

BACKGROUND: Microalgae like Phaeodactylum tricornutum (PT) contain the carotenoid, fucoxanthin, which has been purported to promote fat loss, lower blood lipids, and improve glucose management. This study examined whether dietary supplementation with microalgae extracts from PT containing 4.4 mg/d of fucoxanthin affects changes in body composition or health markers in overweight women during an exercise and diet intervention. MATERIALS AND METHODS: A total of 37 females (28.6 ± 7.9 years, 80.2 ± 14.9 kg, 29.6 ± 3.8 kg/m², 41.4 ± 4.2% fat) fasted for 12 h, donated a fasting blood sample, completed health and mood state inventories, and undertook body composition, health, and exercise assessments. In a counterbalanced, randomized, and double-blind manner, participants ingested a placebo (PL), or microalgae extract of Phaeodactylum tricornutum standardized to 4.4 mg of fucoxanthin (FX) for 12 weeks while participating in a supervised exercise program that included resistance-training and walking (3 days/week) with encouragement to accumulate 10,000 steps/day on remaining days of the week. The diet intervention involved reducing energy intake by about -300 kcal/d (i.e., ≈1400-1600 kcals/d, 55% carbohydrate, 30% fat, 15% protein) to promote a -500 kcal/d energy deficit with exercise. Follow-up testing was performed at 6 and 12 weeks. A general linear model (GLM) with repeated measures statistical analysis was used to analyze group responses and changes from baseline with 95% confidence intervals. RESULTS: Dietary supplementation with microalgae extract from PT containing fucoxanthin for 12 weeks did not promote additional weight loss or fat loss in overweight but otherwise healthy females initiating an exercise and diet intervention designed to promote modest weight loss. However, fucoxanthin supplementation preserved bone mass, increased bone density, and saw greater improvements in walking steps/day, resting heart rate, aerobic capacity, blood lipid profiles, adherence to diet goals, functional activity tolerance, and measures of quality of life. Consequently, there appears to be some benefit to supplementing microalgae extract from PT containing fucoxanthin during a diet and exercise program. Registered clinical trial #NCT04761406.

The Head, the Heart, and the Community: Piloting a Brief Home-Based Mindfulness Intervention for Couples With Low Income.

Although mindfulness is documented to reduce both individual and relationship stress and has the flexibility to be taught anywhere (e.g., at home, clinic setting, etc.), research examining mindfulness interventions among individuals with low income and economic marginalization (LIEM; APA, 2019), or persons whose economic position negatively impacts their health or well-being due to factors such as access to healthcare, is limited. To address this gap, the author and colleagues used Community Based Participatory Research methods to develop a brief, couple-based, mindfulness intervention tailored for communities with LIEM (see Lenger et al., 2022). The present study tested this newly developed brief, couple-based, mindfulness intervention's effectiveness in improving individual and relationship health through 1- and 2-months post-intervention. The intervention was piloted on a sample of 39 couples with an overrepresentation of couples with LIEM. To improve access to care, couples could participate in their home or a variety of local clinics. Thirty-nine couples received the intervention and completed assessments on mindfulness, depression, anxiety, stress, relationship satisfaction, and communication at baseline, 1-month, and 2-months post-intervention. Results revealed that mindfulness, depression, and relationship satisfaction improved from baseline to 1-month post-intervention. Mindfulness improved at a greater rate for couples with LIEM relative to couples with higher incomes. From baseline to 2-months post-intervention, depression and stress significantly improved at similar rates for couples with higher income and couples with LIEM. Thus, this study indicates that mindfulness can be taught in a brief, two-session format, and can have favorable outcomes on individual and relationship functioning.

Gut Microbiome in Patients With Early-Stage and Late-Stage Melanoma.

Importance: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression. Objective: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma. Design, Setting, and Participants: This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment-naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021. Main Outcomes and Measures: Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups. Results: A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy. Conclusions and Relevance: The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.

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.

Spinal cord stimulation for treatment of chronic neuropathic pain in adolescent patients: a single-institution series, systematic review, and individual participant data meta-analysis.

OBJECTIVE: Neuropathic pain is undertreated in children. Neurosurgical treatments of pediatric chronic pain are limited by the absence of both US Food and Drug Administration approval and pediatric-specific hardware, as well as weak referral patterns due to a lack of physician education. This study presents a single-institution retrospective case series of spinal cord stimulation (SCS) in children ≤ 19 years of age and a systematic review of SCS in children. The authors' findings may further validate the role of SCS as an effective treatment modality for varied neuropathic pain syndromes found in pediatric patients. METHODS: The study was a single-center, single-surgeon, retrospective case series of individuals treated between July 2017 and May 2022. The outcomes for pediatric patients with chronic neuropathic pain syndromes indicated by the multidisciplinary pain clinic for evaluation for SCS were cataloged. A systematic review and individual participant data (IPD) meta-analysis was performed for cases treated until May 2022, using PubMed, EMBASE, and Scopus to characterize outcomes of children with neuropathic pain treated with SCS. RESULTS: Twelve patients were evaluated and 9 were indicated for percutaneous or buried lead trials. Seven female and 2 male patients between the ages of 13 and 19 years were implanted with trial leads. Eight of 9 (89%) patients went on to receive permanent systems. The average trial length was 6 days, and the length of stay for both trial and implant was less than 1 day. Complication rates due to CSF leaks were 22% and 0% for trial and implant, respectively. Visual analog scale pain scores decreased from 9.2 to 2.9 (p = 0.0002) and the number of medications decreased from 4.9 to 2.1 (p = 0.0005). Functional status also improved for each patient. A systematic review identified 13 studies describing pediatric patients with SCS, including 12 providing IPD on 30 patients. In the IPD meta-analysis, pain was reduced in 16/16 (100%) of patients following surgery and in 25/26 (96.2%) at last follow-up. Medication use was decreased in 16/21 (76.2%), and functional outcomes were improved in 29/29 (100%). The complication rate was 5/30 (16.7%). CONCLUSIONS: SCS effectively decreases pain and medication use for pediatric neuropathic pain syndromes. Patients also report improved functional status, including improved matriculation, gainful employment, and physical activity. There is minimal high-quality literature describing neuromodulation for pain in children. Neuromodulation should be considered earlier as a viable alternative to escalating use of multiple drugs and as a potential mechanism to address tolerance, dependence, and addiction in pediatric patients.

The Role of Impulsivity and Stress Mind-Set in Understanding the Mindfulness-Intimate Partner Aggression Relationship.

Perpetration of relational aggression, which is estimated to occur in 60% to 90% of relationships, has been demonstrated to have lasting negative effects both systemically and for its victims. Relational aggression has also been demonstrated to be impacted, in part by impulsivity, stress mind-set, and mindfulness. The present study examined a path analysis model of the relation between mindfulness and relational aggression, utilizing impulsivity as the mediating variable. Furthermore, the present study incorporated an examination of the potential moderating effects of stress mind-set on the relation between impulsivity and relational aggression. Three hundred eighty-three participants were recruited from across the United States, using Facebook ads. Participants completed online questionnaires assessing key study variables. We hypothesized that the negative urgency aspect of impulsivity would mediate the relation between the five facets of mindfulness and relational aggression, and further that this relationship would be moderated by stress mind-set, such that a stress mind-set which conceptualizes stress as negative would make the relation between impulsivity and relational aggression stronger. We hypothesized that the negative urgency aspect of impulsivity would mediate the relation between mindfulness and relational aggression. Furthermore, we hypothesized that the relation between impulsivity and aggression would be moderated by stress mind-set. Results indicated that the negative urgency component of impulsivity mediated the relation between all five facets of mindfulness and perpetration of relational aggression. Furthermore, stress mind-set moderated the relation between negative urgency and relational aggression, such that a lower stress mind-set was related to a stronger association between negative urgency and aggression. Implications for clinical intervention and future research efforts are discussed.

Mindfulness-based intervention in adolescents at risk for excess weight gain: 1.5-year follow-up of pilot randomized controlled trial.

BACKGROUND: Mindfulness-based intervention (MBI) may offer a novel means of preventing excess weight gain in adolescents, theoretically by decreasing stress-eating through altering executive functioning (EF) and food-reward sensitivity. METHODS: N = 54 12-17y girls and boys at-risk for excess weight gain (i.e., BMI ≥70th percentile or two biological parents with reported obesity [BMI ≥30 kg/m2]) participated in a 1.5-year follow-up of a pilot randomized controlled trial comparing 6-week/6-session MBI (n = 29) and a health education (HE) control (n = 25). Laboratory stress-eating, food-reward sensitivity, EF, perceived stress, and BMI/adiposity were re-assessed at 1.5-years with validated measures. Changes from baseline to 1.5-year follow-up were explored with ANCOVA, accounting for the respective baseline outcome, age, and sex. RESULTS: Compared to MBI (M = -21, SE = 59), HE had greater increases in stress-eating from baseline to 1.5-years (M = 194, SE = 63, Cohen's d = 0.59, p = .01). There were no other between-condition differences. DISCUSSION: MBI may prevent worsening stress-eating for adolescents at-risk for excess weight gain. The potential for MBI as an intervention for stress-eating and ultimately, weight stabilization warrants testing in an adequately-powered trial.

Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.

Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m-2; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.

Health effects of COVID-19 for vulnerable adolescents in a randomized controlled trial.

Emerging evidence suggests the coronavirus disease 2019 (COVID-19) pandemic is adversely affecting adolescents' mental health and health behaviors, particularly among those with preexisting mental health conditions and from lower socioeconomic backgrounds. However, direct tests of changes in health outcomes among vulnerable adolescents from before to during COVID-19 are limited. In addition, little is known about how to buffer adolescents, particularly those who are most vulnerable, against stress-related decrements in health. This randomized controlled trial begins to fill these gaps in the literature by exploring changes in mental health, health behaviors, executive function, emotion regulation, and mindfulness among vulnerable adolescents involved in a mentoring program during the COVID-19 pandemic. It also examined to what extent there were protective benefits of incorporating mindfulness training within a mentoring program for buffering adolescents from negative pandemic health effects. Thirty-five adolescents (Mage = 12.9, 37% female) and 32 parents (Mage = 44.75, 80% female) completed questionnaires at baseline (February 2020) and follow-up (July 2020). There were few significant reductions in health; instead, on average, youth reported improvements in sleep, emotion regulation, executive function, and mindfulness over time. Adolescents randomized to mentoring + mindfulness displayed significantly less posttraumatic stress disorder (PTSD) symptomatology and emotional impulsivity at follow-up, compared to the mentoring-as-usual condition. These pilot findings suggest that mentoring with a mindfulness training component may offer an effective strategy for protecting adolescents from deteriorations in health outcomes during COVID-19. Further, there may be unique benefits of mindfulness training for vulnerable youth as a way to adapt to stressful events. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The role of mindfulness in associations among depression symptoms, sleep duration, and insulin resistance in adolescents.

Sleep difficulties may be one explanatory factor in the association between depression and insulin resistance; yet, explicit tests of this hypothesis are lacking. We determined if there was an indirect effect of depression symptoms on insulin resistance through sleep duration in adolescents at risk for excess weight gain. We also investigated whether dispositional mindfulness moderated the interconnections among depression, sleep, and insulin resistance. Ninety adolescents (14.2 ± 1.6y; 50% female) at risk for excess weight gain (body mass index [BMI, kg/m2] z score 1.6 ± 0.6) participated in the cross-sectional, baseline phase of a health behaviors study. Depression was assessed with the Center for Epidemiologic Studies-Depression Scale, sleep duration with the Sleep Habits Survey, and mindfulness with the Mindful Attention and Awareness Scale. Homeostatic model assessment of insulin resistance was determined from fasting insulin and glucose. The product-of-coefficients method was used to test the indirect effect of depression on insulin resistance through sleep duration, accounting for age, sex, BMIz, puberty, and socioeconomic status (SES). Dispositional mindfulness was tested as a moderator of the associations among depression, sleep, and insulin resistance. There was a significant indirect effect of depression on insulin resistance through sleep duration, controlling for age, sex, BMIz, puberty, and SES, 95%CI [0.001, 0.05]. Dispositional mindfulness moderated the association between sleep duration and insulin resistance, such that lower sleep duration related to greater insulin resistance only among adolescents with lower mindfulness (p < .001). Short sleep may be one explanatory factor in the depression-insulin resistance connection in adolescents at risk for excess weight gain. Adolescents with poorer mindfulness and short sleep are at highest risk for insulin resistance, whereas higher mindfulness may be protective.

Examining the Gastrointestinal and Immunomodulatory Effects of the Novel Probiotic Bacillus subtilis DE111.

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain-specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a pilot randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-intervention, as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an increase in anti-inflammatory immune cell populations in response to ex vivo LPS stimulation of PBMCs in the DE111 intervention group. Overall perceived gastrointestinal health, microbiota, and circulating and fecal markers of inflammation (Il-6, sIgA) and gut barrier function (plasma zonulin) were largely unaffected by DE111 intervention, although the study may have been underpowered to detect these differences. These pilot data provide information and justification to conduct an appropriately powered clinical study to further examine the immunomodulatory potential of B. subtilis DE111 in human populations.

Effects of a mindfulness-induction on subjective and physiological stress response in adolescents at-risk for adult obesity.

BACKGROUND: Mindfulness-training may benefit stress response and stress-eating, yet few studies have experimentally tested these effects in adolescents. In this short communication, we report whether a brief mindfulness-induction affected acute stress response and stress-eating in adolescents at-risk for adult obesity. We explored disordered eating as a moderator. METHOD: Twenty-nine adolescents (age 14 ± 2 y) at-risk for adult obesity participated in a within-subjects, randomized crossover experiment. Following a 10-minute mindfulness or neutral-induction on different days in random order, the Trier Social Stress Test adapted for adolescents was administered, followed by an ad libitum lunch meal. Physiological stress response (heart rate, blood pressure) and subjective stress response (anxiety, mindlessness) were determined with area under the curve with respect to increase. Stress-eating was measured as test meal energy consumed. Global disordered-eating and binge-eating were assessed with the Eating Disorders Examination-Questionnaire. RESULTS: Relative to a neutral-induction, a mindfulness-induction reduced state anxiety response (p = .04). There were significant interactions of induction-type by global disordered-eating (p = .02) and binge-eating (p = .03), such that the mindfulness-induction most reduced anxiety response in adolescents with relatively lower global disordered-eating and those with no binge-eating. Induction-type also interacted with binge-eating in predicting diastolic blood pressure (p = .03). A mindfulness-induction, versus neutral-induction, most reduced diastolic blood pressure response in adolescents with binge-eating. CONCLUSIONS: Brief mindfulness-training may alter some aspects of acute stress response, with variations by disordered-eating. Future research should test alternative mindfulness induction-types (e.g., acceptance/self-compassion) to improve our understanding of how mindfulness-training may benefit adolescents at-risk for adult obesity.

Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties.

Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans.

PHAGE-2 Study: Supplemental Bacteriophages Extend Bifidobacterium animalis subsp. lactis BL04 Benefits on Gut Health and Microbiota in Healthy Adults.

Probiotics are increasingly used by consumers and practitioners to reduce gastrointestinal (GI) distress and improve gut function. Here, we sought to determine whether the addition of supplemental bacteriophages (PreforPro) could enhance the effects of a common probiotic, Bifidobacterium animalis subsp. lactis (B. lactis) on GI health. A total of 68 participants were enrolled in a 4-week, randomized, parallel-arm, double-blind, placebo-controlled trial where primary outcomes included self-assessments of GI health, a daily stool log, and 16s rRNA analysis of gut microbial populations. We observed within-group improvements in GI inflammation (p = 0.01) and a trending improvement in colon pain (p = 0.08) in individuals consuming B. lactis with PreforPro, but not in the group consuming only the probiotic. There was also a larger increase in Lactobacillus and short-chain fatty acid-producing microbial taxa detected in the stool of participants taking PreforPro with B. lactis compared to the probiotic alone. Overall, these results suggest the addition of PreforPro as a combination therapy may alter gut ecology to extend the GI benefits of consuming B. lactis or other probiotics.

Microbial metabolite indole-3-propionic acid supplementation does not protect mice from the cardiometabolic consequences of a Western diet.

Emerging evidence suggests that intestinal microbes regulate host physiology and cardiometabolic health, although the mechanism(s) by which they do so is unclear. Indoles are a group of compounds produced from bacterial metabolism of the amino acid tryptophan. In light of recent data suggesting broad physiological effects of indoles on host physiology, we examined whether indole-3-propionic acid (IPA) would protect mice from the cardiometabolic consequences of a Western diet. Male C57BL/6J mice were fed either a standard diet (SD) or Western diet (WD) for 5 mo and received normal autoclaved drinking water or water supplemented with IPA (0.1 mg/mL; SD + IPA and WD + IPA). WD feeding led to increased liver triglycerides and makers of inflammation, with no effect of IPA. At 5 mo, arterial stiffness was significantly higher in WD and WD + IPA compared with SD (WD: 485.7 ± 6.7 and WD + IPA: 492.8 ± 8.6 vs. SD: 436.9 ± 7.0 cm/s, P < 0.05) but not SD + IPA (SD + IPA: 468.1 ± 6.6 vs. WD groups, P > 0.05). Supplementation with IPA in the SD + IPA group significantly increased glucose AUC compared with SD mice (SD + IPA: 1,763.3 ± 92.0 vs. SD: 1,397.6 ± 64.0, P < 0.05), and no significant differences were observed among either the WD or WD + IPA groups (WD: 1,623.5 ± 77.3 and WD + IPA: 1,658.4 ± 88.4, P > 0.05). Gut microbiota changes were driven by WD feeding, whereas IPA supplementation drove differences in SD-fed mice. In conclusion, supplementation with IPA did not improve cardiometabolic outcomes in WD-fed mice and may have worsened some parameters in SD-fed mice, suggesting that IPA is not a critical signal mediating WD-induced cardiometabolic dysfunction downstream of the gut microbiota.NEW & NOTEWORTHY The gut microbiota has been shown to mediate host health. Emerging data implicate gut microbial metabolites of tryptophan metabolism as potential important mediators. We examined the effects of indole-3-propionic acid in Western diet-fed mice and found no beneficial cardiometabolic effects. Our data do not support the supposition that indole-3-propionic acid (IPA) mediates beneficial metabolic effects downstream of the gut microbiota and may be potentially deleterious in higher circulating levels.

Effects of Montmorency Tart Cherry Juice Consumption on Cardiometabolic Biomarkers in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Trial.

Greater than one-third of adults in the United States have metabolic syndrome (MetS), a cluster of risk factors highly associated with the development of cardiovascular diseases. Premature vascular dysfunction in MetS may lead to accelerated age-related atherogenesis and arterial stiffening, thereby increasing cardiovascular risk. Montmorency tart cherries (Prunus cerasus L.) are rich in bioactive compounds, such as anthocyanins, known to exert cardiovascular protective effects. Previous research suggests that tart cherry juice consumption may improve cardiovascular health. The objective of this study was to evaluate the effects of daily consumption of tart cherry juice on hemodynamics, arterial stiffness, and blood biomarkers of cardiovascular and metabolic health in men and women with MetS. In a randomized, single-blind, placebo-controlled, parallel-arm pilot clinical trial, 19 men and women 20 to 60 years of age with MetS consumed 240 mL of tart cherry juice (Tart Cherry; n = 5 males, 4 females) or an isocaloric placebo-control drink (Control; n = 5 males, 5 females) twice daily for 12 weeks. Arterial stiffness (pulse wave velocity), brachial and aortic blood pressures, wave reflection (augmentation index), and blood biomarkers of cardiovascular and metabolic health were assessed at baseline and 6 and 12 weeks. Oxidized low-density lipoprotein and soluble vascular cell adhesion molecule-1 were significantly lower (P = .047 and P = .036, respectively) in Tart Cherry than Control at 12 weeks, but were not significantly lower than baseline values. There was a trend for total cholesterol to be lower (P = .08) in Tart Cherry than Control at 12 weeks. No significant changes were observed in hemodynamics, arterial stiffness, or other blood biomarkers assessed. These results suggest that daily tart cherry consumption may attenuate processes involved in accelerated atherogenesis without affecting hemodynamics or arterial stiffness parameters in this population. The pilot nature of this study warrants interpreting these findings with caution, and future clinical trials with a larger sample size are needed to confirm these findings.

Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults.

Cannabidiol (CBD) is a dietary supplement with numerous purported health benefits and an expanding commercial market. Commercially available CBD preparations range from tinctures, oils, and powders, to foods and beverages. Despite widespread use, information regarding bioavailability of these formulations is limited. The purpose of this study was to test the bioavailability of two oral formulations of CBD in humans and explore their potential acute anti-inflammatory activity. We conducted a pilot randomized, parallel arm, double-blind study in 10 healthy adults to determine differences in pharmacokinetics of commercially available water and lipid-soluble CBD powders. Participants consumed a single 30 mg dose, which is within the range of typical commercial supplement doses, and blood samples were collected over 6 hr and analyzed for CBD concentrations. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and T = 90 min, cultured and stimulated with bacterial lipopolysaccharide (LPS) to induce an inflammatory response. Cell supernatants were assayed for IL-10 and TNF, markers of inflammation, using enzyme-linked immunosorbent assays. The water-soluble powder had Cmax = 2.82 ng/ml, Tmax = 90 min, and was approximately ×4.5 more bioavailable than the lipid-soluble form. TNF was decreased in LPS-stimulated PBMCs collected 90 min after CBD exposure relative to cells collected at baseline. This study provides pilot data for designing and powering future studies to establish the anti-inflammatory potential and bioavailability of a larger variety of commercial CBD products consumed by humans.

Mindfulness-based group intervention in adolescents at-risk for excess weight gain: A randomized controlled pilot study.

OBJECTIVES: To assess feasibility/acceptability of a mindfulness-based approach to excess weight prevention in adolescents at-risk for excess weight gain. To pilot test efficacy of a mindfulness-based intervention for improving food reward sensitivity, stress-eating, executive function (EF), and BMI/adiposity. METHODS: A pilot randomized controlled trial was conducted with 12-17y adolescents at-risk for excess weight gain based on above-average weight (body mass index [BMI]≥70%ile) or parental history of obesity (BMI≥30 kg/m2). Adolescents were randomized to a mindfulness-based (n = 29) or health education control group (n = 25) that met for six weekly one-hour sessions. Feasibility/acceptability were determined from attendance and acceptability survey ratings. At baseline, six-week and six-month follow-up, adolescents' perceived stress was measured with the Perceived Stress Scale, food reward sensitivity with a behavioral task, stress-eating during a laboratory test meal, and EF with the parent-reported Behavior Rating Inventory of Executive Function and NIH Toolbox. At the same intervals, BMI indices and body fat by air displacement plethysmography were assessed in a fasted state. RESULTS: Median session attendance was 6:6 sessions in both conditions; program acceptability ratings were above-average. Compared to health education, adolescents in mindfulness had lower food reward sensitivity at six-months (Cohen's d = 0.64, p = .01). There were no between-condition differences in BMI (mindfulness vs. health educationΔsix-months 95%CI 0.20, 1.52 kg/m2 vs. 0.21, 1.62 kg/m2) or adiposity (-3.64, -0.61% vs. -4.31, -1.04%) changes. CONCLUSIONS: A mindfulness-based group intervention is feasible/acceptable among adolescents at-risk for excess weight. In this pilot sample, mindfulness and health education were equivocal for BMI/adiposity outcomes. Future trials with a larger, adequately-powered sample and longer-term follow-up are necessary to test efficacy of a mindfulness-based intervention for food reward sensitivity, stress-eating, EF, and stabilizing growth trajectories in youth at-risk for adult obesity.

Low oxygen post conditioning prevents thalamic secondary neuronal loss caused by excitotoxicity after cortical stroke.

In the current study, we were interested in investigating whether Low oxygen post-conditioning (LOPC) was capable of limiting the severity of stroke-induced secondary neurodegeneration (SND). To investigate the effect of LOPC we exposed adult male C57/BL6 mice to photothrombotic occlusion (PTO) of the motor and somatosensory cortex. This is known to induce progressive neurodegeneration in the thalamus within two weeks of infarction. Two days after PTO induction mice were randomly assigned to one of four groups: (i) LOPC-15 day exposure group; (ii) a LOPC 15 day exposure followed by a 15 day exposure to normal atmosphere; (iii) normal atmosphere for 15 days and (iv) normal atmosphere for 30 days (n = 20/group). We observed that LOPC reduced the extent of neuronal loss, as indicated by assessment of both area of loss and NeuN+ cell counts, within the thalamus. Additionally, we identified that LOPC reduced microglial activity and decreased activity within the excitotoxic signalling pathway of the NMDAR axis. Together, these findings suggest that LOPC limits neuronal death caused by excitotoxicity in sites of secondary damage and promotes neuronal survival. In conclusion, this work supports the potential of utilising LOPC to intervene in the sub-acute phase post-stroke to restrict the severity of SND.