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Implementing cognitive-behavioral therapy (CBT), the first-line psychological treatment for panic disorder (PD), may be challenging in patients with comorbid coronary artery disease (CAD).This study aimed at assessing the feasibility and acceptability of a CBT for PD protocol that was adapted to patients suffering from comorbid CAD. It also aimed at evaluating the efficacy of the intervention to reduce PD symptomatology and psychological distress and improve quality of life. This was a single-case experimental design with pre-treatment, post-treatment and 6-month follow-up measures. Patients with PD and stable CAD received 14 to 17 individual, 1-h sessions of an adapted CBT for PD protocol. They completed interviews and questionnaires at pre-treatment, post-treatment and at a 6-month follow-up assessing intervention acceptability, PD symptomatology, psychological distress and quality of life. A total of 6 patients out of 7 completed the intervention and 6-month follow-up, indicating satisfactory feasibility. Acceptability was high (medians of ≥ 8.5 out of 9 and ≥ 80%) both at pre and post treatment. Remission rate was of 83% at post-treatment and 6-month follow-up. The intervention appeared to have positive effects on comorbid anxiety and depression symptoms and quality of life. The intervention appeared feasible and acceptable in patients with comorbid CAD. The effects of the adapted CBT protocol on PD symptoms, psychological distress and quality of life are promising and were maintained at the 6-month follow-up. Further studies should aim at replicating the present results in randomized-controlled trials [ABSTRACT FROM AUTHOR]

Background: Patients with noncardiac chest pain (NCCP) report more severe symptoms and lowered health-related quality of life when they present with comorbid panic disorder (PD). Although generalized anxiety disorder (GAD) is the second most common psychiatric disorder in these patients, its impact on NCCP and health-related quality of life remains understudied. This study describes and prospectively compares patients with NCCP with or without PD or GAD in terms of (1) NCCP severity; and (2) the physical and mental components of health-related quality of life.Methods: A total of 915 patients with NCCP were consecutively recruited in two emergency departments. The presence of comorbid PD or GAD was assessed at baseline with the Anxiety Disorder Schedule for DSM-IV. NCCP severity at baseline and at the six-month follow-up was assessed with a structured telephone interview, and the patients completed the 12-item Short-Form Health Survey Version 2 (SF-12v2) to assess health-related quality of life at both time points.Results: Average NCCP severity decreased between baseline and the six-month follow-up (p < .001) and was higher in the patients with comorbid PD or GAD (p < .001) at both time points compared to those with NCCP only. However, average NCCP severity did not differ between patients with PD and those with GAD (p = 0.901). The physical component of quality of life improved over time (p = 0.016) and was significantly lower in the subset of patients with PD with or without comorbid GAD compared to the other groups (p < .001). A significant time x group interaction was found for the mental component of quality of life (p = 0.0499). GAD with or without comorbid PD was associated with a lower mental quality of life, and this effect increased at the six-month follow-up.Conclusions: Comorbid PD or GAD are prospectively associated with increased chest pain severity and lowered health-related quality of life in patients with NCCP. PD appears to be mainly associated with the physical component of quality of life, while GAD has a greater association with the mental component. Knowledge of these differences could help in the management of patients with NCCP and these comorbidities. [ABSTRACT FROM AUTHOR]

This study documented the 6-month incidence of panic disorder and its predictors in emergency department patients with panic attacks and non-cardiac chest pain. The assessment included a validated structured interview to identify panic attacks and questionnaires measuring the potential predictors of panic disorder. Presence of panic disorder was assessed 6 months later. The incidence of panic disorder was 10.1 percent (n = 14/138). Anxiety sensitivity was the only significant predictor of the incidence of panic disorder (odds ratio = 1.06; 95% confidence interval = 1.01–1.12). Patients with panic attacks and non-cardiac chest pain are at an elevated risk for panic disorder. This vulnerability appears to increase with anxiety sensitivity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Low back pain and sciatica caused by herniated lumbar discs (HLDs) are common complaints among patients visiting pain clinics. Among the various therapeutic methods, intradiscal ozone injections have emerged as an effective alternative or additional treatment option for HLDs. OBJECTIVE: This meta-analysis aimed to investigate the effectiveness of intradiscal ozone injections in the treatment of HLDs. METHODS: We searched the PubMed, Embase, Cochrane Library, and Scopus databases for relevant studies published until January 25, 2024. We included studies that investigated the efficacy of intradiscal ozone injections in patients with HLDs. We evaluated the methodological quality of individual studies using the Cochrane Collaboration tool. RESULTS: At ⩾ 6 months after treatment, the therapeutic effect of intradiscal ozone injections in patients with HLDs was greater than that of steroid injections (treatment success rate, 6 months: odds ratio = 3.95, 95% confidence interval [CI] [2.44, 6.39], P < 0.01) or conventional medications (changes in the Visual Analog Scale [VAS], 6 months: standardized mean difference [SMD] = 1.65, 95% CI [1.08, 2.22], P < 0.01; 12 months: SMD = 1.52, 95% CI [0.96, 2.08], P < 0.01) but similar to that of microdiscectomy (changes in VAS, 18 months: SMD = - 0.05, 95% CI [ - 0.67, 0.57], P = 0.87). At < 6 months after treatment, the reduction in the VAS score after intradiscal ozone injections was higher than that after steroid injections (changes in VAS, 1 month: SMD = 2.53, 95% CI [1.84, 3.21], P < 0.01). CONCLUSION: Intradiscal ozone injections may be a useful therapeutic tool in patients with HLDs. Compared with other conventional treatment methods such as steroid injections and oral medications, intradiscal ozone injection has great long-term (⩾ 6 months) effectiveness. [ABSTRACT FROM AUTHOR]

This study examined the prevalence of emergency department visits prompted by panic attacks in patients with non-cardiac chest pain. A validated structured telephone interview was used to assess panic attacks and their association with the emergency department consultation in 1327 emergency department patients with non-cardiac chest pain. Patients reported at least one panic attack in the past 6 months in 34.5 per cent (95% confidence interval: 32.0%–37.1%) of cases, and 77.1 per cent (95% confidence interval: 73.0%–80.7%) of patients who reported panic attacks had visited the emergency department with non-cardiac chest pain following a panic attack. These results indicate that panic attacks may explain a significant proportion of emergency department visits for non-cardiac chest pain. [ABSTRACT FROM AUTHOR]

Objective: To assess work absenteeism and presenteeism, and to identify biopsychosocial predictors of these outcomes in workers with non-cardiac chest pain (NCCP). Methods: This retrospective cohort study included 375 active workers consulting in an emergency room for NCCP. Results: About 66% (247/375) of participants reported work absenteeism in the 3 months preceding the consultation, while 36% (134/375) reported presenteeism during the same period. A family income >$29,999, and reporting at least a mild impact of chest pain on family functioning, social functioning, or physical activities, were associated with work absenteeism. Presenteeism was associated with younger age, symptoms of depression, and heart-focused anxiety. Conclusions: Work absenteeism and presenteeism are highly prevalent among patients with NCCP. Family income and impacts of NCCP on functioning, are associated with increased occupational burden in these patients. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to estimate the incidence of medical consultations six months after an emergency department (ED) consultation for non-cardiac chest pain (NCCP). It also investigated the role of heart-focused anxiety (HFA) and other factors in predicting an increased healthcare utilization in these patients. Method This was a prospective study of 428 patients who came to an ED with NCCP. Patients completed an interview and questionnaires assessing HFA, psychological distress, the characteristics of NCCP, and comorbidities. Their medical consultations were assessed by telephone interview six months later. The contribution of each factor was assessed using a binomial negative regression. Results Eighty-three percent of patients reported at least one medical consultation (mean = 3.1, standard deviation = 3.9). HFA (incident rate ratio 1.01; 95% CI, 1.00–1.02), the presence of a medical condition (2.14; 1.51–3.03), NCCP frequency (1.49; 1.16–1.91) and NCCP-related interference (1.08; 1.04–1.13) were predictive of further medical consultations. Conclusions A significant proportion of patients with NCCP are at risk of multiple medical consultations following discharge from the ED. HFA appears as a determinant of medical consultations after controlling for multiple confounding factors. [ABSTRACT FROM AUTHOR]

Twenty-five percent of children with ADHD also have an anxiety disorder (AD). As per Quay and in light of Barkley's model, anxiety may have a protective effect on cognitive deficits and behaviors associated with ADHD. This study aimed to evaluate the effect of treating AD on cognitive deficits and behaviors associated with ADHD in children with both disorders. Twenty-four children with ADHD and AD were divided into two groups: treatment for AD, and wait list. Participants were assessed at pre-treatment, post-treatment, and 6-month follow-up with the ADIS-C, the CBCL, and neuropsychological measures. The results revealed a significant improvement in automatic response inhibition and flexibility, and a decrease in inattention/hyperactivity behaviors following the treatment for AD. No significant differences were observed in motor response inhibition, working memory, or attention deficits. The results do not seem to support Quay's hypothesis: treating AD did not exacerbate cognitive deficits and behaviors associated with ADHD in our sample. [ABSTRACT FROM AUTHOR]

Objective To compare equivalent doses of a nonparticulate (dexamethasone) with a particulate (betamethasone) corticosteroid in lumbar transforaminal epidural steroid injections (TFESIs) in terms of pain, function, and complications. Design Fifty-six patients presenting with debilitating radicular pain were randomized in a double-blind controlled trial to receive a lumbar transforaminal injection of either dexamethasone 7.5 mg (n = 29) or betamethasone 6.0 mg (n = 27). Setting A pain clinic and physical medicine and rehabilitation department in two academic hospital centres. Outcome Measures Data were collected at 1-, 3-, and 6-month follow-ups. The primary outcome was pain reduction on a visual analog scale (VAS) at 3 months. Secondary outcomes were functional improvement, as measured by the Oswestry Disability Index (ODI), and number and type of complications. Results No differences on the VAS, analyzed either as a continuous ( P = 0.209) or categorical variable (≥50% ( P = 0.058) or ≥75% ( P = 0.865) improvement) and ODI ( P = 0.181) were found between the two groups at 3 months. At 6 months, improvement of ODI score was at the limit of statistical significance in favor of dexamethasone ( P = 0.050). Multivariate regression analysis, adjusting for potential confounding variables, showed that differences on the ODI became statistically significant at the 6 month follow-up, also in favor of dexamethasone (adjusted P = 0.003). No serious complications were observed in either group. Conclusion According to this study, pain relief and functional improvement are similar for both dexamethasone and betamethasone at 3 months. Considering its safety profile, dexamethasone could be considered as first choice for TFESI. However, given that the study was underpowered, more research is needed to support a recommendation of systematically using dexamethasone in TFESI. [ABSTRACT FROM AUTHOR]

• The study examined the influence of a nutritional labelling on food choice strategies of French students in a computer-based meal composition task. • When considering dishes individually, no significant effects of the labelling could be observed but revealed marked effects on meal composition strategies. • Two types of behaviors seemed to emerge under the influence of the nutritional labelling: homogeneous behaviors, where starters and desserts tended to have similar scores and compensatory behaviors where meals composed were made of foods with contrasted nutritional scores. • When considering the composition of an entire meal, the effect of a nutritional labelling can have complex consequences on food decision that extend beyond the selection of food items taken individually. Nutritional information via simplified labelling on products' front of pack has become common in retail stores and is now concerning nowcollective catering. While numerous studies have investigated the effects of such information policies on consumers' decisions in shops, few studies have focused on choices made in collective catering. In such settings, consumers must compose a meal by combining dishes to be eaten during the same occasion. Each choice is then dependent of the selection of other foods, yielding a different decision problem as in a store where items are selected independently of one another. The aim of this study was to understand whether a nutritional labelling, (Nutri-Score®), modified the choices of consumers and more precisely modified the meal composition strategies - the associations between dishes made by consumers. A computerized menu composition task was designed, 371 participants were randomly redirected either to an interface displaying the Nutri-Score® of dishes, or to an interface showing the dishes without Nutri-Score®. Bayesian logistic regressions were used to explore dependency relationships between foods in presence or absence of Nutri-Score®. When considering dishes individually, no significant effects of the Nutri-Score® were observed, but significant effects of the Nutri-Score® on composition strategies could be observed. Two types of strategies seemed to emerge: homogeneous behaviors, where selected dishes had similar scores and, compensatory behaviors where selected dishes had contrasted scores. In conclusion, the effect of a nutritional labelling can have complex consequences on food decisions that extend beyond the selection of food items taken individually. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and function as transcription factors that regulate gene expression in numerous biological processes. Although the PPARβ/δ subtype is highly expressed in the brain, its physiological roles in neuronal function remain to be elucidated. In this study, we examined the presence of PPARβ/δ in the master circadian clock of the Syrian hamster and investigated its putative functional role in this structure. In mammals, the central circadian clock, located in the suprachiasmatic nucleus (SCN), is entrained by the light-dark (LD) cycle via photic6 signals conveyed by a direct pathway whose terminals release glutamate. Using immunocytochemical and qRT-PCR analysis, we demonstrated that the rhythmic expression of PPAR β/δ within the SCN of hamsters raised under an LD cycle was detectable only at the transcriptional level when the hamsters were maintained under constant darkness (DD). The increase in the number of immunoreactive PPARβ/δ cells observed under DD after light stimulation during the early subjective night (CT14), but not during the subjective day (CT06), demonstrated that the expression of PPARβ/δ can be up-regulated according to the photosensitive phase of the circadian clock. All of the PPARβ/δ-positive cells in the SCN also expressed the glutamate receptor NMDAR1. Moreover, we demonstrated that at the photosensitive point (CT14), the administration of L-16504, a specific agonist of PPARβ/δ, amplified the phase delay of the locomotor response induced by a light pulse. Taken together, these data suggest that PPARβ/δ activation modulates glutamate release that mediates entrainment of the circadian clock by light. [ABSTRACT FROM AUTHOR]

Distress tolerance (DT) has been conceptualized as a vulnerability factor for several psychopathologies. A five factor model of DT has been suggested, but its associations with anxiety and anxiety sensitivity have yet to be explored. This study aimed to further validate the five-factor model of DT, identify the associations between its factors and elevated anxiety, and assess if anxiety sensitivity mediates the association between DT and anxiety. This observational study included 330 students and university workers (women = 82.7%; mean age = 27.7 years, SD = 9.4). They completed online questionnaires assessing DT, anxiety sensitivity and anxiety levels. The five-factor model was a good fit to the data (RMSEA =.04). Two factors, and the sex of the participants, contributed to the variance in anxiety (r2 =.418, p <.001). Tolerance of negative emotion was directly (β = −1.98, 95% CI = [−2.53, −1.42]) and indirectly (β = −1.10, 95% CI = [−1.55, -.78]) associated with lower anxiety through anxiety sensitivity. Tolerance of uncertainty was also directly (β = -.08, 95% CI = [-.10, -.06]) and indirectly (β = -.04, 95% CI = [-.05, -.02]) associated with lower anxiety through anxiety sensitivity. Tolerance of negative emotion and uncertainty were associated with anxiety independently of the other factors of DT. These associations seem partially explained by the effect of anxiety sensitivity. [ABSTRACT FROM AUTHOR]

Abstract: Biochemical evidence suggests a role for n-3 polyunsaturated fatty acids (n-3 PUFAs) in the regulation of behavioral disturbances. A number of studies have revealed an association between reduced n-3 PUFA levels and attention-deficit hyperactivity disorder or depression. Here, we summarize the main findings regarding the association between n-3 PUFA and hyperactive and emotional disorders, and discuss potential mechanisms of action. Because the basal ganglia are involved in the control of locomotion and emotion, we examined published data regarding the role of n-3 PUFA in dopamine (DA) regulation in the basal ganglia. These results are discussed in the light of recent data from our laboratory suggesting an association between the drop in melatonin in the pineal gland and the increase in DA in the striatum and nucleus accumbens of n-3 PUFA-deprived rodents. [ABSTRACT FROM AUTHOR]

The existence of a complex population of mRNAs in human sperm is well documented but their role is not completely elucidated. Evidence for a latent transcriptional capacity and/or a potential translation de novo in mature spermatozoa from fertile men has been provided and is helpful in understanding the final steps of sperm maturation (capacitation and/or the acrosome reaction). Spermatogenesis is controlled by gonadotrophins and testosterone, their effects are modulated by locally-produced factors that include estrogens derived from the irreversible transformation of androgens by aromatase. The data demonstrating an additional source of estrogens in rat germ cells along with several studies showing a decreased sperm motility in men deficient in aromatase has led to the further explanation of the expression of aromatase in ejaculated spermatozoa from fertile men. A significant decrease in the amount of aromatase transcripts in the immotile sperm fraction was recorded. In addition, the levels of transcripts encoding for proteins involved in either nuclear condensation protamines 1 and 2 (Prm1 and Prm2) or in capacitation endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide sythase (nNOS) and c-myc were compared in low and high motile sperm prepared from the same sample. No significant change in the ratio of c-myc/Prm2 between the two populations of spermatozoa was observed. Conversely the amount of Prm1 mRNA was significantly higher in the low motile fraction than in the high motile fraction; in most of the high motile sperm samples analyzed, eNOS and nNOS transcripts were undetectable, whereas they were observed in low motile sperm. Moreover, a partial or complete disappearance of c-myc transcripts was observed after capacitation. Analysis of the mRNA profile in human ejaculated sperm could be helpful either as a diagnostic tool to evaluate the male gamete quality and/or as a prognostic value for fertilization and embryo development. [ABSTRACT FROM AUTHOR]

Objectives: The aims of the study are to assess the incidence of systemic adverse effects and complications of ultrasound-guided and fluoroscopy-guided glucocorticoid injections and to identify associated risk factors. Design: This retrospective cohort study compared participants who received a glucocorticoid injection at the outpatient clinic and participants who had an appointment but did not receive a glucocorticoid injection. Participants were called to verify whether they had experienced any of the predetermined systemic adverse effects and complications. Multiple binary logistic regression was used to identify systemic adverse effect and complication risk factors. Results: There were 1010 participants in the glucocorticoid injection group and 328 in the nonglucocorticoid injection group. There was no statistically significant difference in the occurrence of systemic infection and decompensated heart failure between the two groups. More participants in the glucocorticoid injection group developed abnormal uterine bleeding and erectile dysfunction, but the differences did not reach statistical significance. Female participants were 1.9 times more likely to develop systemic adverse effects ( P < 0.001). Younger age ( P < 0.001), diabetes ( P = 0.012), and higher glucocorticoid injection doses ( P = 0.024) were also associated with an increased risk of developing systemic adverse effects. Conclusions: Identified risk factors for developing glucocorticoid injection systemic adverse effects were younger age, female sex, diabetes, tobacco use, and high glucocorticoid injection doses. [ABSTRACT FROM AUTHOR]

This study sought to describe the 2-year evolution of the intensity and frequency of noncardiac chest pain (NCCP), NCCP-related disability and health-related quality of life in a cohort of emergency department (ED) patients. It also aimed to identify and characterize subgroups of patients who share similar NCCP trajectories. 672 consecutive patients with NCCP were prospectively recruited in two EDs. NCCP, physical and mental health-related quality of life and pain-related impairment were assessed at baseline and 6 months, 1 year and 2 years after the index ED visit. Significant reductions in the intensity and frequency of NCCP and in NCCP-related disability were observed over time, with 58.1% of patients being considered NCCP-free at the 2-year follow-up. Four trajectories of NCCP intensity were identified through latent class growth mixture modelling: Worsening Trajectory (6.8%), Persistence Trajectory (20.5%), Limited Improvement Trajectory (13.1%) and Remission Trajectory (59.5%). Physical quality of life was significantly higher in the latter two trajectories at all assessment points. Patients in the Remission Trajectory reported a better mental quality of life and a greater decrease in NCCP-related disability over time than those in the other trajectories. Over 40% of ED patients with NCCP experienced persistent biopsychosocial morbidity that warrants further clinical attention. • At the cohort level, the prognosis of ED patients with NCCP appears favorable. • Patients-centered analyses revealed an heterogenous prognosis of NCCP. • Over 40% of patients with NCCP experienced an unfavorable prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Over the past decade, France has experienced two major reforms of its health system. Reform constitutes of the law of March the 4th 2002 has upset the relationship between health professionals and patients by introducing into the Public Health Code (CSP) a set of provisions on the right of patients and users of the health system (first legislative and regulatory part of the CSP). Reform of July, the 22nd 2009 at amending the relationships between different health professionals by encouraging them to work more through multiple channels (multidisciplinary meeting, personalized patient education…). Furthermore, this reform ended the division between the hospital, that of “city” and the medico-social environment. Consequently, drug regulation has been largely modified from the pivotal role of the pharmacist among health professionals. Nevertheless, the publication of Good Dispensing Practices (BPD) announced in the CSP are still not published. Thus waiting for the publication of these BPD, it seemed appropriate to produce a summary as complete as possible on the regulations related to pharmaceutical dispensing. [Copyright &y& Elsevier]

Anxiety disorder (AD) comorbidity in children with attention deficit hyperactivity disorder (ADHD) is common, with a prevalence ranging from 25 % of youth in the general population to 40 % of youth in the clinical population. Cognitivebehavioral therapy (CBT) is the recommended first line psychotherapy for children with anxiety disorders. However, the presence of comorbid ADHD may affect the response to CBT for anxiety. This systematic review aims to assess whether and how the presence of comorbid ADHD affects the efficacy of CBT for AD in children aged 4 to 18 years. A systematic review of the literature was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA; Moher et al., 2009). The narrative review of the selected studies indicates a significant reduction of anxiety symptoms in children with comorbid AD and ADHD that appears similar to the one observed in children without comorbid ADHD. Parental participation and ADHD-specific adaptations to CBT may explain these results. [ABSTRACT FROM AUTHOR]

Background: A low-protein diet can induce compensatory intake of excess energy. This must be better evaluated to anticipate the obesogenic risk that may result from the dietary recommendations for reducing animal protein consumption.Objectives: We aimed to further characterize the behavioral and physiological responses to a reduction in dietary protein and to identify the determinants of protein appetite.Methods: Thirty-two male Wistar rats [4 wk old, (mean ± SEM) 135 ± 32 g body weight] were fed a low-protein (LP; 6% energy value) or normal-protein (NP; 20%) diet for 8 wk. Food intake and body mass were measured during the entire intervention. During self-selection sessions after 4 wk of experimental diets, we evaluated rat food preference between LP, NP, or high-protein (HP; 55%) pellets. At the end of the experiment, we assessed their hedonic response [ultrasonic vocalizations (USVs)] and c-Fos neuronal activation in the olfactory tubercle and nucleus accumbens (NAcc) associated with an LP or HP meal.Results: Rats fed an LP diet had greater food intake (24%), body weight (5%), and visceral adiposity (30%) than NP rats. All LP rats and half of the NP rats showed a nearly exclusive preference for HP pellets during self-selection sessions, whereas the other half of the NP rats showed no preference. This suggests that the appetite for proteins is driven not only by a low protein status but also by individual traits in NP rats. LP or HP meal induced similar USV emission and similar neuronal activation in the NAcc in feed-deprived LP and NP rats, showing no specific response linked to protein appetite.Conclusions: Protein appetite in rats is driven by low protein status or individual preferences in rats receiving adequate protein amounts. This must be considered and further analyzed, in the context of current recommendations for protein intake reduction. [ABSTRACT FROM AUTHOR]

Background: Noncardiac chest pain (NCCP) is one of the leading reasons for emergency department visits and significantly limits patients' daily functioning. The protective effect of physical activity has been established in a number of pain problems, but its role in the course of NCCP is unknown. This study aimed to document the level of physical activity in patients with NCCP and its association with NCCP-related disability in the 6 months following an emergency department visit. Methods: In this prospective, longitudinal, cohort study, participants with NCCP were recruited in two emergency departments. They were contacted by telephone for the purpose of conducting a medical and sociodemographic interview, after which a set of questionnaires was sent to them. Participants were contacted again 6 months later for an interview aimed to assess their NCCP-related disability. Results: The final sample consisted of 279 participants (57.0% females), whose mean age was 54.6 (standard deviation = 15.3) years. Overall, the proportion of participants who were physically active in their leisure time, based on the Actimètre questionnaire criteria, was 22.0%. Being physically active at the first measurement time point was associated with a 38% reduction in the risk of reporting NCCP-related disability in the following 6 months (ρ =.047). This association remained significant after controlling for confounding variables. Conclusions: Being physically active seems to have a protective effect on the occurrence of NCCP-related disability in the 6 months following an emergency department visit with NCCP. These results point to the importance of further exploring the benefits of physical activity in this population. [ABSTRACT FROM AUTHOR]

The many functions of astrocytes, such as glutamate recycling and morphological plasticity, enable them to stabilize synapses environment and protect neurons. Little is known about how they adapt to glucocorticoid-induced stress, and even less about the influence of dietary factors. We previously showed that omega-3 polyunsaturated fatty acids (ω3PUFA), dietary fats which alleviate stress responses, influence the way astroglia regulate glutamatergic synapses. We have explored the role of docosahexaenoic acid (DHA), the main ω3PUFA, in the astroglial responses to corticosterone, the main stress hormone in rodents to determine whether ω3PUFA help astrocytes resist stress. Cultured rat astrocytes were enriched in DHA or arachidonic acid (AA, the main ω6PUFA) and given 100 nM corticosterone for several days. Corticosterone stimulated astrocyte glutamate recycling by increasing glutamate uptake and glutamine synthetase (GS), and altered the astrocyte cytoskeleton. DHA-enriched astrocytes no longer responded to the action of corticosterone on glutamate uptake, had decreased GS, and the cytoskeletal effect of corticosterone was delayed, while AA-enriched cells were unaffected. The DHA-dependent anti-corticosterone effect was related to fewer glucocorticoid receptors, while corticosterone increased DHA incorporation into astrocyte membranes. Thus, DHA helps astrocytes resist the influence of corticosterone, so perhaps promoting a sustainable response by the stressed brain. [ABSTRACT FROM AUTHOR]

Roundup is the major pesticide used in agriculture worldwide; it is a glyphosate-based herbicide. Its molecular effects are studied following an acute exposure (0.5%) of fifteen 60-day-old male rats during an 8-day period. Endocrine (aromatase, estrogen and androgen receptors, Gper1 in testicular and sperm mRNAs) and testicular functions (organ weights, sperm parameters and expression of the blood-testis barrier markers) were monitored at days 68, 87, and 122 after treatment, spermiogenesis and spermatogenesis. The major disruption is an increase of aromatase mRNA levels at least by 50% in treated rats at all times, as well as the aromatase protein. We have also shown a similar increase of Gper1 expression at day 122 and a light modification of BTB markers. A rise of abnormal sperm morphology and a decrease of the expression of protamine 1 and histone 1 testicular in epididymal sperm are observed despite a normal sperm concentration and motility. [ABSTRACT FROM AUTHOR]

Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized. [ABSTRACT FROM AUTHOR]

Epidemiological data suggest that a poor ω3 status favoured by the low ω3/ω6 polyunsaturated fatty acids ratio in western diets contributes to cognitive decline in the elderly, but mechanistic evidence is lacking. We therefore explored the impact of ω3 deficiency on the evolution of glutamatergic transmission in the CA1 of the hippocampus during aging by comparing 4 groups of rats aged 6-22 months fed ω3-deficient or ω3/ω6-balanced diets from conception to sacrifice: Young ω3 Balanced ( YB) or Deficient ( YD), Old ω3 Balanced ( OB) or Deficient ( OD) rats. ω3 Deficiency induced a 65% decrease in the amount of docosahexaenoic acid ( DHA, the main ω3 in cell membranes) in brain phospholipids, but had no impact on glutamatergic transmission and astroglial function in young rats. Aging induced a 10% decrease in brain DHA, a 35% reduction of synaptic efficacy ( fEPSP/ PFV) due to decreased presynaptic glutamate release and a 30% decrease in the astroglial glutamate uptake associated with a marked astrogliosis (+100% GFAP). The ω3 deficiency further decreased these hallmarks of aging ( OD vs. OB rats: −35% fEPSP/PFV P < 0.05, −15% astroglial glutamate uptake P < 0.001, +30% GFAP P < 0.01). This cannot be attributed to aggravation of the brain DHA deficit because the brains of OD rats had more DHA than those of YD rats. Thus, ω3 deficiency worsens the age-induced degradation of glutamatergic transmission and its associated astroglial regulation in the hippocampus. [ABSTRACT FROM AUTHOR]

Abstract: The pharmacist working in the dispensary, in PUI or in other dispensation structures, is exposed to several types of legal actions for negligence and/or damage. Like all others, the pharmacist is subject to common law allowing her to seek civil or criminal liability. Also as a member of an organized profession in professional, the pharmacist is also subject to an ethics designed to seek its moral responsibility to his peer''s pharmacists. For a decade, the pharmacist has acquired through its pivotal role between the different health professionals, new possibilities for action (therapeutic education, status of matching pharmacist, pharmacist referent status of residential homes for elderly dependents…). This leads to increasing research responsibility of the practitioner during actions in justices. Of the large number and scattered texts that regulate the service of dispensing pharmaceuticals, the pharmacist often has difficulty in understanding the scope and limits of its responsibilities in a dispensation. It therefore seemed appropriate to produce a summary as complete as possible civil liability, criminal and disciplinary related to the pharmacist dispensing the drug. [Copyright &y& Elsevier]

Omega-3 fatty acids are important for several neuronal and cognitive functions. Altered omega-3 fatty acid status has been implicated in reduced resistance to stress and mood disorders. We therefore evaluated the effects of repeated restraint stress (6 h/day for 21 days) on adult rats fed omega-3 deficient, control or omega-3 enriched diets from conception. We measured body weight, plasma corticosterone and hippocampus glucocorticoid receptors and correlated these data with emotional and depression-like behaviour assessed by their open-field (OF) activity, anxiety in the elevated-plus maze (EPM), the sucrose preference test and the startle response. We also determined their plasma and brain membrane lipid profiles by gas chromatography. Repeated restraint stress caused rats fed a control diet to lose weight. Their plasma corticosterone increased and they showed moderate behavioural changes, with increases only in grooming (OF test) and entries into the open arms (EPM). Rats fed the omega-3 enriched diet had a lower stress-induced weight loss and plasma corticosterone peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited an increased startle response, a stressinduced decrease in locomotor activity and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary omega-3 fatty acids increased; diets containing preformed long-chain omega-3 fatty acid were better than diets containing the precursor alpha-linolenic acid. However, the restraint stress reduced the amounts of omega-3 incorporated. These data showed that the response to chronic restraint stress was modulated by the omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment protecting against stress. [ABSTRACT FROM AUTHOR]

This study aims to determine whether the regulation of extracellular glutamate is altered during aging and its possible consequences on synaptic transmission and plasticity. A decrease in the expression of the glial glutamate transporters GLAST and GLT-1 and reduced glutamate uptake occur in the aged (24–27 months) Sprague–Dawley rat hippocampus. Glutamatergic excitatory postsynaptic potentials recorded extracellularly in ex vivo hippocampal slices from adult (3–5 months) and aged rats are depressed by DL-TBOA, an inhibitor of glutamate transporter activity, in an N-Methyl-d-Aspartate (NMDA)-receptor-dependent manner. In aged but not in young rats, part of the depressing effect of DL-TBOA also involves metabotropic glutamate receptor (mGluRs) activation as it is significantly reduced by the specific mGluR antagonist d-methyl-4-carboxy-phenylglycine (MCPG). The paired-pulse facilitation ratio, a functional index of glutamate release, is reduced by MCPG in aged slices to a level comparable to that in young rats both under control conditions and after being enhanced by DL-TBOA. These results suggest that the age-associated glutamate uptake deficiency favors presynaptic mGluR activation that lowers glutamate release. In parallel, 2 Hz-induced long-term depression is significantly decreased in aged animals and is fully restored by MCPG. All these data indicate a facilitated activation of extrasynaptic NMDAR and mGluRs in aged rats, possibly because of an altered distribution of glutamate in the extrasynaptic space. This in turn affects synaptic transmission and plasticity within the aged hippocampal CA1 network. [ABSTRACT FROM AUTHOR]

Abstract: Brain cells are especially rich in polyunsaturated fatty acids (PUFA), mainly the n-3 PUFA docosahexaenoic acid (DHA) and the n-6 PUFA arachidonic acid (AA). They are released from membranes by PLA2 during neurotransmission, and may regulate glutamate uptake by astroglia, involved in controlling glutamatergic transmission. AA has been shown to inhibit glutamate transport in several model systems, but the contribution of DHA is less clear and has not been evaluated in astrocytes. Because the high DHA content of brain membranes is essential for brain function, we investigated the role of DHA in the regulation of astroglial glutamate transport. We evaluated the actions of DHA and AA using cultured rat astrocytes and suspensions of rat brain membranes (P1 fractions). DHA reduced d-[3H]aspartate uptake by cultured astrocytes and cortical membrane suspensions, while AA did not. This also occurred in astrocytes enriched with α-tocopherol, indicating that it was not due to peroxidation products. The reduction of d-[3H]aspartate uptake by DHA did not involve any change in the concentrations of membrane-associated astroglial glutamate transporters (GLAST and GLT-1), suggesting that DHA reduced the activity of the transporters. In contrast with the inhibition induced by free-DHA, we found no effect of membrane-bound DHA on d-[3H]aspartate uptake. Indeed, the uptake was similar in astrocytes with varying amount of DHA in their membrane (induced by long-term supplementation with DHA or AA). Therefore, DHA reduces glutamate uptake through a signal-like effect but not through changes in the PUFA composition of the astrocyte membranes. Also, reactive astrocytes, induced by a medium supplement (G5), were insensitive to DHA. This suggests that DHA regulates synaptic glutamate under basal condition but does not impair glutamate scavenging under reactive conditions. These results indicate that DHA slows astroglial glutamate transport via a specific signal-like effect, and may thus be a physiological synaptic regulator. [Copyright &y& Elsevier]

Perturbations of cholesterol metabolism have been linked to neurodegenerative diseases. Glia–neuron crosstalk is essential to achieve a tight regulation of brain cholesterol trafficking. Adequate cholesterol supply from glia via apolipoprotein E-containing lipoproteins ensures neuronal development and function. The lipolysis-stimulated lipoprotein receptor (LSR), plays an important role in brain cholesterol homeostasis. Aged heterozygote Lsr+/− mice show altered brain cholesterol distribution and increased susceptibility to amyloid stress. Since LSR expression is higher in astroglia as compared to neurons, we sought to determine if astroglial LSR deficiency could lead to cognitive defects similar to those of Alzheimer's disease (AD). Cre recombinase was activated in adult Glast-CreERT/lsrfl/fl mice by tamoxifen to induce astroglial Lsr deletion. Behavioral phenotyping of young and old astroglial Lsr KO animals revealed hyperactivity during the nocturnal period, deficits in olfactory function affecting social memory and causing possible apathy, as well as visual memory and short-term working memory problems, and deficits similar to those reported in neurodegenerative diseases, such as AD. Furthermore, GFAP staining revealed astroglial activation in the olfactory bulb. Therefore, astroglial LSR is important for working, spatial, and social memory related to sensory input, and represents a novel pathway for the study of brain aging and neurodegeneration. [ABSTRACT FROM AUTHOR]

Several studies suggest that (n-3) PUFA may play a role in the regulation of cognitive functions, locomotor and exploratory activity, and affective disorders. Additionally, (n-3) PUFA affect pineal function, which is implicated in the sleep-wake rhythm. However, no studies to our knowledge have explored the role of PUFA on the circadian system. We investigated the effect of an (n-3) PUFA-deficient diet on locomotor and pineal melatonin rhythms in Syrian hamsters used as model species in circadian rhythm research. To assess the possible relationship between voluntary wheel running activity and dopaminergic neurotransmission, we also measured endogenous monoamine concentrations in the striatum. Two-month-old male hamsters, fed either an (n-3) PUFA-deficient or an (n-3) PUFA-adequate diet, were housed individually in cages equipped with run wheels. At 3 mo, cerebral structures were extracted for biochemical and cellular analysis. In {n-3) PUFA-deficient hamsters, the induced changes in the pineal PUFA membrane phospholipid composition were associated with a reduction in the nocturnal peak level of melatonin that was 52% lower than in control hamsters (P < 0.001). The (n-3) PUFA-deficient hamsters also had higher diurnal (P < 0.01) and nocturnal (P = 0.001) locomotor activity than the control hamsters, in parallel with activation of striatal dopaminergic function (P< 0.05). The (n-3) PUFA-deficient hamsters exhibited several symptoms: chronic locomotor hyperactivity, disturbance in melatonin rhythm, and striatal hyperdopaminergia. We suggest that an (n-3) PUFA-deficient diet lessens the melatonin rhythm, weakens endogenous functioning of the circadian clock, and plays a role in nocturnal sleep disturbances as described in attention deficit/hyperactivity disorder. [ABSTRACT FROM AUTHOR]

Although it is agreed that n-3 polyunsaturated fatty acids (PUFAs) are important for brain function, it has yet to be demonstrated how they are involved in precise cellular mechanisms. We investigated the role of enhanced n-3 PUFA in astrocyte membranes on the gap junction capacity of these cells. Astrocytes isolated from newborn rat cortices were grown in medium supplemented with docosahexaenoic acid (DHA), the main n-3 PUFA in cell membranes, or arachidonic acid (AA), the main n-6 PUFA, plus an antioxidant (α-tocopherol or N-acetyl-cystein) to prevent peroxidation. The resulting three populations of astrocytes differed markedly in their n-3 : n-6 PUFA ratios in phosphatidylethanolamine and phosphatidylcholine, the main phospholipids in membranes. DHA-supplemented cells had a physiological high n-3 : n-6 ratio (1.58), unsupplemented cells had a low n-3 : n-6 ratio (0.66) and AA-supplemented cells had a very low n-3 : n-6 ratio (0.36), with excess n-6 PUFA. DHA-supplemented astrocytes had a greater gap junction capacity than unsupplemented cells or AA-supplemented cells. The enhanced gap junction coupling of DHA-enriched cells was associated with a more functional distribution of connexin 43 at cell interfaces (shown by immunocytochemistry) and more of the main phosphorylated isoform of connexin 43. These findings suggest that the high n-3 : n-6 PUFA ratio that occurs naturally in astrocyte membranes is needed for optimal gap junction coupling in these cells. [ABSTRACT FROM AUTHOR]

Abstract: Polyunsaturated fatty acids (PUFAs) of the n-3 series, and notably docosahexaenoic acid (22:6n-3, DHA), are essential nutriments to ensure an optimal development of the central nervous system. Indeed due to its exceptionally high concentration in the excitable membranes of the brain and retina, the DHA exerts a fundamental role in the physiology of these tissues (structural properties, precursor of endoperoxide molecules, regulating action on the synaptic activity and the expression of genes). In experimental animal models (rodents, monkey), the fall of the DHA membrane content, induced by a diet deficient in n-3 PUFAs, is accompanied by the reduction in the learning capacities (memory, attention, motivation) and visual discrimination. Several cases of nutritional deficiencies have also been reported in man, notably in newborn infants who presented a delay in the development of their visual acuity. The consumption of n-3 PUFAs could be crucial in the appearance of some neuropsychiatric disorders (hyperactivity in children, schizophrenia, depression, ...), in relation with a second n-3 PUFA, eicosapentaenoic acid (EPA, 20:5n-3). It could also have beneficial effect in the incidence of neuropathologies associated with ageing as is suggested in recent epidemiological and prospective studies (Alzheimer disease, senile dementia). [Copyright &y& Elsevier]

The cytochrome P450 aromatase (P450arom) is the terminal enzyme responsible for the formation of estrogens from androgens. In the rat testis we have immunolocalized the P450arom not only in Leydig cells but also in germ cells and especially in elongated spermatids. Related to the stage of germ cell maturation, we have shown that the level of P450arom transcripts decreases, it is much more abundant in pachytene spermatocytes (PS) than in mature germ cells whereas the aromatase activity is two- to fourfold greater in spermatozoa when compared to younger germ cell preparations. In rat germ cells, the aromatase gene expression is not only under androgen and cyclic AMP control but also subjected to cytokine (TNFα) and growth factor (TGFβ) regulation. In the bank-vole testis we have evidenced a positive correlation between a fully developed spermatogenesis and a strong immunoreactivity for both P450arom and estrogen receptor (ERβ) not only in Sertoli cells but also in PS and round spermatids (RS). Therefore, the aromatase gene expression and its translation in a fully active protein in rodent germ cells evidence an additional site for estrogen production within the testis. Our recent data showing that human ejaculated spermatozoa expressed specific transcripts for P450arom reinforced the observations reported in germ cells of other mammalian species. Together with the widespread distribution of ERs in testicular cells these data bring enlightenment on the hormonal regulation of spermatogenesis. [Copyright &y& Elsevier]