Multi-cohort analysis of depression-associated gut bacteria sheds insight on bacterial biomarkers across populations.

Gut microbes are associated with the development of depression based on extensive evidence. However, previous studies have led to conflicting reports on this association, posing challenges to the application of gut bacteria in the diagnostics and treatment of depression. To minimise heterogenicity in data analysis, the present meta-analysis adopted a standardised bioinformatics and statistical pipeline to analyse 16S rRNA sequences of 1827 samples from eight different cohorts. Although changes in the overall bacterial community were identified by our meta-analysis, depressive-correlated changes in alpha-diversity were absent. Enrichment of Bacteroidetes, Parabacteroides, Barnesiella, Bacteroides, and Bacteroides vulgatus, along with depletion in Firmicutes, Dialister, Oscillospiraceae UCG 003 and UCG 002, and Bacteroides plebeius, were observed in depressive-associated bacteria. By contrast, elevated L-glutamine degradation, and reduced L-glutamate and L-isoleucine biosynthesis were identified in depressive-associated microbiomes. After systemically reviewing the data of these collected cohorts, we have established a bacterial classifier to identify depressive symptoms with AUC 0.834 and 0.685 in the training and external validation dataset, respectively. Moreover, a low-risk bacterial cluster for depressive symptoms was identified, which was represented by a lower abundance of Escherichia-Shigella, and a higher abundance of Faecalibacterium, Oscillospiraceae UCG 002, Ruminococcus, and Christensenellaceae R.7 group.

Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader-Willi Syndrome.

The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader-Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS.

Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events.

OBJECTIVE: The gut microbiota plays a key role in modulating host immune response. We conducted a prospective, observational study to examine gut microbiota composition in association with immune responses and adverse events in adults who have received the inactivated vaccine (CoronaVac; Sinovac) or the mRNA vaccine (BNT162b2; BioNTech; Comirnaty). DESIGN: We performed shotgun metagenomic sequencing in stool samples of 138 COVID-19 vaccinees (37 CoronaVac and 101 BNT162b2 vaccinees) collected at baseline and 1 month after second dose of vaccination. Immune markers were measured by SARS-CoV-2 surrogate virus neutralisation test and spike receptor-binding domain IgG ELISA. RESULTS: We found a significantly lower immune response in recipients of CoronaVac than BNT162b2 vaccines (p<0.05). Bifidobacterium adolescentis was persistently higher in subjects with high neutralising antibodies to CoronaVac vaccine (p=0.023) and their baseline gut microbiome was enriched in pathways related to carbohydrate metabolism (linear discriminant analysis (LDA) scores >2 and p<0.05). Neutralising antibodies in BNT162b2 vaccinees showed a positive correlation with the total abundance of bacteria with flagella and fimbriae including Roseburia faecis (p=0.028). The abundance of Prevotella copri and two Megamonas species were enriched in individuals with fewer adverse events following either of the vaccines indicating that these bacteria may play an anti-inflammatory role in host immune response (LDA scores>3 and p<0.05). CONCLUSION: Our study has identified specific gut microbiota markers in association with improved immune response and reduced adverse events following COVID-19 vaccines. Microbiota-targeted interventions have the potential to complement effectiveness of COVID-19 vaccines.

Ethnicity Associations With Food Sensitization Are Mediated by Gut Microbiota Development in the First Year of Life.

BACKGROUND AND AIMS: Increasing evidence supports the role of early-life gut microbiota in developing atopic diseases, but ecological changes to gut microbiota during infancy in relation to food sensitization remain unclear. We aimed to characterize and associate these changes with the development of food sensitization in children. METHODS: In this observational study, using 16S rRNA amplicon sequencing, we characterized the composition of 2844 fecal microbiota in 1422 Canadian full-term infants. Atopic sensitization outcomes were measured by skin prick tests at age 1 year and 3 years. The association between gut microbiota trajectories, based on longitudinal shifts in community clusters, and atopic sensitization outcomes at age 1 and 3 years were determined. Ethnicity and early-life exposures influencing microbiota trajectories were initially examined, and post-hoc analyses were conducted. RESULTS: Four identified developmental trajectories of gut microbiota were shaped by birth mode and varied by ethnicity. The trajectory with persistently low Bacteroides abundance and high Enterobacteriaceae/Bacteroidaceae ratio throughout infancy increased the risk of sensitization to food allergens, particularly to peanuts at age 3 years by 3-fold (adjusted odds ratio [OR] 2.82, 95% confidence interval [CI] 1.13-7.01). A much higher likelihood for peanut sensitization was found if infants with this trajectory were born to Asian mothers (adjusted OR 7.87, 95% CI 2.75-22.55). It was characterized by a deficiency in sphingolipid metabolism and persistent Clostridioides difficile colonization. Importantly, this trajectory of depleted Bacteroides abundance mediated the association between Asian ethnicity and food sensitization. CONCLUSIONS: This study documented an association between persistently low gut Bacteroides abundance throughout infancy and sensitization to peanuts in childhood. It is the first to show a mediation role for infant gut microbiota in ethnicity-associated development of food sensitization.

From Birth to Overweight and Atopic Disease: Multiple and Common Pathways of the Infant Gut Microbiome.

BACKGROUND & AIMS: Few studies, even those with cohort designs, test the mediating effects of infant gut microbes and metabolites on the onset of disease. We undertook such a study. METHODS: Using structural equation modeling path analysis, we tested directional relationships between first pregnancy, birth mode, prolonged labor and breastfeeding; infant gut microbiota, metabolites, and IgA; and childhood body mass index and atopy in 1667 infants. RESULTS: After both cesarean birth and prolonged labor with a first pregnancy, a higher Enterobacteriaceae/Bacteroidaceae ratio at 3 months was the dominant path to overweight; higher Enterobacteriaceae/Bacteroidaceae ratios and Clostridioides difficile colonization at 12 months were the main pathway to atopic sensitization. Depletion of Bifidobacterium after prolonged labor was a secondary pathway to overweight. Influenced by C difficile colonization at 3 months, metabolites propionate and formate were secondary pathways to child outcomes, with a key finding that formate was at the intersection of several paths. CONCLUSIONS: Pathways from cesarean section and first pregnancy to child overweight and atopy share many common mediators of the infant gut microbiome, notably C difficile colonization.

[The efficacy of esketamine in resistant major depressive disorder: A systematic review of the literature]. / L'efficacité de l'eskétamine dans le trouble dépressif majeur résistant : une revue systématique de la littérature.

OBJECTIVE: Major depression is a significant public health problem since its lifetime prevalence is estimated at 15-18 %. Its standard treatment is based on the use of antidepressant medications but their effectiveness is limited. Indeed, only two thirds of patients with a major depressive episode will reach remission after two lines of conventional treatment. In major depression, there are arguments in favour of disturbances in neuronal glutamatergic transmission. Esketamine appears to have an antidepressant action through modulation of the NMDA receptors involved in this glutamatergic neurotransmission. The aim of this review to systematically investigate the efficacy of esketamine combined with an SSRI or SNRI for major depressive disorder resistant to treatment. METHOD: A systematic review on the efficacy of esketamine in combination with an SSRI or SNRI for resistant major depressive disorder was performed in July 2021 in the PUBMED database according to the PRISMA criteria. The key words used are: "depressed" [All Fields] OR "depression" [MeSH Terms] OR "depression" [All Fields] OR "depressions" [All Fields] OR "depression s" [All Fields] OR "depressive disorder"[MeSH Terms] OR ("depressive"[All Fields] AND"disorder"[All Fields]) OR"depressive disorder"[All Fields] OR"depressivity"[All Fields] OR"depressive"[All Fields] OR "depressively" [All Fields] OR "depressiveness" [All Fields] OR "depressives" [All Fields]) AND ("esketamine" [Supplementary Concept] OR "esketamine" [All Fields] OR "esketamine" [All Fields]. The inclusion criteria were: efficacy on depressive symptoms of intranasal esketamine combined with an SSRI or an SNRI for major depressive disorder resistant to at least two lines of treatment, RCT and meta-analysis, individual≥18 years, articles in English and French. RESULTS: Four randomized double-blind studies were selected on the basis of these criteria. The included studies are of grade A and B which leads to a high level of scientific evidence. CONCLUSIONS: Intranasal esketamine in combination with sertraline, escitalopram, duloxetine or venlafaxine prolonged release is more effective than the monotherapy use of these four molecules for the treatment of resistant depression. It has been shown to be effective for a population aged between 18 and 74 years at doses between 28mg and 84mg. Currently, based on these results, intranasal esketamine should be proposed as a second level of treatment after an unsuccessful trial of two antidepressants. It is nevertheless advisable to be careful in its use in a clinical psychiatric population: exclusion of suicidal ideation or antecedent of suicidal acting, absence of psychotic depression, use exclusively for unipolar major depressive disorder. The different conditions of use are also notified in the product characteristics of the European Medicines Agency. Finally, further comparative studies are needed in the future, in the absence of funding from the pharmaceutical company producing esketamine.

[Atypical depression as a risk factor for obstructive sleep apnea syndrome in young adults]. / La dépression majeure à caractéristique atypique comme facteur de risque du syndrome d'apnées obstructives du sommeil chez le jeune adulte.

OBJECTIVES: In the literature, several studies have investigated the particular relationship between major depression and obstructive sleep apnoea syndrome (OSAS). However, most of these studies have focused primarily on middle-aged to elderly individuals (≥40 years) which means that this problem has been little studied in young adults (<30 years). Nevertheless, in young adults the prevalence of major depression (particularly its atypical subtype) is not negligible, which seems to justify carrying out additional investigations in order to allow a better understanding of the potential role played by major depression in the pathophysiology of OSAS in this particular subpopulation. The aim of this study was therefore to empirically investigate the prevalence of OSAS in young adults and to study the risk of OSAS associated with major depression in this particular subpopulation. METHODS: Polysomnographic and demographic data from 264 young adults were collected from the Erasme Hospital Sleep Laboratory (Brussels, Belgium) database to enable our analyses. During their two-night stay (including a first night of habituation and a night of polysomnography) at the Sleep Laboratory, these individuals underwent a complete somatic assessment (including blood test, electrocardiogram, daytime electroencephalogram and urinalysis), a systematic psychiatric assessment by a unit psychiatrist and an assessment of their complaints related to sleep. These different steps made it possible to systematically diagnose all somatic pathologies, psychiatric disorders according to the diagnostic criteria of the DSM-IV-TR and sleep pathologies according to the diagnostic criteria of the AASM. This allowed the selection of young adults included in our study based on our inclusion and exclusion criteria. Polysomnographic recordings from our Sleep Laboratory were visually scored according to AASM criteria. An obstructive sleep apnoea-hypopnoea index ≥5/hour was used for the diagnosis of OSAS. At the statistical level, in order to allow our analyses, we subdivided our sample of young adults into two groups: a control group without OSAS (n=215) and a patient group with OSAS (n=49). After checking the normal distribution of our data, normally distributed data were analysed with t-tests whereas asymmetrically or dichotomously distributed data were analysed with Wilcoxon tests or Chi2 tests. Univariate regression models were used to study the risk of OSAS associated with major depression (categorized: absent, typical, atypical) in young adults and potential confounding factors. In multivariate regression models, the risk of OSAS associated with major depression (categorized: absent, typical, atypical) in young adults was adjusted only for confounding factors significantly associated with OSAS during univariate analysis. These confounding factors were introduced in a hierarchical manner in the various multivariate regression models constructed. RESULTS: The prevalence of OSAS in our population of young adults was 18.6 %. During univariate analyses, atypical depression [OR 2.51 (95% CI 1.18-5.32), p-value=0.014], male gender [OR 4.53 (95% CI 2.20-9.34), P-value <0.001], presence of snoring [OR 2.51 (95% CI 1.33-4.75), P-value=0.005], presence of at least one cardio-metabolic alteration [OR 2.26 (95% CI 1.19-4.28), P-value=0.012], body mass index>30 kg/m2 [OR 4.55 (95% CI 2.07-10.03), P-value <0.001] and ferritin ≥150 µg/L [OR 3.28 (95% CI 1.69-6.36), P-value<0.001] were associated with increased risk of OSAS in our population of young adults. After adjusting for these major confounding factors associated with OSAS (gender, body mass index, cardio-metabolic alterations, ferritin level, and snoring) in the four models studied, multivariate regression analyses confirmed that unlike typical depression, atypical depression [OR 3.09 (95% CI 1.26-7.54), P-value=0.019] was a risk factor for OSAS in young adults. CONCLUSIONS: In our study, we demonstrated that the prevalence of OSAS was 18.6 % in young adults referred to the Erasme Hospital Sleep Laboratory. In addition, we have shown that unlike typical depression, atypical depression was associated with an increased risk of OSAS in young adults, which seems to justify more systematic research of this pathology in young adults suffering from atypical depression in order to allow the establishment of adapted therapeutic strategies and avoid the negative consequences associated with the co-occurrence of these two pathologies.

Gestational diabetes mellitus is associated with the neonatal gut microbiota and metabolome.

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood. METHODS: Four hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE. RESULTS: Microbial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed. CONCLUSION: Altogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism.

Saccharomyces cerevisiae fermentation products (SCFP) stabilize the ruminal microbiota of lactating dairy cows during periods of a depressed rumen pH.

BACKGROUND: Effects of Saccharomyces cerevisiae fermentation products (SCFP) on rumen microbiota were determined in vitro and in vivo under a high and a depressed pH. The in vitro trial determined the effects of Original XPC and NutriTek (Diamond V, Cedar Rapids, IA) at doses of 1.67 and 2.33 g/L, respectively, on the abundances of rumen bacteria under a high pH (> 6.3) and a depressed pH (5.8-6.0) using quantitative PCR (qPCR). In the in vivo trial eight rumen-cannulated lactating dairy cows were used in a cross-over design. Cows were randomly assigned to SCFP treatments (Original XPC, Diamond V, Cedar Rapids, IA) or control (No SCFP) before two 5-week experimental periods. During the second period, SCFP treatments were reversed. Cows on the SCFP treatment were supplemented with 14 g/d of SCFP and 126 g/d of ground corn. Other cows received 140 g/d ground corn. During the first 4 wk. of each period, cows received a basal diet containing 153 g/kg of starch. During week 5 of both periods, the rumen pH was depressed by a SARA challenge. This included replacing 208 g/kg of the basal diet with pellets of ground wheat and barley, resulting in a diet that contained 222 g/kg DM of starch. Microbial communities in rumen liquid digesta were examined by pyrosequencing, qPCR, and shotgun metagenomics. RESULTS: During the in vitro experiment, XPC and NutriTek increased the relative abundances of Ruminococcus flavefaciens, and Fibrobacter succinogenes determined at both the high and the depressed pH, with NutriTek having the largest effect. The relative abundances of Prevotella brevis, R. flavefaciens, ciliate protozoa, and Bifidobacterium spp. were increased by XPC in vivo. Adverse impacts of the in vivo SARA challenge included reductions of the richness and diversity of the rumen microbial community, the abundances of Bacteroidetes and ciliate protozoa in the rumen as determined by pyrosequencing, and the predicted functionality of rumen microbiota as determined by shotgun metagenomics. These reductions were attenuated by XPC supplementation. CONCLUSIONS: The negative effects of grain-based SARA challenges on the composition and predicted functionality of rumen microbiota are attenuated by supplementation with SCFP.

Selective Induction of Homeostatic Th17 Cells in the Murine Intestine by Cholera Toxin Interacting with the Microbiota.

Th17 cells play a role as an inflammation mediator in a variety of autoimmune disorders, including inflammatory bowel disease, and thus are widely considered to be pathogenic. However, Th17 cells are present in the normal intestine and show a homeostatic phenotype; that is, they participate in the maintenance of intestinal homeostasis rather than inducing inflammation. We observed an enlarged Th17 population in the small intestine of C57BL/6.IgA-/- mice compared with wild-type mice, which was further amplified with cholera toxin (CT) immunization without causing intestinal inflammation. The increased Th17 induction and the correspondingly 10-fold higher CT B subunit-specific serum IgG response in IgA-/- mice after CT immunization was microbiota dependent and was associated with increased segmented filamentous bacteria in the small intestine of IgA-/- mice. Oral administration of vancomycin greatly dampened both CT immunogenicity and adjuvanticity, and the differential CT responses in IgA-/- and wild-type mice disappeared after intestinal microbiota equalization. Using gnotobiotic mouse models, we found that CT induction of homeostatic intestinal Th17 responses was supported not only by segmented filamentous bacteria, but also by other commensal bacteria. Furthermore, transcriptome analysis using IL-17AhCD2 reporter mice revealed a similar gene expression profile in CT-induced intestinal Th17 cells and endogenous intestinal Th17 cells at homeostasis, with upregulated expression of a panel of immune-regulatory genes, which was distinctly different from the gene expression profile of pathogenic Th17 cells. Taken together, we identified a nonpathogenic signature of intestinal homeostatic Th17 cells, which are actively regulated by the commensal microbiota and can be selectively stimulated by CT.

Postnatal exposure to household disinfectants, infant gut microbiota and subsequent risk of overweight in children.

BACKGROUND: Emerging links between household cleaning products and childhood overweight may involve the gut microbiome. We determined mediating effects of infant gut microbiota on associations between home use of cleaning products and future overweight. METHODS: From the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, we tested associations between maternal report of cleaning product use and overweight at age 3, and whether associations were mediated by microbial profiles of fecal samples in 3- to 4-month-old infants. RESULTS: Among 757 infants, the abundance of specific gut microbiota was associated with household cleaning with disinfectants and eco-friendly products in a dose-dependent manner. With more frequent use of disinfectants, Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of use: adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.08 to 3.45) while genus Haemophilus declined in abundance (highest v. lowest quintile of use: AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74). Lachnospiraceae abundance significantly mediated associations of the top 30th centile of household disinfectant use with higher body mass index (BMI) z score (p = 0.02) and with increased odds of overweight or obesity (p = 0.04) at age 3. Use of eco-friendly products was associated with decreased odds of overweight or obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to 0.86), with no significant mediation (p = 0.2). INTERPRETATION: Exposure to household disinfectants was associated with higher BMI at age 3, mediated by gut microbial composition at age 3-4 months. Although child overweight was less common in households that cleaned with eco-friendly products, the lack of mediation by infant gut microbiota suggests another pathway for this association.

Sex-specific impact of asthma during pregnancy on infant gut microbiota.

Asthma during pregnancy is associated with retardation of fetal growth in a sex-specific manner. Lactobacilli microbes influence infant growth. This study aimed to determine whether lactobacilli and other microbes are reduced in the gut of infants born to an asthmatic mother, and whether this differs by the sex of the infant.Mother-infant pairs (N=1021) from the Canadian Healthy Infant Longitudinal Development full-term cohort were studied. The abundance of infant faecal microbiota at 3-4 months, profiled by gene sequencing, was compared between both women with and without asthma treatment during pregnancy. Infant sex, maternal ethnicity, pre-pregnancy overweight and atopy status, birth mode, breastfeeding status and intrapartum antibiotic treatment were tested as covariates.Independent of birth mode and other covariates, male, Caucasian infants born to women with prenatal asthma harboured fewer lactobacilli in the gut at 3-4 months of age. If asthmatic mothers had pre-pregnancy overweight, the abundance of Lactobacillus in males was further reduced in the infant gut, whereas the microbiota of female infants was enriched with Bacteroidaceae Similar differences in infant gut microbial composition according to maternal prenatal asthma status were also more evident among women with food or environmental allergies.Gut lactobacilli were less abundant in male infants, but Bacteroidaceae were more abundant in female infants at 3-4 months of age, following maternal asthma during pregnancy.

[Support for insomnia : Recommendations for practice in general medicine]. / Prise en charge de l'insomnie : Recommandations pour la pratique en médecine générale.

In Belgium, poor sleep complaints are numerous and frequent in the general population. Of these complaints, one of the most important is insomnia. Acute onset and chronicity of insomnia can be explained by different models based on genetic criteria, neurophysiological, neuroendocrine, neuroimmunological and neuroimaging. Insomnia can be associated with a lot of somatic and psychiatric comorbidities. The diagnosis of insomnia is primarily a clinical diagnosis based on medical history and physical examination. Different tools can help us in our approach, such as self-questionnaires and sleep diaries while additional tests (polysomnography and actigraphy) should be reserved for research of associated sleep disorders and for unclear situations. The management of insomnia can be non-drug treatment (exercise, light therapy, acupuncture and self-treatment cognitive behavioral therapy) but also drug treatment (benzodiazepine, Z-DRUGS, melatonin, antidepressants, herbal medicines, neuroleptics and antihistaminics). Each of these approaches has advantages and disadvantages that must be considered when choosing treatment. The aim of this review is to allow general practitioners to better understand the mechanisms of insomnia and to have recommendations for the diagnosis and treatment of insomnia.

En Belgique, les plaintes de mauvais sommeil sont multiples et fréquentes dans la population générale. Parmi ces plaintes, l'une des plus importantes est l'insomnie. La survenue aiguë et le passage à la chronicité de l'insomnie peuvent être expliqués par différents modèles reposant sur des critères génétiques, neurophysiologiques, neuroendocriniens, neuroimmunologiques et de neuroimageries. L'insomnie peut être associée à de nombreuses comorbidités somatiques et psychiatriques. Le diagnostic de l'insomnie est avant tout un diagnostic clinique reposant sur l'anamnèse médicale et l 'examen physique. Différents outils peuvent nous aider dans notre démarche, tels que les auto-questionnaires et les agendas de sommeil tandis que les examens complémentaires (polysomnographie et actimétrie) sont à réserver à la recherche de pathologies du sommeil associées et pour les situations peu claires. La prise en charge de l'insomnie peut être non médicamenteuse (exercice physique, luminothérapie, acupuncture, auto-traitement et thérapie cognitivocomportementale), mais aussi médicamenteuse (benzodiazépines, Z-DRUGS, mélatonine, antidépresseurs, médicaments à base de plantes, neuroleptiques et antihistaminiques). Chacune de ses approches présente des avantages et des inconvénients dont il faudra tenir compte lors du choix du traitement. Le but de cette revue est de permettre aux médecins généralistes de mieux comprendre les mécanismes de l'insomnie et de disposer de recommandations pour le diagnostic et le traitement de l'insomnie.

Insular infarct size but not levosimendan influenced myocardial injury triggered by cerebral ischemia in rats.

Cerebral injuries can trigger stress-related cardiomyopathy. The extent of cerebral injury and the involvement of the insular cortex influence the incidence and extent of myocardial injury (MI), and drugs with proven neuroprotective and cardioprotective properties such as levosimendan might be beneficial. This hypothesis was addressed in a rat model of transient middle cerebral artery occlusion. Transient brain ischemia was induced for 60 min by intraluminal occlusion of the middle cerebral artery in 40 male Wistar rats. Treatment with levosimendan (24 µg/kg) was started briefly before reperfusion. Hemodynamic parameters were recorded and cerebral and MI quantified after 24 h. Levosimendan treatment significantly reduced cerebral infarct size in the cortex, but not in the striatal and insular regions. However, its effects on survival (28 vs. 45%), incidence of MI (8 vs. 33%) as indicated by a troponin I (sTnI) threshold of 4.8 µg/L and large insular infarcts of ≥10 mm(3) (23 vs. 50%) failed to reach statistical significance. Blood pressure demonstrated significant differences related to insular infarct size during reperfusion. Levosimendan demonstrated no relevant effects on markers of MI (sTnI = 1.5 ± 2.8 vs. 5.3 ± 7.2 µg/L, P = 0.121). Insular infarct size could be identified as the only predictor of MI (odds ratio = 1.86, P = 0.037). In conclusion, the current investigation confirmed insular infarct size as a predictor of MI and source of hemodynamic compromise, but failed to demonstrate an effect of levosimendan on MI trigged by brain ischemia. A hardly protectable insular region might explain this.

Predictors for postoperative nausea and vomiting after xenon-based anaesthesia.

BACKGROUND: In contrast to volatile anaesthetics, xenon acts by antagonism at N-methyl-d-aspartate receptors and antagonizes 5-hydroxytryptamine type 3 receptors that mediate nausea and vomiting. Therefore, it is unknown whether the same risk factors for postoperative nausea and vomiting (PONV) after volatile anaesthetics apply to xenon-based anaesthesia. METHODS: With ethics committee approval and written informed consent, 502 consecutive patients undergoing xenon-based anaesthesia were included in a multicentre prospective observational study. Antiemetic prophylaxis was administered at the discretion of the attending anaesthetists. Postoperative nausea and vomiting and need for antiemetic rescue medication were assessed for 24 h after anaesthesia. Multivariate logistic regression analysis was performed to quantify risk factors for PONV and need for rescue medication. RESULTS: Four hundred and eighty-eight subjects were available for the final analysis. The incidence of PONV in subjects without prophylaxis was lower than expected according to the Apfel Score (28% observed; 42% expected, P<0.001). Independent predictors for PONV were (adjusted odds ratio; 95% confidence interval) female sex (1.76; 1.08-2.89), younger patient age (0.82 per 10 yr; 0.69-0.97), and longer duration of anaesthesia (1.36 per hour; 1.17-1.59). CONCLUSIONS: The incidence of PONV was significantly lower than predicted by the Apfel Score. Female sex, younger age, and longer duration of anaesthesia are risk factors for PONV after xenon-based anaesthesia. CLINICAL TRIAL REGISTRATION: German Federal Institute for Drugs and Medical Devices number AL-PMS-01/07GER.

Acute effects of superimposed electromyostimulation during cycling on myokines and markers of muscle damage.

OBJECTIVES: The purpose of the present study was to evaluate the effects of superimposed electromyostimulation (E) during cycling on myokines and markers of muscle damage, as E might be a useful tool to induce a high local stimulus to skeletal muscle during endurance training without performing high external workloads. METHODS: 13 subjects participated in three experimental trials each lasting 60 min in a randomized order. 1) Cycling (C), 2) Cycling with superimposed E (C+E) and 3) E. Interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), creatine kinase (CK) and myoglobin were determined before (pre) and 0', 30', 60', 240' and 24h after each intervention. RESULTS: Only C+E caused significant increases in levels of CK and myoglobin. BDNF and IL-6 significantly increased after C and C+E, however increases for IL-6 were significantly higher after C+E compared to C. CONCLUSION: The present study showed that superimposed E during cycling might be a useful tool to induce a high local stimulus to skeletal muscle even when performing low to moderate external workloads. This effect might be due the activation of additional muscle fibers and mild eccentric work due to the concomitant activation of agonist and antagonist. However the higher load to skeletal muscle has to be taken into account.

Simplified detection of myocardial ischemia by seismocardiography. Differentiation between causes of altered myocardial function.

Seismocardiography (SCG) is a noninvasive technique for recording cardiac vibrations. Changes in these waves have been correlated with chronic and acute alterations in myocardial function. This analysis is complex and clinical integration limited. The current study aimed to simplify the utilization of SCG by fast Fourier transformation for a reliable discrimination between different intra- and postoperative causes of hypotension (i.e., myocardial ischemia or hypovolemia). We operated on nine pigs and recorded SCG at baseline, at hypovolemia (occlusion of the inferior vena cava), and at ischemia (occlusion of the right coronary artery). In conclusion, SCG enables detection and differentiation of ischemia and hypovolemia as important causes of altered myocardial function during and after surgery. Thus, this simple and noninvasive diagnostic tool may be used intra- and postoperatively to identify patients at risk.

Influence of Feeding Practices on Intestinal Microbiota Composition in Healthy Chinese Infants: A Prospective Cohort Study.

INTRODUCTION: This study investigates the impact of different feeding methods (direct breastfeeding, expressed milk feeding, formula feeding) on the infant microbiota at 6 weeks of age. METHODS: A total of 217 healthy infants stool samples were collected from Hong Kong between August 2018 and December 2019. RESULTS: Various microbial taxa, including the genera Enterobacter and Raoultella were identified in the expressed breast milk feeding group. The richness and composition of the major bacterial phyla showed similar abundance between direct breastfeeding and expressed breast milk. DISCUSSION: These findings suggests that these bacteria may have colonized the milk during expression or could be introduced from other external sources. The mode of breastfeeding did not significantly alter microbiota parameters in the infant gut at 6 weeks.