Grape/Blueberry Anthocyanins and Their Gut-Derived Metabolites Attenuate LPS/Nigericin-Induced Inflammasome Activation by Inhibiting ASC Speck Formation in THP-1 Monocytes.

Inflammasomes are multi-protein complexes, which are formed in response to tissue injury, infections, and metabolic stress. However, aberrant inflammasome activation has been linked to several inflammatory diseases. Anthocyanins have been reported to attenuate NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, but the influence of grape/blueberry anthocyanins and especially their gut-derived metabolites on NLRP3 inflammasome activation in human monocytes remains unclear. Therefore, human leukemic monocytes (THP-1 cells, Tohoku Hospital Pediatrics-1 cells) were preincubated with different concentrations of grape/blueberry anthocyanins, homovanillyl alcohol, or 2,4,6-trihydroxybenzaldehyde (THBA) before the NLRP3 inflammasome was activated by lipopolysaccharide and/or nigericin. Apoptosis-associated speck-like protein containing a CARD (ASC) speck formation, as well as ASC and NLRP3 protein expression, were determined using flow cytometry. Caspase-1 activity was measured in cultured cells, and pro-inflammatory cytokine secretion was determined using enzyme-linked immunosorbent assays. Anthocyanins and their metabolites had no effect on ASC or NLRP3 protein expression. However, THBA significantly inhibited ASC speck formation in primed and unprimed THP-1 monocytes, while caspase-1 activity was significantly declined by grape/blueberry anthocyanins. Furthermore, reduced inflammasome activation resulted in lower pro-inflammatory cytokine secretion. In conclusion, our results show for the first time that grape/blueberry anthocyanins and their gut-derived metabolites exert anti-inflammatory effects by attenuating NLRP3 inflammasome activation in THP-1 monocytes.

Association between disordered eating and clinical outcomes following a surgical or endoscopic bariatric procedure: A real-world exploratory study.

Problem: Disordered eating, such as binge, graze, and emotional eating, has been strongly linked to weight gain. Improved understanding of disordered eating by adults who elect bariatric weight loss procedures in a real-world setting is required. Purpose: To determine the association between the number and type of disordered eating patterns (DEPs), as described by healthcare professionals during routine care without standardized assessment, with clinical outcomes in adults who elected a bariatric weight loss procedure. Method: An observational cohort study recruited laparoscopic sleeve gastrectomy (LSG) and endoscopic sleeve gastroplasty (ESG) patients. DEPs documented in the medical record during routine care were observed and tested for association with events (symptoms, side-effects, or adverse events), micronutrient deficiencies, weight loss, and attrition. Data were observed up to 12-month post-procedure. Results: 215 LSG and 32 ESG patients were recruited. The mean number of DEPs was 6.4 (SD: 2.1) and 6.4 (SD: 2.1) in the LSG and ESG cohorts, respectively. Night eating was associated with a higher number of events (p < 0.008) in the LSG cohort, and non-hungry eating was associated with a higher number of events in the ESG cohort (p < 0.001). ESG patients who had a surgical or medical event by 6-months post-procedure had mean 1.78 (95%CI: 0.67, 2.89) more DEPs (p = 0.004). DEPs were not associated with weight loss, micronutrient deficiencies, nor attrition. Conclusion: The treating healthcare team believed the LSG and ESG patients experienced a wide variety and high frequency of DEPs requiring multidisciplinary support. Non-hungry eating and night eating were associated with poorer outcomes following an LSG or ESG. Trial registration: The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000332729).

Species-specific effects of production practices on genetic diversity in plant reintroduction programs.

Plant production practices can influence the genetic diversity of cultivated plant materials and, ultimately, their potential to adapt to a reintroduction site. A common step in the plant production process is the application of seed pretreatment to alleviate physiological seed dormancy and successfully germinate seeds. In production settings, the seeds that germinate more rapidly may be favored in order to fill plant quotas. In this study, we investigated how the application of cold-moist stratification treatments with different durations can lead to differences in the genetic diversity of the propagated plant materials. Specifically, we exposed seeds of three Viola species to two different cold stratification durations, and then we analyzed the genetic diversity of the resulting subpopulations through double-digestion restriction site-associated sequencing (ddRADseq). Our results show that, in two out of three species, utilizing a short stratification period will decrease the genetic diversity of neutral and expressed loci, likely due to the imposition of a genetic bottleneck and artificial selection. We conclude that, in some species, the use of minimal stratification practices in production may jeopardize the adaptive potential and long-term persistence of reintroduced populations and suggest that practitioners carefully consider the evolutionary implications of their production protocols. We highlight the need to consider the germination ecology of target species when selecting the length of dormancy-breaking pretreatments.

Reproductive strategies and their consequences for divergence, gene flow, and genetic diversity in three taxa of Clarkia.

Differences in reproductive strategies can have important implications for macro- and micro-evolutionary processes. We used a comparative approach through a population genetics lens to evaluate how three distinct reproductive strategies shape patterns of divergence among as well as gene flow and genetic diversity within three closely related taxa in the genus Clarkia. One taxon is a predominantly autonomous self-fertilizer and the other two taxa are predominantly outcrossing but vary in the primary pollinator they attract. In genotyping populations using genotyping-by-sequencing and comparing loci shared across taxa, our results suggest that differences in reproductive strategies in part promote evolutionary divergence among these closely related taxa. Contrary to expectations, we found that the selfing taxon had the highest levels of heterozygosity but a low rate of polymorphism. The high levels of fixed heterozygosity for a subset of loci suggests this pattern is driven by the presence of structural rearrangements in chromosomes common in other Clarkia taxa. In evaluating patterns within taxa, we found a complex interplay between reproductive strategy and geographic distribution. Differences in the mobility of primary pollinators did not translate to a difference in rates of genetic diversity and gene flow within taxa - a pattern likely due to one taxon having a patchier distribution and a less temporally and spatially reliable pollinator. Taken together, this work advances our understanding of the factors that shape gene flow and the distribution of genetic diversity within and among closely related taxa.

Impacts of Flowering Density on Pollen Dispersal and Gametic Diversity Are Scale Dependent.

AbstractPollen dispersal is a key evolutionary and ecological process, but the degree to which variation in the density of concurrently flowering conspecific plants (i.e., coflowering density) shapes pollination patterns remains understudied. We monitored coflowering density and corresponding pollination patterns of the insect-pollinated palm Oenocarpus bataua in northwestern Ecuador and found that the influence of coflowering density on these patterns was scale dependent: high neighborhood densities were associated with reductions in pollen dispersal distance and gametic diversity of progeny arrays, whereas we observed the opposite pattern at the landscape scale. In addition, neighborhood coflowering density also impacted forward pollen dispersal kernel parameters, suggesting that low neighborhood densities encourage pollen movement and may promote gene flow and genetic diversity. Our work reveals how coflowering density at different spatial scales influences pollen movement, which in turn informs our broader understanding of the mechanisms underlying patterns of genetic diversity and gene flow within populations of plants.

What is the efficacy of dietary, nutraceutical, and probiotic interventions for the management of gastroesophageal reflux disease symptoms? A systematic literature review and meta-analysis.

BACKGROUND: Treatments for Gastroesophageal Reflux Disease (GERD) symptoms include pharmaceutical, surgical, dietary, and lifestyle behaviors; however, dietary interventions lack evidence synthesis. RESEARCH QUESTION: What is the effect of dietary, probiotic, and nutraceutical interventions on GERD symptoms, with or without pharmaceutical therapy, in adults with a history of GERD or functional dyspepsia compared to no intervention, placebo, or usual care? METHOD: A systematic review and meta-analysis was performed according to PRISMA. The search strategy was implemented in MEDLINE, CINAHL, CENTRAL, and Embase on the 28th October 2020 and updated to 27th July 2021. Intervention studies were eligible if they evaluated the effect of a dietary, nutraceutical, or probiotic intervention on GERD symptoms in adults with a history of GERD or functional dyspepsia. The internal validity of studies was assessed using the Academy Quality Criteria Checklist; Review Manager software was used to perform meta-analysis; and certainty in the body of evidence was assessed using GRADE. RESULTS: 6,608 study records were retrieved from the search, with 21 studies (n = 24 highly heterogenous intervention groups) included (n = 10 restrictive dietary interventions; n = 3 non-restrictive dietary interventions; n = 8 nutraceutical interventions; and n = 3 probiotic interventions). GERD symptoms were clinically and statistically improved by a test-based elimination diet (n = 1 study), low nickel diet (n = 1 study), probiotic yoghurt (n = 1 study), psyllium husk (n = 1 study), prickly pear and olive leaf extract supplement (n = 1 study), and melatonin, amino acid and b-group vitamin supplement (n = 1 study) according to qualitative synthesis. Ginger-containing supplements could be meta-analyzed, and improved incidence of GERD symptom alleviation (n = 2 studies, OR: 7.50 [95%CI: 3.62-15.54], GRADE: high). No clinically and/or statistically significant effects were found for the remaining n = 16 highly heterogenous interventions. CONCLUSION: Evidence to guide the dietary management of GERD symptoms is limited in scope, quality, and feasibility. Based on the limited evidence available, dietary GERD management should be long-term, individualized, and consider both dietary restrictions and/or additions. PROSPERO ID: CRD42021224082.

Forest cover at landscape scales increases male and female gametic diversity of palm seedlings.

Genetic diversity shapes the evolutionary potential of plant populations. For outcrossing plants, genetic diversity is influenced by effective population size and by dispersal, first of paternal gametes through pollen, and then of paternal and maternal gametes through seeds. Forest loss often reduces genetic diversity, but the degree to which it differentially impacts the paternal and maternal contributions to genetic diversity and the spatial scale at which these impacts are most pronounced are poorly understood. To address these questions, we genotyped 504 seedlings of the animal-dispersed palm Oenocarpus bataua collected from 29 widely distributed sites across Ecuador and decomposed the contribution of paternal and maternal gametes to overall genetic diversity. The amount of forest cover at a landscape scale (>10 km radius) had an equally significant positive association with both male and female gametic diversity. In addition, there was a significant positive association between forest cover and effective population size. Stronger fine-scale spatial genetic structure for female versus male gametes was observed at sites with low forest cover, but this did not scale up to differences in male versus female gametic diversity. These findings show that reductions in forest cover at spatial scales much larger than those typically evaluated in ecological studies lead to significant, and equivalent, decreases of diversity in both male and female gametes, and that this association between landscape level forest loss and genetic diversity may be driven directly by reductions in effective population size of O. bataua, rather than by indirect disruptions to local dispersal processes.

Corrigendum: Music Therapy in the Psychosocial Treatment of Adult Cancer Patients: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fpsyg.2020.00651.].

Goats Follow Human Pointing Gestures in an Object Choice Task.

Dogs (Canis lupus familiaris) are extremely adept in interpreting human-given cues, such as the pointing gesture. However, the underlying mechanisms on how domestic non-companion species use these cues are not well understood. We investigated the use of human-given pointing gestures by goats (Capra hircus) in an object choice task, where an experimenter surreptitiously hid food in one of two buckets. Subjects first had to pass a pre-test where the experimenter indicated the location of the food to the subject by a proximal pointing gesture. Subjects that succeeded in the use of this gesture were transferred to the actual test. In these subsequent test trials, the experimenter indicated the location of the food to the subject by using three different pointing gestures: proximal pointing from a middle position (distance between target and index finger: 30 cm), crossed pointing from the middle position (distance between target and index finger: 40 cm), asymmetric pointing from the position of the non-baited bucket (distance between target and index finger: 90 cm). Goats succeeded in the pointing gestures that presented an element of proximity (proximal and crossed) compared to when the experimenter was further away from the rewarded location (asymmetric). This indicates that goats can generalize their use of the human pointing gesture but might rely on stimulus/local enhancement rather than referential information. In addition, goats did not improve their responses over time, indicating that no learning took place. The results provide a greater understanding of human-animal interactions and social-cognitive abilities of farm animals, which allows for the provision of enhanced management practices and welfare conditions.

Taking care of our future doctors: a service evaluation of a medical student mental health service.

BACKGROUND: Studies suggest medical students experience high levels of mental distress during training but are less likely, than other students, to access care due to stigma and concerns regarding career progression. In response, The School of Clinical Medicine, University of Cambridge supported the development of the 'Clinical Student Mental Health Service' to provide specialist input for this vulnerable group. This study evaluates the efficiency and effectiveness of this service. METHODS: Using mixed-methods, cross-sectional analysis of validated psychiatric rating scales and qualitative feedback, 89 responses were analysed from 143 clinical students referred, between 2015 and 2019. The care pathway included initial review by a psychiatrist, who triaged students to psychologists delivering therapies including: Cognitive Behavioural Therapy, Interpersonal Therapy, Eye Movement Desensitization Reprocessing Therapy or Cognitive Analytic Therapy. Efficiency was assessed by waiting times for psychiatry and psychology interventions, and number of sessions. Academic outcomes included school intermission and graduation. Clinical effectiveness was analysed by measuring global distress, depression, anxiety, functioning and suicidal risk. Pre/post intervention changes were captured using t-test and McNemar test with thematic analysis of qualitative feedback. RESULTS: Referral rates increased from 3.93% (22/560) in 2015 to 6.74% (45/668) in 2018. Median waiting times for initial psychiatric assessment and start of therapy was 26 and 33 days, respectively. All graduating students moved on to work as junior doctors. Levels of distress, (t = 7.73, p < 0.001, df = 31), depression (t = 7.26, p < 0.001, df = 34) anxiety (Z = - 4.63, p < 0.001) and suicide risk (Z = - 3.89, p < 0.001) were significantly reduced. Participant's functioning was significantly improved (p < 0.001, 99.5% CI 4.55 to 14.62). Feedback indicated high satisfaction with the rapid access and flexibility of the service and the team clinicians. CONCLUSIONS: A significant proportion of medical students attending the service scored highly on validated rating scales measuring emotional distress, suicidality and mental illness. Reassuringly they benefitted from timely specialist mental health input, showing improvements in mental well-being and improved functioning. The development and design of this service might serve as an exemplar for medical schools developing similar support for their students.

Music Therapy in the Psychosocial Treatment of Adult Cancer Patients: A Systematic Review and Meta-Analysis.

Introduction: Music therapy is used as an adjunct oncological treatment aiming at the improvement of psychological and physical well-being through music. A growing body of randomized and non-randomized controlled trials has been published and reviewed recently. However, a global, quantitative assessment of the effectiveness of music therapy in adult cancer care is missing. The present study thus aims to synthesize the evidence of music therapy in different oncological treatment phases. Methods: We conducted a pre-registered systematic review and meta-analysis (PROSPERO-ID: CRD42019133084) following standard guidelines. We searched electronic databases for studies on music therapy performed by a therapist with adult cancer patients. Results: The narrative synthesis included thirty studies showing that music therapy overall had positive effects on a broad range of outcomes, with techniques and effects varying in different phases. During curative treatment, results were most promising with regard to anxiety, depression, and pain medication intake, while in palliative settings, improvements with regard to quality of life, spiritual well-being, pain, and stress were reported. Twenty-one studies were included in the meta-analysis which showed small but significant effects of music therapy on psychological well-being (d = 0.35, p < 0.001), physical symptom distress (d = -0.26, p = 0.017), and quality of life (d = 0.36, p = 0.023). Heterogeneity between effect sizes was small to medium. Moderator analyses identified studies with a single session of music therapy and the use of receptive techniques to produce larger effects regarding psychological well-being. Conclusion: Music therapy can improve relevant health-outcomes in cancer patients and should therefore be offered in various treatment phases. Future research should include potential moderators such as individual information about patients to find out who benefits most from different kinds of music therapy.

Common mental disorder including psychotic experiences: Trailblazing a new recovery pathway within the Improving Access to Psychological Therapies programme in England.

Psychotic experiences, depressive and anxiety symptoms may be manifestations of a latent continuum of common mental distress. The Improving Access to Psychological Therapies (IAPT) programme has increased the reach of psychological treatments to people with common mental disorders in England. However, psychotic experiences are neither measured nor considered in therapy. We aimed to confirm the presence of psychotic experiences among IAPT service-users and determine whether these experiences are associated with higher depression/anxiety levels and poorer recovery. All service-users that attended the Fenland and Peterborough IAPT teams in Cambridgeshire between November 16, 2015 and January 29, 2016 participated in a service evaluation. In addition to routine mesures, such as the Generalized Anxiety Disorder-7 questionnaire (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9), we introduced a shortened version of the Community Assessment of Psychic Experiences (CAPE-P15) to measure psychotic experiences. Classes of individuals were identified with latent class analysis. Associations were reported using Pearson correlation coefficient. One hundred and seventy-three services-users were included, mostly females (N = 133; 76.9%). The mean age was 36.6 (SD = 13.3). Around 30% likely belonged to a class with psychotic experiences. CAPE-P15 frequency was significantly correlated to PHQ-9 (r = 0.44; P < .001) and GAD-7 (r = 0.32; P < .001). Similarly, CAPE-P15 distress and both PHQ-9 (r = 0.43; P < .001) and GAD-7 (r = 0.38; P < .001) were highly correlated. These associations were replicated after the initial period of the therapy, indicating poor recovery. Some IAPT service-users suffer psychotic experiences. Tailoring available evidence-based psychological therapies for these people in IAPT settings might trailblaze a new care pathway to improve recovery in this group.