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A randomized trial of probiotic supplementation in nurses to reduce stress and viral illness.
Slykerman, RF, Li, E
Scientific reports. 2022;12(1):14742
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Dynamic communication occurs between the gut microbiota and the central nervous system along multiple physiological pathways. Stress increases glucocorticoid production and activation of the hypothalamic–pituitary–adrenal axis, affecting immunological function and neuronal changes. The aim of this study was to investigate whether supplementation with the probiotic Lactobacillus rhamnosus HN001 could reduce symptoms of stress and anxiety and improve psychological wellbeing in nurses working during the COVID19 pandemic. This study was a large double-blind, placebo-controlled randomised trial of probiotic supplementation with two parallel arms and a ratio of allocation to probiotic or placebo of 1:1. Results showed that following the intervention, stress, anxiety, and psychological wellbeing were not significantly different between nurses supplemented with the probiotic and those who received the placebo. Furthermore, the average number of days per week that nurses reported symptoms of cold or flu-like illness did not significantly differ between the probiotic and placebo supplemented groups. Authors conclude that there weren’t significant differences in outcomes between the probiotic and placebo groups.
Abstract
Animal studies demonstrate how the gut microbiota influence psychological health and immunity to viral infections through their actions along multiple dynamic pathways in the body. Considerable interest exists in probiotics to reduce stress and illness symptoms through beneficial effects in the gut, but translating pre-clinical evidence from animal models into humans remains challenging. We conducted a large trial in nurses working during the 2020 COVID19 pandemic year to establish whether daily ingestion of the probiotic Lactobacillus rhamnosus HN001 reduced perceived stress and the number of days participants reported symptoms of a viral illness. Our results showed no significant difference in perceived stress or the average number of illness days between probiotic supplemented nurses and the placebo group. Stress and viral illness symptoms reduced during the study for all participants, a trajectory likely influenced by societal-level factors. The powerful effect of a well-managed public health response to the COVID19 pandemic and the elimination of COVID19 from the community in 2020 may have altered the trajectory of stress levels and reduced circulating viral infections making it difficult to detect any effect of probiotic supplementation. Our study highlights the challenge in controlling environmental factors in human trials.
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Association between postmenopausal vulvovaginal discomfort, vaginal microbiota, and mucosal inflammation.
Mitchell, CM, Ma, N, Mitchell, AJ, Wu, MC, Valint, DJ, Proll, S, Reed, SD, Guthrie, KA, Lacroix, AZ, Larson, JC, et al
American journal of obstetrics and gynecology. 2021;225(2):159.e1-159.e15
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Close to half of postmenopausal women report bothersome symptoms of vulvar, vaginal or urinary discomfort collectively referred to as genitourinary syndrome of menopause. These are associated with negative impacts on sexual function and quality of life. The study’s hypothesis is that vaginal microbiota and inflammatory markers (i.e. increased Lactobacillus abundance and decreased inflammation) would differ significantly between women with the largest reductions in most bothersome symptom (MBS) severity compared to those women with smaller reductions, regardless of treatment arm. This study is a sub-study (secondary analysis of samples collected) of the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Vaginal Health Trial. Of 302 women randomised in the parent trial, 120 were enrolled in this sub-study. Results did not show significant associations between change in MBS severity and vaginal microbiota composition, Lactobacillus dominance, soluble immune markers, vaginal maturation index or vaginal fluid metabolites. Authors conclude that efforts to change superficial features of the vaginal microenvironment, such as pH or Lactobacillus colonization, may not address the primary underlying mechanism that leads to postmenopausal vaginal discomfort and is unlikely to be effective in relieving moderate to severe bothersome symptoms.
Abstract
BACKGROUND Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood. OBJECTIVE To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve. STUDY DESIGN This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm. RESULTS Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm. CONCLUSION Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.
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Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.
Quero, CD, Manonelles, P, Fernández, M, Abellán-Aynés, O, López-Plaza, D, Andreu-Caravaca, L, Hinchado, MD, Gálvez, I, Ortega, E
Nutrients. 2021;13(4)
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Synbiotic, a mixture of prebiotics and probiotics, is known to improve neurotransmitter interactions, immune, inflammatory, and stress responses by modulating the gut microbial composition. It is also believed that physical activity plays an important role in the modulation of immune function and stress response. The purpose of this triple-blinded, randomized, placebo-controlled pilot study was to evaluate the health benefits of symbiotic intervention in fourteen sedentary students and thirteen soccer players, especially in terms of improving immunophysiological and metabolic parameters. The 300mg of symbiotic intervention contained Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, Bifidobacterium longum ES1(109 colony-forming unit), and fructooligosaccharides (200 mg) plus 1.5 mg of zinc, 8.25 µg of selenium, 0.75 µg of vitamin, and maltodextrin. Following a one-month intervention with synbiotic formulation, soccer players showed improvements in anxiety, sleep quality and stress, a slight reduction in proinflammatory cytokine IL-1β, an exercise-induced significant increase in dopamine and a slight elevation of corticotropin-releasing hormone. For confirmation of results of this pilot study and to assess more significant effects of symbiotic intervention in athletes as well as in the general population, longer-term robust studies are required. The findings of this study can help healthcare professionals understand the extensive health benefits of synbiotic intervention and its relationship to physical activity.
Abstract
The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1β, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1β (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1β, CRH, and dopamine are clearly involved.
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Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly.
Despeghel, M, Reichel, T, Zander, J, Krüger, K, Weyh, C
Cells. 2021;10(4)
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As age advances, a gradual deterioration of immune function happens termed Immunosenescence, where different components of the immune system make a behavioural shift towards gradual decline. Immune ageing is characterized by changes in the ratio of naive memory T cells and CD4:CD8 and is associated with inflammatory cytokine production, which accelerates inflammatory ageing. This randomised controlled trial aimed to examine the effect of low-dose combined resistance and endurance training on the ageing immune system and inflammation in elderly subjects. Thirty participants (between the ages of 65 and 75) took part in a controlled low-threshold and care-oriented combined resistance and endurance training program for six weeks. This study showed an increase in CD4:CD8 ratio, decrease in low-grade inflammation and an improvement in strength capacity denoting improved immunosenescence and inflammaging among elderly participants. However, the study was conducted on a small sample for a short period. Therefore, robust long-term studies are required to elucidate further positive effects of different levels of physical activities in the elderly. Healthcare professionals can use these findings to understand how exercise influences immunosenescence and inflammation in the ageing body.
Abstract
With increasing age, the immune system undergoes a remodeling process, affecting the shift of T cell subpopulations and the development of chronic low-grade inflammation. Clinically, this is characterized by increased susceptibility to infections or development of several diseases. Since lifestyle factors can play a significant role in reducing the hallmarks of immune aging and inflammation, we investigated the effect of a 6 week low-dose combined resistance and endurance training program. Forty participants (70.3 ± 5.0 years) were randomly assigned to either a training (TG) or control group (CG) and performed a controlled low-threshold and care-oriented 6-week-long combined resistance and endurance training program. Changes in anthropometrics as well as strength capacity were measured. In subgroups of TG and CG, T cells and their subpopulations (CD4+, CD8+, naïve, central, effector memory, T-EMRA) were analyzed by flow cytometry. The changes of various plasma cytokines, chemokines, growth factors and adipokines were analyzed by luminex assays. The exercise program was followed by an increase in strength capacities. Participants of TG showed an increase of the CD4+/CD8+ T cell ratio over time (p < 0.05). Significant decreases in systemic levels of interleukin (IL-) 6, IL-8, IL-10 and vascular endothelial growth factor (VEGF) (p < 0.05) were observed for participants of TG over time. Even short-term and low-threshold training can reduce some of the hallmarks of immune aging in elderly and thus could be beneficial to stimulate immunity. The specific characteristics of the program make it easily accessible to older people, who may benefit in the longer term in terms of their immunocompetence.
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The Specific Carbohydrate Diet and Diet Modification as Induction Therapy for Pediatric Crohn's Disease: A Randomized Diet Controlled Trial.
Suskind, DL, Lee, D, Kim, YM, Wahbeh, G, Singh, N, Braly, K, Nuding, M, Nicora, CD, Purvine, SO, Lipton, MS, et al
Nutrients. 2020;12(12)
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Crohn’s disease is a painful chronic lifelong condition where the digestive tract gets inflamed. Environmental insults and gut microbial changes may contribute to immune dysregulation by activating and upregulating the immune system in Crohn’s disease. During this single-centre, randomised, double-blind, diet-controlled study, ten male active Crohn's disease patients aged seven to eighteen were randomly assigned to either a specific carbohydrate diet, a modified specific carbohydrate diet, or a whole food diet. All diet groups showed a reduction in symptoms, inflammation, and a positive change in the gut microbial composition after 12 weeks, depending on the degree of variability in the dietary regimen. Based on the results of this study, an exclusionary diet eliminating grains, sugar, dairy, and processed foods may have a positive impact on reducing Crohn's disease symptoms, inflammation, and improving gut microbial composition and biochemical markers. In the future, robust studies with a larger sample size will be needed to figure out better dietary strategies for Crohn's disease. Healthcare professionals can, however, use these results to identify dietary choices that can reduce Crohn's disease symptoms.
Abstract
BACKGROUND Crohn's disease (CD) is a chronic inflammatory intestinal disorder associated with intestinal dysbiosis. Diet modulates the intestinal microbiome and therefore has a therapeutic potential. The aim of this study is to determine the potential efficacy of three versions of the specific carbohydrate diet (SCD) in active Crohn's Disease. METHODS 18 patients with mild/moderate CD (PCDAI 15-45) aged 7 to 18 years were enrolled. Patients were randomized to either SCD, modified SCD(MSCD) or whole foods (WF) diet. Patients were evaluated at baseline, 2, 4, 8 and 12 weeks. PCDAI, inflammatory labs and multi-omics evaluations were assessed. RESULTS Mean age was 14.3 ± 2.9 years. At week 12, all participants (n = 10) who completed the study achieved clinical remission. The C-reactive protein decreased from 1.3 ± 0.7 at enrollment to 0.9 ± 0.5 at 12 weeks in the SCD group. In the MSCD group, the CRP decreased from 1.6 ± 1.1 at enrollment to 0.7 ± 0.1 at 12 weeks. In the WF group, the CRP decreased from 3.9 ± 4.3 at enrollment to 1.6 ± 1.3 at 12 weeks. In addition, the microbiome composition shifted in all patients across the study period. While the nature of the changes was largely patient specific, the predicted metabolic mode of the organisms increasing and decreasing in activity was consistent across patients. CONCLUSIONS This study emphasizes the impact of diet in CD. Each diet had a positive effect on symptoms and inflammatory burden; the more exclusionary diets were associated with a better resolution of inflammation.
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Effects of Yeast (1,3)-(1,6)-Beta-Glucan on Severity of Upper Respiratory Tract Infections: A Double-Blind, Randomized, Placebo-Controlled Study in Healthy Subjects.
Dharsono, T, Rudnicka, K, Wilhelm, M, Schoen, C
Journal of the American College of Nutrition. 2019;38(1):40-50
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Upper respiratory tract infections (URTIs) significantly impact the quality of life in susceptible individuals and account for considerable economic costs in days of work lost and medical visits. Previous studies have shown that URTIs may be reduced by the consumption of yeast beta-glucans through their affect on the immune system. This randomised double-blind placebo controlled study aimed to investigate whether the incidence and severity of the common cold could be altered by consumption of yeast (1,3)-(1,6)-beta-glucan. 291 subjects susceptible to URTI’s were randomly assigned to placebo or (1,3)-(1,6)-beta-glucan for 16-weeks. There were no statistically significant differences on overall symptom severity or duration of URTIs with beta-glucans at 16 weeks. Feelings of joy were significantly reduced with placebo. Further analysis showed that the beta-glucan group did experience reduced severity of symptoms in the first 7 days of contracting the URTI. Interesting to note was a significant reduction in blood pressure with beta-glucans, which was even more pronounced in subjects with clinically high blood pressure. Nutrition practitioners working with individuals suffering from chronic URTIs may wish to consider beta-glucans for their ability to reduce symptom severity in the first week of infection and increase feelings of wellbeing.
Abstract
OBJECTIVES Each year, adults suffer about two to four upper respiratory tract infections (URTIs), mostly in winter. The aim of the study was to evaluate the effects of brewers' yeast (1,3)-(1,6)-beta-glucan on incidence and severity of upper respiratory tract infections (URTIs). METHODS Generally healthy men and women (n = 299) reporting at least three URTIs during the previous year were randomized to receive either a placebo or 900 mg of yeast beta-glucan daily for 16 weeks during winter. In cases of acute URTI, the severity of URTI symptoms was assessed via the WURSS-21 questionnaire and the Jackson scale, and a clinical confirmation was implemented by the investigator. RESULTS Overall, 70 subjects under placebo and 71 subjects under yeast beta-glucan experienced at least one clinically confirmed URTI episode. The global severity using WURSS-21 had been quite similar between the study groups (p = 0.5267), whereas during the first days of URTIs the severity was less pronounced in the yeast beta-glucan group. On the episode level, the severity of physical symptoms was significantly lower for all investigated time intervals up to 7 days under yeast beta-glucan (WURSS (Q2-11) (days 1-2: p = 0.0465, days 1-3: p = 0.0323, days 1-4: p = 0.0248, days 1-7: p = 0.0278), also confirmed for the Jackson scale). The reduction of severity was accompanied by a significant increase in the joy subscore of the Perceived Stress Questionnaire (PSQ20) (p = 0.0148). In addition, there was a reduction of systolic (p = 0.0458) and diastolic (p = 0.1439) blood pressure. CONCLUSION Subjects supplementing with yeast beta-glucan benefit by a reduced severity of physical URTI symptoms during the first week of an episode, even though the incidence and global severity of common colds could not be altered in comparison to placebo. Furthermore, accompanying benefits in terms of blood pressure and mood were identified. Altogether, yeast beta-glucan supports the immune function.
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Effects of Lactobacillus plantarum and Lactobacillus paracasei on the Peripheral Immune Response in Children with Celiac Disease Autoimmunity: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Håkansson, Å, Andrén Aronsson, C, Brundin, C, Oscarsson, E, Molin, G, Agardh, D
Nutrients. 2019;11(8)
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An abnormal immune response to gluten may lead to lifelong digestive symptoms in patients with celiac disease. Several species of beneficial bacteria in the gut may reduce inflammation by reducing the amount of proinflammatory cytokines released in response to antigens. The purpose of this randomized, double-blind, controlled trial was to investigate the effects of Lactobacillus plantarum HEAL9 and L. paracasei 8700:2 on the development of celiac disease in children who are at high risk of developing the celiac disease while eating a gluten-containing diet. A total of seventy-eight children with celiac autoimmunity were given either 10¹ºCFU/day of L. plantarum HEAL9 and L. paracasei 8700:2 or maltodextrin for six months. It has been observed that six months of intervention with probiotics modulated the immune response in celiac disease autoimmunity. In the intervention group, there were no signs of celiac disease progression. There is a need for further robust and long-term studies to examine more specifically the benefits of Lactobacillus in the prevention of celiac disease as well as modulating effects on the intestinal mucosa. It is important to point out that healthcare professionals can use the results of this study to better understand the immunomodulatory effects of specific Lactobacillus strains in celiac disease.
Abstract
Two Lactobacillus strains have proven anti-inflammatory properties by reducing pro-inflammatory responses to antigens. This randomized double-blind placebo-controlled trial tested the hypothesis that L. plantarum HEAL9 and L. paracasei 8700:2 suppress ongoing celiac disease autoimmunity in genetically at risk children on a gluten-containing diet in a longitudinally screening study for celiac disease. Seventy-eight children with celiac disease autoimmunity participated of whom 40 received 1010 CFU/day of L. plantarum HEAL9 and L. paracasei 8700:2 (probiotic group) and 38 children maltodextrin (placebo group) for six months. Blood samples were drawn at zero, three and six months and phenotyping of peripheral blood lymphocytes and IgA and IgG autoantibodies against tissue transglutaminase (tTG) were measured. In the placebo group, naïve CD45RA+ Th cells decreased (p = 0.002) whereas effector and memory CD45RO+ Th cells increased (p = 0.003). In contrast, populations of cells expressing CD4+CD25highCD45RO+CCR4+ increased in the placebo group (p = 0.001). Changes between the groups were observed for NK cells (p = 0.038) and NKT cells (p = 0.008). Median levels of IgA-tTG decreased more significantly over time in the probiotic (p = 0.013) than in the placebo (p = 0.043) group whereas the opposite was true for IgG-tTG (p = 0.062 respective p = 0.008). In conclusion, daily oral administration of L. plantarum HEAL9 and L. paracasei 8700:2 modulate the peripheral immune response in children with celiac disease autoimmunity.
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The Effect of Olive Leaf Extract on Upper Respiratory Illness in High School Athletes: A Randomised Control Trial.
Somerville, V, Moore, R, Braakhuis, A
Nutrients. 2019;11(2)
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When an individual exercises, there is a 3 to 72 hour subsequent period known as the ‘open window’ where they are susceptible to illness due to altered immune function and activity. The aim of this study was to determine the effect of olive leaf extract (OLE) supplementation on upper respiratory illness (URI) incidence and duration in high school athletes. The study was a two-month parallel double-blind randomised controlled trial. The study recruited 32 students (females n = 22) aged between 16 and 19 years. The participants were randomly allocated to one of the two groups: OLE or placebo tablets group. Results indicate that there were 17 participants who experienced a total of 26 URI episodes. There was no significant difference in incidence; however, there was a significant 28% reduction in sick days. Authors conclude that OLE supplementation could be used to alleviate the effect of URI on high school athletes.
Abstract
Upper respiratory illness (URI) has a major impact on both training and competition in an athletic setting. High school athletes are a sub-category who have reported higher illness rates than professional and sub-elite high school athletes of the same sport. Olive leaf extract (OLE) is an over-the-counter supplement that contains polyphenols, notably oleuropein and hydroxytyrosol, that have antiviral, antibacterial, anti-inflammatory and antioxidant properties that may reduce URI rates. Thirty-two high school students who play sport for the elite team at their school were recruited to a randomised controlled trial and allocated to a daily placebo or OLE (extent equivalent to 20 g of olive leaf, containing 100 mg oleuropein) supplementation for nine weeks during their competitive season. Twice weekly measures of wellbeing, training load and respiratory illness (sporting upper respiratory illness (SUPPRESS) questionnaire) were recorded at trainings, meetings or games. There was no significant difference in illness incidence (odds ratio (OR): 1.02 (95% confidence interval (CI) 0.21⁻4.44)), but there was a significant 28% reduction in sick days (OR: 0.72 (95% CI 0.56⁻0.93) p-value = 0.02) when supplemented with OLE. The dietary intakes of the athletes were sub-optimal with regard to immune support. OLE supplementation over a season did not significantly reduce URI incidence, but did decrease duration in high school athletes, potentially aiding return to play.