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As the population ages, the incidence of age-related neurodegenerative diseases is rapidly increasing, and novel approaches to mitigate this soaring prevalence are sorely needed. Recent studies have highlighted the importance of gut microbial homeostasis and its impact on brain functions, commonly referred to as the gut-brain axis, in maintaining overall health and wellbeing. Nonetheless, the mechanisms by which this system acts remains poorly defined. In this review, we will explore how (poly)phenols, a class of natural compounds found in many plant-based foods and beverages, can modulate the gut-brain axis, and thereby promote neural health. While evidence indicates a beneficial role of (poly)phenol consumption as part of a balanced diet, human studies are scarce and mechanistic insight is still lacking. In this regard, we make the case that dietary (poly)phenols should be further explored to establish their therapeutic efficacy on brain health through modulation of the gut-brain axis, with much greater emphasis on carefully designed human interventions.

The therapeutic effects of saffron have been reported and described in relation to its major derivatives. Among them, in terms of saffron's properties, crocin and crocetin absorption and bioavailability have been the most studied. Nevertheless, the metabolism of these major compounds of saffron has not yet been entirely elucidated. Current data indicate that the phase 2 metabolism of crocetins go through conjugation reactions. Crocetins could also be present in isomeric forms such as other carotenoids. Nonetheless, there are still shadow areas in regard to the measurements of the different circulating forms of crocetins after oral saffron extract administration (Safr'Inside™). In using various approaches, we propose the identification of a new cis isomeric form of crocetin, the 6- cis -crocetin. This compound was found in human serum samples after an oral administration of saffron extract. The 6- cis -crocetin represents 19% of the total crocetin measured after 45 min of consumption. These data mark, for the first time, the presence of a cis isomeric form of crocetin in human serum samples. Moreover, this study led to the development of an analytical method that is able to identify and quantify both isomeric forms ( trans and cis ).

Safe and anti-inflammatory plant-based natural products present an increasing focus in the treatment of chronic inflammatory diseases such as osteoarthritis or inflammatory bowel diseases. Among them, saffron, a spice derived from the stigma of Crocus sativus, could have anti-inflammatory properties and would be therefore a promising therapeutic agent for the treatment of such conditions. However, the anti-inflammatory molecular mechanisms of saffron in humans are still understudied and unclear. In this study, combining human serum metabolites and cell cultures, we evaluated the effect of circulating metabolites from the consumption of a patented saffron extract (Safr'Inside TM ) on the chondrocytes and colon epithelial cell responses to inflammatory stress. Parametric or non-parametric Analysis of Variance with post hoc tests was performed. We demonstrated that human serum containing metabolites from saffron intake attenuated IL-1β-stimulated production of PGE2 and MMP-13 in chondrocyte cells and limited the increase in ICAM-1, MCP-1, iNOS, and MMP-3 in human epithelial cells following combined IL-1β and TNF-α inflammatory stimulation. Altogether, these data provide new findings into the mechanisms underlying the beneficial effects of saffron on chondrocytes and enterocyte cells at the cellular level and in the context of chronic inflammatory disorders.

The Mediterranean diet (MD) and its bioactive constituents have been advocated for their neuroprotective properties along with their capacity to affect gut microbiota speciation and metabolism. Mediated through the gut brain axis, this modulation of the microbiota may partly contribute to the neuroprotective properties of the MD. To explore this potential interaction, we evaluated the neuroprotective properties of a novel bioactive blend (Neurosyn240) resembling the Mediterranean diet in a rodent model of chronic low-grade inflammation. Behavioral tests of cognition, brain proteomic analysis, 16S rRNA sequencing, and 1 H NMR metabolomic analyses were employed to develop an understanding of the gut-brain axis interactions involved. Recognition memory, as assessed by the novel object recognition task (NOR), decreased in response to LPS insult and was restored with Neurosyn240 supplementation. Although the open field task performance did not reach significance, it correlated with NOR performance indicating an element of anxiety related to this cognitive change. Behavioral changes associated with Neurosyn240 were accompanied by a shift in the microbiota composition which included the restoration of the Firmicutes: Bacteroidota ratio and an increase in Muribaculum, Rikenellaceae Alloprevotella , and most notably Akkermansia which significantly correlated with NOR performance. Akkermansia also correlated with the metabolites 5-aminovalerate, threonine, valine, uridine monophosphate, and adenosine monophosphate, which in turn significantly correlated with NOR performance. The proteomic profile within the brain was dramatically influenced by both interventions, with KEGG analysis highlighting oxidative phosphorylation and neurodegenerative disease-related pathways to be modulated. Intriguingly, a subset of these proteomic changes simultaneously correlated with Akkermansia abundance and predominantly related to oxidative phosphorylation, perhaps alluding to a protective gut-brain axis interaction. Collectively, our results suggest that the bioactive blend Neurosyn240 conferred cognitive and microbiota resilience in response to the deleterious effects of low-grade inflammation.

Background: While the microstructure of the left ventricle (LV) has been largely described, only a few studies investigated the right ventricular insertion point (RVIP). It was accepted that the aggregate cardiomyocytes organization was much more complex due to the intersection of the ventricular cavities but a precise structural characterization in the human heart was lacking even if clinical phenotypes related to right ventricular wall stress or arrhythmia were observed in this region., Methods: MRI-derived anatomical imaging (150 µm 3 ) and diffusion tensor imaging (600 µm 3 ) were performed in large mammalian whole hearts (human: N = 5, sheep: N = 5). Fractional anisotropy, aggregate cardiomyocytes orientations and tractography were compared within both species. Aggregate cardiomyocytes orientation on one ex-vivo sheep whole heart was then computed using structure tensor imaging (STI) from 21 µm isotropic acquisition acquired with micro computed tomography (MicroCT) imaging. Macroscopic and histological examination were performed. Lastly, experimental cardiomyocytes orientation distribution was then compared to the usual rule-based model using electrophysiological (EP) modeling. Electrical activity was modeled with the monodomain formulation., Results: The RVIP at the level of the inferior ventricular septum presented a unique arrangement of aggregate cardiomyocytes. An abrupt, mid-myocardial change in cardiomyocytes orientation was observed, delimiting a triangle-shaped region, present in both sheep and human hearts. FA's histogram distribution (mean ± std: 0.29 ± 0.06) of the identified region as well as the main dimension (22.2 mm ± 5.6 mm) was found homogeneous across samples and species. Averaged volume is 0.34 cm 3  ± 0.15 cm 3 . Both local activation time (LAT) and morphology of pseudo-ECGs were strongly impacted with delayed LAT and change in peak-to-peak amplitude in the simulated wedge model., Conclusion: The study was the first to describe the 3D cardiomyocytes architecture of the basal inferoseptal left ventricle region in human hearts and identify the presence of a well-organized aggregate cardiomyocytes arrangement and cardiac structural discontinuities. The results might offer a better appreciation of clinical phenotypes like RVIP-late gadolinium enhancement or uncommon idiopathic ventricular arrhythmias (VA) originating from this region., (© 2023. The Author(s).)

Background: Although activation of inflammatory processes is essential to fight infections, its prolonged impact on brain function is well known to contribute to the pathophysiology of many medical conditions, including neuropsychiatric disorders. Therefore, identifying novel strategies to selectively counter the harmful effects of neuroinflammation appears as a major health concern. In that context, this study aimed to test the relevance of a nutritional intervention with saffron, a spice known for centuries for its beneficial effect on health., Methods: For this purpose, the impact of an acute oral administration of a standardized saffron extract, which was previously shown to display neuromodulatory properties and reduce depressive-like behavior, was measured in mice challenged with lipopolysaccharide (LPS, 830 μg/kg, ip)., Results: Pretreatment with saffron extract (6.5 mg/kg, per os ) did not reduce LPS-induced sickness behavior, preserving therefore this adaptive behavioral response essential for host defense. However, it interfered with delayed changes of expression of cytokines, chemokines and markers of microglial activation measured 24 h post-LPS treatment in key brain areas for behavior and mood control (frontal cortex, hippocampus, striatum). Importantly, this pretreatment also counteracted by that time the impact of LPS on several neurobiological processes contributing to inflammation-induced emotional alterations, in particular the activation of the kynurenine pathway, assessed through the expression of its main enzymes, as well as concomitant impairment of serotonergic and dopaminergic neurotransmission., Conclusion: Altogether, this study provides important clues on how saffron extract interferes with brain function in conditions of immune stimulation and supports the relevance of saffron-based nutritional interventions to improve the management of inflammation-related comorbidities., Competing Interests: CMdO, DG, and LP are employees of Activ’Inside which provided the saffron extract. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Monchaux de Oliveira, Morael, Guille, Amadieu, Vancassel, Gaudout, Capuron, Pourtau and Castanon.)

According to animal studies, saffron and its main volatile compound safranal may reduce biological and behavioral signs of acute stress. However, little is known about its impact in humans. This study investigated the acute effect of a saffron extract and safranal on the biological and psychological stress responses in healthy men experiencing a laboratory stress procedure. In this double-blind, placebo-controlled, randomized, cross-over study, 19 volunteers aged 18-25 received a single dose of 30 mg saffron extract (Safr'Inside TM) , 0.06 mg synthetic safranal, or a placebo on three visits separated by a 28-day washout. Thirteen minutes after administration, participants were exposed to the Maastricht acute stress test (MAST). Salivary cortisol and cortisone were collected from 15 min before the MAST (and pre-dose), 3 min before the MAST, and then 15, 30, 45, 60, and 75 min after the MAST, and stress and anxiety were measured using visual analogic scales. Compared to the placebo, stress and anxiety were significantly toned down after Safranal and Safr'Inside TM administration and coupled with a delay in the times to peak salivary cortisol and cortisone concentrations ( p < 0.05). Safr'Inside TM and its volatile compound seem to improve psychological stress response in healthy men after exposure to a lab-based stressor and may modulate the biological stress response.

Background: There is growing interest on how social capital and related social environmental factors impact overall population health and well-being. The nature of asylum-seekers' social environment alters once they migrate to a new context and these changes influence their mental health and well-being. However, there is limited scholarship on how these social environmental factors impact the mental health, well-being, and capacity to flourish of asylum-seekers., Methods: The aim of the study, therefore, was to examine how specific social environmental factors-social networks, social support, and social cohesion at various levels (micro, meso, and macro)-influence the mental health, well-being, and capacity to flourish of asylum-seekers in France. In collaboration with a community-based organization, we used a qualitative research design to conduct 120 semi-structured interviews with asylum-seekers in France., Results: The emerging salient themes depicted how the asylum-seekers' usual informal social networks comprised of family and friends had been disrupted since they migrated to France, which impacted their mental health and well-being. Conversely, staying connected with their informal transnational social networks via social media and developing ties with new local informal and formal social networks allowed them to receive different forms of social support, and buffered some of the negative mental health consequences. However, the lack of social cohesion due to a lack of belonging, marginalization, and current harmful migration-related policies impeded asylum-seekers' capacity to flourish., Conclusion: While social support derived from social networks buffered some negative impacts on mental health and well-being, the overall lack of social cohesion ultimately impeded asylum-seekers' capacity to flourish within their host communities, which was further exacerbated by harmful migration policies of exclusion within France. Introducing more inclusive policies related to the governance of migration and an intersectoral approach that views health in all policies is key to promoting social cohesion and flourishing among asylum-seekers in France., (© 2023. The Author(s).)

Background: Polyphenols are naturally occurring organic compounds found in plants. Research suggests that their intake reduces the risk of cognitive decline and related dementias. Grapes and blueberries are polyphenol-rich foods that have attracted attention for their potential cognitive-enhancing effects., Purpose: Examine the effects of supplementation with a standardized and patented polyphenol-rich grape and blueberry extract (Memophenol™) on cognitive function in older adults with mild cognitive impairment., Study Design: Two-arm, 6 month, parallel-group, randomized, double-blind, placebo-controlled trial., Methods: One hundred and forty-three volunteers aged 60 to 80 years with mild cognitive impairment were supplemented with either 150 mg of Memophenol™, twice daily or a placebo. Outcome measures included computer-based cognitive tasks, the Behavior Rating Inventory of Executive Function (BRIEF-A), the Cognitive Failures Questionnaire, and the CASP-19., Results: Compared to the placebo, Memophenol™ supplementation was associated with greater improvements in the speed of information processing ( p = 0.020), visuospatial learning ( p = 0.012), and the BRIEF-A global score ( p = 0.046). However, there were no other statistically significant between-group differences in the performance of other assessed cognitive tests or self-report questionnaires. Memophenol™ supplementation was well-tolerated with no reports of significant adverse reactions., Conclusion: The promising results from this trial suggest that 6-months of supplementation with Memophenol™ may improve aspects of cognitive function in adults with mild cognitive impairment. Further research will be important to expand on the current findings and identify the potential mechanisms of action associated with the intake of this polyphenol-rich extract., Competing Interests: AL is the managing director of Clinical Research Australia, a contract research organization that has received research funding from nutraceutical companies. AL has also received presentation honoraria from nutraceutical companies. SS is an employee of Clinical Research Australia and declares no other conflicts of interest. PD and VP declare no conflicts of interest. DG, CP, and LP are employed at Activ’Inside and provided the Memophenol™ and placebo capsules., (Copyright © 2023 Lopresti, Smith, Pouchieu, Pourtau, Gaudout, Pallet and Drummond.)

The COVID-19 pandemic has exposed health and social inequities among migrant populations. Less empirical evidence exists about the impact of COVID-19 lockdown measures on migrants. This study aimed to investigate the impact of the first lockdown in France between March and May 2020 on migrants' lives and livelihoods. We adopted a social vulnerability framework to conceptualize how the pandemic and the consequential lockdown in France contributed to a 'compounded crisis' for asylum seekers and undocumented migrants. This crisis encompassed health, protection, and socio-economic challenges for migrants and exposed the shortcomings of existing government policies that exclude migrants and do not address the root causes of health inequities. The study draws on in-depth qualitative interviews conducted with 75 asylum seekers and undocumented migrants during the pandemic lockdown in the French regions of Auvergne-Rhône-Alpes and Île-de-France. The findings of this paper highlight the importance of implementing a cohesive pandemic response approach that views health as a fundamental inclusive right for all human beings and all policies as health policies to promote well-being for all.

Aims: Left ventricular assist devices (LVADs) have reduced the mortality of patients with advanced heart failure both as bridge-to-transplant and as destination therapy. However, LVADs are associated with various complications, including bleedings, which affect the prognosis. The aim of the study was to explore the prevalence, management, and outcomes of haemorrhagic adverse events in LVAD recipients., Methods and Results: We conducted a retrospective, single-centre, cohort study including all patients who received an LVAD from January 2008 to December 2019 in our tertiary centre (Rangueil University Hospital, Toulouse, France). Bleeding events, death, and heart transplantation were collected from electronic medical files. Eighty-eight patients were included, and 43 (49%) presented at least one bleeding event. Gastrointestinal (GI) bleeding was the most frequent (n = 21, 24%), followed by epistaxis (n = 12, 14%) and intracranial haemorrhage (n = 9, 10%). Bleeding events were associated with increased mortality [hazard ratio (HR) 3.8, 95% confidence interval (CI) 1.5-9.3, P < 0.01], particularly in case of intracranial haemorrhage (HR 14.6, 95% CI 4.2-51.1, P < 0.0001). GI bleedings were associated with a trend towards increased mortality (HR 3.0, 95% CI 0.9-9.3, P = 0.05). Each bleeding episode multiplied the risk of death by 1.8 (95% CI 1.2-2.7, P < 0.01). Finally, only early bleedings (<9 months post-implantation) had an impact on mortality (HR 4.2, 95% CI 1.6-11.1, P < 0.01). Therapeutic management was mainly based on temporary interruption of anticoagulation and permanent interruption of antiplatelet therapy. Invasive management was rarely performed., Conclusions: Haemorrhagic events in LVAD recipients are frequent and associated with increased mortality. GI bleedings are the most frequent, and intracranial haemorrhages the most associated with mortality. Management remains empirical requiring more research., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Cardiac fiber direction is an important factor determining the propagation of electrical activity, as well as the development of mechanical force. In this article, we imaged the ventricles of several species with special attention to the intraventricular septum to determine the functional consequences of septal fiber organization. First, we identified a dual-layer organization of the fiber orientation in the intraventricular septum of ex vivo sheep hearts using diffusion tensor imaging at high field MRI. To expand the scope of the results, we investigated the presence of a similar fiber organization in five mammalian species (rat, canine, pig, sheep, and human) and highlighted the continuity of the layer with the moderator band in large mammalian species. We implemented the measured septal fiber fields in three-dimensional electromechanical computer models to assess the impact of the fiber orientation. The downward fibers produced a diamond activation pattern superficially in the right ventricle. Electromechanically, there was very little change in pressure volume loops although the stress distribution was altered. In conclusion, we clarified that the right ventricular septum has a downwardly directed superficial layer in larger mammalian species, which can have modest effects on stress distribution. NEW & NOTEWORTHY A dual-layer organization of the fiber orientation in the intraventricular septum was identified in ex vivo hearts of large mammals. The RV septum has a downwardly directed superficial layer that is continuous with the moderator band. Electrically, it produced a diamond activation pattern. Electromechanically, little change in pressure volume loops were noticed but stress distribution was altered. Fiber distribution derived from diffusion tensor imaging should be considered for an accurate strain and stress analysis.

Increases in oxidative stress have been reported to play a central role in the vulnerability to depression, and antidepressant drugs may reduce increased oxidative stress in patients. Among the plants exerting anti-inflammatory and anti-oxidant properties, saffron, a spice derived from the flower of Crocus sativus , is also known for its positive effects on depression, potentially through its SSRI-like properties. However, the molecular mechanisms underlying these effects and their health benefits for humans are currently unclear. Using an original ex vivo clinical approach, we demonstrated for the first time that the circulating human metabolites produced following saffron intake (Safr'Inside TM ) protect human neurons from oxidative-stress-induced neurotoxicity by preserving cell viability and increasing BNDF production. In particular, the metabolites significantly stimulated both dopamine and serotonin release. In addition, the saffron's metabolites were also able to protect serotonergic tone by inhibiting the expression of the serotonin transporter SERT and down-regulating serotonin metabolism. Altogether, these data provide new biochemical insights into the mechanisms underlying the beneficial impact of saffron on neuronal viability and activity in humans, in the context of oxidative stress related to depression.

Social inequalities tended to increase in the context of the pandemic, particularly in relation to the measures taken to manage and reduce the risk of COVID-19. When lockdown measures required the general population "to stay home", what were homeless people expected to do? The ECHO study is a cross-sectional, descriptive study with a convergent mixed-method design. Data were collected across shelters in France both during and immediately following the lockdown (April - June 2020). This article presents the study's qualitative findings, with a focus on understanding both the experiences and perceptions among these populations of the measures taken to limit the COVID-19 infection. A total of 26 semi-directed individual interviews were conducted across seven shelters in both Lyon (42%) and Paris (58%). Data were analysed using thematic content analysis with partial blinded coding. Four key themes were identified: 1- Reactions to the introduction of lockdown: a sudden implementation reminiscent of prior violent or traumatic circumstances amongst participants, 2- Accommodation during lockdown: participants' conflicting visions of the shelter, 3- Influence of the media and public communication: an abundant flow of information impacting participant's wellbeing and representations on the pandemic, and 4- The individual impact of lockdown: perceived health and limitations to daily life activities. The most vulnerable populations have borne the heaviest burden during the pandemic. It is therefore crucial that we improve both the availability of information, and the health literacy of, all groups within the national population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

Depressive disorders are a major public health concern. Despite currently available treatment options, their prevalence steadily increases, and a high rate of therapeutic failure is often reported, together with important antidepressant-related side effects. This highlights the need to improve existing therapeutic strategies, including by using nutritional interventions. In that context, saffron recently received particular attention for its beneficial effects on mood, although the underlying mechanisms are poorly understood. This study investigated in mice the impact of a saffron extract (Safr'Inside™; 6.25 mg/kg, per os ) on acute restraint stress (ARS)-induced depressive-like behavior and related neurobiological alterations, by focusing on hypothalamic-pituitary-adrenal axis, inflammation-related metabolic pathways, and monoaminergic systems, all known to be altered by stress and involved in depressive disorder pathophysiology. When given before stress onset, Safr'Inside administration attenuated ARS-induced depressive-like behavior in the forced swim test. Importantly, it concomitantly reversed several stress-induced monoamine dysregulations and modulated the expression of key enzymes of the kynurenine pathway, likely reducing kynurenine-related neurotoxicity. These results show that saffron pretreatment prevents the development of stress-induced depressive symptoms and improves our understanding about the underlying mechanisms, which is a central issue to validate the therapeutic relevance of nutritional interventions with saffron in depressed patients.

Depressive disorders represent a major public health concern and display a continuously rising prevalence. Importantly, a large proportion of patients develops aversive side effects and/or does not respond properly to conventional antidepressants. These issues highlight the need to identify further therapeutic strategies, including nutritional approaches using natural plant extracts with known beneficial impacts on health. In that context, growing evidence suggests that saffron could be a particularly promising candidate. This preclinical study aimed therefore to test its antidepressant-like properties in mice and to decipher the underlying mechanisms by focusing on monoaminergic neurotransmission, due to its strong implication in mood disorders. For this purpose, the behavioral and neurobiochemical impact of a saffron extract, Safr'Inside™ (6.5 mg/kg per os ) was measured in naïve mice. Saffron extract reduced depressive-like behavior in the forced swim test. This behavioral improvement was associated with neurobiological modifications, particularly changes in serotonergic and dopaminergic neurotransmission, suggesting that Safr'Inside™ may share common targets with conventional pharmacological antidepressants. This study provides useful information on the therapeutic relevance of nutritional interventions with saffron extracts to improve management of mood disorders.

Anxiety, stress, and low mood are closely related and may contribute to depressive symptoms. Among non-pharmacological solutions to improve subclinical mood symptoms and resilience to stress, natural products such as saffron-identified as promising following preliminary beneficial effects in major depressive disorder-represent a relevant strategy. This study aimed to assess the efficacy of 8 weeks' supplementation with 30 mg standardized saffron extract on emotional well-being in healthy adults with subclinical feelings of low mood and anxiety and/or stress and evaluate the acute effect of saffron in response to a lab-based psychosocial stressor. The study adopted a double-blind, randomized, parallel groups design in which 56 healthy male and female individuals (18-54 years) received either a saffron extract or a placebo for 8 weeks. Chronic effects of saffron on subjective anxiety, stress, and depressive feelings were assessed using a questionnaire battery [including Profile of Mood State-2, (POMS)] and acute effects in response to a lab-based psychosocial stressor were measured through psychological and physiological parameters. Urinary crocetin levels were quantified. Participants who received the saffron extract reported reduced depression scores and improved social relationships at the end of the study. Urinary crocetin levels increased significantly with saffron supplementation and were correlated with change in depression scores. The typical stress-induced decrease in heart rate variability (HRV) during exposure to the stressor was attenuated following acute saffron intake. Saffron extract appears to improve subclinical depressive symptoms in healthy individuals and may contribute to increased resilience against the development of stress-related psychiatric disorders. Clinical trials number: NCT03639831., Competing Interests: CP, SD, DG, BM, and LP are employees of Activ'Inside. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jackson, Forster, Khan, Pouchieu, Dubreuil, Gaudout, Moras, Pourtau, Joffre, Vaysse, Bertrand, Abrous, Vauzour, Brossaud, Corcuff, Capuron and Kennedy.)

Despite an increasing level of evidence supporting the individual beneficial effect of polyphenols on cognitive performance, information related to the potential synergistic action of these phytonutrients on cognitive performance during a prolonged cognitive effort is currently lacking. This study investigated the acute and sustained action of a polyphenols-rich extract from grape and blueberry (PEGB), on working memory and attention in healthy students during a prolonged and intensive cognitive effort. In this randomised, cross-over, double blind study, 30 healthy students consumed 600 mg of PEGB or a placebo. Ninety minutes after product intake, cognitive functions were assessed for one hour using a cognitive demand battery including serial subtraction tasks, a rapid visual information processing (RVIP) task and a visual analogical scale. Flow-mediated dilation (FMD) and plasma flavan-3-ols metabolites quantification were also performed. A 2.5-fold increase in serial three subtraction variation net scores was observed following PEGB consumption versus placebo ( p < 0.001). A trend towards significance was also observed with RVIP percentage of correct answers ( p = 0.058). No treatment effect was observed on FMD. Our findings suggest that consumption of PEGB coupled with a healthy lifestyle may be a safe alternative to acutely improve working memory and attention during a sustained cognitive effort.

Smoking is the major preventable cause of disease and premature death in many countries, including France, where approximately 30% of adults are daily smokers. About 60% of them want to quit, however, long-term smoking cessation rates are low, particularly among individuals with low socio-economic position. The aim of this study is to examine whether motivations for smoking cessation among young adults differ across socio-economic groups. 3 focus groups of smokers and former smokers aged 22-40 years were constituted and conducted in November 2014 in Paris. Data from the focus groups were analyzed thematically and in a cross-cutting manner. Our study shows the existence of social "communities" of smokers, in occupational and festive contexts. In addition, new forms of resistance to public health messages are observed ("neutralization"), particularly among smokers with low socioeconomic position. Finally, stress is often cited as a source of unsuccessful smoking cessation or smoking relapse. Tobacco smoking is a social behavior and is associated with symbolic as well as relational benefits, particularly among smokers who have low socioeconomic position. To be effective, interventions aiming to decrease smoking levels in the population should aim to create group dynamics encouraging smokers to quit and address the physical as well as the psychological consequences of smoking withdrawal.

Background Papillary muscles are an important source of ventricular tachycardia (VT). Yet little is known about the role of the right ventricular (RV) endocavity structure, the moderator band (MB). The aim of this study was to determine the characteristics of the MB that may predispose to arrhythmia substrates. Methods Ventricular wedge preparations with intact MBs were studied from humans (n=2) and sheep (n=15; 40-50 kg). RV endocardium was optically mapped, and electrical recordings were measured along the MB and septum. S1S2 pacing of the RV free wall, MB, or combined S1-RV S2-MB sites were assessed. Human (n=2) and sheep (n=4) MB tissue constituents were assessed histologically. Results The MB structure was remarkably organized as 2 excitable, yet uncoupled compartments of myocardium and Purkinje. In humans, action potential duration heterogeneity between MB and RV myocardium was found (324.6±12.0 versus 364.0±8.4 ms; P<0.0001). S1S2-MB pacing induced unidirectional propagation via MB myocardium, permitting sustained macroreentrant VT. In sheep, the incidence of VT for RV, MB, and S1-RV S2-MB pacing was 1.3%, 5.1%, and 10.3%. Severing the MB led to VT termination, confirming a primary arrhythmic role. Inducible preparations had shorter action potential duration in the MB than RV (259.3±45.2 versus 300.7±38.5 ms; P<0.05), whereas noninducible preparations showed no difference (312.0±30.3 versus 310.0±24.6 ms, respectively). Conclusions The MB presents anatomic and electrical compartmentalization between myocardium and Purkinje fibers, providing a substrate for macroreentry. The vulnerability to sustain VT via this mechanism is dependent on MB structure and action potential duration gradients between the RV free wall and MB.

Glucocorticoids are released after hypothalamus-pituitary-adrenal axis stimulation by stress and act both in the periphery and in the brain to bring about adaptive responses that are essential for life. Dysregulation of the stress response can precipitate psychiatric diseases, in particular depression. Recent genetic studies have suggested that the glucocorticoid carrier transcortin, also called corticosteroid-binding globulin (CBG), may have an important role in stress response. We have investigated the effect of partial or total transcortin deficiency using transcortin knockout mice on hypothalamus-pituitary-adrenal axis functioning and regulation as well as on behaviors linked to anxiety and depression traits in animals. We show that CBG deficiency in mice results in markedly reduced total circulating corticosterone at rest and in response to stress. Interestingly, free corticosterone concentrations are normal at rest but present a reduced surge after stress in transcortin-deficient mice. No differences were detected between transcortin-deficient mice for anxiety-related traits. However, transcortin-deficient mice display increased immobility in the forced-swimming test and markedly enhanced learned helplessness after prolonged uncontrollable stress. The latter is associated with an approximately 30% decrease in circulating levels of free corticosterone as well as reduced Egr-1 mRNA expression in hippocampus in CBG-deficient mice. Additionally, transcortin-deficient mice show no sensitization to cocaine-induced locomotor responses, a well described corticosterone-dependent test. Thus, transcortin deficiency leads to insufficient glucocorticoid signaling and altered behavioral responses after stress. These findings uncover the critical role of plasma transcortin in providing an adequate endocrine and behavioral response to stress.