Circulating perturbation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is associated to cardiac remodeling and NLRP3 inflammasome in cardiovascular patients with insulin resistance risk.

Lipidome perturbation occurring during meta-inflammation is associated to left ventricle (LV) remodeling though the activation of the NLRP3 inflammasome, a key regulator of chronic inflammation in obesity-related disorders. Little is known about phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as DAMP-induced NLRP3 inflammasome. Our study is aimed to evaluate if a systemic reduction of PC/PE molar ratio can affect NLRP3 plasma levels in cardiovascular disease (CVD) patients with insulin resistance (IR) risk. Forty patients from IRCCS Policlinico San Donato were enrolled, and their blood samples were drawn before heart surgery. LV geometry measurements were evaluated by echocardiography and clinical data associated to IR risk were collected. PC and PE were quantified by ESI-MS/MS. Circulating NLRP3 was quantified by an ELISA assay. Our results have shown that CVD patients with IR risk presented systemic lipid impairment of PC and PE species and their ratio in plasma was inversely associated to NLRP3 levels. Interestingly, CVD patients with IR risk presented LV changes directly associated to increased levels of NLRP3 and a decrease in PC/PE ratio in plasma, highlighting the systemic effect of meta-inflammation in cardiac response. In summary, PC and PE can be considered bioactive mediators associated to both the NLRP3 and LV changes in CVD patients with IR risk.

Children can rate perceived effort but do not follow intensity instructions during soccer training.

The perception of effort is elementary for the self-regulation of exercise intensity in sports. The competence for rating perceived effort (RPE) seems to be related to physical and cognitive development. Children accurately rate perceived effort during incremental exercise tests when loads progressively increase, but it remains unclear how children perform when they participate in sports games, which are characterized by complex tasks with varying intensity profiles. The present study investigates children's competencies for rating perceived effort and producing predetermined intensities during soccer training. Twenty-five children aged 11-13 years performed two similar training sessions. In the first session, the children trained without intensity instructions and continuously rated their effort. In the second session, the children were instructed to produce predefined intensities. Before the first training session, executive functions were assessed by cognitive performance tests and a self-report measure. RPE correlated significantly with heart rate measures (R2 = 0.27, p < 0.001). As confirmed by factor analysis, individual differences in these correlations were related to the outcomes of the cognitive tests and the self-report measure. RPE in training session 2 differed from RPE in training session 1 (d = 1.22, p < 0.001), although the heart rate data did not differ significantly between training sessions (d = -0.19, p = 0.780). Thirteen-year-old children performed significantly better than eleven-year-old children (d = 1.69, p = 0.027). The results suggest that children are able to rate perceived effort during soccer training and that this ability is related to executive functions. Conversely, children may not be able to alter their intensities in response to instructions, although their ratings suggest that they have largely succeeded in doing so.

Potential Pathogenic Impact of Cow's Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma.

Epidemiological evidence supports an association between cow's milk consumption and the risk of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma worldwide. This narrative review intends to elucidate the potential impact of milk-related agents, predominantly milk-derived exosomes (MDEs) and their microRNAs (miRs) in lymphomagenesis. Upregulation of PI3K-AKT-mTORC1 signaling is a common feature of DLBCL. Increased expression of B cell lymphoma 6 (BCL6) and suppression of B lymphocyte-induced maturation protein 1 (BLIMP1)/PR domain-containing protein 1 (PRDM1) are crucial pathological deviations in DLBCL. Translational evidence indicates that during the breastfeeding period, human MDE miRs support B cell proliferation via epigenetic upregulation of BCL6 (via miR-148a-3p-mediated suppression of DNA methyltransferase 1 (DNMT1) and miR-155-5p/miR-29b-5p-mediated suppression of activation-induced cytidine deaminase (AICDA) and suppression of BLIMP1 (via MDE let-7-5p/miR-125b-5p-targeting of PRDM1). After weaning with the physiological termination of MDE miR signaling, the infant's BCL6 expression and B cell proliferation declines, whereas BLIMP1-mediated B cell maturation for adequate own antibody production rises. Because human and bovine MDE miRs share identical nucleotide sequences, the consumption of pasteurized cow's milk in adults with the continued transfer of bioactive bovine MDE miRs may de-differentiate B cells back to the neonatal "proliferation-dominated" B cell phenotype maintaining an increased BLC6/BLIMP1 ratio. Persistent milk-induced epigenetic dysregulation of BCL6 and BLIMP1 expression may thus represent a novel driving mechanism in B cell lymphomagenesis. Bovine MDEs and their miR cargo have to be considered potential pathogens that should be removed from the human food chain.

The Role of Cow's Milk Consumption in Breast Cancer Initiation and Progression.

PURPOSE OF REVIEW: This review evaluates cow milk's impact on breast carcinogenesis by linking recent epidemiological evidence and new insights into the molecular signaling of milk and its constituents in breast cancer (BCa) pathogenesis. RECENT FINDINGS: Recent prospective cohort studies support the association between cow's milk consumption and the risk of estrogen receptor-α-positive (ER+) BCa. Milk is a complex biological fluid that increases systemic insulin-like growth factor 1 (IGF-1), insulin and estrogen signaling, and interacting hormonal promoters of BCa. Further potential oncogenic components of commercial milk include exosomal microRNAs (miR-148a-3p, miR-21-5p), bovine meat and milk factors, aflatoxin M1, bisphenol A, pesticides, and micro- and nanoplastics. Individuals with BRCA1 loss-of-function mutations and FTO and IGF1 gain-of-function polymorphisms enhancing IGF-1/mTORC1 signaling may be at increased risk for milk-induced ER+ BCa. Recent prospective epidemiological and pathobiochemical studies identify commercial milk consumption as a critical risk factor of ER+ BCa. Large meta-analyses gathering individuals of different ethnic origins with milk derived from dairy cows of varying genetic backgrounds and diverse feeding procedures as well as missing data on thermal processing of milk (pasteurization versus ultra-heat treatment) make multi-national meta-analyses unsuitable for BCa risk estimations in susceptible populations. Future studies are required that consider all vulnerable periods of breast carcinogenesis to cow's milk exposure, beginning during the perinatal period and puberty, since these are the most critical periods of mammary gland morphogenesis. Notwithstanding the need for better studies including detailed information on milk processing and vulnerable periods of human breast carcinogenesis, the available evidence suggests that dietary guidelines on milk consumption may have to be reconsidered.

Milk Exosomal microRNAs: Postnatal Promoters of ß Cell Proliferation but Potential Inducers of ß Cell De-Differentiation in Adult Life.

Pancreatic ß cell expansion and functional maturation during the birth-to-weaning period is driven by epigenetic programs primarily triggered by growth factors, hormones, and nutrients provided by human milk. As shown recently, exosomes derived from various origins interact with ß cells. This review elucidates the potential role of milk-derived exosomes (MEX) and their microRNAs (miRs) on pancreatic ß cell programming during the postnatal period of lactation as well as during continuous cow milk exposure of adult humans to bovine MEX. Mechanistic evidence suggests that MEX miRs stimulate mTORC1/c-MYC-dependent postnatal ß cell proliferation and glycolysis, but attenuate ß cell differentiation, mitochondrial function, and insulin synthesis and secretion. MEX miR content is negatively affected by maternal obesity, gestational diabetes, psychological stress, caesarean delivery, and is completely absent in infant formula. Weaning-related disappearance of MEX miRs may be the critical event switching ß cells from proliferation to TGF-ß/AMPK-mediated cell differentiation, whereas continued exposure of adult humans to bovine MEX miRs via intake of pasteurized cow milk may reverse ß cell differentiation, promoting ß cell de-differentiation. Whereas MEX miR signaling supports postnatal ß cell proliferation (diabetes prevention), persistent bovine MEX exposure after the lactation period may de-differentiate ß cells back to the postnatal phenotype (diabetes induction).

Enhanced cognitive performance after multiple adaptations to visuomotor transformations.

Several studies reported that adaptation to a visuomotor transformation correlates with the performance in cognitive performance tests. However, it is unclear whether there is a causal relationship between sensorimotor adaptation and cognitive performance. The present study examined whether repeated adaptations to double steps and rotated feedback increase cognitive performance assessed by neuropsychological tests in a pre-post design. The participants of the intervention group adapted in 24 sessions their hand movements to visuomotor transformations with increasing size. Pre-post changes were significantly larger in the intervention group than in a control group without training. This result suggests a causal relationship between sensorimotor adaptation training and cognitive performance.

How to orchestrate a soccer team: Generalized synchronization promoted by rhythmic acoustic stimuli.

Interpersonal coordination requires precise actions concerted in space and time in a self-organized manner. We found, using soccer teams as a testing ground, that a common timeframe provided by adequate acoustic stimuli improves the interplay between teammates. We provide quantitative evidence that the connectivity between teammates and the scoring rate of male soccer teams improve significantly when playing under the influence of an appropriate acoustic environment. Unexpectedly, female teams do not show any improvement under the same experimental conditions. We show by follow-up experiments that the acoustic rhythm modulates the attention level of the participants with a pronounced tempo preference and a marked gender difference in the preferred tempo. These results lead to a consistent explanation in terms of the dynamical system theory, nonlinear resonances, and dynamic attention theory, which may illuminate generic mechanisms of the brain dynamics and may have an impact on the design of novel training strategies in team sports.

Loudness affects motion: asymmetric volume of auditory feedback results in asymmetric gait in healthy young adults.

BACKGROUND: The potential of auditory feedback for motor learning in the rehabilitation of various diseases has become apparent in recent years. However, since the volume of auditory feedback has played a minor role so far and its influence has hardly been considered, we investigate the volume effect of auditory feedback on gait pattern and gait direction and its interaction with pitch. METHODS: Thirty-two healthy young participants were randomly divided into two groups: Group 1 (n = 16) received a high pitch (150-250 Hz) auditory feedback; group 2 (n = 16) received a lower pitch (95-112 Hz) auditory feedback. The feedback consisted of a real-time sonification of the right and left foot ground contact. After an initial condition (no auditory feedback and full vision), both groups realized a 30-minute habituation period followed by a 30-minute asymmetry period. At any condition, the participants were asked to walk blindfolded and with auditory feedback towards a target at 15 m distance and were stopped 5 m before the target. Three different volume conditions were applied in random order during the habituation period: loud, normal, and quiet. In the subsequent asymmetry period, the three volume conditions baseline, right quiet and left quiet were applied in random order. RESULTS: In the habituation phase, the step width from the loud to the quiet condition showed a significant interaction of volume*pitch with a decrease at high pitch (group 1) and an increase at lower pitch (group 2) (group 1: loud 1.02 ± 0.310, quiet 0.98 ± 0.301; group 2: loud 0.95 ± 0.229, quiet 1.11 ± 0.298). In the asymmetry period, a significantly increased ground contact time on the side with reduced volume could be found (right quiet: left foot 0.988 ± 0.033, right foot 1.003 ± 0.040, left quiet: left foot 1.004 ± 0.036, right foot 1.002 ± 0.033). CONCLUSIONS: Our results suggest that modifying the volume of auditory feedback can be an effective way to improve gait symmetry. This could facilitate gait therapy and rehabilitation of hemiparetic and arthroplasty patients, in particular if gait improvement based on verbal corrections and conscious motor control is limited.

Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development.

Multiple biologically active components of human milk support infant growth, health and development. Milk provides a wide spectrum of mammary epithelial cell-derived extracellular vesicles (MEVs) for the infant. Although the whole spectrum of MEVs appears to be of functional importance for the growing infant, the majority of recent studies report on the MEV subfraction of milk exosomes (MEX) and their miRNA cargo, which are in the focus of this review. MEX and the dominant miRNA-148a play a key role in intestinal maturation, barrier function and suppression of nuclear factor-κB (NF-κB) signaling and may thus be helpful for the prevention and treatment of necrotizing enterocolitis. MEX and their miRNAs reach the systemic circulation and may impact epigenetic programming of various organs including the liver, thymus, brain, pancreatic islets, beige, brown and white adipose tissue as well as bones. Translational evidence indicates that MEX and their miRNAs control the expression of global cellular regulators such as DNA methyltransferase 1-which is important for the up-regulation of developmental genes including insulin, insulin-like growth factor-1, α-synuclein and forkhead box P3-and receptor-interacting protein 140, which is important for the regulation of multiple nuclear receptors. MEX-derived miRNA-148a and miRNA-30b may stimulate the expression of uncoupling protein 1, the key inducer of thermogenesis converting white into beige/brown adipose tissue. MEX have to be considered as signalosomes derived from the maternal lactation genome emitted to promote growth, maturation, immunological and metabolic programming of the offspring. Deeper insights into milk's molecular biology allow the conclusion that infants are both "breast-fed" and "breast-programmed". In this regard, MEX miRNA-deficient artificial formula is not an adequate substitute for breastfeeding, the birthright of all mammals.

Acoustic Feedback in Gait Rehabilitation-Pre-Post Effects in Patients With Unilateral Hip Arthroplasty.

It is known that patients after unilateral hip arthroplasty still suffer from a deficient gait pattern compared to healthy individuals one year after surgery. Through the method of gait sonification, it may be possible to achieve a more efficient training and a more physiological gait pattern. Increased loads on the musculoskeletal system could thus be reduced and rehabilitation times shortened. In a previous investigation with this patient group, we found immediate gait pattern changes during training with dual mode acoustic feedback [real-time feedback (RTF) and instructive model sequences (IMS)]. To determine whether an effect persists without the immediate use of acoustic feedback, we analyze data from four times of testing. Following unilateral hip arthroplasty 22 patients participated in an intervention of ten gait training sessions of 20 min each. During gait training the sonification group (SG) (n = 11) received an acoustic feedback consisting of RTF and IMS compared to a control group (CG) (n = 11). Pre-test, intermediate test, post-test, and re-test were conducted using an inertial sensor-based motion analysis system. We found significant effects (α = 0.05) regarding step length and range of motion (RoM) of the hip joint. Step length of the affected leg increased in the SG from intermediate test to post-test but decreased in the CG [intermediate test: (SG) 0.63 m ± 0.12 m, (CG) 0.63 m ± 0.09 m; post-test: (SG) 0.66 m ± 0.11 m, (CG) 0.60 m ± 0.09 m]. However, from the post-test to the re-test a reverse development was observed [re-test: (SG) 0.63 m ± 0.10 m, (CG) 0.65 m ± 0.09 m]. Also, from post-test to re-test a decrease in the RoM of the unaffected hip for the SG but an increase for the CG could be observed [post-test: (SG) 44.10° ± 7.86°, (CG) 37.05° ± 7.21°; re-test: (SG) 41.73° ± 7.38°, (CG) 40.85° ± 9.28°]. Regarding further parameters, significant interactions in step duration as well as increases in stride length, gait speed, cadence, and a decrease in ground contact time from pre-test to re-test were observed for both groups. Clinical Trial Registration: https://www.drks.de/drks_web/, identifier DRKS00022570.

A comparative study on the lipidome of normal knee synovial fluid from humans and horses.

The current limitations in evaluating synovial fluid (SF) components in health and disease and between species are due in part to the lack of data on normal SF, because of low availability of SF from healthy articular joints. Our study aimed to quantify species-dependent differences in phospholipid (PL) profiles of normal knee SF obtained from equine and human donors. Knee SF was obtained during autopsy by arthrocentesis from 15 and 13 joint-healthy human and equine donors, respectively. PL species extracted from SF were quantitated by mass spectrometry whereas ELISA determined apolipoprotein (Apo) B-100. Wilcoxon's rank sum test with adjustment of scores for tied values was applied followed by Holm´s method to account for multiple testing. Six lipid classes with 89 PL species were quantified, namely phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, plasmalogen, and ceramide. Importantly, equine SF contains about half of the PL content determined in human SF with some characteristic changes in PL composition. Nutritional habits, decreased apolipoprotein levels and altered enzymatic activities may have caused the observed different PL profiles. Our study provides comprehensive quantitative data on PL species levels in normal human and equine knee SF so that research in joint diseases and articular lubrication can be facilitated.

[Health risks related to milk consumption: a critical evaluation from the medical perspective]. / Gesundheitsrisiken durch Milchkonsum : Eine kritische Bewertung aus ärztlicher Sicht.

BACKGROUND: Recent epidemiological studies associate the consumption of non-fermented cow's milk, but not fermented milk products, with an increased risk of diseases of civilization. OBJECTIVES: Presentation of epidemiological and pathophysiological data on health risks associated with milk consumption. METHOD: Selective PubMed surveys between 2005-2020 considering epidemiological studies which clearly differentiate between non-fermented versus fermented milk and its potential health risks. RESULTS: Epidemiological studies confirm a correlation between milk consumption and birthweight, linear growth during puberty, acne vulgaris, type 2 diabetes mellitus, prostate cancer, breast cancer, hepatocellular carcinoma, non-Hodgkin lymphoma, Parkinson's disease and over-all mortality. In comparison to milk consumption, the intake of fermented milk/milk products exhibits neutral to beneficial health effects, which are explained by attenuated mTORC1 signaling due to bacterial fermentation of milk. CONCLUSIONS: Long-term persistent consumption of non-fermented milk, but not fermented milk/milk products, might increase the risk of diseases of civilization. The avoidance of milk, especially pasteurized fresh milk, may enhance the prevention and reduce the recurrence of common Western diseases of civilization.

Pasteurized non-fermented cow's milk but not fermented milk is a promoter of mTORC1-driven aging and increased mortality.

Recent epidemiological studies in Sweden, a country with traditionally high milk consumption, revealed that the intake of non-fermented pasteurized milk increased all-cause mortality in a dose-dependent manner. In contrast, the majority of epidemiological and clinical studies report beneficial health effects of fermented milk products, especially of yogurt. It is the intention of this review to delineate potential molecular aging mechanisms related to the intake of non-fermented milk versus yogurt on the basis of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Non-fermented pasteurized milk via its high bioavailability of insulinotropic branched-chain amino acids (BCAAs), abundance of lactose (glucosyl-galactose) and bioactive exosomal microRNAs (miRs) enhances mTORC1 signaling, which shortens lifespan and increases all-cause mortality. In contrast, fermentation-associated lactic acid bacteria metabolize BCAAs and degrade galactose and milk exosomes including their mTORC1-activating microRNAs. The Industrial Revolution, with the introduction of pasteurization and refrigeration of milk, restricted the action of beneficial milk-fermenting bacteria, which degrade milk's BCAAs, galactose and bioactive miRs that synergistically activate mTORC1. This unrecognized behavior change in humans after the Neolithic revolution increased aging-related over-activation of mTORC1 signaling in humans, who persistently consume large quantities of non-fermented pasteurized cow's milk, a potential risk factor for aging and all-cause mortality.

The Pro-Differentiation Effect of Doxycycline on Human SZ95 Sebocytes.

BACKGROUND: Despite their widespread clinical use in both acne vulgaris and rosacea, the effects of tetracyclines on sebocytes have not been investigated until now. Sebaceous glands are central to the pathogenesis of acne and may be important in the development of rosacea. OBJECTIVE: The aim of this study was to assess the effects of doxycycline on the immortalized SZ95 sebaceous gland cell line as a model for understanding possible effectiveness on the sebaceous glands in vivo. METHODS: The effects of doxycycline on SZ95 sebocyte numbers, viability, and lipid content as well as its effects on the mRNA levels of peroxisome proliferator-activated receptors α and γ, in comparison to the peroxisome proliferator-activated receptor γ agonist troglitazone, were investigated. RESULTS: Doxycycline reduced the cell number and increased the lipid content of SZ95 sebocytes in vitro after 2 days of treatment. These doxycycline effects may be explained by an upregulation of peroxisome proliferator-activated receptor γ mRNA levels at 12 and 24 h, whereas troglitazone already upregulated peroxisome proliferator-activated receptor γ levels after 6 h. Both compounds did not influence peroxisome proliferator-activated receptor α mRNA levels. CONCLUSION: These new findings illustrate a previously unknown effect of doxycycline on sebocytes, which may be relevant to their modulation of disorders of the pilosebaceous unit, such as acne vulgaris and rosacea.

The dysregulation of metabolic pathways and induction of the pentose phosphate pathway in renal ischaemia-reperfusion injury.

Lipid accumulation is associated with various forms of acute renal injury; however, the causative factors and pathways underpinning this lipid accumulation have not been thoroughly investigated. In this study, we performed lipidomic profiling of renal tissue following ischaemia-reperfusion injury (IRI). We identified a significant accumulation of cholesterol and specific phospholipids and sphingolipids in kidneys 24 h after IRI. In light of these findings, we hypothesised that pathways involved in lipid metabolism may also be altered. Through the analysis of published microarray data, generated from sham and ischaemic kidneys, we identified nephron-specific metabolic pathways affected by IRI and validated these findings in ischaemic renal tissue. In silico analysis revealed the downregulation of several energy and lipid metabolism pathways, including mitochondrial fatty acid beta-oxidation (FAO), peroxisomal lipid metabolism, fatty acid (FA) metabolism, and glycolysis. The pentose phosphate pathway (PPP), which is fuelled by glycolysis, was the only metabolic pathway that was upregulated 24 h following IRI. In this study, we describe the effect of renal IRI on metabolic pathways and how this contributes to lipid accumulation. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Moderators of Perceived Effort in Adolescent Rowers During a Graded Exercise Test.

Physical activity promotes mental health. A key factor is self-regulation. In the field of sports, self-regulation is related to the psychophysiological competence of rating of perceived effort (RPE). It was reported that adolescents have lower RPE competencies than adults, and it was hypothesized that this effect depends on physiological and cognitive development. The present study investigated in a sample of adolescents whether the RPE is related to basic cognitive competencies. Twelve rowers performed cognitive tests and a graded exercise test on a rowing ergometer, in which they continuously rated their perceived effort. Objective load measures and subjective perceptions were highly correlated (rho = 0.95-0.99). Furthermore, these correlations were inter-individually moderated by measures of mental speed and spontaneous flexibility. The results confirm the significance of basal cognitive competencies for conscious load perception. It is discussed whether regular sport has beneficial effects on the development of RPE competencies by enhancing cognitive regulation.

MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors.

DNA mutation-induced activation of RAS-BRAF-MEK-ERK signaling associated with intermittent or chronic ultraviolet (UV) irradiation cannot exclusively explain the excessive increase of malignant melanoma (MM) incidence since the 1950s. Malignant conversion of a melanocyte to an MM cell and metastatic MM is associated with a steady increase in microRNA-21 (miR-21). At the epigenetic level, miR-21 inhibits key tumor suppressors of the RAS-BRAF signaling pathway enhancing proliferation and MM progression. Increased MM cell levels of miR-21 either result from endogenous upregulation of melanocytic miR-21 expression or by uptake of miR-21-enriched exogenous exosomes. Based on epidemiological data and translational evidence, this review provides deeper insights into environmentally and metabolically induced exosomal miR-21 trafficking beyond UV-irradiation in melanomagenesis and MM progression. Sources of miR-21-enriched exosomes include UV-irradiated keratinocytes, adipocyte-derived exosomes in obesity, airway epithelium-derived exosomes generated by smoking and pollution, diet-related exosomes and inflammation-induced exosomes, which may synergistically increase the exosomal miR-21 burden of the melanocyte, the transformed MM cell and its tumor environment. Several therapeutic agents that suppress MM cell growth and proliferation attenuate miR-21 expression. These include miR-21 antagonists, metformin, kinase inhibitors, beta-blockers, vitamin D, and plant-derived bioactive compounds, which may represent new options for the prevention and treatment of MM.

PCSK9 Expression in Epicardial Adipose Tissue: Molecular Association with Local Tissue Inflammation.

Epicardial adipose tissue (EAT) has the unique property to release mediators that nourish the heart in healthy conditions, an effect that becomes detrimental when volume expands and proinflammatory cytokines start to be produced. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a proinflammatory mediator involved in atherosclerosis, is also produced by visceral fat. Due to the correlation of inflammation with PCSK9 and EAT enlargement, we evaluated whether PCSK9 was expressed in EAT and associated with EAT inflammation and volume. EAT samples were isolated during surgery. EAT thickness was measured by echocardiography. A microarray was used to explore EAT transcriptoma. The PCSK9 protein levels were measured by Western Blot in EAT and ELISA in plasma. PCSK9 was expressed at both the gene and protein levels in EAT. We found a positive association with EAT thickness and local proinflammatory mediators, in particular, chemokines for monocytes and lymphocytes. No association was found with the circulating PCSK9 level. The expression of PCSK9 in EAT argues that PCSK9 is part of the EAT secretome and EAT inflammation is associated with local PCSK9 expression, regardless of circulating PCSK9 levels. Whether reducing EAT inflammation or PCSK9 local levels may have beneficial effects on EAT metabolism and cardiovascular risk needs further investigations.

Tilting Together: An Information-Theoretic Characterization of Behavioral Roles in Rhythmic Dyadic Interaction.

Every joint collaborative physical activity performed by a group of people, e.g., carrying a table, typically leads to the emergence of spatiotemporal coordination of individual motor behavior. Such interpersonal coordination can arise solely based on the observation of the partners' and/or the object's movements, without the presence of verbal communication. In this paper, we investigate how the social coupling between two individuals in a collaborative task translates into measured objective and subjective performance indicators recorded in two different studies. We analyse the trends in the dyadic interrelationship based on the information-theoretic measure of transfer entropy and identify emerging leader-follower roles. In our experimental paradigm, the actions of the pair of subjects are continuously and seamlessly fused, resulting in a joint control of an object simulated on a tablet computer. Subjects need to synchronize their movements with a 90° phase difference in order to keep the object (a ball) rotating precisely on a predefined circular or elliptic trajectory on a tablet device. Results demonstrate how the identification of causal dependencies in this social interaction task could reveal specific trends in human behavior and provide insights into the emergence of social sensorimotor contingencies.